Podcasts about music playing

In this new episode, I have the pleasure of talking to Toku, vocalist and flugelhorn player from Japan. With his deep distinctive voice Toku takes us on a journey beyond musical genres, where artistry and improvisation only matter.The informations about Toku are on his website. You can also follow his Instagram page.Credits :- 10:37 - Toku – Love Is Calling You- 22:18 - Toku – I Think I Love You- 31:32 - Toku Ft. Aisha - Moonshine- 40:15 - Toku, Sarah Lancman, Noé Zagroun – How Do You Keep the Music Playing?- 50:33 - Toku – Be CarefulHébergé par Ausha. Visitez ausha.co/politique-de-confidentialite pour plus d'informations.

It's going to be a special Passover seder this year in Victoria, B.C. for The Klezbians, an all-woman musical group that performs Klezmer music. They're marking 10 years since the band formed to play professionally in 2014. And even before that, the band and their wider group of Jewish lesbian friends have been holding annual inclusive seders, by invitation only, at a private home. These seders started as an alternative to the women's unpleasant memories of their experiences as lesbians at their own traditional family seders, which were usually not welcoming spaces for them or their partners. Over the years, guests have created their own seder rituals, including making their own haggadah. The seder is usually accompanied by live klezmer performances of their favourite Passover songs. For a special Erev Passover edition of The CJN Daily, we're joined by two of The Klezbians to hear their heartwarming story: Debby Yaffe is a retired women's studies professor from the University of Victoria who plays guitar, and Susan Dempsey is a psychotherapist and counsellor who plays the accordion. What we talked about: Read more about the Klezbians on their official Facebook page Check out their music on YouTube Check out Bonjour Chai's “Third Annual Great Canadian Seder” Credits: The CJN Daily is written and hosted by Ellin Bessner (@ebessner on Twitter). Zachary Kauffman is the producer. Michael Fraiman is the executive producer. Our theme music is by Dov Beck-Levine. Our title sponsor is Metropia. We're a member of The CJN Podcast Network. To subscribe to this podcast, please watch this video. Donate to The CJN and receive a charitable tax receipt by clicking here. Hear why The CJN is important to me.

Morning Mixers shared their unique middle names. One Mixer stopped a long family tradition. Nikki's surgeon played "A Space Between" by the Dave Matthews Band during her colonoscopy, so Mixers called in with the music that was playing during their visits. Learn more about your ad choices. Visit megaphone.fm/adchoices

To be fari sometimes I don't know what's going on in my house either

Hilario Durán, the Juno-winning and National Jazz Award-winning pianist and bandleader, is back with his first big band record in 17 years. Hilario joins Tom in the Q studio to talk about the new album, titled “Cry Me a River”. He also tells Tom about his musical journey from growing up in Havana to playing with some of the most influential figures in Cuban music, and what brought him to Canada in the late 1990s.

Episode 2364: Our random article of the day is How Do You Keep the Music Playing? (Johnny Mathis album).

https://www.andrewfreemanmusic.com/home --- Support this podcast: https://podcasters.spotify.com/pod/show/shawn-ratches/support

Introducing Deep Sleep Sounds - the ultimate solution for enhancing your relaxing moments. Immerse yourself in a world of tranquility with our carefully curated collection of soothing sounds. Whether you're studying, working, or simply seeking to unwind, Deep Sleep Sounds is your gateway to a heightened state of calm and serenity.For a better relaxation Deep Sleep Sounds Podcast offers a no ads program that helps you sleep during a full night without the ads: https://www.patreon.com/FullSoundsPodcastSubscribe to our email list for to get notifications every time a new episode comes out: https://full-sounds-podcast.ck.page/99b061d339 Subscribe to our Youtube Channel where we offer black screen sounds the perfect way to listen to our sounds without any distractions: https://www.youtube.com/@FullSoundsPodcastWant to listen to specific sounds please click here and select the sounds you want to listen to. We have a big variety of sounds: https://linktr.ee/fullsoundspodcastAmazon AffiliateThe perfect way to start your day is by exercising and meditating for that we research the best products that will help you archive exercising, meditation and start your day on a positive note:Links:Sleep Headphones Wirelesshttps://amzn.to/439rjvwAir Purifier for Homehttps://amzn.to/3D0pkicDiffuser & Essential Oil Sethttps://amzn.to/3rcHISrCopyright & FAQAll sounds from Deep Sleep Sounds Podcast are copyrighted and not permitted to be reused for commercial purposes.Study, Study Sounds, study time, study nature sounds, study meditation, fall, fall sleep, fall Deep Sleep Sounds, fall relaxing music, fall asleep fast, focus, focus sounds, focus meditation, focus relax, focus music for work, focus time, focus study, anxiety, anxiety relief, anxiety sounds, anxiety meditation, anxiety Deep Sleep Sounds, mental, mental sounds, mental meditation, mental health, mental Deep Sleep Sounds, sleep, Deep Sleep Sounds, sleep time, sleep massage, sleep rain, deep, Deep Sleep Sounds, deep sounds, deep meditation, deep relax, rest, rest time, rest sleep, rest sounds, rest music, stress, stress sounds, stress relax, stress meditation, stress peace, piano, piano sounds, piano relaxing music, piano to relax, piano songs, piano meditationAdvertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy

On today's 1-18-22 Wednesday show: Move over "quiet quitting" there is a new job trend taking over, there's a new website that will tell you if you are getting in to Heaven, Selena is having second thoughts about her bachelorette party destination after her man decides where he is going for his bachelor party, a Lyft driver stabbed an annoying rider in Daly City, Netflix is looking for a flight attendant for their private jet, ticket prices are skyrocketing for the Niner game this Sunday, and a bunch of luxury cars were ruined in San Francisco flooding. Plus tons more!

In this episode I have fun conversation with singer, song writer and writer of young adult books. We has such a fun conversation in which she shares about her music career and her new album "Dear Dairy." She shares some very emotional feelings in this album. I highly recommend checking it out. Also in this podcast episode we have music by  --- Send in a voice message: https://anchor.fm/jody-shuffield/message

As a marriage and family therapist in private practice for more than 4 decades, Sally Strosahl (LCPC) has heard countless stories from couples about distresses in their relationship as they move into retirement and get older. She felt called to write Loving Your Marriage in Retirement: Keep the Music Playing (2018). Sally offers an authentic and reassuring voice for couples who face a myriad of changes during this critical phase in their long-term relationship.  Connect with Sallysally@sallystrosahl.comStrosahl, S. (2018). Loving Your Marriage in Retirement: Keep the Music Playing. In the Round Publishing.

"Teenage Mutant Ninja Turtles, Teenage Mutant Nija Turtles, Teenage Mutant Ninja Turtles, Heroes in a half-shell turtle power". Yep, that's about it.  You watched the show, read the comics, saw the movies, and bought the merch.  Now it's time to re-live that and play this new beat 'em up game by Tribute Games.  Play single player or up to 6 friends.  Play as your favorite turtle or play as Splinter or April.Get ready to kick some butt!!Support the show

Welcome to Secrets of Organ Playing Podcast #693! Today's guest is harpsichordist Alina Rotaru. Alina studied piano and choral conducting at the music academy in her hometown of Bucharest. After moving to Germany, she studied harpsichord with Siegbert Rampe and Wolfgang Kostujak at the Folkwang University of the Arts Essen, with Bob van Asperen at the Conservatorium van Amsterdam, and with Carsten Lohff and Detlef Bratschke at the University of the Arts Bremen. She is an active soloist and ensemble player, and also in charge of various orchestral, opera, and sacred music projects of the German Early and Late Baroque as an artistic director. As a soloist, she has performed across most of Europe, as well as in Japan, South America and USA. She teaches at the University of the Arts in Bremen. Her solo recordings of harpsichord works by JP Sweelinck, JJ Froberger, and English virginalists have earned excellent reviews in the music press and among their peers. Together with viol player Darius Stabinskas, Alina is the co-founder of the ensemble MORGAINE, which focuses on the music of the Polish-Lithuanian Commonwealth. In this conversation, we talk about her love for early music, playing harpsichord and Sigismundus Lauxmin International Harpsichord Contest which she organised the 2nd time this year. Relevant links: https://alinarotarumusic.wordpress.com http://www.bmfestival.lt http://www.bmfestival.lt/bmf2022/en/contest.html​ http://fontesmusicae.pl/notes-editions-c-series/​ http://fontesmusicae.pl/szelest-en/​

https://www.linkedin.com/in/kelsey-tempel/ (Kelsey Tempel) is a Senior Product Manager at https://www.sonos.com/en-us/home (Sonos), a wireless home sound system that fills your home with brilliant sound, room by room. Kelsey comes on the show to dive into all things product development like how to stay focused on your customer through the development process and how to find innovation even with an established product. She discusses what makes Sonos so unique and how they've adapted to significant changes like the prevalence of the cloud and covid. She highlights the importance of automation and rapid iteration in product update cycles and shares what skills she thinks make the best product developers successful. 1:09 - How Kelsey got into product development 6:40 - What makes Sonos different and innovative 11:50 - Best ways to identify customer pain points and evolve a product 12:55 - Impact of Covid at Sonos 15:20 - Role of automation and rapid iteration in product development 18:44 - How to keep innovation going as a product leader  There's A Device For That is hosted by https://www.linkedin.com/in/sjvreddy/ (Sudhir Reddy), SVP of Engineering, of Esper. For more about Esper, visit us. https://blog.esper.io/ (Esper Blog) https://www.esper.io/ (Official Esper site) https://www.esper.io/book-a-demo (Book an Esper Demo)

"Montana (Main Theme)" by Blanck Mass from the soundtrack to Ted K; "Fields of Remembrance" by Plankton Wat from Hidden Path; "I Never Lose, Never Really" by Belong from October Language; "Major Beef" by The Party Dozen from The Real Work; The title track from Beat by Bowery Electric; "Le Palace" by Arp from New Pleasures; "Interstate" by Oog Bogo from Plastic; "A Year Ago" by Carmen Villain from CV x Actress; "A Breath of Fresh Air" by Scout Island from Laurentian Voyage; "Mindflight" by Flying Lotus from the soundtrack to Yasuke; "And Then I Watch It Fall Apart" by Madeleine Cocolas from Spectral; "Lineal" by J. Zunz from Del Aire.

Double T Mornings is the morning show on 96.7 The Eagle in Rockford, Illinois. Not only does Double T play Rockford's favorite Classic Rock each day, he's also joined by many fascinating guests including music legends, comedians, pro athletes, and his own stable of experts on random subjects. Plus, it's a local show, so he's all in for Rockford.

HBK Boom talks getting into music , playing college basketball & more

Hey Kings and Queens, this is a message for my single parents, y'all be encouraged!!! !! **I DO NOT OWNT THE RIGHTS TO THE MUSIC PLAYING!!*** Music Playing in background: Soaking In His Presence by William Augusto. Source: Youtube music.

2022 is music mania! There is so much music playing this year. That winter frost is finally thawed and with it comes a year of music, concerts, and festivals. In this episode, I'm talking about all the live music that I would love to check out this year. Get a full transcript of the show here. What live music are you looking forward to? This episode is sponsored by Anchor: The easiest way to make a podcast. https://anchor.fm/app --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/eat-sleep-breathe-music/message

Markus B Music stops by to chat with Uncle Vinny. Markus is the definition of "Versatile" as he shares his experiences as a drummer, producer, rapper, engineer, and more. We also discuss his upbringing in Parkdale, his interest in the Music Business, being a current Paralegal Student, "Toronto Artist Collective" and much more. Follow Markus @MarkusBMusic to keep up with new projects and performances! Check the following links to keep up with new Versatile Vigilante content: Website: https://versatilevigilante.com Instagram: https://www.instagram.com/VersatileVigilante/ Soundcloud: https://soundcloud.com/versatilevigilante Spotify: https://podcasters.spotify.com/podcast/6rbWSYZP9asHUv431qHZfK/overview Apple Podcasts: https://podcasts.apple.com/ca/podcast/versatile-vigilante/id1384221180?mt=2 SmartURL: https://smarturl.it/versatilevigilante

Vieques Beach ambiance w/ Latin music playing & waves crashing | Outdoor Beach Restaurant Ambience _____ Please subscribe for *DAILY* videos: https://bit.ly/3nKXe3u Link to video: https://youtu.be/C7AUfoC6RQQ ________ Get access to subscriber-only content: 1) 3-Hour episodes 2) Early access to new episodes 3) ** As part of your subscription, you can send us photos/videos of your pet and we'll feature them on the podcast cover art & in the YouTube video along with their name & cute little story subscription link: https://anchor.fm/soothing-soundzzz/subscribe Vieques Beach ambiance outdoor beach restaurant ambience Vieques Beach at night sound Vieques Beach music Latin Music Ambience Vieques Beach at night Vieques Beach ambience seaside cafe ambience outdoor cafe ambience ocean cafe ambience beach cafe ambience tropical music sea cafe ambience beach cafe night beach cafe night ambience beach cafe ambience at night sea cafe ambience at night ocean cafe ambience at night ocean cafe at night ambience sea cafe at night ambience beach cafe at night ambience beach restaurant ambience seaside restaurant ambience surfside restaurant ambience outdoor restaurant ambience _______ BEST 4 AROMAS TO GO WITH VIDEO If you'd like to try combining this audio with the best aroma, here are the 4 best scents for different moods... 1) BEST SCENT FOR SLEEPING, RELIEVING STRESS & ANXIETY *Lavender* https://amzn.to/3D5hIbL Lavender contains linalool that has anti-anxiety effects, but without the negative side effects of many medications. Studies show that the scent of lavender soothes you and helps you relax. It inhibits anxiety, depression -- some studies have shown that it even has a 20% 'better than average' increase on quality of sleep 2) BEST SCENT FOR RELAXING, FEELING GOOD *Vanilla* https://amzn.to/3E38IoW Vanilla oil's powerful aroma stimulates your brain to release endorphins -- Studies have shown that Vanilla fragrance makes you calmer 3) BEST SCENT FOR SHARPER FOCUS *Eucalyptus* https://amzn.to/3xD8pPl Sharp and highly pungent -- inhaling eucalyptus opens your sinuses and clears your head -- widely believed to decrease symptoms of stress -- In one study, 62 healthy people experienced significant reductions in pre-surgery anxiety after inhaling eucalyptus oil. Eucalyptus contains eucalyptol, which has been found to possess anti-anxiety properties 4) BEST SCENT FOR GENERAL ALERTNESS, CLARITY *Peppermint* https://amzn.to/3nZisen The smell of peppermint can mentally perk you up. _________________ SOOTHING SOUNDzzz ON SOCAL MEDIA: TikTok https://www.tiktok.com/@soothingsounds000?lang=en Instagram https://www.instagram.com/soothingsoundzzz/ Facebook https://www.facebook.com/Soothing-Soundzzz-271614694688828/ Spotify (Podcast) https://open.spotify.com/show/6vHMEcA5DQdriv4SBNePwe _________________ More Videos: - SUV Tent Camping in Heavy Rain w/ dimming & brightening candle | Car camping & sleet sounds -- https://youtu.be/Xjwf0-aFARY - Wind Chimes Ocean Waves

In the second of this two-part ASCO Education Podcast episode, Drs. Stephen Berns (University of Vermont), Tyler Johnson (Stanford Medicine), and Katie Stowers (Oregon Health & Science University) continue their discussion about what it takes to deliver serious news to people with cancer effectively and compassionately. If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org.   TRANSCRIPT [MUSIC PLAYING]   STEVE BURNS: Hello, and welcome to the second part of ASCO's Education Podcast focused on clinician-patient communication in the context of delivering serious news to patients and families. My name is Steve Burns. I'm an internist, hospice, and palliative care physician and associate professor of medicine at the University of Vermont College of Medicine. Once again, I'm joined by Katie Stowers, a hospice and palliative care physician and assistant professor of medicine at the Oregon Health Science University, and Tyler Johnson, a medical oncologist and clinical assistant professor of medicine at Stanford University. In our previous episode, we spoke about what constitutes serious news, the best modalities for delivering serious news particularly in the wake of COVID, who might be the best person to deliver it, and the importance of the care team as a whole. We left off on the question, how do we prepare for delivering serious news? Let's continue the conversation. [MUSIC PLAYING]   TYLER JOHNSON: Katie was talking about how we need to be realistic about the way that a conversation is going to impact us in addition to the way that it's going to impact the patient. And one thing that I have realized is that a headline, for those who maybe haven't had evals of training, is just a concise summary statement of sort of the big picture of what's going on, just like buying a newspaper article. And what I have recognized is that oftentimes, I have this almost visceral reaction against giving a headline. And if I drill down just a little bit, what I find is I don't want to give the headline because then I'm really going to have to say things the way that they are, right? If I give a five minute disquisition on creatinine and edema and chemotherapy, immunotherapy, therapeutic options and whatever, right? Then, I can just like talk a cloud around things and never actually say what it is that I'm trying to say, which then gives me the advantage of feeling like I said it, but actually sort of knowing that I never actually said it, right? And so I think the thing that the headline does is it forces me to say the thing. And then once the thing is out in the open, then we can talk about, if necessary and appropriate, some of the other nuances and whatever. But all of that is to say that often, the greatest barrier to doing that is an unwillingness to be real with myself about the information that I'm really trying to convey. KATIE STOWERS: I think this is another really great opportunity where when partners go in together, it's easier to get into the moment if you get the opportunity. Someone with a little bit of accountability, but also somebody to help you. Maybe you're able to get out the facts and they're able to tie-in the meaning. Or you end up going bigger than your headline and they're able to say, I think what you were trying to say was dah-dah-dah-dah-dah, and help really get back to that core. STEVE BURNS: It does say that we all, before we share serious news, making sure whoever you're going in with, you're on the same page. And having a pre-meeting is so important. And what I often do with my pre-meetings is I come up with the headline as the group, right? So we're all clear about what is that headline so that when we go in, we can, in some ways, also hold each other accountable for that headline. KATIE STOWERS: I think also, a little bit of who's going to say it too. Like, is that something that you feel comfortable saying, or would it be easier for somebody else to say? Are there parts of it, and then parts of it that I can do, I think, can be really helpful. TYLER JOHNSON: Yeah. It's funny, because sometimes, even though I'm pretty tuned into these things and I try really hard to do them well, I still find that there are times as a medical oncologist when the palliative care doctor who is unfailingly ever so nice and gracious about it, ends up being like the real human translator for my medical leads. So I, like, say some word cloud. And then the palliative care doctor, like Katie just said, is like, if I can say that what Dr. Johnson was trying to say right there is something in normal human English speak. And then, as soon as they do that, I'm like, oh. But that can actually be really helpful. And again, I think it's obviously not meant to slight me. It's not meant as an affront, right? It's just sometimes, it's just kind of hard to quite get there, right, and to quite say the thing. And sometimes, having someone to help. Like, you get 80% of the way there, and then having somebody else get the other 20% is really, really meaningful. And it also, in a strange way, kind of allows us to share the emotional burden a little bit, right? So that it doesn't feel like, oh my gosh, this is just me saying this thing. There's something about having other members of the team there to kind of hold your arms up as you're doing that that's really meaningful. KATIE STOWERS: I worry that part of this conversation is saying like, oh. Some people are really good at this. Some people aren't. I don't think that this is a palliative care physician's good the whole time. I think this is a normal human experience. This just happened to me. This week in clinic where my patient was like, you just told me like a five minute story of things I already know. And I still don't know any more information. And I was like, oh, that wasn't really clear at all, was it? So I mean, I think it's when our nerves pop up. When we are uncertain or unclear about what it is that we want to say or just really nervous about doing it, like, I think this is our normal human default to go back to beating around the bush. But it definitely, as Steve mentioned, is a skill that we can learn and continue to practice. And it's also really helpful to have somebody there who can hold your feet to the fire and help you in the moment. STEVE BURNS: Katie, I'm so glad you mentioned that. I just think about even for us as palliative care physicians, who do serious illness conversations all the time, catching ourselves doing some things because we are being affected by the conversation and our well-being. I remember a couple of weeks ago, how hard it was for me to say dying and death. And I know. I've been teaching my learners say the D word. It's OK. It's direct. It's straightforward. And then all of a sudden, I was in the middle of the conversation and I noticed I was struggling saying death. And so again, just to say we are human, that these conversations affect us. And having team support is so helpful in the moment. Because the chaplain who I was with said, what we're saying is we're worried that she's dying. And I was like, oh thank god. She said it. TYLER JOHNSON: And the other thing too, right, is that I think it's helpful in a sense to recognize that the difficulty with giving a headline or with saying death or dying or whatever is an impulse borne of human compassion. I mean, it's not because we're bad people. It's because we have good hearts and because short of maybe clergy members, there's really nobody else in the way that human ecosystems are set up that does this, right? It's just a hard thing to do. And recognizing that it's hard and recognizing that we ourselves are having a hard time with it, is not some failing of doctoring. I would say that actually, this is one of those weird instances where having that consistent struggle, that should be a tension that should define part of how we doctor. Because if the tension goes away, that's actually more worrisome than if the tension continues to be there, though we have to find productive ways to engage with it. STEVE BURNS: Yeah. We did a study in 2016, the Vermont Hospice Study, and similar to actually, what Cambia Health Foundation found, why people don't engage in serious illness conversations. And one of the biggest reasons was taking away hope or hurting people's feelings and in causing emotional distress. We also know with the literature that most patients, up to like 90%, 95%, want to know the truth because it helps them better make decisions. And I think we can deliver prognosis in a compassionate way. And I think practicing that in the kind and caring way that's person-centered, asking them, what do you know? Is it all right if we talk about this right now? Delivering in a headline and responding to emotion can help make that a more compassionate conversation. Although it still doesn't take away the human feeling that I'm worried I'm going to hurt someone in this conversation. TYLER JOHNSON: Almost always in my experience, patients who have metastatic disease, or for some other reason, disease that is known from the get-go to be incurable, in one of our first discussions, they will ask some version of the question of how long do I have, or what are things going to look like going down the road? There's good evidence to demonstrate, and it has also been my personal experience, that we're really bad at answering that question at the time of diagnosis, right? Because we don't know anything about the biology of the tumor, the response of chemotherapy, what the molecular markers are. There's a whole host of things that just make it so we almost always cannot answer the question accurately even if we try. And so what I will usually do is I will tell patients, I'll say, when they ask some version of that question, I'll say, look. I need you to know that, first of all, I can't answer that question right now. I'm not obfuscating. It's just, I would be lying if I gave you an answer because we just don't know. But I want to let you know that what is true is that I can usually tell when things are starting to go in the wrong direction. And unless you ask me specifically to do otherwise, I promise you, the patient, that as soon as I recognize that things are heading in a direction that I'm concerned about, I will tell you that in so many words so that you understand what I'm talking about. And then we will have a discussion about where to go from there. And then, when we get to that point, whether it's six weeks later or six months later, or sometimes six years later, I will say-- because I do this with all my patients-- I'll say, do you remember when I made you that promise way back when or a few months ago, whatever it is? And then I'll say, I hope that I'm wrong here. But I'm concerned that we may now be in that place. And I want to tell you why, and then I want to talk about where to go from there. Because that then situates this difficult discussion in the context of this relationship of trust that we've been building over however long I've known the patient. And I have found that that provides a trusting context within which to have the more difficult conversation that has been really helpful. STEVE BURNS: Noticing the time, I'm curious, how does the task of delivering bad news affect your own well-being? TYLER JOHNSON: Just to remind people, we said this before, but I just think it's important to recognize that this being a heavy thing is normal. And recognizing that is normal and that it really is-- I mean, there's some degree to which you can do this well and that will lighten the burden to some degree. But you have to make sure that you're filling your own reservoir, right? You can't pour empathy out of an empty reservoir. And so I think you have to make sure that you're filling that in whatever the ways are that you do. KATIE STOWERS: I just think I was thinking about that too, Steve. One other thing that I wanted to build off of, this fear and this worry that we bring to these conversations, that I'm going to send them into a tailspin of depression. Or I'm going to take away all of their hope. I think there is the other part of this that I get to see as a palliative care physician, which is the high degrees of distress that often come from not knowing this information, that's really helpful in preparing and planning for the future and almost this sense of relief. Even when it's unfavorable, even when it's not what they wanted to hear, there's a relief in knowing and being able to do something with it. So that limbo and uncertainty. the idea that something terrible is out there or they can't prepare for it can be really distressing. And so to some degree, we're helping to heal by being able to move into some planning. STEVE BURNS: Yeah, I totally agree that it's such an important thing to minimize the stress of uncertainty. And the other piece that I think about is these are really sacred moments where we can really connect with our patients, share the news, find out how they're doing with it, and then find out what really matters in their lives. I think that really helps be my north star when it comes to continuing the care that I'll provide for them in their families. TYLER JOHNSON: Yeah. You know, there's a really harrowing, in some ways, but beautiful moment. And many of you will probably have read the book Just Mercy, which is written by this lawyer who's fighting for justice, particularly racial justice, for people who have been unfairly treated by the justice system in the deep South. And there's this moment towards the end of the book where a person who he had been fighting for who was on death row has just finally been executed. And he goes home and sort of just collapses crying. And then he writes really beautifully about how this moment of sort of shared vulnerability, where he kind of recognized that the reason that this was so hard was because even though he was vulnerable and broken in different ways than the person who had just been executed, it was still sort of a shared sense of vulnerability. It was what made his work hard, but also what made his work beautiful. And I think that in a similar fashion, when we have these really difficult discussions, I think that while there is a real moral weight and difficulty to it, there is also just as you said, they also end up being some of the most meaningful, memorable, and beautiful moments. STEVE BURNS: As a clinician, what have you learned over the years regarding communication with patients that may help others navigate scenarios where they can deliver serious news? I was just on service with a trainee. The team was delivering serious news. It was serious news around lung cancer. And the team's like, this patient's just not getting it. And we tried to explain it over and over again. And they're not getting it. And then my trainee went in and attempted and said, yes. Here's your diagnosis. We're concerned it's incurable. And you likely will die in the next year or so. And the patient said, no. I'll be fine. So we hypothesized before going in the room with me, like, what it would be. And what it came out is maybe it's not they're not understanding it. Maybe it's emotion. So we went back in. And sure enough, my trainee did wonderful and responded to emotion and said. It must be really hard hearing this news. And the patient immediately got sad and said, I'm really scared. And we unpacked that a little bit. And when we left the room, he said to me, yeah. That was emotion. He totally gets it. He's just upset. And so I just want to reiterate the idea, sometimes, it's not that they're not understanding it. It's that it's a lot to process. And there's a lot of feelings behind it. KATIE STOWERS: Building on that, one of the things that I see happen a lot around emotion is the health system is not set for people to process and to come to terms with these hugely life things and life-altering things. There's not time for people to process what this means for their life to term and process that emotion. And we're constantly pushing. And sometimes it almost could feel like badgering, really trying to get a decision to come where, with some degree of autonomy and some degree of time, allowing them to really process. People, a lot of times, get to where they need to go. But it's a process of really being able to deal with. STEVE BURNS: Yeah. TYLER JOHNSON: Yeah, the only thing that I will add is that these conversations, when they need to happen, work best when I have been mindful of laying the groundwork for the conversation over the entire arc of the illness. Rather than thinking of, oh, this is the thing that I do right when someone is getting close to dying. Because if you've never laid the groundwork and then you try to have the discussion, then when the person is really, really sick and in the hospital or whatever, of course, there's still a better and a worse way to do that. But even the best conversation if it's that isolated incident, in my experience, is nowhere near as good as if we have been transparent and building trust and building a sort of a shared vocabulary with the patient over the course of the illness. So that then, when they get to having to have quote, "the discussion" unquote, it becomes just one part of this longer chain rather than an isolated happening. And that really gets to what I was saying earlier about the promise that I make my patients when they first ask that sort of big picture question. That even though I'm not in a good place to talk about it right then, that I promise them that when it comes time, I will talk with them about that with candor. That makes an enormous amount of difference. I know I had a trainee who was with me one time who was a continuity fellow with me and had heard me make that promise to a number of patients and the first time he was with that same patient when it came time to have that discussion. And I said, well, you remember that promise that I made the first time I met you? And he could, for the first time, see all of the dots connect over the arc of the illness. It was like, whoa. Like, there's just really this power that comes. But you have to have been building it piece by piece over time. STEVE BURNS: I think both of you are highlighting for me two reminders that I want to keep in mind every day when I'm delivering serious news. One is sort of having an agenda but being flexible with my agenda. And I remember during my training, one of my mentors said, keep your agenda out the door. Don't force your agenda on the patient, as Katie mentioned. And yet, have a plan and still go in with that plan. The other piece that Tyler, you're reminding me of, is the importance of the arc of the conversation and how continuity. Because we build off of conversations from visit to visit. And yet, sometimes, someone else is taking over for us or they end up in a hospital or they end up in a nursing home. And it reminds me how important documentation is to convey what happened in that encounter. What was said, what was the headline that was shared, how did the patient respond, and then what was the plan. And far too often, we usually just write the results of the conversation. TYLER JOHNSON: Yeah. One last thing that I want to put a specific plug in that I have found to be enormously important, I think all of us would agree that amidst all the conversations that we might have as part of taking care of a patient, this is the one where shared decision-making matters the most. And yet, if you ask most people, even experienced doctors, how do you engage in shared decision-making around this kind of question? That's really tricky, right? Because I think what often ends up happening is that we either default to being very prescriptive where we go in and say, well, you should do this or shouldn't do this. Or we default to being waiters with the menu. Like, well. OK, so would you like some intubation on the side of CPR? And so, I think that both of those models are equally problematic and that the tool, the specific tool that has helped me really learn about how to do shared decision-making and even provides the specific words, is what's called the Serious Illness Conversation Guide from the Ariadne group at Harvard, which is the group founded by Atul Gawande and his colleagues. And I think that that gives a very brief script which, I mean, you can literally almost just read. You can get a little card that you can carry in your pocket or whatever. And it gives-- and the entire conversation in most cases, takes maybe 10 or 12 minutes. But it gives you the point-by-point things to say and really allows you to meaningfully engage in shared decision-making so that you spend the first half of the conversation listening to the patient's priorities and values, and then the last maybe third of the conversation, using that to make meaningful recommendations. And so again, it's called the Serious Illness Conversation Guide. And I would really recommend to listeners that they look it up. STEVE BURNS: That's a really great segue to what training and resources are there for clinicians and oncology trainees to improve their communication skills. The three resources that I can think about are Vital Talk, the Serious Illness Conversation Program out of Harvard and Ariadne Labs, and then they have a rich program which is from the American Academy of Communication of Health Care. All three are different ways of approaching communication skills training. I always think about the Serious Illness Conversation Programs about raising the floor to make sure that we hit the basics. And then Vital Talk is if you want to flex your muscles or flex your skills when it comes to how do I respond to really intense emotion, or if someone's avoiding the conversation, what do I do? They train with raising the ceiling or their goals to raise the ceiling. And Vital Talk actually came out of oncology conversations first with OncoTalk almost 20 years ago. And really thinking about not didactic-based, but practice and skills-based training. And I certainly have found it rewarding and life-changing for me, where I could actually label the things that I do every day, give myself some feedback, and then teach my trainees. TYLER JOHNSON: And I will just add, as a medical oncologist who has both taken the Vital Talk course and now is trained and teaching Vital Talk courses, that this is not just for palliative care doctors. And I think that it is particularly-- I mean, you may not have the interest or passion to want to become a Vital Talk trainer, which is understandable if you're a medical oncologist, either a busy practice or a heavy research portfolio. But it's just to say that they offer 1 and 2 and various iterations of courses, depending on how intensely you want to study these things. But it's just to say that the skills that they teach are concrete. This is not some sort of head in the clouds theoretical exercise. I mean, they're taught very concrete skills that you can wake up the next morning and employ you in your practice. And that I think to a point that is often counterintuitive to us, I think that we are almost afraid, as oncologists, to know about this because we think, oh my gosh. I didn't have time to engage in these long discussions. There's no way. But my experience has actually been what this does at the end, is it actually makes you more efficient. I know that seems counterintuitive, but we spend so much time sort of beating around the bush around this stuff that we actually end up making ourselves take longer. And having really concrete skills for how to have these discussions can actually make your practice more efficient for things that otherwise can really eat up a lot of time. KATIE STOWERS: I do a lot of teaching in Vital Talk incentives. It sounds like both of you do as well. But the piece of feedback that I hear from trainees that come take courses-- and I do a lot with oncologists and oncology fellows as well-- is oh, these are the things that I've seen in conversations at work that I never had a name for. Like, you're putting a name on something that I've seen. And maybe I've done a couple of times, but I didn't know that I was doing it this way. And especially for my colleagues who are practicing providers who teach others, they really love having a name and a framework for being able to teach these skills to others. It's not some magic fairy dust that you either have or you don't. It's actually, here's a skill that I can pass on to you and you can practice. And I can watch for, and we can have some feedback about. And I have seen that being a really enjoyable part of doing this framework. We have that, right, for almost every other part of medicine. But because communication is something that's so innate and personal, that hasn't always been the case around communication. And so I really love that about Vital Talk, that they've taken these pieces and put names on them. Because this is how you give communication clearly, information clearly, is the headline. This is how you show someone that you care about them. These are empathic statements. And that's something that we can use as a third language when we're going into team meetings together or when we're teaching a trainee. STEVE BURNS: It's one of the most important skills that we do every day, and probably the most important procedure that we do on a regular basis in all of our fields. TYLER JOHNSON: And I think you can tell from the way that the three of us have discussed delivering a headline during this podcast, that this is not like a thing that we learned seven years ago and then just sort of left in a drawer somewhere, right? Like, this is something that we're actively thinking about as we actually take care of patients every day, which is to say that it really is very applicable. STEVE BURNS: I feel like that's the time for today. This has been a really great conversation. Thanks so much for both of your insights and participation in this episode of the ASCO Educational Podcast. KATIE STOWERS: Thanks for inviting us. It's been great to be here. TYLER JOHNSON: Thanks so much. It's been a pleasure. [MUSIC PLAYING]   SPEAKER 1: Thank you for listening to the ASCO Education Podcast. To stay up to date with the latest episodes, please click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive education center at Education.ASCO.org. SPEAKER 2: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hey King and Queens, I pray all is well with each of you!!!! Listen, GOD is speaking in this season, He that has an ear let him hear what the spirit of the Lord is saying!!!!! **I DO NOT OWNT THE RIGHTS TO THE MUSIC PLAYING!!*** Music Playing in background: Soaking In His Presence by William Augusto. Source: Youtube music.

Hey Kings and Queens, this is a word from the Lord, he that has an ear let him hear what the spirit of the Lord is saying!!!! **I DO NOT OWNT THE RIGHTS TO THE MUSIC PLAYING!!*** Music Playing in background: Soaking In His Presence by William Augusto. Source: Youtube music.

Hey Kings and Queens, its time to let GOD complete us!!!! Get a personal relationship with GOD, marry him; man or woman you need to be in covenant with GOD!! **I DO NOT OWNT THE RIGHTS TO THE MUSIC PLAYING!!*** Music Playing in background: Soaking In His Presence by William Augusto. Source: Youtube music.

My guest today is Dr Hane Aung Co-Founder of GroovSense - a leading global UK MusicTech company on a mission to automate the social music playing experiencevia their AI Music Selection App. In this episode, Dr Hane and I discuss the ins and outs of automating the social music playing experience. Using artificial emotionally intelligent technologiesto create the perfect playlist.Podcast or vlog: The Power of Audio + Science + AI with Jasmine Moradi (https://www.jasminemoradi.com, Spotify, Apple Music & Google Play)Soundbites:#1 Dr Hane Aung's career journey from breakdancer, to Behavioural Computer Scientist to the Co-Founding GrooveSense. #2 How GroovSense is combing Artificial Emotionally Intelligent technology to automatically analyse the mood of the party crowd as it changes. (12:50)#3 Now music fans around the world can create the perfect real-time ‘hosted' party playlist with GroovSense. (23:46)#4 The ABBA Journey - how GroovSense scientifically learns about the crowd (30:28)#5 The GroovSense DJ Dashboard helps DJs make the best music selections based on the crowd's tastes. (43:23)#6 How businesses such as restaurants, clubs and retail can utilize GroovSense to automatically measure the behaviour customer sentencing to maximize their in-store music. (49:05)#7 GroovSense App vs. Social Jukebox App (56:35)#8 Dr Hane Aung' predicting the future of real-time behavioural sensing technology and GroovSense. (1:01:39)Host:

In this Oncology, Etc. episode, Drs. Patrick Loehrer and David Johnson Speak with Drs. Lecia Sequist (Massachusetts General Hospital) and Melissa Dillmon (Harbin Clinic) on how ASCO's Leadership Development Program (LDP) has taken them down varying paths, as well as the ways it has influenced their lives, careers, and the lives of those around them. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 2/1/22   TRANSCRIPT [MUSIC PLAYING]   PAT LOEHRER: Hi, I'm Pat Loehrer. I'm director of the Center of Global Oncology here at Indiana University. DAVID JOHNSON: And hello. My name is David Johnson. I'm at UT Southwestern in Dallas, Texas. So Pat, we've got a couple of really great guests today. PAT LOEHRER: Yeah. I'm really excited. I've been looking forward to this. DAVID JOHNSON: So have I. Listen. Before we get started, I have a book I want to recommend to you. This one I got over the holidays and just finished it recently. It's called The Doctors Blackwell by Janice Nimura. So as many of our listeners know, Elizabeth Blackwell was the first female physician in America. Her sister Emily also followed her into the medical profession. Nimura really writes, I think, a fascinating biography about both ladies, particularly Elizabeth. And one point she made, and I think it's interesting, it's not really clear why Elizabeth went into medicine. Certainly at the point that she did in the mid-1800s wasn't a profession of great reputation at that time. And, in fact, Nimura describes Elizabeth as, quote, "lacking a caring instinct," which I thought was an interesting characterization of the first female physician. And she indicated that she was hardly a feminist. She was actually opposed to Women's Suffrage, for example. According to Nimura, she became a doctor largely just to show that she could. And then, really, the rest of her career I won't give away. The subplot is really quite interesting. I think you would find it most interesting to recommend to you and our listeners who have a particular interest in medical history. PAT LOEHRER: Actually, I've ordered the book. I can't wait to read it. DAVID JOHNSON: Excellent. PAT LOEHRER: I got a book for Christmas, Lyrics by Paul McCartney. And I read through that. That's fascinating, actually. So 158 of his songs were detailed and the backgrounds for it. So that was kind of fun. We're excited today because we're going to talk to a couple of graduates of our Leadership Development Program. That was a program of ASCO that was conceived a little over a decade ago. It's been, to my mind, one of the best programs that ASCO has done. It has taken younger faculty and oncologists from around the country, and Dave and I were among the first leaders of the program as mentors. I think that was one of the bigger mistakes ASCO has ever done. But despite that, we have a lot of fun. There were 12 graduates each year. They all had projects they presented to the board of directors. There were, if you will, classes and lectures throughout the year on leadership. And they all had projects. And for me, it was the best three years of my life, I think, through ASCO. It was just a lot of fun. And part of it was getting to know a lot of people, including Melissa and Lecia, who are with us today. Lecia is a Professor of Medicine at Harvard and Mass General Hospital. She did her medical school at Harvard, residency at Brigham and Women's Hospital, fellowship at Dana-Farber. She is currently the co-leader of the Cancer Risk Prevention and Early Detection Program at Dana-Farber and director-- I think I want to hear more about this-- she's the director of the Center for Innovation in Early Cancer Detection at MGH. Melissa, she went to Converse College in Spartanburg, South Carolina, went to medical school at Wake Forest. Then did her internship and residency at UAB. She did her fellowship at UAB. And she now serves as the Chairman of the Department of Oncology and the Board of Directors at the Harbin Clinic. And we're so excited to have both of you here. DAVID JOHNSON: Yeah. Very much so. And why don't we get started by just getting a little background information. Melissa, let's start with you. Can you tell us a little bit about how you got into medicine and, more specifically, why did you choose oncology? MELISSA DILLMON: That's a great question. I was a political science major at a women's college in South Carolina and was destined for the State Department. And we used to have January terms. And I mistakenly got put with-- and I don't think it's a mistake-- former graduate of Emigre Medical School, who is a medical oncologist in Greenville, South Carolina, for a six-week term and fell in love with medicine, fell in love with the ministry that he provided to his patients, and followed him to Bowman Gray and went back years later and told him thank you for changing my life. So that's how I got interested in medicine. I come from a long line of accountants and engineers. There is no person in my family in medicine. PAT LOEHRER: I was an engineer. Some of the best people in life are engineers. DAVID JOHNSON: I didn't know you drove a train. [CHUCKLES] PAT LOEHRER: Eat your heart out. DAVID JOHNSON: So Melissa, before you leave, I actually grew up very close to where you practice. How did you end up in Rome, Georgia? MELISSA DILLMON: Well, my dad and his twin are proud graduates of Georgia Tech. So he found me a job. And I said, well, I'm grown up. I was going to stay on faculty at UAB but came to Rome, Georgia and really was excited about the multispecialty group that I ended up joining. There's about 250 of us now. And kind of had the feeling of a university but in a small town. Kind of best of both worlds. Neither of my two daughters have gone to Georgia Tech. One of them is at Georgia. Just won that national championship. But my third one, we're hoping maybe she'll be the one that goes to Georgia Tech. PAT LOEHRER: So you stayed up and watched the game. I have to ask this, right? MELISSA DILLMON: I did. I stayed up to the very end. PAT LOEHRER: And so who are cheering for? Alabama or Georgia? MELISSA DILLMON: Definitely Georgia. PAT LOEHRER: Interesting. Good. Good. DAVID JOHNSON: And Lecia, why don't you tell us about your background and how you got interested in oncology. And let us know if MGH has a football team. [CHUCKLES] LECIA SEQUIST: Oh, sure. Thanks for having me here. This is going to be a fun conversation. So I grew up in the Midwest, in Michigan. But I've been on the East Coast now for the majority of my life. And when I was a resident, I was actually in a primary care track residency program, because I thought I wanted to be a primary care physician. And I really liked the idea of sticking with people, getting to know them over long periods of time, and kind of standing by them through the highs and the lows of their lives. Well, I was finding out in residency that primary care wasn't really like that. That was for television shows. People change primary care doctors and move around so much, it's rare that you actually do get to take care of people for a long time, at least in a big city. And I also found that, for me, primary care was a lot of asking people to do things they didn't want to do-- exercise, lose weight, stop smoking, do this, do that. And I always felt that I was at odds with my patients or nagging them. And then, when I would be in the hospital on oncology rotations, trying that out, I really felt like I was allied with my patients and not nagging them or pushing them, but really here we were together against this fight against cancer. And cancer was what we were fighting together. And I just fell in love with that. So much to the disappointment of the residency program that was really trying to get people to go into primary care, I said, I've got to be a specialist. And here I am. PAT LOEHRER: It's interesting, though, that you do risk reduction and prevention. So you're back to telling patients to lose weight and exercise again, you know? [CHUCKLES] LECIA SEQUIST: Yeah. I guess, in some ways that's true, although I'm not really taking care of primary care patients. But after spending a lot of years doing a more traditional medical oncology track of drug development and targeted therapies, the last five years I have switched my research over, kind of a midlife crisis situation, where I said I've got to do something different. I'm in a rut. And I started looking at new technologies for early detection. And I really enjoyed it because it's something different. For one thing, I just felt like I was in a rut. But it's really a way to be a lot more proactive with the community and to work on issues of social justice, thinking about cancer screening, and who has access and who doesn't, and what can we do better. So I'm really enjoying that in this phase of my career. PAT LOEHRER: Terrific. The four of us are linked because of this Leadership Development Program that the American Society of Clinical Oncology put together. And I think Dave and I are really curious whether, here it is many years later now. It's been almost 9 or 10 years later now. As you reflect on the LDP, what are some of the highlights? What did you learn about yourselves and was the program worthwhile for you? MELISSA DILLMON: Well, I'll start. I was part of the class, 2010-2011, best class ever. And it was the second class in the Leadership Development Program. I applied for the first year's class and didn't get it. And one of my friends and partners, a radiation oncologist, who was very involved in ASCO, encouraged me strongly. Said, don't give up. Try again. And I did. And it was instrumental in developing both my career within ASCO as well as pushing me to leadership positions in my own clinic and in my own state. And helped develop a lot of skills that have made me successful in pushing state legislative efforts. My political science background did not go away, just like her primary care roots. And so I think that the program also made friends with Pat and with Dave and with my co-classmates. And as the years have gone by, and I've gone to ASCO, when you see that LDP ribbon on somebody's tag, you immediately have a connection with them and know that you've been through a similar experience. So I think it's been really instrumental in developing my career. And I'm currently serving as a mentor for the leadership program. So I'm living your life 10 years ago, Pat and Dave, and it's great. DAVID JOHNSON: Oh, I'm sorry. PAT LOEHRER: Terrific. DAVID JOHNSON: [INAUDIBLE] LECIA SEQUIST: I would echo what Missy was saying about how much it's influenced my career. I was in the 2011 class. So I think the year after she was. And I also applied multiple times, and I always tell people who are thinking of applying that it often does take multiple attempts to get in and not to lose faith. The selection committee does like to see that persistence. So definitely apply more than once. I learned so much about what leadership is. I thought it was about being the best in a group of people. So then, being selected to have a certain title. And I just really learned so much during that year, that it doesn't really have anything to do with a title, although that can be a part of it for some people. But it's just more about a style, an approach to your profession, and that you can be a leader if you are the designated head or chief of something, but you can also be a leader if you don't have that designation. And there are many different styles and ways to lead and to help people to ultimately get a group to do the very best that they all can together. And the friends that I made that year from my co-classmates as well as you guys and Jamie, who are our leaders, are just lifelong friends and mentors. And you know, I think it really got me thinking seriously about my choices in my career too and not to just kind of cruise through a career and see what happened and where life took you, but to really plan and to chart your own course and to make sure to reevaluate. And if it's not going the way you want it to, to rechart and replan. DAVID JOHNSON: We had a bunch of different lectures on different topics. Was there one of the lectures or areas that was particularly beneficial to you? PAT LOEHRER: I can think of one. I'll start out by doing this. We threw this in the second year, just for the heck of it. We did this personality testing. And I thought it was fascinating because, in my group, there was a little bit of conflict going on with one of the people in my group. And I realized that we were both acting out our personalities. I like to look at the big picture, and he liked to just zoom in the middle one. And the other thing that I do remember is that we showed the profiles, and it turned out Dave and I were exactly opposite. And then we both said at the same time, we should be married. [CHUCKLES] MELISSA DILLMON: One lesson that stands out in my mind was the press preparation lesson that we received from Press Relations group at ASCO. And I think that was essential for developing skills with regards to preparing for difficult conversations and being able to redirect questions that were difficult. I use that as leader of the Government Relations Committee oftentimes. I will also say that the other lesson that stands out in my mind is conflict resolution because, at the time, I was not chair of my department and was having significant conflicts with the current chair of my department. And that lesson helped me to go back week after week and more constructively work towards a solution and then eventually became chair of that department. So I think those two lessons gave me lifelong skills that I've used in all my leadership roles. LECIA SEQUIST: Yes, it's amazing how 10 years later, we can still remember the specific lectures and specific comments that people made. I remember those that you were talking about Melissa, but yeah, before you had said yours, Pat, I was going to say the same thing, that personality test was extremely helpful. And I certainly don't remember all of the different initials of the personality types. But just to understand that concept that people have different emotional skills and blind spots that very much influence how they deal with others in the workplace. And to be able to think about that when you're having conflict with someone and think about how to take that into a strategy where you can kind of play to their strengths and understand where they're coming from, that was extremely helpful. And then, I also think that talking in small groups with our teams about specific problems we were having or obstacles that we were facing and getting advice from others on how to overcome them, that really started me on a recurrent mission to find friends who I could share that with outside of my institution, over the course of my career. I think that was a real exercise in how valuable that could be. It's so critical to have peer mentors that you can talk to and strategize with and get advice about how to handle something that you're struggling with at work and have people that aren't in the same room full of people or aren't living in it. So they're a little bit more objective. DAVID JOHNSON: Let me ask a question of the two of you. Do you think your home institutions in your case, Lecia, MGH and in your case, Missy, Harbin Clinic, valued that training that you received? Did they recognize it as something that was worth the time that you spent or do you think it just something that happened and they didn't really take notice? MELISSA DILLMON: I learned in LDP that institutions don't love you back. PAT LOEHRER: They don't love you to begin with. Joe Simone. Joe Simone. DAVID JOHNSON: So I take that as a no. Your institution really said, eh, OK, great. We're glad you did it, but so what? LECIA SEQUIST: I wouldn't say that. I don't know that they said, so what? I just, I'm not sure that they-- there was no rolling out the red carpet, thank goodness you did this. But I do think it's had an institutional impact in that I have since encouraged other people to apply from my institution. And I think that only strengthens the institution, to have multiple people going through that program. MELISSA DILLMON: So my clinic, being private practice, when I take time out, it is just a cut from my salary. There's no support given from the institution. But in order to be in positions of leadership, department chair or on the board of directors, which I later was elected to of the clinic, you have to have completed a leadership development program. And the clinic will pay for you to go do those things. But my participation in Leadership Development Program met all those criteria. So my clinic highly values professional development classes or meetings or programs and encourages that. Even if there's no financial support necessarily, it is encouraged, if you want to assume positions of leadership within our clinic. And so I think that it's important for institutions, whether they're private practice or university, to recognize the benefits that come from participation in a program like this. And it was interesting as a mentor this year, we did a personality test, but this time they did an interesting look at what our priorities, our top five priorities or values are. I think it was values. And it was a list of 300 things basically you go through. And you listed your top five values. And then you listed the values of your institution or employer. And then you wanted to look at, did they match? And did your university value what you value? And that was a really interesting exercise to go through because a lot of these young leaders who are taking their time out to do this program did not feel that support necessarily for them seeking out this program. PAT LOEHRER: It's no coincidence that Dave and I asked both of you to join because you both come from different places, if you will. And I think, Melissa, you've just been a rock star in terms of the community practices and so many things that you have done in the leadership roles. And Melissa's, you can't get any more prestigious in being in one of the Boston medical schools and particularly at Mass General. But the other reason we wanted to have you come in is to talk a little bit about your perspective as women and women in leadership roles. And if you could maybe share a little bit about your thoughts and perspectives of gender leadership and what you have noticed in men in leadership roles and women and what lessons you might give to other people, particularly other women in this capacity. MELISSA DILLMON: Well, I think we both were trained in a day. And I might be speaking for you, but when there were, at least here at the institutions where I trained, not that many women in internal medicine. Medical school was probably 45% female by the time I was in medical school. But when you look at the faculty of those medical schools that I went to and trained at, there were very few women in positions of leadership. And so there weren't very many role models. My dean of students at Wake Forest was a female nephrologist. And so she was a huge role model for me. And then I went to UAB, and I remember being asked in my interview, are you OK with being in a male-dominated program? Because you will be in a male-dominated program. I think there were 45 of us in my intern class, and eight of us were female. And I said, that's fine. But I had gone to a women's college, where obviously there were only women leading. So it was a big change for me to go back into a situation where I had to assert my unique female leadership qualities, which are different, and still use those in an effective way to lead. Right now, I'm serving as a mentor also for a small liberal arts college, primarily those interested in going into medicine or nursing, and usually most of those have been female. And so it's been a really great opportunity, because I've had very few mentors who were female, who were positive role models for me. So I think Leadership Development Program, one of the things they taught me was to go back and say thank you to your leaders and to be a leader for others. And specifically, as a female leader, I think that has been an important call for me. After leaving Leadership Development Program, I went back and ran for the board of my clinic as the first female to be on my board. My clinic was started in the 1860s, I think right after the Civil War, and I'm still the only female on that board. And I feel that it's important for me to stay there or to promote up more females within my clinic to be on that board because I think that having a diverse board helps in bringing different skill sets to the table. So I think Leadership Development Program gave me that courage to step up. LECIA SEQUIST: That's inspiring. Congratulations on being the first woman and may there be more soon. Yeah. I don't know that I've felt that I was in as much of a male-dominated field up in Boston. But certainly, leadership in my hospital and in my cancer center has been more male-dominated. And I think as I'm getting older now, I definitely appreciate-- of course, every individual has different leadership style. So you can't just paint a broad brush and say men are this type of leader and women are that type of leader. Everyone's a little bit different. But in general, I think women do tend to have a different leadership style and one that is maybe, present company not included, one that's less talking and more listening. And I think, when I was younger and trying to become a leader, I really felt out of peer pressure that I needed to talk more and sort of demonstrate more what a good leader I could be or what great thoughts I had. And I've really come to embrace a more listening type of leadership, which I have been happy to say that younger women that I work with have come up to me privately and thanked me for. And so I do think it's important to have all different types of role models for our junior faculty and all different types of styles, sort of on display and doing their best so that people can find something that matches with their own unique style to emulate. PAT LOEHRER: One of the lessons I learned a long time ago from someone, and I loved it, a great leader is one that changes the conversation. And to your point of listening, but it's really changing the conversation, deflecting it around it so that other people are talking. But you have a little role in moving that around. And I always liked that. MELISSA DILLMON: Today, I was listening to the National Press Conference, and I heard a definition of leadership that disturbed me. And I thought, I don't think that's my definition of leadership. So I think that defining what your type of leadership style is, is something that leadership development helped me with. And then, once I knew what my leadership style was, then using those skills to pull together a team and achieve a goal, a common goal, not the description of leadership today, which was pushing something up a mountain and rolling over boulders and doing whatever you had to do to get your way. I thought, well, that's not leadership, not my leadership. So I think that that was something that Leadership Development Program help me do is identify what my leadership style is and what kind of leader I want to be. DAVID JOHNSON: So I want to follow up on a point that both of you are making in a slightly different way. And that is, who are your role models? I mean, apart from Pat and me, but who are your role models? [CHUCKLES] LECIA SEQUIST: I've had lots of role models over the years, and I think at the beginning, my role models were really people that I wanted to emulate and be just like them. And that probably started with Tom Lynch, who was my initial research mentor when I started in lung cancer. And a lot of it was just the way he was with patients. I wanted to have that ability to make a patient feel just right at home from the first minute they walked in the door, which Tom is a master at. But over time, I think my mentors or my heroes have more become people that are different than me. And I'm not trying to be like them. But I appreciate the ways in which they lead or in which they conduct something, like balancing their home life and their professional life in a way that's just different but I appreciate. And that, in lung cancer, I would say another real big influence on my career has been Heather Wakely. She really has been my main female role model in my career. And she's given so much of her time to me and to so many to kind of sit and have personal talks and pep talks and strategies about what we're doing in our home institutions. DAVID JOHNSON: Missy, what about you? MELISSA DILLMON: So I would say from a professional standpoint, someone I respect and see as a mentor is actually now the female CEO of my clinic, who has been with my clinic for 20 years and worked her way up. And I think that's because she has retained her femininity, but she is recognized as a tiger that no hospital or other clinic wants to make mad. So she has a way of leading and listening that is unique. And I have learned a lot from her over the years and watched her rise in her leadership skills as I have alongside of her. And then, I will say from a personal perspective, one of the books I have enjoyed reading recently really talks a lot about servant leadership. And so I've really tried to identify servant leaders in my community and why it is that they're able to weather the storms of the last couple of years, for instance, and why their teams rally behind them and support them. And they're successful. And my husband is a restaurant owner times three, opening two of those, one right before COVID and one during COVID and yet has been able to mobilize a team. And that's because he's a servant leader that will get back in the kitchen and make pastry cream if that's what needs to be done or make reservations. And so I think during the last two years, what I have learned from that is to be a servant leader in the tough times has really helped rally my team and my clinic to be better and to continue to work, despite the challenges for our patients, for the bigger goal. PAT LOEHRER: Love it. We recently had a guy give a talk here at IU, and the lecture was on being a visionary leader. And to be honest, it was fine. It was good, but being a servant leader and being part of a group is more important than being the one right up in front. And it's good to be a follower too as a leader. So I really appreciate those comments. Just in a couple of sentences, I don't know if you guys could do this and reflect a little bit about your younger self. Say you're 21, and you could give yourself some advice now, what would those pieces of advice be? LECIA SEQUIST: I think one thing, and that's the common thread I've heard among a lot of more senior people in medicine, or in any profession probably, is that the things that you think are disappointments at the time often turn out to be some of the greatest opportunities that you're faced with. You plan and you think things are going to go a certain way, and then something doesn't work out, and you're very disappointed. But it's usually that process of how you deal with that disappointment that actually brings so much opportunity back to you. You can't see it at the moment. All you see is the disappointment. But I think that's a big lesson. PAT LOEHRER: Terrific. MELISSA DILLMON: So kind of similar to that, Lecia, doing our personality test this time, I wish I had done that same exact test 10 years ago, because I'd like to see what my leadership personality was 10 years ago versus now. I would not have scored as high in certain areas that I think I do now. And I think that one of the biggest things I have learned is, I'm very much a person of tradition. And I like things to continue the way I expect them, and I like things to be planned and done in medical school in four years, done with fellowship. So I like a regimen and a routine. And I have learned over the years to be comfortable with change. And I wish I had learned that earlier and to be open to change and listening to new ideas. I think that probably for the first few years of my practice and training, I was very much, this is the way it's done. And I think that that expressive part of my leadership had not developed yet. And I think that being open to change and looking at things in new ways, I wish I had learned that earlier. DAVID JOHNSON: So we only have a few minutes left. And what we have done in previous episodes, we like to ask our guests to tell us the book they've read recently or maybe a documentary or something they've watched recently that they would recommend to our listeners. LECIA SEQUIST: I really enjoyed the book The Four Winds by Kristin Hannah. That is a historical fiction about the Great Depression and the Dust Bowl and the migration of farmers from the Central Plains out to the West. And it was a really captivating book with a female protagonist. I enjoyed it quite a bit. MELISSA DILLMON: It's funny. I read that one just a few months ago. I love historical fiction, but I would say recently, and I know it's not a new book, Andre Agassi's Open, his autobiography, I found fascinating. I love sports, but it was very interesting to me to see how someone who's thrown into the limelight at a very early age and the pressure put on him by his parents and how that affected the course of his life. I found it a fascinating book and very insightful. And I like to play tennis, but I'm not a tennis player. But I found it interesting as a parent, who's got several sports-minded children, it gave me some lessons about parenting and how to just raise your children and where the focus should be. DAVID JOHNSON: Both my wife and daughter had been tennis players. I'm sure they would both love reading that book. Thanks for that recommendation. LECIA SEQUIST: It's a great book. DAVID JOHNSON: Well, that's really all the time we have for today. And Pat and I want to thank both of you, Missy and Lecia, for joining us. It's been a terrific conversation. Thank you so much for what you do. You're both, in our minds, fantastic leaders. You were when you arrived, and you certainly have been ever since. So thanks so much for that. I want to thank all of our listeners for tuning in. This is Oncology, Et Cetera an ASCO Educational Podcast. And we really have talked about anything and everything. And we'd like to continue to do so. So if you have an idea for a topic or a guest, please email us at education@asco.org. Thanks again for tuning in. And Pat, I just wanted you know I've ordered a chicken and an egg from Amazon. [CHUCKLES] PAT LOEHRER: It's because you couldn't quite make up your mind which was going to come first. I love it. I love it. You're the best. Thanks for doing this. And Dave, it's good to see you, as always. Take care. DAVID JOHNSON: Thank you so much. We really, really appreciate it. LECIA SEQUIST: Thank you. MELISSA DILLMON: Great to speak with you. Bye. [MUSIC PLAYING]   SPEAKER 1: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org. [MUSIC PLAYING]   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]

How do you talk to patients about medicinal cannabis? Dr. Ashley Glode (University of Colorado) moderates a discussion on effectiveness and safety, misconceptions and more. Featuring Drs. Ilana Braun (Dana-Farber Cancer Institute), Daniel Bowles (University of Colorado), and Kent Hutchison (University of Colorado). Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 1/19/22   TRANSCRIPT ASHLEY GLODE: Hello, and welcome to ASCO Education's podcast on medical cannabis, also referred to as medical marijuana. My name is Ashley Glode, and I am an associate professor with the University of Colorado School of Pharmacy. It's my pleasure to introduce our three guest speakers Dr. Ilana Braun is chief of the division of adult psychosocial oncology at Dana-Farber Cancer Institute, and an assistant professor of psychiatry at Harvard Medical School. Dr. Daniel Bowles is an associate professor of Medical Oncology at the University of Colorado. We're also joined by Dr. Kent Hutchison, a professor of psychology and neuroscience at the University of Colorado Institute of Cognitive Science. Let's start with a simple but fundamental question. What is medical cannabis or medical marijuana? ILANA BRAUN: So Ashley, I think that's such a great first question. I think of medicinal cannabis as herbal nonpharmaceutical cannabis products that patients use for medicinal purposes. And typically they're recommended by a physician in compliance with state law. DANIEL BOWLES: Dr. Braun makes a really good point. And I think it's important to know when patients are referring to medical cannabis, there's a wide variety of different things they could be referring to. Sometimes they would be referring to smoked herbal products, but there are also edibles, tinctures, ointments, creams, all sorts of herbal-based products that people use and call medical cannabis. And then there are also the components that make up medical cannabis-- largely, the cannabinoids. And I think the big ones people think about are THC and CBD. And sometimes those are used in their own special way. So I think that it's important for us as providers to be able to ask our patients, what is it that you mean when you say, I'm using medical cannabis? ILANA BRAUN: I think that's such a great point. And I will add I think it's also important to remember that when you offer a medicinal cannabis card to a patient, you're giving them license in most states to access any number of products. It's not an insurmountable challenge, but it's a whole new world for traditional prescribers who are used to writing a prescription and defining what is the active ingredient, how often a patient will take the medicine, by what means. DANIEL BOWLES: I think the other thing we need to be very aware of, as hopefully people are listening to this across the country and elsewhere, is the laws vary wildly from jurisdiction to jurisdiction about what consists of medical cannabis, who is allowed to use it, and in what quantities. So I think it's really important that as we learn about these and we think about these, we think about how they apply to any of our specific situations in which we live in practice. KENT HUTCHISON: So it's interesting-- just follow up on what Dr. Braun and Dr. Bowles, what they're saying, those two words-- right-- medical and cannabis. I think the medical part is somewhat easier because it can refer to the reason the person is using. Are they using for medical reasons are they using for recreational reasons, even though that's a blur? But the cannabis part I think is what's really complicated. And this is what Dan was getting at. All the different products, all the different cannabinoids, I mean all the different bioactive terpenes and everything else in the material, all different forms of administration. That is where it gets super complicated to really define what that is. And then of course, there's so little research we don't really know what all those constituents do. ASHLEY GLODE: Now that we kind of have a little bit of familiarity with medical cannabis, can you comment on adult use cannabis and what that might mean for a patient? ILANA BRAUN: Ashley, I think it's a really good question. And in some of the early research I did to try to understand where medicinal ended and adult use began, or adult use ended and medicinal began, I began to discover a theme that emerged, which is they sort of blend into each other often. In other words, some of the oncologists that I spoke to believed that it was not such a bad thing for a patient with serious illness, and pain, and many other symptoms to have a sense of high or well-being. And conversely, when I spoke to patients using cannabis, sometimes a cancer patient used medicinal cannabis for enjoyment, and sometimes they used it for symptom management, and sometimes they used it for both. And so I think it is somewhat of a slippery slope between the two. Would you agree? DANIEL BOWLES: I think there are definitely blurred lines between the two. I think that the advantages of what most states would recognize as medicinal cannabis is usually they're less expensive, patients can use them in larger quantities. There are certain advantages. But there's also paperwork that goes along with medicinal cannabis that some patients don't feel comfortable with. Or particularly I think when you have a patient who's interested in trying cannabis or a cannabinoid for the first time, they might not want to go through all the extra steps required getting that medical marijuana card, whereas adult use, I think people feel more comfortable, at least in my state, sometimes walking into a dispensary to discuss the options with people who work at the dispensary and then get it from more of an adult use or recreational cannabis initially. And then if that's something that they find helpful for their symptom management, to then take those extra steps and try to get a medicinal card. ILANA BRAUN: I agree with Dr. Bowles that the target symptoms or the target effect is often similar and access can differ. KENT HUTCHISON: Yeah. Just to chime in, I agree. I agree also. It's definitely-- the lines get blurred. The recreational user might also appreciate-- for example, college students, I hear them say a lot of times that they appreciate some of the anxiety-reducing aspects-- right-- even though they're not necessarily a person who has an anxiety disorder. And then of course, patients appreciate a slight increase in euphoria or positive affect, and what does that mean? Is I mean they're also using for recreational reasons? Or is that completely, I guess, legitimate? On the other hand, there are sometimes I feel like when-- especially on the recreational side-- when people are using for the more psychological effects, the sort of psychotropic effects, I know sometimes the medical patients refer to that as being a little bit loopy as a side effect. So I feel like there's definitely some blurred lines. And maybe there are some places where we can think about in perhaps in a less blurred kind of way. ASHLEY GLODE: How often do you guys have a patient ask you about medical cannabis? And what are the most common questions they might have for you? ILANA BRAUN: In my psycho-oncology practice, patients frequently tell me they're using cannabis, often with good effect and minimal side effects for polysymptom management-- for instance to address nausea, or pain, or poor appetite, or sleep, or mood, or quality of life. But they don't ask me a lot of questions. For instance, one of my longest-standing patients. A man with metastatic cancer and gastroparesis. Vaporizes cannabis before meals to keep his weight up. And many of my patients also use cannabis as cancer-directed therapy. And for these patients, side effects can sometimes be more pronounced. For instance, I have a lovely patient with metastatic cancer who follows a Rick Simpson protocol. So what is that? That's an online recipe marketed with an antineoplastic claim. And so this patient targets hundreds milligrams of cannabinoids daily. And with such high cannabinoid doses, she sometimes feels spicy, or out of it, as she describes it. And then I had another patient who targeted high daily doses and developed a debilitating nausea and vomiting that was initially diagnosed as chemotherapy-induced nausea vomiting because it was so hard to tease out in the setting of so many medicinal agents, what was what. But the symptoms resolved completely within weeks of the cannabinoids being halted. And so as I mentioned, what's notable about all three of these patients, and many of the others I see, is that they are quite open with their oncology teams and me about their medicinal cannabis use. But they don't seem to rely me or other members of their oncology team for their therapeutic advice . We insert ourselves when we see potential harm, but much of the decision-making seems to be made-- I don't know in the naturopath's office, at the dispensary counter, or by trial and error. And this anecdotal experience in my practice is borne out in my research findings as well. Patients are just not getting the bulk of their cannabis therapeutics information from their medical teams. DANIEL BOWLES: In my clinical practice, I am asked about cannabis or cannabinoids a fair, amount often in the context that Dr. Braun is describing, where a patient is coming in and they're already using a cannabinoid or they are planning on doing it and they just want my opinion. And I think unlike talking about more conventional cancer-directed therapies where they really rely, I think, on their medical team for information and guidance, we are often more a supplement I think in terms of information. In terms of the patients who come to ask me about cannabis or let me know that they're using cannabis, it's a very wide selection of people. I see young people, old people talking about it, men, women, a variety of different malignancies. So there really is a lot of usage or are thought about usage of cannabis or cannabinoids amongst our cancer patients. I think if you look at the studies, they'll tell us that depending on where we're working, anywhere between 20% to 60% of patients have used cannabis in the last year to help manage some sort of cancer-related symptoms. And I think the other thing that is notable is you'll find people asking about cannabis or cannabinoids who I think we might not have otherwise expected. So for instance, Just this past week, I had a patient with anaplastic thyroid cancer in his 70s, and his daughter was wondering whether he could try CBD to help with his sleep and anxiety. She wanted to make sure that it wasn't going to interact with this cancer therapies. And I appreciated her bringing it up, and we could have a frank discussion about the pluses and minuses of it, just like we might any other therapeutic intervention. So I think that particularly as the laws have changed across the country, more and more people are willing to tell us that they're trying cannabinoids and cannabis than maybe would have even 10 or 15 years ago. KENT HUTCHISON: I think in an ideal world, patients would be talking a lot more with their physicians about this topic. And I think unfortunately that a lot of people do get their information from dispensaries. From the media, from social media, from their kids, and from whoever. And I think that's something that I hope will change in the future. DANIEL BOWLES: In terms of questions that I'm often asked, I'll be asked if it's going to interact with their cancer treatments, in terms of making their medications more or less effective. I do get questions about how I think their cannabis use might affect some of their symptoms. I get questions about other drug-drug interactions-- let's say, interactions with opiates, or benzodiazepines, or some of these other medications that a lot of our patients are on. ASHLEY GLODE: In a recent survey 80% of medical oncologists who discussed medical cannabis with their patients, 50% recommended it in the past year, but only 30% felt knowledgeable enough to make recommendations. What do you guys think needs to be done to address this knowledge gap? And what resources do clinicians have to get and stay informed? DANIEL BOWLES: So I'm a big fan of the NCI's PDQ as a great resource. It has a fairly objective information about cannabis and cancer specifically. So I think that's a nice reference for people who are interested in getting an initial overview on the topic. I think there are also a number of different educational programs. I know the University of Colorado, for instance, has a Cannabis Science Master's and also a certificate program. So there are courses available for people who want to educate themselves more on this topic. ILANA BRAUN: Yeah. I guess when I think about what needs to be done, I think that cannabis needs to become a routine part of medical training curricula and CME programs. I think that a federal funding for high-quality clinical trials and a loosening of federal restrictions on accessing study drug were to occur, that would be really a big boon for the medical community. And my colleagues on this podcast I know are doing some very creative pragmatic clinical trials naturalistic studying what is happening in the field. And I am doing clinical trials using an FDA-approved version of cannabinoids. But it's still very hard to study whole-plant cannabis in a form that is sort of a standardized trial drug in a cancer patient. And then when I think about where I would begin to read, I don't think there is a single source, unfortunately. But a great place to start reading is actually a project that Dr. Hutchinson was a part of, which was an expert panel that was assembled by the National Institute of Science Engineering and Medicine in 2017. And they produced a monograph on the health effects of cannabis and cannabinoids. And it's several hundred pages long, including sections devoted just to oncology. So in other words, there is scientific evidence to evaluate, and it's sizable. DANIEL BOWLES: The Austrian Center for Cannabinoid Clinical and Research Excellence also is a helpful resource. One of the nice things about that is they actually give some dosing suggestions or ideas for people who really don't quite know where to start. Right now, there aren't a lot of people in that position to say, here's how it should be done. Here's how it gets dosed. Here are the data to support those decisions. And so the folks in the next level of training don't learn it in the same way that we have learned how to prescribe other medications. And they can't then lay it down. So because the data are scant, in some respects, and particularly for herbal products that So. Many of our patients are using, I think it falls outside the medical model that we've all become so used to using to learn how to take care of patients. And I think that's one reason that so many oncology providers feel interested in learning more about this topic, but don't feel comfortable giving patients guidance on how to use them. KENT HUTCHISON: So both Dr. Braun and Dr. Bowles identified some of the key resources out there. And certainly the training issues that Dr. Bowles just talked about are important. And I do want to emphasize the one thing that Dr. Braun mentioned, which is basically that we do-- we lack research and we lack data on some key important issues, like dosing, for example. What dose is effective? So cannabidiol has been out there for a long time, but what dose is effective for what? We don't know, right? So we definitely lack research. And there are definitely obstacles to doing that research. ASHLEY GLODE: So you guys brought up some good points about there being a lack of data, but also there is some evidence. So what is the current research and evidence on the efficacy of medical cannabis for management of cancer symptoms and cancer pain, specifically? DANIEL BOWLES: So there was a really nice review article that just came out in the BMJ looking at cannabis and cannabinoids, not specific to cancer pain, but including cancer pain. And what they found-- they looked at different preparations from herbal products-- smoked herbal products, oral agents-- cannabinoids, more specifically. They found there is a modest, but a real improvement in pain in patients or research subjects treated with cannabinoids versus those usually typically treated with placebo. In particular, the data are supported in neuropathic pain, I'd say more so than the other pains. I think the data are less compelling with regards to many of the other symptoms that people often use cannabinoids for, such as sleep, anxiety, appetite, things along those lines. ILANA BRAUN: So I'll tell you a little bit about how I think about the evidence base in oncology for cannabis use. So I'll preface this with two points. The first is that, as I mentioned, cannabis products tend not to be one active ingredient, but hundreds of active ingredients-- cannabinoids, phenols, terpenes, they all have bioactivity. And they don't work individually, they work through complicated synergistic and inhibitory interactions that have been termed entourage effects. So I don't think one can easily extrapolate from clinical trials of, say, purified THC, to understand whole-plant cannabis' activity in the body and how it might perform in humans. And then the other point I'll make is that when I think about the types of clinical evidence that we as clinicians hold dearest, it's clinical trials of our agent of interest in our population of interest. So cancer patients using whole-plant full-spectrum cannabis that they would access at a dispensary or grow in their own home. With this in mind, I believe the strongest evidence, randomized double-blind placebo controlled trials of whole-plant cannabis and oncology populations begins to support its utility for chemotherapy-induced nausea and vomiting. So there have been a few studies that have looked at this. But just in 2020, the most recent is a study by Grimison, et al. It was a multicenter randomized double-blind placebo controlled crossover trial comparing cannabis extract. And I think the extract they use was a 1 to 1 THC to CBD ratio versus a placebo in patients with refractory chemotherapy-induced nausea and vomiting. And what they found was that with active drug, there was a complete response in 25% of participants versus only 14% with the placebo. And although a third of participants experienced additional side effects with the active drug-- so remember, this was a crossover trial, so they saw both arms-- 80% preferred cannabis to the placebo medication. So that's clinical trials of cannabis and cancer. But if we expand the base of the pyramid of acceptable evidence to include high-quality clinical trials for health conditions other than cancer and extrapolate back, then I agree fully with Dr. Bowles that there's a growing body of evidence that cannabis may be beneficial in pain management. And there have been many clinical trials done in this arena, and they span myriad pain syndromes, including diabetic neuropathy, post-surgical pain, MS pain, sickle cell pain. And so it does seem like cannabis works for pain management in several other illness models, so we could extrapolate back and hope that it works in cancer pain. And then there is a small body of evidence with nabiximols, which is a pharmaceutical that has a 1 to 1 THC to CBD ratio. And it's a sublingual metered dose spray. And it has been trialed for opioid-resistant cancer pain. And this is not as a single agent, but as an adjuvant to opioids. In early trials, two times as many participants in the active arm as compared to the placebo arm demonstrated a 30% pain reduction. And for the pain specialists who are listening, they will know that is a substantial pain reduction. But then, additional studies fail to meet primary endpoints. I think there were three clinical trials that followed. Nabiximols was found to be safe and effective by some secondary measures, but the FDA opted not to approve nabiximols for cancer pain. So I think there's some suggestion of effect, but there's some smoke, but no fire-- no pun intended. DANIEL BOWLES: I think many of the studies that have been done looking at cannabis-- or cannabinoids-- have been compared to placebo or they've been crossover. And I would say fairly consistently, there is some improvement in pain scores with the cannabis products versus placebo kind of across a wide variety of disease spectrums with regards to pain. I think one of the other questions that a lot of people have asked is, can you decrease people's opiate usage using cannabis? As we know, there's a huge epidemic of opiate misuse in the United States of America right now. And I think many people are looking for ways to decrease opiate usage. There was a nice study done from Minnesota in conjunction with the Minnesota dispensaries-- or state marijuana program-- where some researchers randomized people to starting kind of herbal cannabis products early in their study or three months into their study. So it was kind of a built-in control. And they looked at opiate usage rates, pain scores, quality of life scores, et cetera. What they found is there, again, was some improvement in pain control overall in the cannabis users. However, it did not equate to a decrease in opiate usage. So I think that it's an open question that I think a lot of people want to know the answers to before they start recommending or incorporating cannabis or cannabinoids more widely into their practice. KENT HUTCHISON: It's certainly a complicated issue, in some ways, right? Because the research which is summarized very nicely by both Dr. Braun and Dr. Bowles, it is suggested, but not overwhelming, by any stretch, right? It's not clear-cut. And I think that one of the big issues here we talked about the very beginning is how complicated this cannabis thing is. and Dr. Braun alluded to this also, that there are obviously many different formulations, many potentially active constituents in cannabis. And so what has mostly been studied so far is either synthetic versions of THC or nabiximols, which is probably the closest thing to what some people are using. So I think the jury's still out, for sure. And I think hopefully at some point, what will happen is that some of the products that are actually being used by people-- because most people aren't using nabiximols, most people are not using THC only, hopefully there'll be some trials of the things that people are actually using out there in the real world that will tell us something more about whether it's effective or not. And maybe even more specifically, which constituents-- which parts, together are most effective with respect to pain. DANIEL BOWLES: I think one of the other topics that some of my colleagues have alluded to already is not just cannabis' role in symptom management. I think pain is often what people think of, and people are using it for chemo-induced nausea and vomiting, anxiety, sleep, appetite, but a fair number of patients are also using cannabis or cannabinoids with the hopes that it is going to treat their cancer like a chemotherapy or an immunotherapy may. And oftentimes, patients will point to preclinical studies looking at oftentimes very high doses of THC or CBD that might show tumor cell death or tumor reduction in test tubes. And I spent a fair amount of time-- and I know some of my colleagues spent a fair amount of time-- talking with patients about how it's a big step between cannabis or cannabinoids working to slow cancer growth in a test tube, to working in an animal system, to working in people. ASHLEY GLODE: So what are the most important considerations clinicians should keep in mind before recommending medical cannabis to patients with cancer? DANIEL BOWLES: We should be asking why they want to use cannabinoids. I think just like we might any other medication that people are thinking about trying-- or herbal product that people are thinking about trying-- I think we need to ask why they're interested in using these products. So is it for symptom management? Is it for some of the ancillary side effects of cannabinoids or cannabis? Why are they wanting to use it? And I think trying to incorporate that more than into the medical model, I ask my patients, hey, if you're using this particular product, do you feel like it's doing what you intended it for it to do? If it is and it's legal in your state, great. Do it as you feel fit. If it's not meeting your goals, if it's not helping with the pain, or if it's not helping with the anxiety, or it's not helping with the nausea and vomiting, maybe we should rethink whether we would use it. Just as if I was prescribing more conventional anti-nausea medication and you didn't think it was working, we wouldn't keep using it. So I think that's a really important thing to keep in mind. I think the other thing to know from a safety standpoint is, who else is in the household? We have a psychiatrist on the call with us today. I think there is an ample amount of data that cannabis is not safe for young people. It's not safe for growing brains. And I think we need to make sure, just as we would want people's opiates to be secured, that their cannabinoids and cannabis products are secured as well, from those who do not want to use them. ILANA BRAUN: And the thing I would keep in mind is that in most states, giving patients a medicinal cannabis card is allowing them to access any number of products with different ratios of active ingredients, delivery mechanisms, onset of action, potencies. And if you don't discuss all of these issues with your patients, these are things that they will decide at the dispensary counter, or by discussing with friends and family, or by trial and error. And I think it's really important that we clinicians guide this narrative. ASHLEY GLODE: So what kinds of patients are not good candidates for medical cannabis? DANIEL BOWLES: I would not recommend medical cannabis for people who can't meet some of the criteria we already discussed. So people who can't keep it safe in their households or have concerns about diversion in their own households. Those are people who I think would not be great candidates for medicinal cannabis or cannabinoids. ILANA BRAUN: As the psychiatrist on the call, I would add that I worry for people with a strong history of psychosis, or currently psychotic, or with a strong family history of psychosis. And perhaps those severely immunocompromised, since there is evidence of fungal and mold contamination in some cannabis products. DANIEL BOWLES: The other group of people I discussed this with are patients on immunotherapies. One of the ways that cannabis may be effective in some of the symptoms we discussed is it's an anti-inflammatory agent. One of the ways it could be detrimental for patients on immunotherapies is that it's an anti-inflammatory agent. There is one small study that suggested that patients might have worse responses to immunotherapy who are cannabis users versus those who are not. So that is a conversation I like to have, just so patients feel like they can be informed. I think lastly, cannabis even for people with medical cards, is not free. So there can be a financial burden for people who are using it. So that's something that I'll often bring up with people as well. KENT HUTCHISON: One thing I would add to this would be history of a substance use disorder might also be a consideration here as well. Mainly because you don't know what the person is going to get, and it could be something that lends itself to relapse or encourages a problem. So I would add that to list. ILANA BRAUN: And I would second what Dr. Bowles said about the financial challenges of using cannabis regularly medicinally. It's not something that's covered by insurance, either. So these are out-of-pocket expenses, and they can add up fast, particularly for patients in the oncology space using it for antineoplastic therapy. ASHLEY GLODE: So is there a concern about drug-drug interactions for patients currently undergoing active cancer treatment? DANIEL BOWLES: There are some data that there can be drug-drug interactions with cannabis and certain agents. In particular, cannabidiol, or CBD, is a CYP3A4 inhibitor. And there are a lot of drugs that are metabolized through that particular system. So I think that that's the clinical relevance of those interactions, I think, is sometimes unknown. But that is another topic that I do think we need to make sure we bring up with our patients. ASHLEY GLODE: Thank you. Yeah. So a lot of what we'll do is from a drug interaction perspective, use the FDA-approved products that we have available to run through a drug interaction checker, like Dr. Bowles mentioned. So we'll use dronabinol as the THC-based product and epidiolex as the CBD-based product. There's also some resources, such as natural Medicines Database. And some of the pharmacy programs that we use, you can actually put in marijuana or cannabis as a drug and run drug interaction checks. So there's multiple potential interactions, like he mentioned, through the immune system. But through the cytochrome P450 pathway, cannabis has been shown in some instances to be an inhibitor, sometimes an inducer of certain enzymes, as well as a substrate. So it's really important to work with your pharmacy colleagues to run through different potential interactions that may be present. ILANA BRAUN: I'll just add one thing, just in case that's helpful. I mentioned earlier in the episode that I had a patient who used cannabis as an antineoplastic drug, and targeted very high doses and developed a terrible nausea and vomiting. And when she stopped, so did the nausea and vomiting, even though her chemotherapeutic continued. And I, to this day, don't know if that was a cyclic nausea and vomiting syndrome, which has been known to plague some heavy cannabis users, or whether drug-drug interactions led to her high-dose cannabis triggering high blood concentrations of her cancer-directed therapy at the time. And so I think that drug-drug interactions do need to be carefully weighed. ASHLEY GLODE: So wrapping up, has the medical community stance on medical marijuana shifted in recent years with legalization in many states? ILANA BRAUN: I don't think we know the answer to this, about how sentiment has shifted because there aren't longitudinal studies that I know of examining this question. But we need some. And one could imagine that as medicinal cannabis becomes are commonplace, providers are increasingly confronted with questions about how to guide care and the desire for high-quality clinical trials and in-depth cannabis therapeutics trainings increases-- and as one piece of evidence for this, at the end of 2020 the National Cancer Institute held a first-in-kind four-day conference at the intersection of cannabis and cancer. And so I'm hopeful that grant opportunities will follow from that. DANIEL BOWLES: I think overall there has been more willingness to discuss cannabis in the context of patient care in the last decade. A couple of ways that I see this is I much more frequently see cannabis use described not necessarily in the drug history, or in the social history, but in the medical history, or in their medications, if they're using it for medical or therapeutic purposes. I think the other place that I've noticed cannabis usage become a bit more mainstream is in the clinical trial setting-- not in clinical trials of cannabis, but one of the things that many of us do is clinical trials of new drugs. And very frequently, 10 years ago we ran into trouble trying to get our patients who were using cannabis products for cancer symptom control onto these clinical trials because of potential drug-drug interactions, or just the fear of the unknown. And I feel like we run into that less commonly now. KENT HUTCHISON: I think it's also worth pointing out that there have been more and more podcasts like this one, right? So to the credit of this organization, I think we are seeing some change. I just wanted to highlight that. And I compliment everyone here for putting us together and putting it out there. ASHLEY GLODE: All right. Well, thank you. That is all we have for today. And thank you very much Drs. Braun, Bowles, and Hutchison for a delightful conversation. Thank you so much to all the listeners tuning into this episode of the ASCO Education Podcast. [MUSIC PLAYING]   SPEAKER: Thank you for listening to this week's episode to make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit elearning.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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An interview with Dr. Nancy Baxter from the University of Melbourne in Melbourne, Australia, and Dr. Jeffrey Meyerhardt from Dana-Farber Cancer Institute in Boston, MA, co-chairs on “Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update.” This guideline updates recommendations for adjuvant therapy for patients with resected stage II colon cancer. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines.   TRANSCRIPT [MUSIC PLAYING] ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Nancy Baxter from the University of Melbourne in Melbourne, Australia, and Dr. Jeffrey Meyerhardt from the Dana-Farber Cancer Institute in Boston, Massachusetts, co-chairs on adjuvant therapy for stage II colon cancer ASCO guideline update. Thank you for being here, Dr. Baxter and Dr. Meyerhardt. NANCY BAXTER: Thank you for having us. JEFFREY MEYERHARDT: Thanks. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines in ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Baxter, do you have any relevant disclosures that are directly related to this guideline topic? NANCY BAXTER: I don't, Brittany. BRITTANY HARVEY: Thank you. And Dr. Meyerhardt, do you have any relevant disclosures that are directly related to this guideline topic? JEFFREY MEYERHARDT: I don't, either. Thank you. BRITTANY HARVEY: Thank you, both. And getting into the content of this guideline, what prompted this guideline update, and what is the scope of this guideline? NANCY BAXTER: Well, it's been since 2004 that we've had a guideline that gives us advice about stage II colon cancer and the use of adjuvant therapy in this group of patients. And it's one where clinicians often have a lot of challenges in helping patients make decisions about what's best for them in terms of long-term survival from colon cancer. There have been changes in guidelines for stage III colon cancer. And so we thought it was timely to reevaluate our best practice recommendations for stage II colon cancer patients. JEFFREY MEYERHARDT: Yeah, I agree, Dr. Baxter. I think that this is one of the most challenging conversations that oncologists have with patients. Should they get chemotherapy? What type of chemotherapy? And as you know, there are a variety of higher risk features, of which we're able to sort of tease out a little better relatively, in terms of thinking about someone's stage II disease and trying to bring all that data together and provide some framework in the conversation for clinicians to have with patients. BRITTANY HARVEY: Great, thank you both for that background information. So then this guideline covers four clinical questions. And I'd like to review the recommendations for each question. So Dr. Baxter, starting with question 1, what does the guideline recommend for patients with resected stage II colon cancer regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy versus surgery alone? NANCY BAXTER: So overall, what we did was we looked at the risk that individual patients with stage II colon cancer have. So for patients that are at low risk of recurrence-- and so those are patients with stage IIA or T3 tumors that have at least 12 sample lymph nodes in the surgical specimen and don't have any high-risk features, and I'll go over those with the later recommendations-- these patients do not need adjuvant chemotherapy. It should not be routinely offered to them because the harms may outweigh the benefits. And so the evidence of that, although the quality of the evidence was relatively low, there is quite a bit of evidence that, really, the benefits do not outweigh the risks in this particular group. That is different for patients that are at higher risk, though, within the stage II group. And so those are the patients with stage IIB or stage IIC colon cancer. So those are T4 lesions that either penetrate through the visceral peritoneum or invade surrounding organs. And in those patients, adjuvant chemotherapy may have more benefit. And so a discussion of the potential benefits and risks of harms associated with chemotherapy should be had with patients. And those are patients that should be offered adjuvant chemotherapy for their disease. Now, there's a group of patients with high-risk features-- so not the stage IIB or stage IIC-- but there's a group of patients within stage IIA. So these are patients that are T3 patients where there are high-risk features. And chemotherapy may be offered to these patients, based on their risk features. So I'll go over a little bit about what the high-risk features are that might make patients included in this group. So that is sampling of fewer than 12 lymph nodes in the surgical specimen, perineural or lymphatic invasion, poor or undifferentiated tumor grade, intestinal obstruction, tumor perforation, and grade BD3 tumor budding. That's more than, or equal to, 10 buds in the tumor. And so that's because these patients are at higher risk of recurrence, and the chemotherapy may be more beneficial in these patients because they have a higher baseline risk of recurrence. There were a few risk factors that it was really challenging to make any decision on. And that was specifically circulating DNA. We know that that's an area of great interest, but there really was not enough evidence of the predictive value of ctDNA when you're looking at adjuvant chemotherapy in this group to make a recommendation. We'd expect future versions of this guideline to have some recommendations about that. We do know that there is controversy around the timing of chemotherapy. So we didn't include reports on this for the guideline because we didn't have enough related to stage II colon cancer and the role of adjuvant therapy. But the trials have generally started patients on chemotherapy within six to seven weeks of surgery. And finally, all of this needs to be a part of shared decision-making. So particularly for patients at higher risk-- so stage 2A at higher risk-- it's important that this is discussed-- the risks and benefits of chemotherapy, and the possible benefits with respect to the risk of recurrence for these patients-- is discussed as part of the shared decision-making process to come to an ultimate decision about the use of chemotherapy. BRITTANY HARVEY: Understood. Thanks for detailing those recommendations stratified by risk and identifying what those high-risk features are. So then, additionally, Dr. Meyerhardt, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for patients with tumors that exhibit mismatch repair deficiency or microsatellite instability or patients with proficient mismatch repair, or microsatellite-stable, tumors? JEFFREY MEYERHARDT: Yeah, so this was a specific question that we also looked at. What we know is about 15% of stage II colon cancers have evidence of mismatch repair or microsatellite insufficiency. And data that was realized now several decades ago on several different papers-- one larger one published in The New England Journal by Dan Sargent-- showed that patients who have stage II disease who receive a fluoropyrimidine only seem to not benefit if they have microsat instability. And there was actually some evidence that they may actually have harm, or have a worse outcome. So it is not a routine recommendation to use a fluoropyrimidine-only treatment regimen in patients who have MSI-high or deficiency of mismatch repair in stage II disease. However, there are some qualifying statements that we reviewed and were important to think about in patients. So what we know is, again, some of those patients will have some high-risk features and particularly T4 tumors or some other high-risk features, except for poor differentiation, that the use of oxaliplatin may actually be a consideration in those patients. And that's basically from indirect evidence of a disease-free survival benefit with the addition of oxaliplatin in the population of patients with stage II disease that were included in the MOSAIC trial, one of the original trials that looked at the addition of oxaliplatin to a fluoropyrimidine as adjuvant therapy for colon cancer. We specifically carved out poor differentiate is not considered a high-risk prognostic feature in those patients. And so poorly differentiated tumors alone should not be a part of the decision in offering adjuvant therapy with a fluoropyrimidine or fluoropyrimidine-oxaliplatin for MSI-high or deficient mismatch repair protein tumors. And the other patients who have either proficient mismatch repair proteins or microsatellite instability are actually including the other parts of the guideline, so what Dr. Baxter just talked about and some of the other questions that we tackled that you'll be going to next. BRITTANY HARVEY: Great. Thank you for covering those recommendations for that particular patient population. So then, Dr. Baxter, if adjuvant therapy is recommended, is there a benefit to adding oxaliplatin to fluoropyrimidine-based chemotherapy? NANCY BAXTER: Well, this is obviously a question that oncologists will face when they're deciding to give adjuvant chemotherapy to high-risk stage II colon cancers or people with T4 stage IIB or C colon cancers. And you know, here's where it's challenging to make recommendations. Because we don't have a lot of evidence for this specific group. And this is why clinicians have such a challenge making recommendations for these patients. Because actually, there's insufficient evidence to routinely recommend the addition of oxaliplatin, meaning that we have to base our decisions on the best evidence that we have. And the best evidence we have, as we've talked about, is the MOSAIC trial. And so in the MOSAIC trial, a time to recurrence was longer with oxaliplatin-based adjuvant chemotherapy. And so it may be for some patients that the addition of oxaliplatin makes sense in terms of improving their overall outcome. And again, it needs to be a shared decision-making approach with the discussion of the potential benefits and risks of harms of the addition of oxaliplatin to fluoropyrimidine-based chemotherapy, so again, discussions between the oncologist and the patient. But that is with the exception of patients who are MSI-high. So those patients need oxaliplatin. If they're going to get chemotherapy, they shouldn't have 5FU-based chemotherapy alone, as we've just discussed. BRITTANY HARVEY: Great. And definitely, that shared decision-making is key. And I appreciate you reviewing the evidence behind these recommendations, as well. So then, the last clinical question addressed in this guideline, Dr. Meyerhardt, if adjuvant oxaliplatin-containing chemotherapy is considered, are outcomes affected by reducing the treatment duration from six months to three months? JEFFREY MEYERHARDT: Sure. So this was the last clinical question that the committee considered. And it is based on the IDEA collaboration. So the IDEA collaboration was the International Duration Evaluation of Adjuvant Chemotherapy. It was six trials that were done internationally-- one in the United States, one in Japan, and four in Europe-- that included patients both with stage II and stage III colon cancer. They receive three versus six months of therapy. Each of the trials had different chemotherapy choices in the sense that the United States trial, FOLFOX was the only choice that could be offered to patients, where in all the other trials, it was a physician and patient choice regarding the use of FOLFOX or capecitabine and oxaliplatin. And that, as people who know the data, is relevant to some of the discussion. And so the goal of the collaboration was to look at if we can give patients three months of therapy and not compromise outcome. And the main reason for that is we know that the peripheral neuropathy that's cumulative with oxaliplatin increases with more months of treatment. So patients who only receive three months of oxaliplatin have less likelihood of more significant cumulative neuropathy and will have less impact on function by receiving less oxaliplatin overall. Four of the trials included patients with stage II disease. And those trials, again, pooled their data and looked at the duration question in terms of for stage II patients. Those patients had high-risk disease, some high-risk feature, as discussed earlier. And what was shown is that for the patients, overall, there was not clear evidence of noninferiority with three versus six months. But when you looked at the patients who received capecitabine and oxaliplatin, the absolute five-year disease-free survival was 81.7% versus 82% for three versus six months of CAPOX, so essentially the same, with a hazard ratio of 1.02, and the confidence interval spanned across 1. And so those really didn't look like there was any compromise in outcome for patients to receive CAPOX for three months versus six months. For those patients who received FOLFOX, three months of chemotherapy led to a five-year disease-free survival of 79.2% versus 86.5% if you received six months of FOLFOX with a hazard ratio 1.41. So again, those data would suggest that if one was to choose FOLFOX, giving six months of therapy for high-risk stage II patients may be preferable to not potentially compromise some benefit in terms of disease-free survival. So again, the overall conclusion was it's a discussion with a patient regarding choice of therapy, whether receiving capecitabine, oxaliplatin or FOLFOX and then, based on that, consideration of the duration where we were most comfortable saying that three months of capecitabine, oxaliplatin is sufficient for high-risk patients when appropriate discussion between the clinician and the patient. BRITTANY HARVEY: Great. Thank you for explaining the nuance of that trial and your recommendation. So finally, to wrap us up, in your view, how does this guideline impact both clinicians and patients? JEFFREY MEYERHARDT: Yeah, so again, the last time ASCO had addressed guidelines for stage II patients was over 15 years ago. And there are more data. It was really early in the days of understanding the incorporation of oxaliplatin. There was no data versus the three versus six months. And there were less analyses trying to look at some of those particular high-risk features. So these are all important considerations in those discussions with stage II patients. And the importance of the guidelines are really to provide that framework on the various things you think about when you have a stage II patient and how to have those shared decision-making discussions with the patient. Again, it's not, probably, appropriate for all patients to receive adjuvant therapy, particularly lower risk. And even for higher risk patients, it is weighing the plus or minuses of the potential toxicities with what we know potentially are benefits. NANCY BAXTER: Yeah, I think that's very true. And I think, as anyone who treats colon cancer, or stage II colon cancer patients, is aware, this is not a homogeneous population. So in terms of the outcomes, there are people that do extremely well with surgery alone and people who, unfortunately, recur even after chemotherapy and surgery. And the future needs to focus on being able to differentiate those patients most likely to benefit from chemotherapy from those that are not likely to benefit. What we found in reviewing the evidence is we've moved forward from 2004, but we still have a long way to go. So I really hope when the next guideline is written that we're much closer to being able to identify those patients who would most benefit from chemotherapy in this group. Because we know there are patients who benefit from chemotherapy in this group. It's just we're still not perfect at identifying those people. So again, these conversations with patients are so important to talk about the limits of our knowledge, which I think is another important thing of this guideline is establishing what the limits of our knowledge are. But I think there are patients that you can confidently not give chemotherapy to. And that's very reassuring, both to clinician and to patients. And then this guideline kind of outlines the limits of our knowledge. And that's also important for clinicians and patients to understand. BRITTANY HARVEY: Definitely. I appreciate you both highlighting the importance of shared decision-making throughout this conversation that we've had. So I want to thank you so much for your work on this important guideline update and for taking the time to speak with me today, Dr. Baxter and Dr. Meyerhardt. NANCY BAXTER: Thank you very much. JEFFREY MEYERHARDT: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/gastrointestinal cancer guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Megan Daly from University of California in Davis, California and Dr. Navneet Singh from the Postgraduate Institute of Medical Education & Research in Chandigarh, India, co-chairs on “Management of Stage III Non–Small-Cell Lung Cancer: ASCO Guideline.” They summarize guideline recommendations on five subtopics – evaluation & staging, surgery, neoadjuvant therapy, adjuvant therapy, and unresectable disease. Read the full guideline at www.asco.org/thoracic-cancer-guidelines.   TRANSCRIPT [MUSIC PLAYING]   ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Megan Daley from University of California in Davis, California, and Dr. Navneet Singh from the Post-Graduate Institute of Medical Education and Research in Chandigarh, India, co-chairs on management of stage III non-small cell lung cancer ASCO guideline. Thank you for being here, Dr. Daley and Dr. Singh. MEGAN DALEY: Thank you for having us. NAVNEET SINGH: Thank you for having us, too. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Daley, do you have any relevant disclosures that are directly related to this guideline topic? MEGAN DALEY: I have research funding from EMD Serono, Merck, and Genentech. BRITTANY HARVEY: Thank you for those disclosures. Then Dr. Singh, do you have any relevant disclosures that are directly related to this guideline? NAVNEET SINGH: No, I have no financial conflicts of interest. BRITTANY HARVEY: Thank you. Getting into the content of this guideline, Dr. Singh, can you give us an overview of both the scope and the purpose of this guideline? NAVNEET SINGH: Yes, absolutely. So this guideline has been developed to assist clinicians involved in the management of patients with stage III non-small-cell lung cancer, or NSCLC, as we call it briefly. Now, stage III NSCLC represents one of the most heterogeneous subgroups of lung cancer. Consequently, it is also the subgroup in which the choice of multimodality treatment and the sequence of multimodality treatment varies significantly amongst clinicians, with variations being observed across institutes, as well as within an institute. And we sincerely hope that, with the help of this guideline, clinicians can accurately confirm the presence of stage III disease and offer the most appropriate treatment based on clinical and radiographic characteristics, as well as other medical factors that influence treatment decision-making. This evidence-based guidance also seeks to provide clarification on the common clinical dilemmas that clinicians may have while evaluating a patient with suspected or known stage III NSCLC. BRITTANY HARVEY: Thank you for that background information, Dr. Singh. Then, Dr. Daley, this guideline addresses five main sections, evaluation and staging, surgery, neoadjuvant therapy, adjuvant therapy, and unresectable disease. So starting with evaluation and staging, what are the key recommendations for workup for patients with suspected stage III non-small cell lung cancer? MEGAN DALEY: Our first recommendation for such patients is that they should undergo a history and physical exam and a CT scan of the chest and upper abdomen with contrast, unless it's contraindicated. If metastatic disease is not identified on CT, those patients should go on to a PET CT scan and MRI of the brain. If the patients are being considered for curative intent treatment, the guideline recommends pathologic mediastinal lymph node assessment. And we recommend that endoscopic techniques should be offered as the initial staging modality, if available. If not available, invasive surgical mediastinal staging should be offered. And finally, for patients who have suspected or confirmed stage III lung cancer, we recommend that multidisciplinary discussion should occur prior to any initiation of a treatment plan. BRITTANY HARVEY: Great, I appreciate your reviewing those recommendations. So following that, Dr. Singh, what does the guideline recommend regarding which patients with stage III non-small-cell lung cancer should be considered for surgical resection? NAVNEET SINGH: So in this guideline, the recommendation which has come forth is that for patients with stage IIIA, basically N2 disease, induction therapy should be followed by surgery with or without adjuvant therapy if several conditions are met. Basically, a complete resection of the primary tumor and the involved lymph nodes is deemed feasible, and three nodes or contralateral lymph nodes are deemed to be not involved, and the expected perioperative 90-day mortality is low, typically 5% or less. Another recommendation is that for selected patients with the P4N0 disease, surgical resection may be offered if medically and surgically feasible following multidisciplinary review. We would like to emphasize here that surgeons should always be involved in decisions regarding the feasibility of surgical resection. And they are an integral part of a multidisciplinary evaluation for surgical resection for stage III NSCLC patients. BRITTANY HARVEY: Great. Then Dr. Singh just reviewed who should be considered for surgical resection. So Dr. Daley, for patients with potentially resectable stage III non-small-cell lung cancer, what are the key recommendations for neoadjuvant therapy? MEGAN DALEY: Our first recommendation is that patients who are planned for a multimodality approach that will incorporate surgery should receive systemic neoadjuvant therapy. Second, that those patients with N2 disease who are planned for surgical resection should receive either neoadjuvant chemotherapy or neoadjuvant concurrent chemoradiation. And finally, for patients with a resectable superior sulcus tumor, neoadjuvant concurrent chemoradiation should be administered. BRITTANY HARVEY: Understood. Then in addition, Dr. Singh, for patients with resected stage III non-small-cell lung cancer, what are the key recommendations for adjuvant therapy? NAVNEET SINGH: So the panel came up with three recommendations for adjuvant treatment. The first is that patients with resected stage III NSCLC who did not receive neoadjuvant systemic therapy should be offered adjuvant platinum-based chemotherapy. The second recommendation which we came up was that for patients with resected stage III disease and presence of a sensitizing EGFR mutation-- classically, exon 19 deletion or the L858R exon 21 point mutation-- they may be offered adjuvant osimertinib, which is an EGFR inhibitor, after platinum-based chemotherapy. And this is based upon the ADAURA trial, which was published last year. And the third recommendation was that for patients with completely resected NSCLC and mediastinal involvement N2 disease, but without extracapsular extension, post-operative radiotherapy should not be routinely offered. BRITTANY HARVEY: OK. And then the last section of recommendations covers unresectable disease. So Dr. Daley, what does the guideline recommend regarding the management of unresectable stage III non-small-cell lung cancer? MEGAN DALEY: The guideline first recommends that these patients who have a good performance status should be offered concurrent, rather than sequential, chemoradiation, that concurrent chemotherapy delivered with radiation should include a platinum-based doublet, preferably cisplatin-etoposide, carboplatin-paclitaxel, or cisplatin-pemetrexed or cisplatin-vinorelbine. The patients who are not candidates for concurrent chemoradiation, but who are potentially candidates for chemotherapy, should be offered sequential chemoradiation, rather than radiation alone, that patients receiving concurrent chemoradiation should be treated to 60 gray. And that's based on the results of RTOG 0617. We also recommend within the guideline that doses higher than 60 gray and up to 70 gray could be considered for selected patients, with careful attention to doses to the heart, lung, and esophagus, among other organs. The guideline also recommends that patients receiving definitive radiation without chemotherapy, that hypofractionation using slightly larger doses could be considered-- over 2 gray per fraction, and up to 4 gray per fraction, and that patients without disease progression during concurrent chemoradiation should be offered consolidation durvalumab, based on the PACIFIC trial. BRITTANY HARVEY: Thank you both, then, for reviewing the key recommendations of this guideline. So, Dr. Singh, in your view, what is the importance of this guideline, and how does it impact clinicians? NAVNEET SINGH: I think this guideline will go a long way in helping clinicians who are involved in the diagnosis and treatment of lung cancer, especially stage III NSCLC. As mentioned earlier, this is a very heterogeneous disease. And there are several challenging situations, both in the context of diagnosis, as well as treatment. And using this guideline, which has an extensive evidence review, as well as the development of two very helpful algorithms, we sincerely hope that clinicians who are both in academic centers as well as in practice in the community are able to accurately diagnose stage III, appropriately stage it, and offer the best treatment, given the patient characteristics and the disease characteristics and available resources. BRITTANY HARVEY: Great. Those are important points. So then, finally, Dr. Daley, how will these guideline recommendations affect patients? MEGAN DALEY: Well, we hope very much that these guidelines will help patients consistently receive high-quality care for their stage III lung cancer. In particular, we're hoping that the recommendation from multidisciplinary assessment of patients prior to treatment is carefully followed. We're hoping that some of the recommendations surrounding the appropriate workup for patients may help ensure that all patients receive a thorough and complete workup prior to initiation of treatment. And the guideline, in particular, is highlighting some of the more recent developments in stage III lung cancer, such as the use of consolidation durvalumab based on the PACIFIC trial, the use of osimertinib in resectable disease based on the ADAURA trial. And we're hoping to make sure that these results are disseminated to practitioners everywhere so that patients can receive the latest and best care for their stage III lung cancer. BRITTANY HARVEY: Understood. Yeah, as you both mentioned, we hope that this has a positive impact for both clinicians and patients. So I want to thank you both for all of your hard work to develop this guideline and the evidence-based recommendations along with it. And thank you for taking the time to speak with me today, Dr. Daley and Dr. Singh. MEGAN DALEY: Thank you so much for having us. NAVNEET SINGH: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, VA, and Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, FL, co-chairs on “Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline.” This guideline comprehensively addresses the treatment of brain metastases from non-hematologic solid tumors, including surgery, systemic therapy, radiation therapy, and timing of therapy. Read the full guideline at www.asco.org/neurooncology-guidelines.   TRANSCRIPT [MUSIC PLAYING] SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, Florida, and Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, Virginia, Co-chairs on Treatment for Brain Metastases, American Society of Clinical Oncology, Society for Neuro-Oncology, and American Society for Radiation Oncology Guideline. Thank you for being here, Dr. Vogelbaum and Dr. Schiff. MICHAEL VOGELBAUM: My pleasure. BRITTANY HARVEY: Before we begin, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in The Journal of Clinical Oncology Dr. Vogelbaum, do you have any relevant disclosures that are directly related to this guideline topic? MICHAEL VOGELBAUM: I have no disclosures relevant to this guideline. BRITTANY HARVEY: Thank you. Then, Dr. Schiff, do you have any relevant disclosures that are directly related to this guideline topic. DAVID SCHIFF: Hi, Brittany. No, I do not. BRITTANY HARVEY: Great. Then first, Dr. Schiff, can you give us an overview of the scope and the purpose of this guideline? DAVID SCHIFF: Sure. Our overall purpose was to provide guidance on the appropriate treatment of adult patients with parenchymal brain metastases from solid tumors, encompassing surgery, radiation, and systemic therapy, as well. Previous guidelines in this area were for the most part produced by neurosurgeons and radiation oncologists for their respective professional organizations, although they did incorporate multidisciplinary input. But over the last decade, treatment options for certain types of brain metastases have undergone a substantial change. The expanding armamentarium for medical oncologists in treating both extra-CNS disease as well as brain metastases highlighted the need for a new set of guidelines to evaluate the role of systemic approaches, such as targeted agents and immunotherapy, for the primary treatment of brain metastases in the context of more established treatments like surgical resection, radiosurgery, and fractionated radiotherapy. Additionally, recent studies have clarified the role of radiation techniques like whole brain radiation with hippocampal avoidance and radiosurgery to surgical resection cavities. By assembling a multidisciplinary group of experts from surgical neuro-oncologists, medical oncologists, neuro-oncologists, and radiation oncologists, we sought to provide as comprehensive and up to date a set of therapeutic guidelines as possible. In order to accomplish this, the panel performed a systematic review of randomized as well as nonrandomized evidence from 2008 through April, 2020. We focused on the roles of surgery, systemic therapy, and radiation therapy, as well as the timing and interactions among these modalities. And we included all randomized clinical trials, as well as large single arm phase II studies and institutional case series, and we also reviewed case control and cohort studies. BRITTANY HARVEY: OK, great. That's helpful background. And then you mentioned a couple focus areas, as well, of the systematic review. And so I'd like to review the key recommendations that were based off that evidence. So, starting with surgery, Dr. Vogelbaum, what are the key recommendations for surgery in adult patients with brain metastases? MICHAEL VOGELBAUM: So, the role of surgery, I think, was well established via randomized trials to some degree, and then via some of the larger single arm studies. Patients with suspected brain metastases without a primary cancer diagnosis were felt to benefit from surgery to obtain a diagnosis and undergo removal of the tumor. But more to the point, patients with larger tumors with mass effect-related symptoms are the ones most likely to benefit from surgery. What we also noted was that patients who have multiple brain metastases with extensive and uncontrolled systemic disease are unlikely to benefit from surgery unless the remaining disease is controlled via other measures, typically medical measures. We also contemplated the type of resection performed, the technique being used. There was some developing literature looking at the techniques of either an en bloc resection or a piecemeal resection. And when we critically evaluated the literature, we felt that no recommendation could be made regarding the method of resection, as there was not sufficient evidence to support one approach over another. Another technique that is being used more recently is the use of laser interstitial thermal therapy, which is a minimally invasive technique to treat tumors in general. But again, there was insufficient evidence to really be able to make a recommendation for or against the use of LITT, as it's called. BRITTANY HARVEY: OK, thank you for reviewing both those techniques and those recommendations and highlighting where there wasn't enough evidence to actually make a recommendation. So, then, following that, Dr. Schiff, what does the guideline recommend for patients with brain metastases regarding systemic therapy, including chemotherapy, immunotherapy, and targeted agents? DAVID SCHIFF: Brittany, there is a role for systemic therapy as the initial or primary modality in some cases, but I think it's really important to emphasize this only pertains to patients whose brain metastases are asymptomatic and those with particular histologies or molecular profiles. So, there are really-- there are three primary sites for which targeted or immunotherapy can be considered. The first is non-small cell lung cancer, for which osimertinib, or if you're in China, where there's access to another drug called icotinib, specifically for EGFR-mutated disease, alectinib, brigatinib, and ceritinib are appropriate approaches in ALK-rearranged asymptomatic brain metastases. And finally, pembrolizumab in combination with pemetrexed and a platinum agent in immunotherapy naive patients whose tumors express PD-L1. The second primary tumor is melanoma. And for melanoma patients who have asymptomatic BRAF V600E mutant brain metastases, dabrafenib with trametinib is an appropriate option to consider. For all melanoma patients with asymptomatic brain metastases, ipilimumab with nivolumab is also an option. And finally, for breast cancer, the combination of tucatinib, trastuzumab, and capecitabine for HER2 positive asymptomatic brain metastases in patients who have progressed on previous anti-HER2 antibody therapy. When patients treated with systemic therapy progress intracranially, local therapies such as surgery, radiation, and radiosurgery should not be deferred. BRITTANY HARVEY: OK, those are helpful notes for clinicians, and particularly around the primary tumor sites. So, then, Dr. Vogelbaum, what are the key recommendations for radiation therapy in patients with brain metastases? MICHAEL VOGELBAUM: So, Brittany, the panel started by noting which patients would not benefit from radiation therapy, in particular, those with asymptomatic brain metastases and a poor performance status, with a Karnofsky Performance Score, or KPS, of less than or equal to 50, or performance status of less than 70 and no systemic therapy options. In those cases, radiation therapy is unlikely to be of real benefit. But then when speaking to the different modalities of radiation to be used, a lot of the review focused on the two most commonly used modalities, which is Stereotactic Radiosurgery, or SRS, versus Whole Brain Radiotherapy, or WBRT. And the first recommendation was that SRS alone as opposed to either whole brain radiotherapy alone or a combination of the two should be offered to patients with one to four unresected brain metastases, except for the situation of small cell carcinoma, which has a different approach that's used often with prophylactic cranial irradiation. So, that's a separate group. But for others, SRS is the modality that should be offered. And then for patients who underwent surgical resection of their brain metastases, we know that there needs to be some form of radiation treatment to the surgical cavity. And the recommendation was that SRS alone should be offered to those patients if the surgical cavity can be safely treated, and considering the extent of remaining intracranial disease. Obviously, for patients who have a lot of disease but otherwise have a treatable systemic disease, then whole brain radiotherapy may make more sense. But for the ones that are more limited after surgery, it should be SRS. And then when the panel considered a situation where you have patients with more than four unresected metastases and the options included radiosurgery, whole brain radiotherapy, or radiosurgery plus whole brain radiotherapy-- and in general, these are reasonable options. But it was felt that SRS may be preferred for patients with better prognosis or where systemic therapy that is known to be active in the central nervous system is available. Additional recommendations revolved around both protective, radioprotective, and radiosensitizing agents. So, in terms of trying to protect memory, there are two approaches that are used. One is to give memantine during whole brain radiotherapy, or to do whole brain radiotherapy using a hippocampal avoidance technique. And it was felt that either one of those or both should be offered to patients who will receive whole brain radiotherapy and have no tumors in the hippocampus, and they're expected to live more than four months. And then finally, that radiation sensitizing agents should not be offered to patients, because they've not been shown to be effective. BRITTANY HARVEY: Understood. And it's helpful to know both what those recommendations are for specific approaches, and as you said, critical to know who will and who will not benefit from radiation therapy. So, then we've just reviewed the key surgery, systemic therapy, and radiation therapy recommendations. Dr. Schiff, did the panel recommend anything regarding the timing of surgery, radiation therapy, and systemic therapy? MICHAEL VOGELBAUM: The panel had just a couple of points in this regard. Although there are some recent data suggesting a decreased incidence of leptomeningeal metastases in patients who undergo radiosurgery before craniotomy, as compared to the reverse sequence, the panel concluded no recommendation on this point regarding the specific sequence of therapy could be made. And to reiterate, for those circumstances in which systemic therapy may be of use for brain metastases, that therapy should proceed, local therapy like surgery or radiation, only if the brain metastases are asymptomatic. BRITTANY HARVEY: Great. Thank you both for reviewing these recommendations. In your view, Dr. Vogelbaum, what is the importance of this guideline, and how will it impact clinicians? MICHAEL VOGELBAUM: I think one of the important points that David raised that at the beginning was that this really is the most comprehensive look at the evidence revolving around the treatment of patients with brain metastases and leptomeningeal disease. And in particular, this may be new information for an audience that has not been involved in that treatment for many decades, the medical oncology community. So, I think some of the impact on clinicians may be that the guidelines will help them understand the durability of surgery and radiosurgery, and those had been the only treatments available for a long time. And so now we have these new medical therapies that are showing activity in the brain, but one needs to balance that against what is known about the effective treatments in the past. Some of the new targeted immunotherapies may not provide as consistent or durable of a benefit as has been shown previously with surgery and radiotherapy. Hopefully, understanding this challenge with respect to consistency and durability will serve to support the development of phase 0 or window of opportunity clinical trials to better understand the determinants the biological determinants of response or resistance to systemic therapies we want to improve on that, for sure, and those clinical trials are going to be essential for us to be able to do that. And then ultimately, also, identify opportunities to synergistically combine radiation and medical therapies and better understand the timing of these combinations. This is a great area for clinical trial development in the future. BRITTANY HARVEY: Definitely. We'll look forward to future research in those areas. So then, finally, Dr. Schiff, to wrap us up, how will these guideline recommendations affect patients? DAVID SCHIFF: Yeah. Over the last 30 years, the management of brain metastases have involved hugely, from an area where almost everyone got whole brain radiation therapy and many patients died from their brain disease. The use of local therapies like surgical resection and radiosurgery has greatly improved local control of brain metastases. And with options like radiosurgery alone for a limited number of brain metastases, systemic therapies as the initial approach, and hippocampal avoidant whole brain radiation therapy with memantine, patients are experiencing improved long term cognitive function and quality of life, as well. So, I think the careful delineation of the role of each of these modalities that these guidelines provide will really help maximize benefit and minimize the risk for this very large number of cancer patients. BRITTANY HARVEY: Definitely, improve quality of life is always a goal. So, I want to thank you both for your work on these guidelines and thank you for taking the time to speak with me today, Dr. Vogelbaum and Dr. Schiff. DAVID SCHIFF: My pleasure. MICHAEL VOGELBAUM: Thank you, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/neurooncology guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe, so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Jaishri Blakeley from Johns Hopkins University School of Medicine in Baltimore, MD, and Dr. Nimish Mohile from the University of Rochester Medical Center in Rochester, NY, co-chairs on “Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline”. This guideline addresses evidence-based therapies for patients with newly diagnosed and recurrent gliomas. Read the full guideline at www.asco.org/neurooncology-guidelines.   TRANSCRIPT [MUSIC PLAYING]   SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. SPEAKER 2: Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Jaishri Blakeley from Johns Hopkins University School of Medicine in Baltimore, Maryland, and Dr. Nimish Mohile from the University of Rochester Medical Center in Rochester, New York, co-chairs on therapy for diffuse astrocytic and oligodendroglial tumors in adults American Society of Clinical Oncology and Society for Neuro-Oncology guideline. Thank you for being here, Dr. Blakeley and Dr. Mohile. SPEAKER 3: Thank you. SPEAKER 4: Thank you. SPEAKER 2: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with a publication of the guideline in the Journal of Clinical Oncology. Dr. Blakeley, do you have any relevant disclosures that are directly related to this guideline topic? SPEAKER 3: No, I do not. SPEAKER 2: Thank you. And Dr. Mohile, do you have any relevant disclosures that are related to this guideline topic? SPEAKER 4: No, I don't have any relevant disclosures. SPEAKER 2: Great. Thank you. Then let's get into the content of this guideline. So Dr. Mohile, can you start by giving us a general overview of the scope and purpose of this guideline? SPEAKER 4: Yeah, so over the past 10 years, there have been several positive clinical trials in various glioma subtypes, and several of them have demonstrated a benefit for chemotherapy. The primary purpose of this guideline is to help practicing clinicians understand how these trials might impact treatment for patients with gliomas. During this period, there's also been two updates to the World Health Organization classification of gliomas, and the terminology of gliomas has changed. So what we call tumors today is different from what we might have called them 10 years ago. And so a second purpose of our guideline is essentially to provide a key or a translator so a clinician can look at a pathology report today in 2021 with a current terminology and know what to do with that patient and what treatment best fits for that patient today based on what they would have been called in a trial several years ago. SPEAKER 2: Great. That makes a lot of sense. So then Dr. Blakeley, looking at this guideline, it addresses four clinical questions, which are after maximal safe surgical resection, what are the evidence-based therapies for adults with newly diagnosed glioma including optimal regimens, settings, and timing of therapy? Then also, what are the appropriate therapies for adults with recurrent glioma, including optimal regimens, settings, and timing of therapy, followed by what should the effect of MGMT promoter methylation status be on choice of therapy and if there are subpopulations that should affect the choice of therapy. I'd like to review the key recommendations for those clinical questions. In reading through the guideline, the expert panel provided recommendations based on the IDH mutation status and the diagnostic categories in the WHO 2016 and 2021 classification systems for tumors of the central nervous system. So it seems appropriate to review the recommendations in this manner as well. Starting with IDH mutant astrocytic and oligodendroglial tumors, what is recommended for patients with oligodendroglioma, IDH mutant, 1p19q deleted CNS WHO grade 2 or 3? SPEAKER 3: Absolutely, and I'll just summarize for our listeners to help simplify that as you said, essentially, all of the guidelines are divided along molecular markers. And the first cohort are 1p19q co-deleted gliomas. Something that is a 1p19q deleted gliomas also an oligodendroglioma. Those are interchangeable. If you are 1p19q co-deleted, you have oligodendroglioma and vise versa. In general, 1p19q co-deleted tumors also are IDH mutant. So you can consider that one bundle. And oligodendroglioma is something that is 1p19q co-deleted and IDH mutant. And for that whole classification, whether it's WHO grade 2 or WHO grade 3, the recommendation is for radiation followed by the combination of procarbazine, CCNU, and vincristine, based on two prospective studies that showed similar results at different time points. There are a couple of modifications to that guideline. There is a statement that if people feel that the combination of Procarbazine, CCNU, and Vincristine, also called PCV, is too toxic, they can consider temozolomide as an alternative for this subclass of tumors 1p19q co-deleted IDH mutant. And also, importantly, the 1p19q co-deleted grade 2 gliomas are some of the best performing tumors in terms of prognosis of all glial tumors and maybe all CNS tumors. And so there is a statement in the recommendations that say-- it says it is reasonable to defer therapy under appropriate circumstances. And the text goes into what those appropriate circumstances might be, including how much of a resection could be achieved, what the functional status of the person is, how old they are, et cetera. But big picture-- 1p19q co-deleted tumor equals an oligodendroglioma, and those are almost all IDH mutant. And the bottom line recommendation is radiation followed by PCV with the parentheses saying temozolomide might be a reasonable alternative to PCV, and if you have a particularly benign presentation with a grade 2 tumor, you can consider deferring that therapy start for a time. The next big bundle is astrocytic tumors that are not 1p19q co-deleted. So in the guidelines, those are termed as 1p19q non-co-deleted. And those tumors do come in two flavors-- IDH mutant or IDH wild type. And I'm going to focus on the IDH mutant because they track closer to the oligodendroglioma, but they are kind of a bridge between the very good prognosis associated with oligodendrogliomas and the more aggressive prognosis associated with malignant gliomas. And for this cohort, the 1p19q non-co-deleted IDH mutant cohort, the recommendation is for radiation therapy with adjuvant chemotherapy, and there is data that supports that adjuvant chemotherapy being either PCV or temozolomide. We don't prioritize between those two regimens. And why I'm highlighting the word adjuvant is in some centers, there is a tendency to use temozolomide concurrent with radiation therapy. And the recommendation for these 1p19q non-co-deleted IDH mutant WHO grade 2 tumors is not to use it concurrent but to use it in the adjuvant setting. And then I will round out with talking about IDH wild type. So now we're, again, 1p19q non-co-deleted but IDH wild type. Those tumors may act closer to the glioblastoma. And in that setting, we would say-- the recommendations say to treat with radiation and consider concurrent temozolomide as you would with glioblastoma or only adjuvant temozolomide as you would with the lower grade astrocytoma. SPEAKER 2: Great. Thank you for going through that and providing such clarity to those recommendations. Then following that, Dr. Mohile, moving on to glioblastoma and other IDH wild type diffuse glioma, what are the key recommendations for people with newly diagnosed glioblastoma IDH wild type CNS WHO grade 4? SPEAKER 4: So in the current classification, IDH wild type CNS World Health Organization grade 4 is what we've known of classically as glioblastoma. And for patients with glioblastoma who are fit and can tolerate therapy, we recommend treatment with radiation, concurrent temozolomide, and a six month course of adjuvant temozolomide. We also recommend that they can receive alternating electric field therapy along with the adjuvant temozolomide. Now the recommendations become a little bit more complicated for patients who might not be as fit-- so patients who might be older, have poor performance status, have other measures of frailty. And the way we wrote this is we said that if a patient who is undergoing a six week course of radiation, if that course of radiation, if the benefits did not outweigh the harm, then you could consider alternate regimens. And these include shorter courses or hypofractionated courses of radiation with or without chemotherapy and also includes courses that are chemotherapy alone. So in people who have tumors that have MGMT promoter methylation, we can consider the option of temozolomide alone. So this would be specifically for patients who either are older, more frail, who we feel are going to have difficulty going through a radiation course. There is some data to support this temozolomide alone approach. SPEAKER 2: Thank you. I appreciate you going through those recommendations very clearly as well. You clearly put a lot of effort into these recommendations. So then, Dr. Blakeley, what is recommended for patients with astrocytomas IDH wild type CNS WHO grade 2 or 3? SPEAKER 3: Yes, thank you. So as Dr. Mohile was just saying, for glioblastoma, you can really think about the recommendations for WHO grade 4 very similarly for IDH wild type independent of grade. And that is a new shift in the management of gliomas in adults. Previously, the histologic grading had a lot of weight on whether or not we would offer radiation and chemotherapy. But with the new prognostic and predictive value known associated with the IDH1 mutation or lack of mutation being IDH wild type, the recommendation is if somebody is IDH wild type CNS WHO grade 2 astrocytoma or grade 2 or grade 3, they would be offered treatment similar to a glioblastoma, which would be concurrent radiation and temozolomide followed by adjuvant temozolomide as long as performance status and all other factors support doing so. SPEAKER 2: Understood. I appreciate you providing that information as well. So were there additional areas where the expert panel found evidence either insufficient or was unable to make a recommendation? SPEAKER 4: Yeah, so there's two tumor types where we didn't have enough data to make a specific therapeutic recommendation. The first, unfortunately, is in recurrent glioblastoma. And there were no randomized controlled trials that demonstrated a benefit of one therapy over another. And so our recommendation is that when available, patients should be referred for a clinical trial. The other area is in a tumor type called diffuse midline glioma. This is a tumor characterized by the h3k27 mutation more commonly seen in children. But we do see this in adults. And here as well, there were no randomized trials that could clearly give us guidance on what the best therapy was even in the newly diagnosed setting. And our recommendation here also was, if available, to be considering a clinical trial. SPEAKER 2: Understood. It's important to recognize where there are areas where we're lacking evidence as well. So then, Dr. Blakeley, in your view, why is this guideline important and how will it change practice? SPEAKER 3: Thank you. Well, as Dr. Mohile said at the start, it is quite challenging to review the literature for gliomas in adults because we've had different nomenclature applied across clinical trials and diagnostic studies over the last 10 to 15 years. And this document and these guidelines really seek to be the clearinghouse to help clinicians match up what they see on the pathology report for their patient to the data that is published on phase III studies that has influenced our current standards of care. So I think the most important way it will change practice is bringing clarity to the data that already exists but has not been accessible to providers trying to help patients make the best decisions for them. It also importantly highlighted how much more work is needed. We desperately need new clinical trials for patients with glioblastoma and patients with astrocytoma IDH wild type 1p19q non-co-deleted WHO grade 2 and 3 and the other areas that Dr. Mohile highlighted. But we're hopeful that this will help provide clarity on both what we do know to help us identify patients who have the best chance of truly meaningful benefit from chemotherapy and where we need to invest more resources. SPEAKER 2: Absolutely. It seems like this will be a helpful resource for how to treat now and a guide as to what areas of research should be investigated in the future. So in addition to that, Dr. Mohile, finally, how do you view that these guideline recommendations will impact patients? SPEAKER 4: Yeah, my hope is that this will help standardize our approach to patients with gliomas. In the United States, patients with gliomas get care in all kinds of different settings. And when they're seeing an oncologist, particularly in the community, this might be a very small percentage of the types of cancers that they might be seeing, and it's hard to keep up with all of these trials and hard to keep up with the changes in classification. So our hope is that this guideline helps that oncologist in providing them the clarity, as Dr. Blakeley said, on how to approach treatment here so that all of our patients are getting the best standard of care based on the best available evidence and that they're being considered in those areas where there is not good evidence or referral for clinical trials so that in 10 years, when we put together the next guideline, that we're able to make some progress on some of these questions. SPEAKER 2: Great. Well, thank you both for all of your work that you did to review the literature and produce these evidence-based recommendations and, as you said, provide a real clear and helpful resource to both clinicians and to improve the quality of care for patients. And thank you for taking the time to speak with me today, Dr. Mohile and Dr. Blakeley. Finally, thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/neurooncology guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Loretta Nastoupil from MD Anderson Cancer Center, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She discusses the identification, evaluation, and management of hematologic toxicities in patients receiving ICPis, including hemolytic anemia among others in Part 10 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts. My name is Brittany Harvey. And today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Loretta Nastoupil from the University of Texas M.D. Anderson Cancer Center in Houston, Texas, author on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy, ASCO Guideline Update, and Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy ASCO Guideline. And today, we're focusing on hematologic toxicities in patients treated with immune-checkpoint inhibitor therapy. Thank you for being here, Dr. Nastoupil. LORETTA NASTOUPIL: Thanks, Brittany. I'm happy to be here. BRITTANY HARVEY: Great. Then first I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Nastoupil, do you have any relevant disclosures that are related to these guidelines? LORETTA NASTOUPIL: Yes, Brittany. So I have received honorarium for participation in advisory boards from the following companies, including BMS/Celgene, Genentech, Janssen, Novartis, Merck, MorphoSys TG Therapeutics, and Takeda. And I've also received research funding support from BMS/Celgene, Gilead Kite, Genentech, Janssen, Novartis and Takeda. BRITTANY HARVEY: I thank you for those disclosures. Then let's get into what we're here today to talk about. So what are the immune-related hematologic toxicities addressed in this guideline? LORETTA NASTOUPIL: So it's important to recognize that hematologic toxicities that are immune-related as a result of immune therapy are infrequent occurrences. So it's important to recognize when they do occur and some of the unique workups given that they are so infrequent. So probably one of the most common is hemolytic anemia. It's important to recognize that these are cancer patients. And they may have multiple reasons for the development of acute or new onset anemia, but recognizing if they're on either checkpoint inhibitors or immune therapies, it's important to recognize that it might be spurred on as a result of immune-mediated anemia. We advise in terms of history and workup to consider whether or not they've been exposed to new drugs, whether or not they've had a recent insect or snakebite exposure. The recommended workup includes a CBC with also a peripheral blood smear to look for evidence of hemolysis or macroketosis. In addition, other hemolytic anemia workup includes evaluation for LDH, haptoglobin, reticulocyte count, bilirubin, and free hemoglobin. Other potential diagnoses on the differential include DIC, so a panel, including coags, PT, INR, and PTT, exploring autoimmune serologies, PNH screening, evaluation for infection such as viral or bacterial causes of hemolysis, and also consideration for bone marrow failure syndrome, including evaluation for potentially reversible causes, such as B12, folate, copper, parvovirus, iron, thyroid, infection, et cetera. G6PD level is helpful in the evaluation, as well as exploration as I mentioned of potentially new drugs that might be linked, including ribavirin, rifampin, dapsone, interferon, some of the antibiotics, such as cephalosporins, penicillins, NSAIDs, ciprofloxacin, for instance, et cetera. So as part of the workup, if we have excluded alternative causes and we think that the immune-checkpoint inhibitor might be the underlying cause of the autoimmune hemolytic anemia, then generally we will continue unless they have grade 2 or higher toxicity, which is generally a hemoglobin less than 10. In which case, we would recommend to hold the immune-checkpoint inhibitor, again, with significant anemia. So those with grade 2 or higher, you might consider initiating corticosteroids, including 1.5 to 1 milligram per kilogram per day until improvement. For grade 3 or higher-- so this is more severe anemia So hemoglobin is less than 8. Generally, we're recommending permanent discontinuation of the checkpoint inhibitor and potentially higher doses, including up to 2 milligrams per kilogram per day of prednisone or corticosteroid equivalent to speed up the recovery. In regards to transfusion requirements or consideration, we are suggesting you evaluate or consider your local or regional guidelines. We generally do not transfuse for a target hemoglobin greater than seven to eight. And we also recommend supplementation with folic acid. BRITTANY HARVEY: Great. And then beyond those recommendations for hemolytic anemia, what are the key recommendations for identification, evaluation, and management of acquired thrombotic thrombocytopenia purpura? LORETTA NASTOUPIL: Sure. So fortunately, TTP is quite rare, but, again, something that is worth exploring. Some of the challenges are in the clinical syndrome. And that it can mimic some of the other toxicities that are covered in other sections, particularly the neurotoxicity section. But essentially, for patients who have pretty dramatic change in platelet count, again, they may have additional clinical sequelae such as neurologic toxicity or adverse events. It's important to recognize that TTP might be an underlying cause, again, for patients who are on immune-checkpoint inhibitors. This is where a hematology consult early in the clinical course would be particularly of importance to recognize it and potentially to minimize offending agents. Drug exposure is always important, because many of these patients might have other drugs, in addition to their immune-checkpoint inhibitors, such as chemotherapy, sirolimus, tacrolimus, antibiotics et cetera. And so exploring offending agents is important. An ADAMTS13 level, an inhibitor titer, would be important to send if you're considering TTP, in addition to evaluating the peripheral smear, and the hemolytic anemia workup, as I just mentioned, including LDH, haptoglobin and reticulocyte count. Exploring infectious etiology, including CMV titers or serology, would be particularly helpful, an additional clinical evaluation, such as brain imaging with CT or MRI, echocardiogram, and EKG would be of help. For all grades of TTP, again, even with a clinical suspicion for the diagnosis, in addition to hematology consult, we recommend stabilizing the patient. That might require care in an acute care setting, making sure that they have adequate organ function and that this is stabilized. For grade 1 or higher, we recommend holding the immune-checkpoint inhibitor. And you might consider, again, initiation of corticosteroids with 0.5 to 1 milligram per kilogram per day of prednisone or an equivalent. For grade 3 or higher, we would, again, in addition to holding the checkpoint inhibitor and in conjunction with your hematology colleagues, you might initiate a therapeutic plasma exchange. Again, in accordance with existing guidelines, you may consider higher doses of steroids, including methylprednisolone 1 gram IV daily for three days. You could consider some additional supportive agents, such as rituximab or pembrolizumab if the ADAMTS13 level is less than 10 or less than 10% of normal and an inhibitor or elevated ADAMTS13 IgG has been detected. BRITTANY HARVEY: I appreciate you going through the details for TTP. So then, additionally, this guideline addresses aplastic anemia. So what are the key recommendations for identification, evaluation, and management of aplastic anemia? LORETTA NASTOUPIL: Yeah. So fortunately, again, these are quite rare situations. So with aplastic anemia, similar to what we've discussed in terms of workup of anemia, globally, it's important to explore potentially causes of, again, bone marrow failure syndrome. And aplastic anemia is one of those such causes. Exploration of a bone marrow biopsy in conjunction, again, with your hematology consult would be critically important, and exploring potentially reversible causes, again, such as deficiencies and important nutrients, viral etiologies, in addition to parvovirus, CMV, HHV-6 is important to consider and rule out. But I think the end of the day, a bone marrow biopsy and aspirate is going to be the most helpful assessment to ensure that aplastic anemia has been considered and worked up. In regards to management of aplastic anemia, we're going to hold the immune-checkpoint inhibitor. You may need to provide additional support such as growth factors. And close follow-up, I think is the most critical aspect of this. Sometimes we initiate patients on corticosteroids. We hold the checkpoint inhibitor. And then we may monitor them less frequently. Oftentimes, these patients with high malignancies are going to need to be followed very closely, sometimes weekly or multiple times a week. So in regards to management of aplastic anemia that might be immune mediated as a result of immune-checkpoint inhibitors and in conjunction with your hematology and colleagues, consideration of management might include administration of horse ATG and cyclosporine, but again transfusion support, growth factor support, even consideration for HLA typing and evaluation first. Stem cell transplantation might be appropriate, particularly for a young patient with minimal comorbidities. For grade 3 or higher, in addition to these considerations, we're going to hold the checkpoint inhibitor and monitor weekly for improvement. If no response, you might consider repeating immune suppression with Rabbit ATG plus cyclosporine or cyclophosphamide. And for refractory patients, consider eltrombopag plus best supportive care. BRITTANY HARVEY: Great. Thank you. Those are important notes on the management of aplastic anemia. So then, additionally, what are the key recommendations for the identification, evaluation, and management of lymphopenia? LORETTA NASTOUPIL: Yeah. I think one of the challenges with lymphopenia, it's common for patients who've had cancer-directed therapy, particularly things like chemotherapy. And so understanding whether or not this is a new onset after exposure to checkpoint inhibitors is one of the critical aspects, in addition to considering alternative causes. But for patients in which we do think the lymphopenia is a result of the immune-checkpoint inhibitor, we're not generally advising discontinuation or holding of the immune-checkpoint inhibitor, but it is important to consider best supportive measures, including whether or not patients might benefit from monitoring for reactivation of certain viral etiologies, including CMV and HHV-6, for instance, in addition to potential consideration for prophylactic strategies, such as PJP prophylaxis. Also, zoster reactivation might be something that these patients might indeed be at risk for. So as opposed to holding your checkpoint inhibitor and initiating things like corticosteroids, if we have excluded alternative causes and think lymphopenia is a result of the immune-checkpoint inhibitor or as immune mediated, ensuring that they are receiving best supportive care to mitigate some of their toxicity that may result as the result of the lymphopenia. BRITTANY HARVEY: Understood. And it's important to note for clinicians that management is different from a lot of the management of the other hematologic toxicities. So then the last hematologic toxicity that was addressed in this guideline was acquired hemophilia A. So what are those key recommendations? LORETTA NASTOUPIL: Acquired hemophilia A, again, fortunately is very rare and uncommon, but this is one situation where engagement of a hematologist, who is an expert in management of hemophilia, will be critical. So that would potentially be step one. In terms of laboratory assessment, that would be helpful, in addition to your CBC, where you're assessing things like platelet count, coagulation workup, including fibrinogen, PT, PTT, INR, that would be informative. Patients with acquired hemophilia A will likely have a prolonged activated PTT with a normal PT. So that might be one of the clues. Imaging would be helpful to ensure the patients don't have any signs of spontaneous bleeding or hematoma basis, such as MRI, CT, or ultrasound, if particularly they have any localizing symptoms. Medication review to look for alternative causes would always be helpful. And determination of the Bethesda unit level of inhibitor would be critical. In regards to management, we would hold the checkpoint inhibitor, initiate corticosteroids, transfusion support as indicated, and you want to treat the underlying acquired hemophilia with conjunction of a hematologist. For grade 2 or higher, this may require factor replacement. And the choice is usually based on the Bethesda unit of the titer. Administration of prednisone, in addition to rituximab 375 milligrams per meter squared weekly for four weeks or cyclophosphamide dosed at 1 to 2 milligrams per kilogram per day may be patient specific. And, again, that decision should be made in conjunction with your hematology consult. Prednisone, rituximab, and cyclophosphamide should be given for a minimum of five weeks. And factors should be prescribed to increase the level, particularly during bleeding episodes. And, again, the choice of the factor is based on the presence or absence of an inhibitor. For grade 3 or higher, we advise to permanently discontinue the immune-checkpoint inhibitor. These patients generally will be admitted for stabilization. They do require factor replacement. Bypassing agents may also be required, including factor VII. Caution should be taken in elderly patients and those with coronary artery disease. Corticosteroids, rituximab, and cyclophosphamide should also be considered, transfusion support, if they're having active bleeding. And if worsening or no improvement, you could consider adding cyclosporine or immune suppression to try and stabilize these patients. Again, acquired hemophilia A requires special clinical and laboratory expertise. This would require consult and potentially even transfer to a specialized center, and consultation with a hemophilia center should be initiated as soon as this is considered or confirmed. BRITTANY HARVEY: That's a great summary of these recommendations. The expert panel and you clearly put in a lot of work into these recommendations. So then in your view, how will these recommendations for the management of hematologic toxicities impact both clinicians and patients? LORETTA NASTOUPIL: I think the most important thing are disseminating this information. I think ASCO plays a critical role in helping clinicians first recognize some of the toxicities that are different from what we have traditionally seen with chemotherapy and may have different management strategies. So guidelines, such as this, are critically helpful. Podcasts, such as this, are incredibly helpful to get the information out, recognizing that all of us authors are more than willing to provide additional guidance and are willing to be contacted in this situation where someone's facing one of these unique and rare toxicities and would like some additional guidance in terms of further management. Hematologic toxicities are sometimes hard to distinguish or maybe potentially hard to recognize, given many of these patients may have been on prior chemotherapy agents, and anemia or thrombocytopenia may not be unusual, but recognizing if it's new or more severe than what has been seen previously and that, at least, consideration of an immune-mediated hematologic toxicity, be considered, because the management might be unique. And so I hope that we've outlined today some of the hematologic toxicities that are rare that may be seen with immune therapy and some of the strategies to work up alternative diagnoses and management if it is indeed immune-mediated toxicity. BRITTANY HARVEY: Definitely. And I really appreciate you going through these rare but very important toxicities. So thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Nastoupil. LORETTA NASTOUPIL: Thanks, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.ASCO.org/supportive care guidlines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She reviews neurologic toxicities in patients receiving ICPis, such as myasthenia gravis, Guillain-Barre Syndrome, peripheral neuropathy, aseptic meningitis & encephalitis in Part 9 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey. And today, we're continuing our series on the management of immune related adverse events. I am joined by Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center in New York, New York, author on Management of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy ASCO Guideline Update and Management of Immune Related Adverse Events in patients Treated with Chimeric Antigen Receptor T Cell Therapy ASCO Guideline. And today, we're focusing on nervous system toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Santomasso. BIANCA SANTOMASSO: Thank you for having me. BRITTANY HARVEY: Then I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Santomasso, do you have any relevant disclosures that are directly related to these guidelines? BIANCA SANTOMASSO: Yes, I'd like to disclose that I've served as a paid consultant for Celgene, Janssen Pharmaceutical, and Legend Biotech for advising them on the topics of T cell therapy side effects. BRITTANY HARVEY: Thank you. Then getting into the content of this guideline, what are the immune related nervous system toxicities addressed in this guideline? And what are the overarching recommendations for evaluation of these neurologic immune related adverse events? BIANCA SANTOMASSO: So neurologic immune related adverse events actually encompass a very diverse spectrum of neurologic syndromes that can occur as a complication of treatment with checkpoint inhibitors. So the spectrum that is covered by this guideline includes myasthenia gravis, Guillain-Barre syndrome, polyneuropathy, aseptic meningitis, and encephalitis. And although these are rarer than many of the other immune related adverse event types affecting other organ systems, they're increasingly being encountered due to more patients being treated with novel combinations of immunotherapies. And they're important to recognize, because along with myocarditis, they have generally more morbidity and even more mortality than irAEs affecting other organ systems. So it's important for clinical care providers to have a high index of suspicion for these events. Studies have suggested that these tend to occur in about 3% to 12% of patients, probably between 1% and 2% of patients developing severe events. So they're rare. But again, the events are probably more commonly seen in patients treated with combination checkpoint blockade. And we're increasingly seeing more combinations. So we should be on the lookout for these. Neurologic immune related adverse events can be divided into syndromes that affect the peripheral nervous system, so meaning the peripheral nerves, the neuromuscular junction, and muscle. So that would be Guillain-Barre syndrome, myasthenia gravis, and myositis. And those that affect the central nervous system, such as the brain, spinal cord, or leptomeninges. So those would be aseptic meningitis and encephalitis. The peripheral nervous system irAE appear to be more common than those affecting the central nervous system. And patients can present with a number of different symptoms that kind of relate to these syndromes. That can be as diverse as a headache to numbness, tingling, or focal weakness, such as a foot drop or facial weakness. You may see patients with severe altered mental status or personality changes or gait difficulty, walking difficulty, which could actually mean any number of syndromes. It's generally important to be aware that the timing of onset is generally early, a median of four weeks after the start of treatment, but can range anywhere from one week after the start of treatment to greater than a year. And because we know that cancer can spread to many parts of the nervous system, neurologic toxicity should be considered a diagnosis of exclusion. So that means that as part of the workup for neurologic immune related adverse events, it's imperative to rule out nervous system metastasis, stroke, and infection, which we know can occur at higher rates in patients with cancer. So for most neurologic immune related adverse events, diagnostic workup is similar. It should include MRI brain and/or of the spine, with and without contrast, and often a lumbar puncture for cerebrospinal fluid analysis, including cytology to rule out leptomeningeal metastasis. BRITTANY HARVEY: Thank you for that overview. In addition to those points for evaluation for all nervous system toxicities, what are the key recommendations for identification, evaluation, and management of myasthenia gravis? BIANCA SANTOMASSO: So for myasthenia gravis, presenting symptoms usually include fatiguable or fluctuating muscle weakness. It's generally more proximal than distal. And there's frequently ocular and/or bulbar involvement. So that means either ptosis, like a droopy eyelid, diplopia, or double vision, difficulty swallowing, dysarthria, facial muscle weakness, and/or head drop or neck weakness. Again, for any patient with new neurologic symptoms, an MRI of the brain or spine should be performed depending upon the symptoms to rule out central nervous system involvement by disease or some alternative diagnosis. And similar to idiopathic myasthenia gravis, acetylcholine receptor antibodies can be positive. So these should be checked. This is a blood test. But it's important to note that while these antibodies may be confirmatory, their absence does not rule out the syndrome. The rate of acetylcholine receptor antibody positivity in immune related myasthenia gravis has not been definitively established. So depending on the presentation, one might also consider sending a paraneoplastic panel for Lambert-Eaton myasthenic syndrome. The single most important point I'd like to make regarding suspected immune related myasthenia gravis is that orbital myositis and generalized myositis from immune checkpoint inhibitors can present similarly. For this reason, early neurology consultation and electrodiagnostic testing with repetitive stimulation or single fiber EMG becomes important and helpful to distinguish the two. And to make matters even more complicated, we've learned that there's an overlap syndrome, where patients may develop not only myasthenia gravis, but also myositis and/or myocarditis at the same time. So basically, the neuromuscular junction is affected. But the local muscle and myocardium, which is heart muscle that's kind of related, may be affected all at once. And this overlap of syndromes may increase disease severity and mortality. So they're important to recognize. So what this means is that when you encounter a patient with suspected myasthenia gravis, you should also be checking CPK, muscle enzymes, aldolase to evaluate for myositis, and troponin and electrocardiogram to evaluate for myocarditis. And this should be done even if there are no obvious symptoms. So onto the treatment of myasthenia gravis, this is similar to the management of the idiopathic form. Therefore, it's helpful to have the involvement of a neurologist. The immune checkpoint inhibitor therapy should be held. And patients with mild symptoms are often started on pyridostigmine and corticosteroids. And patients with more severe symptoms should initiate IVIG or plasmapheresis. And patients with more severe symptoms may need to be admitted to the hospital. So that their neurologic and pulmonary status can be monitored closely for improvement. Some patients may require ICU level of monitoring. And considering adding rituximab if symptoms are refractory, and often, as symptoms improve, the steroids can be de-escalated. BRITTANY HARVEY: Understood. Those are all very important points for clinicians to consider. So then following that, what are the key recommendations for identification, evaluation, and management of Guillain-Barre syndrome? BIANCA SANTOMASSO: So Guillain-Barre syndrome, like myasthenia gravis, also presents with weakness. Most often, patients present with a progressive ascending muscle weakness. The syndrome can start with sensory symptoms or neuropathic pain that can be localized to the lower back and thighs. In addition to the classic ascending weakness, there may be facial weakness, double vision, numbness or tingling in the hands or feet, loss of balance, and coordination. And shortness of breath may occur due to respiratory muscle weakness. The autonomic nerves can also be affected and can present as new severe constipation or nausea, urinary problems, or orthostatic hypotension. The reflexes are often reduced or absent, deep tendon reflexes. So again, as for all of the syndromes, early involvement by a neurologist is recommended, if possible. Usually, MRI imaging of the spine is important to rule out spinal cord compression. And it also may show cauda nerve thickening or enhancement, which can occur with this syndrome. And the second aspect is cerebrospinal fluid analysis is important for diagnosis. This is important really for ruling out leptomeningeal metastasis, since that could present similarly. And often, what can be seen in GBS is an elevated protein level in the cerebrospinal fluid. In addition, unlike idiopathic GBS, there can be an elevated white blood cell count in the cerebrospinal fluid. Electrode diagnostic testing can also be helpful for confirmation, and serum tests for antiganglioside antibodies, and a paraneoplastic antibody workup may also be considered. Bedside pulmonary function test and swallowing evaluation should be performed if there's a concern for respiratory or swallowing dysfunction. And some patients do need to have inpatient admission and monitoring if symptoms are severe or if they appear to be progressing from mild. For management, the checkpoint inhibitor therapy should be held. And patients are most often treated with IVIG or plasmapheresis. Corticosteroids can be added to the IVIG or plasmapheresis. These are not usually recommended for idiopathic Guillain-Barre syndrome. However, in immune checkpoint inhibitor related forms, a trial is reasonable. And steroids are usually given at a higher dose for five days and then tapered over several weeks. BRITTANY HARVEY: Understood. I appreciate that overview. So then what are the key recommendations for identification, evaluation, and management of peripheral neuropathy? BIANCA SANTOMASSO: So peripheral neuropathy, or polyneuropathy, is a rare but likely underreported complication of immune checkpoint inhibitor therapy. So in the large databases and meta-analyses, those have really focused on Guillain-Barre syndrome for reporting. But other types of neuropathies, such as painful length dependent sensory and motor axonal neuropathies, or polyradiculopathies or sensory neuropathies do occur after immune checkpoint inhibitors and are probably under-recognized. So evaluation of immune related neuropathy should include neurology consultation to guide the neurology phenotype determination and also the workup. The evaluation primarily relies on a combination of electrodiagnostic studies, serologic tests, and MRI neuroimaging. Because peripheral nervous syndromes can overlap, screening for neuromuscular junction dysfunction with electrodiagnostic testing and myopathy is recommended for any patient who presents with at least motor symptoms that are thought to be peripheral. Serum testing can be helpful for ruling out reversible causes of neuropathy. Spinal imaging is recommended to exclude metastatic disease. And for management, it usually involves holding the checkpoint inhibitor in mild cases, using neuropathic pain medication or steroids in more severe cases. And very severe cases that kind of resembled GBS would be managed as per the GBS algorithm with IVIG or plasmapheresis. BRITTANY HARVEY: Understood. And it's key to look out for those overlapping adverse events. So then following that, what are the key recommendations for aseptic meningitis? BIANCA SANTOMASSO: Right, so now we're getting into the central nervous system toxicity. So aseptic meningitis is an inflammation of the meninges. And it can present with headache, photophobia, neck stiffness. Patients can have nausea, and vomiting, and occasionally fever. The mental status is usually normal. And in patients presenting with headache, which in isolation, could suggest an aseptic meningitis, it's important to evaluate if they have any confusion or altered behavior, which might suggest an encephalitis. And this distinction is important, because suspected encephalitis triggers a different workup, which we'll be discussing later, and also even different management. So the workup for aseptic meningitis includes neuroimaging, usually an MRI of the brain. And on that imaging, we sometimes see abnormal leptomeningeal enhancement. It's important not to assume that this is cancer and to do a lumbar puncture to evaluate cerebrospinal fluid both for inflammation and to exclude other causes of meningeal disease, particularly neoplastic and infectious causes. So cytology, Gram stain, and culture, and other infectious studies should be negative. And it's recommended that empiric antibiotics or antiviral therapy be considered to cover for infectious meningitis until the cerebrospinal fluid results return negative. What's seen in the cerebrospinal fluid in aseptic meningitis is typically reactive lymphocytes, but also neutrophils or histiocytes may be prominent on the cytology. And while the symptoms can be severe, sometimes requiring hospitalization, the management of this entity, these are usually quite treatable. Aseptic meningitis generally responds very well to corticosteroids. So management involves holding the checkpoint inhibitor. And you can often get away with starting a fairly modest dose of corticosteroids, such as oral prednisone, 0.5 to 1 milligram per kilogram or the equivalent. And steroids can usually be tapered over two to four weeks. BRITTANY HARVEY: Great, thank you for reviewing those recommendations. So then you just mentioned the distinction of aseptic meningitis and encephalitis. So what are those key recommendations for identification, evaluation, and management of encephalitis? BIANCA SANTOMASSO: So in encephalitis, the mental status is not normal. It's characterized by, really, an acute or subacute confusion, altered mental status, altered behavior, memory deficits, including working memory and short-term memory. There can be, as associated symptoms, headaches, new onset seizures, psychiatric symptoms, which can include delusions or hallucinations. There could be weakness, sensory changes, imbalance, or gait instability, along with the mental status changes. And so similar to aseptic meningitis, the other central nervous system toxicity, it's important to distinguish encephalitis from other causes of altered mental status, such as CNS metastases, stroke, or infection. And as for the other syndromes, it's very helpful to have neurologic consultation early, if possible. An MRI of the brain is critical. And in addition, MRI of the spine may be obtained to evaluate for inflammatory demyelinating ischemic or metastatic lesions. In immune related encephalitis, MRI brain imaging may reveal T2 flare changes, typical of what can be seen in idiopathic autoimmune or limbic encephalitis. But most often, the MRI imaging is normal. So in this situation, a lumbar puncture for CSF studies to evaluate for evidence of inflammation can be very helpful. You can expect to see either a lymphocytic pleocytosis or an elevated protein, or CSF restricted oligoclonal bands. CSF analysis is also helpful for excluding other causes of encephalitis, particularly viral encephalitis. So HSV, Herpes Simplex Virus, or varicella zoster virus encephalitis should be ruled out and treated with antivirals while the tests are pending. So typically, these entities can be excluded by PCR testing for HSV and VZV. Electroencephalogram, or EEG, can also be helpful for revealing subclinical seizures or status epilepticus, which can occur as a complication of encephalitis or as a cause of persistently depressed sensorium. But these are not specific to encephalitis. Other testing that's done includes screening metabolic tests to look for alternative etiologies. And for this entity, serum and CSF autoimmune antibody evaluation should be sent to assess for malignancy associated neurologic syndromes. And your neurologist can help you with the workup and management, in particular which tests to send. There have been reported cases of antibody positive checkpoint inhibitor related encephalitis. For management, in contrast to aseptic meningitis, these are generally not as steroid sensitive. So you often have to treat with either higher steroid doses, even pulsed steroid doses, along with IVIG or plasmapheresis. If no improvement, escalation to rituximab and cyclophosphamide can be considered, with the assistance of neurology. This management guidance is taken from how to treat autoimmune encephalitities that are not related to checkpoint inhibitors. Unfortunately, these can be difficult to treat. The response may only be partial. So this is one area in need of better understanding of best therapeutics. BRITTANY HARVEY: OK, thank you for reviewing that and pointing out where there's future research needed as well. And I appreciate your reviewing the recommendations for each of these neurologic immune related adverse events. So then to wrap us up, in your view, how will these recommendations for the management of nervous system toxicities impact both clinicians and patients? BIANCA SANTOMASSO: Yeah, so I think this is a daunting list of toxicities. But I'll say that in most situations, the immune checkpoint inhibitor side effects are often manageable and reversible with proper supportive care. They can be serious, and they require close vigilance and prompt treatment and identification. But by knowing what to look for in early identification, that allows early intervention, which is really the key to reversibility and the best outcomes. So having these toxicities on your differential diagnosis is critical. And I think these guidelines really help inform both clinicians, and care providers, and patients on what the possible manifestations are. So we believe this guideline and its recommendations will help members of clinical teams with the recognition and the management of these unique toxicities. And again, it's timely recognition and early intervention that helps patients, really, by increasing their safety with early management. BRITTANY HARVEY: Great, well, thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Santomasso. BIANCA SANTOMASSO: My pleasure. Thank you so much. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. Stay tuned for additional episodes on the management of immune related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast. And be sure to subscribe. So you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Umang Swami from the Huntsman Cancer Institute, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” He discusses the identification, evaluation, and management of renal toxicities in patients receiving ICPis, focusing on nephritis/acute kidney injury in Part 8 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, we're continuing our series on the management of immune related adverse events. I am joined by Dr. Umang Swami from the Huntsman Cancer Institute at the University of Utah in Salt Lake City, Utah, author on Management of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy ASCO guideline update, and Management of Immune Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T Cell Therapy ASCO guideline. And today, we're focusing on renal toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Swami. UMANG SWAMI: Thank you, Brittany. And I appreciate the invitation to be here today. BRITTANY HARVEY: Great. Then first, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Swami, do you have any relevant disclosures that are directly related to these guidelines? UMANG SWAMI: No, I do not have any relevant disclosures that are directly related to these guidelines. BRITTANY HARVEY: Thank you. Then let's dive into what we're here today to talk about. So what are these immune related renal toxicities that are addressed in this guideline? UMANG SWAMI: So this guideline focuses on nephritis, or acute kidney injury, as an adverse event due to immunotherapy. Acute kidney injury, or AKI, an uncommon complication of immune checkpoint inhibitor therapy. Just to give a little context before we start, the incidence of any grade AKI around 1% to 2% in patients treated with a single agent immune checkpoint inhibitor, such as ipilimumab, nivolumab or pembrolizumab, and 4.5% in those treated with anti-CTLA-4 for and anti-PD-1 combination of nivolumab plus ipilimumab therapy. The incidence of grade 3 or grade 4 AKI is very low. I will say less than 1% with single agents, and around 1.6% with the combination of nivolumab plus ipilimumab. While initial studies had quoted a small incidence of AKI with immune checkpoint inhibitor use, emerging data now suggests that a higher incidence might be present, which might range between 9.9% to around 29% of AKI with the immune checkpoint inhibitors. However, most of this extra toxicity is grade 1. The median time to onset of renal toxicity with these agents is around 14 weeks, but can range from 6.5 to 21 weeks. BRITTANY HARVEY: Thank you for that background information. I think it's helpful for clinicians to understand how rare or common these adverse events are. So then, what are the key recommendations for identification, evaluation, and management of nephritis or acute kidney injury? UMANG SWAMI: That's a great question. Presenting symptoms related to immune therapy induced renal toxicities may include urinary frequency, dark, cloudy urine, fluid retention, or edema of face, abdomen, extremities. There might be sudden weight gain. There might be associated abdominal or pelvic pain. Patients might have nausea, vomiting, high blood pressure, or they may have a change in mental status such as drowsiness. However, we should remember that a vast majority of them will be asymptomatic at presentation. Therefore, patients should have their renal function, that is, serum creatinine, checked prior to administration of each dose of checkpoint inhibitor therapy. For patients with new elevations in creatinine, one should consider holding checkpoint inhibitor therapy while other potential causes are evaluated. These other causes may include recent IV radiographic contrast administration, dehydration, urinary tract infection, other natural toxic medications, including concurrent chemotherapy, herbals, or other supplements. Patients without their obvious causes or who don't respond to alternative treatment measures should be presumed to have immune related renal toxicity and treated empirically depending on the grade of AKI. Safe treatment of autoimmune component is important. So with regards to the grading of AKI, grade 1 means a creatinine level increase of more than 0.3 milligrams per deciliter, or creatinine 1.5 to two times above baseline. And in this situation, physicians should consider temporarily holding checkpoint inhibitor therapy and evaluating other potential contributing agents in combination regimes, pending consideration of potential alternative pathologies. A change that is still less than 1.5 times of upper limit of normal could be meaningful and should be remembered. For grade 2 AKI, which is creatinine two to three times above baseline, apart from holding immune checkpoint inhibitor and evaluating for alternative causes, nephrology should be consulted. If other ideologies are ruled out, administer 0.5 to 1 milligram per kg per day prednisone or its equivalent. If kidney function worsens or does not improve after one week, increase the dose of prednisone to 1 to 2 milligrams per kg per day or its equivalent, and permanently discontinue immune checkpoint inhibitor. If the AKI improves to grade 1 or less, taper steroids over at least four weeks, otherwise we might see recurrence. If there is no recurrence, a physician might discuss resumption of immune checkpoint inhibitor with patient after taking into account what are the risks and what are the benefits. Resumption of immune checkpoint inhibitor can be considered once steroids have been successfully tapered to 10 milligrams per day or less, or discontinued. However, if elevation persists for more than seven days or worsens, and no cause is found, then the grade 2 AKI needs to be treated as grade 3. Now grade 3 and grade 4 AKI are managed similarly. Grade 3 AKI is defined as creatinine more than three times the baseline, or more than 4 milligrams per deciliter, or when hospitalization is indicated. And grade 4 AKI defined as an AKI associated with life-threatening consequences, when dialysis is indicated, or creatinine six times above baseline. Management includes nephrology consult, evaluation for alternative causes, and permanent discontinuation of immune checkpoint inhibitor. If they are directly implicated in renal toxicity, the administration of corticosteroids in grade 3 or grade 4 AKI is at an initial dose of 1 to 2 milligrams per kg per day of prednisone or its equivalent. If and when the AKI improves to grade 1, corticosteroids can be tapered over at least four weeks. However, if elevation persists for more than three to five days for grade 3 or more than two to three days for grade 4 or worsens, we should consider additional immunosuppression, such as infliximab as a time frame, cyclophosphamide, cyclosporine, or mycophenolate. Usually, reflex renal biopsy is typically not necessary or recommended unless the AKI is refractory to steroids or other immunosuppressive agents. BRITTANY HARVEY: I appreciate your reviewing those details for immune related renal toxicity. So then, in your view, Dr. Swami, how will these recommendations for the management of renal toxicities impact both clinicians and patients? UMANG SWAMI: This guideline presents a concise, up to date, and a stepwise approach to diagnose, grade, and treat this rare, but serious side effect of immunotherapy. In my view, this would be immensely helpful to clinicians in busy practices. Prompt identification and treatment is also expected to help our patients experiencing immune related kidney injury. For patients, it will provide a readily available document to refer to for information regarding side effects of immune checkpoint inhibitor therapy. I applaud the efforts by the ASCO and the authorship team in developing the patient focused version of this guideline. This may allow patients, especially when between clinic visits, to identify this unusual condition and seek medical help in a timely fashion. BRITTANY HARVEY: Great. Thank you for highlighting the importance of this guideline, for all your work you did on this guideline, and for your time today, Dr. Swami. UMANG SWAMI: Thanks so much, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can find many of our guidelines and interactive resources in the free ASCO guidelines app, available on iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

A physician attempts to ease a patient's pain, a painful moment somewhat eased by the joy of music.   TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   RICHARD LEITER: Ode to Joy. "Is now an OK time?" I asked as I quietly entered the dimly lit room on a Saturday afternoon. "Yes, we've been waiting for you," my patient's wife Julie responded in the same calm, composed voice she had maintained all week. "Before we start, what questions do you have?" "I think you answered all of them this morning. I'm ready. Tom is ready. We just don't want him to suffer anymore." "OK, we'll get started." When I was in training, I had seen my preceptors initiate palliative sedation, but this was my first experience doing so as an attending physician. After being dormant for so long, my impostor syndrome returned. Though I was confident that I was taking the clinically-appropriate next step, I was nervous. I asked Tanya, our charge nurse and the nurse who was primarily caring for him over the last few days, to draw up the syringe. She did so with practiced confidence and handed it to me. I held it between my fingers, wondering how slowly I would need to push it to ensure the 2 milliliters of midazolam went in over a full five minutes. Tanya cleaned off the side port of his IV. I twisted the syringe into place. I looked up at Julie. She squeezed Tom's hand. I had first heard about Tom nearly a week earlier, when my colleague was handing off the service to me. "He's in his 50s, metastatic cancer. He was home on hospice and came in yesterday with uncontrolled pain. We started him on ketamine and he looks much better. The plan is to wean his ketamine, increase his methadone, and get him back home, hopefully in the next day or two." Stoic from years of pain from cancer eating away at his bones, Tom lay in bed with his eyes closed, his furrowed brow the only sign of his ongoing agony. When the nurses tried to move him, he screamed. After we weaned his ketamine, his pain quickly worsened. We increased methadone and hydromorphone. Neither gave him adequate relief. We restarted ketamine, but it proved to be no match for his pain. On rounds one morning, Julie asked if Tom could make it home. I told her I didn't think so and explained how worried I was about his pain. If we sent him home, I was concerned the pain would force him to come right back. Julie told me her kids would be disappointed, but that they'd understand, as she did. Easing Tom's suffering was more important. The hospital bed his family had set up in the living room would remain empty, a physical manifestation of cancer's unending cruelty. The hospital bed his family had set up in the living room would remain empty, a physical manifestation of cancer's unending cruelty. We talked about what would come next. If further titrating his medications proved ineffective, which I worried it would be, we would need to consider palliative sedation. "Whatever you need to do," Julie responded, her voice barely betraying the exhaustion I imagine she was feeling. Palliative sedation is a procedure used to relieve refractory suffering in a terminally-ill patient. Clinicians carefully sedate the patient, often to the point of unconsciousness, to relieve symptoms such as pain, nausea, shortness of breath, or agitated delirium. It is a procedure of last resort, and in our hospital, requires the approval of two attending physicians and the unit's nursing director. Though palliative sedation may shorten a patient's life, ethicists and clinicians have long regarded it as acceptable because its goal is not to hasten death but rather to relieve suffering. This is known as the doctrine of double effect, by which an action with at least one possible good effect and at least one possible bad effect can be morally permissible. Back in his room on that Saturday afternoon, I looked over at Tanya, the nurse, then at Harry, my fellow, who had been caring for Tom all week. I took in a breath under my mask, then slowly began to inject the contents of the syringe into his IV. In the quiet, I could hear the music coming from Julie's phone, which she had placed on the pillow beside his head. A pianist played a slow, mournful rendition of the final movement of Beethoven's Ninth Symphony, the Ode to Joy. In my head, I sang along. (SINGING) Joyful, joyful, we adore thee. I went to a traditionally Anglican school. 600 boys of all faiths and backgrounds, we'd rise each morning in assembly and sing hymns together. We cheered, yelled, and thumped on our pews-- a few minutes of raucous togetherness before we devolved into the usual bullies and cliques for the rest of the day. Tom's room couldn't have been more different. He remained completely still. Though Julie held his hand, he was alone, as we all felt in that room. (SINGING) Hearts unfold like flowers before thee, opening to the sun above. I felt the soft resistance of the syringe's plunger hitting the barrel. I looked back up at Tom. His chest fell, but didn't rise. I waited. He didn't breathe. The music slowed down. I felt Harry's eyes pivoting back and forth between my face and Tom's chest. I fixed my eyes on Julie's hands wrapped around her husband's. Despite the tension of the last week, she was calm, gentle. I matched my breath to hers. If she could exude such peace, so could I, I thought. I noticed Tom's hands. He had a piano player's fingers, long and slender. I pictured him sitting at the piano in their living room. I wondered who would take his place on the bench. I wondered if he could hear the song playing beside him. Had he and Julie chosen it for this moment? Did it bring back joyful memories, as it did for me? (SINGING) Melt the clouds of sin and sadness, drive the dark of doubt away. He didn't breathe. Did my first attempt at palliative sedation become euthanasia? Even if so, was this OK? I rehashed our conversations from the last few days. We talked about the risks. I went over the dose. Double effect, I reassured myself. Even so, as bedside nurses have told me, it's easier to talk about philosophy when you're not holding the syringe. I thought about how I would explain Tom's death to Julie. I wondered if she would be angry, upset, relieved? With the help of my outpatient colleagues, they had spent years preparing for his death. His financial affairs were in order, and he had done legacy work with his kids. More than nearly anyone I had cared for, they were ready. Were we? Was I? (SINGING) Mortals join the happy chorus which the morning stars began. He breathed in. Not a grand gasp, a slow, soft inhalation. Tom's hand flexed ever so slightly around Julie's. In my head, I thumped a pew. [MUSIC PLAYING]   SPEAKER 2: Welcome to "JCO's Cancer Stories-- The Art of Oncology," brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. SPEAKER 3: The guest on this podcast episode has no disclosures to declare. [MUSIC PLAYING] LIDIA SCHAPIRA: Welcome to "Cancer Stories-- The Art of Oncology" podcast series. I'm your host Lidia Schapira. And with me today is Dr. Richard Leiter, physician and member of the Psychosocial Oncology and Palliative Care team at Dana-Farber Cancer Institute in Boston and the Brigham and Women's Hospital. Welcome to our podcast. RICHARD LEITER: Thank you so much for having me. LIDIA SCHAPIRA: It's a real pleasure. You submitted a beautiful narrative piece called "Ode to Joy." And I'd like to start today, Richard, by just focusing first on the case that you present to us. Let me tell you how I understand Tom's history, and then you can correct me if this is not the way that you'd like him to be understood. And remember, Tom is a man in his 50s who's lived with metastatic cancer to bones for years. In your narrative, you're very careful and document the fact that you've worked with many members of your palliative medicine team for a long time, that there had been many efforts to control his pain, his suffering, and he had to be hospitalized for pain management. He was already receiving home hospice care. There was a bed in the living room in the center of the family home. And he had a very supportive family and a wife that we'll call Julie at bedside. Is that the proper framing for the story? RICHARD LEITER: Exactly. Yep. Yeah. I think what I would add is that the goal was really to control his pain and get him back home. LIDIA SCHAPIRA: So now you're there as the fresh attending in palliative medicine, and you're called in, and it becomes quite clear to you after a few days of changing his medications that the pain is refractory. And that it-- you note here that he screams when he is moved, that the level of pain reaches what you have called agony. So tell us a little bit more about how a palliative medicine consultant or physician approaches this kind of situation in hospital today. RICHARD LEITER: Yeah, no. Great. Thanks so much. So we were, I would say, lucky enough to have him on our intensive palliative care unit, where we're caring for patients with difficult and sometimes refractory symptoms at any stage of the disease. So not only for end of life. But we do see a number of cases like his every year, every few months, where someone is getting closer to the end of life. The goal is to really focus on intensive symptom management. And their symptoms are challenging to control. So I think the first step, always, is a good history, right? Where is this pain coming from? What treatments have they tried already? What's worked? What hasn't? We're going to titrate medications, but select medications based on that and titrate them. I think someone who has been involved with my outpatient colleagues and has been receiving hospice services at home has often gone through many treatment modalities. So it's really taking what they've been on before and starting to add to it. So for Tom, I had inherited him from one of my colleagues, who had admitted him a couple of days earlier. And at that point, he was already on a hydromorphone infusion and ketamine, as I talk about in the piece. Ketamine had been started, hopefully, as a bridge to get him back home. And he had been on methadone, which is one of our most potent agents for, not only nociceptive pain, so our basic kind of bony pain or visceral organ pain, but also if there's pain with a neuropathic component. Methadone is an opioid that can be particularly effective there. So I think it's saying, OK, well, have we hit all of our receptors in managing their pain? Are we managing the anxiety on top of that? Are we doing everything we can? Are there procedures that we could do to help with their pain? Sometimes we're talking about intrathecal pumps for instance. And obviously, that's a more involved discussion. How much time does someone have left? Are the goals really to put them through a procedure in order to get their pain under control? But we frequently work with our interventional pain colleagues to tease out whether a procedure would be helpful for a particular patient. So those are the thoughts that always go through my mind when I'm approaching someone with severe cancer-related pain. LIDIA SCHAPIRA: So this is a very thoughtful approach. And I think one of the messages is that it seems palliative medicine and pain management are integrated into the care of patients with advanced cancer, which is a very important message for our listeners and our readers. And here you are, you have all of this, you have good communication, it seems, with your team members, with the patient's family, and there's nothing more that you can think of doing. And you're now starting to think about interventions that we normally don't think of, except as a last resort. Bring this to the bedside. Tell us a little bit about the recommendation for palliative sedation and when that's indicated in care. RICHARD LEITER: Yeah. So palliative sedation, as I write in the piece, it's a measure of last resort. And certainly, in our hospital's protocol, it explicitly states it's when all other options have been tried. As we start to integrate more options, it's always a conversation we're having among our team-- is when is palliative sedation truly indicated. How many boxes do we need to check before going down the palliative sedation route? And I think-- so we started to think about-- we had him on ketamine. We tried to wean him off, it didn't go well. We restarted ketamine. We started dexmedetomidine, which can be useful. Precedex, the brand name, they oftentimes use it in the ICU for sedation, but we find that it can be helpful in cases of refractory pain as well. And my practice has been-- and though I haven't gotten to palliative sedation until this case-- when I'm thinking about Precedex, I'm also starting conversations with the patient or their family, and certainly our team, about palliative sedation to say if this doesn't work, this is where we're headed. LIDIA SCHAPIRA: And why is this situation so difficult, so personally anxiety-provoking for you? You do use words that convey that you are feeling nervous, or perhaps even anxious. Tell us why. RICHARD LEITER: I think it's-- relieving our patient's suffering, relieving their families suffering is certainly the core of much of medicine and very much the core of what we do in palliative care. And I think to have someone in just such a terrible situation-- putting aside the pain, right? This is a man who's dying of his cancer, has a relatively young family. That alone is an awful situation. And my job is to make that situation a little bit less bad, is to ease the suffering. LIDIA SCHAPIRA: And there's something about this particular procedure, however, that adds a level of intensity and nervousness for you, and that is that perhaps-- you can describe this better than I-- but the fact that in some cases, this could have the unintended effect of actually causing respiratory depression or even hastening death and something that you have explained in your piece, if I understood you correctly, as the double effect. Did I get that right? RICHARD LEITER: Yeah, that's right. So the worry or one of the considerations with palliative sedation is that it could hasten someone's death. Oftentimes, the doses of the medications that we're using, if we're titrating them slowly, there are studies that show that it doesn't necessarily. I do think, though, when we tie it into withholding artificial nutrition and hydration, in that case, had the person been awake enough to eat and drink before, we do know that it would probably hasten their death, right, from that part of it, but not necessarily the sedation aspect. So double effect is basically saying this is ethically OK-- and there are a number of criteria. But if we are intending the good effect and not the bad effect and that it's proportional to the gravity of the situation so that not every patient who comes in with bad pain undergoes palliative sedation. LIDIA SCHAPIRA: My favorite line, Richard, in the piece-- and one that I now have read probably dozens of times-- is this-- "the double effect, I reassured myself. Even so, as bedside nurses have told me, it's easier to talk about philosophy when you're not holding the syringe." And that just gives me goosebumps thinking about it. What did you feel when you were holding the syringe? RICHARD LEITER: Exactly as I wrote about. There's all of the cognitive processes going on. And I ran it by another attending, I ran it by the nursing director, I ran-- everyone was on the same page, that this was medically indicated in this situation. And yet, when I'm standing there in the room-- patient, his wife, my fellow, and the nurse-- and I'm the one holding the syringe, watching the medication go in, it felt completely different to me. And there's a power that comes with it. In one sense, I felt like I was there for my patient. Here I am, standing here doing this to ease his suffering. And then the other, the unintended consequences of the sedation are real, and that feels different when you're the one physically doing it. LIDIA SCHAPIRA: I think one of the incredible gifts you've given us as readers is to share this with us and really adds a different dimension to the discussion of the complexity of what it is to be present, not just as a witness, in this case, but as somebody, as you say, with a power to really control so many things in the situation. And I thank you for sharing that with us. And question to you is, did writing about it in any way help you process this emotional, very powerful experience? RICHARD LEITER: Absolutely. I write to process. I write when I feel like I have something to say. And oftentimes, I write when a particular moment struck me. And I think that that moment, sitting there, pushing the medication, waiting for that breath while the music was playing was so poignant for me that I walked out of the room and I remember thinking to myself that night as I was decompressing on my walk home from work, I think I need to write about this. LIDIA SCHAPIRA: So thank you for writing about it, and then, of course, for submitting for review and to share it with people. Let me bring the music in. Music is such an important part of our sensory experience. So as you were holding the syringe, Julie, Tom's wife, puts the phone on the pillow and she plays the piano version of Ode to Joy from Beethoven's Ninth Symphony, which I want to play for our listeners now. [MUSIC PLAYING]   So Ode to Joy meant something, clearly, to Tom and Julie. And you said that you watched-- perhaps you were watching for his reactions. But tell me a little bit about what it meant to you. You sprinkled your essay with the lines for the choral for Ode to Joy, which has a religious significance as well. So tell us a little bit about that. RICHARD LEITER: Yeah. So I grew up in Toronto. I went to an all-boys school there that had a traditionally Anglican background, though I'm not-- I'm Jewish. We would sing hymns. And over the course of my time there, the hymns became less denominational and more multicultural and inclusive. And it was a moment-- it was a nice moment where everyone got into it. It's 600 boys singing, and so I still remember the words to Ode to Joy vividly. Anytime I hear it, I can replay the words in my head. And I found myself, in those moments in the room, really thinking about it. And the words were still-- as I was processing and watching Tom and Julie and making sure I was pushing the medication at the right speed, there was this soundtrack. It's a strange moment too, because they're good memories for me, and yet I'm in this incredibly solemn, intimate moment in my patient's room. LIDIA SCHAPIRA: And so as we're getting to the end of the piece and there's all of this tension that you've built up in the writing and the narrative-- and here you are, you're waiting and you hear the music and so on-- and then you finally let the tension out and he breathes. It's not a huge breath, but it's a soft, slow inhalation. And you see that the hand is flexed slightly around his wife, so he's still breathing. And you finish with this line that you say, "In my head, I thumped a pew." And I have to ask you about that. What does that mean to you? RICHARD LEITER: Yeah. So in that moment, it was relief, is what it was. Just the sense of, OK, this went-- it's my first time doing this, and this went OK. He appears more comfortable. He is still breathing. This is OK. And it just brought me back when we would thump the pews as we were singing the hymns. Our principal did not like it, but-- [LAUGHTER] But I think it was just that it was relief. I hesitate to say it was joy because I don't think there's joy in a situation like that, in the room. But there was a sense of satisfaction maybe, or professional satisfaction, the, OK, this is what we can do. And as bad as the situation is, there was something that we could do to make him somewhat more comfortable. LIDIA SCHAPIRA: Well, I certainly learned a lot. I wonder if now that some time has passed since this event, if you have any additional reflections on how this story has impacted your professional delivery of care, or perhaps the way you teach others, and if there are any parting comments that you'd like to leave us with. So I haven't had another case where I've needed to do palliative sedation, though we've thought about it in a couple of cases. I do think it's helped me, when I talk about palliative sedation with our trainees, to add the emotional valence. I think I was pretty good at talking about the importance of making sure everyone's on the same page and talking to the patient and the family and nursing staff. But to really talk about the significance of that moment for us as clinicians and how it does feel different-- at least it did for me-- and I think drawing on my personal experience is helpful in teaching it to the fellows that it's OK to feel like that when you're doing this. LIDIA SCHAPIRA: There are moments in medicine-- certainly in what you do-- that are really difficult. And this, probably, I would imagine, ranks as one of the top things. And it should never be easy. It will never be easy. The day that you think it's easy, you need to find something else, right? RICHARD LEITER: I think that's right. I think that's right. LIDIA SCHAPIRA: Well, thank you so much, Richard. You made me laugh, you made me cry reading this, and I thank you very much. My last question is, have you had a chance to talk with Tom's widow Julie about what that moment felt like to her? RICHARD LEITER: I have not, although I hope to in the near future. LIDIA SCHAPIRA: And that will be your next piece for us. [CHUCKLES] All right. Well, thank you very much and until the next time. Hope you all enjoy reading Ode to Joy. RICHARD LEITER: Thank you so much. SPEAKER 1: Until next time, thank you for listening to this "JCO's Cancer Stories-- The Art of Oncology" podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. "JCO's Cancer Stories-- The Art of Oncology" podcast is just one of ASCO's many podcasts. You can find all of the shows at podcast.asco.org. [MUSIC PLAYING]

An interview with Dr. Maria Suarez-Almazor from MD Anderson Cancer Center, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She reviews identification, evaluation & management of musculoskeletal toxicities in patients receiving ICPis, including inflammatory arthritis, myositis & polymyalgia-like syndrome in Part 7 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts. My name is Brittany Harvey, and today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Maria Suarez-Almazor from the University of Texas M.D. Anderson Cancer Center in Houston, Texas, author on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update and Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. And today, we're focusing on musculoskeletal toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Suarez-Almazor. MARIA SUAREZ-ALMAZOR: Thank you. BRITTANY HARVEY: First I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for the guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Suarez-Almazor, do you have any relevant disclosures that are directly related to these guidelines? MARIA SUAREZ-ALMAZOR: Thank you, Brittany. I don't have any disclosures directly related to the guidelines. BRITTANY HARVEY: Thanks very much. Then getting into the content of this, what are the immune-related musculoskeletal toxicities addressed in this guideline? MARIA SUAREZ-ALMAZOR: There are three major musculoskeletal syndromes covered in this guideline-- inflammatory arthritis, myositis, and polymyalgia rheumatica. BRITTANY HARVEY: Great. Then let's start with that first one that you mentioned. So what are the key recommendations for identification, evaluation, and management of inflammatory arthritis? MARIA SUAREZ-ALMAZOR: The diagnosis of inflammatory arthritis is primarily based on a thorough joint exam to detect the presence of synovitis and how many joints and what joints are actually involved. For this reason, we recommend early referral to a rheumatologist. From a diagnostic perspective, we recommend testing for antinuclear antibodies or ANA, rheumatoid factor, and cyclic citrullinated peptide antibodies or anti-CCP. These are only positive in 10% to 20% of patients but may be indicative of a more persistent disease. As inflammatory arthritis does not have any specific biochemical parameters for follow up, we use inflammatory markers such as sed rate and CRP in conjunction with the clinical exam as indicators of disease activity. For grades 1 and 2, we recommend treatment with nonsteroidal anti-inflammatory drugs or NSAIDs, or low-dose steroids up to 20 milligrams of oral prednisone or equivalent. If there is involvement of only one or two joints, local treatment with steroid injections can be indicated. For grade 3 and higher, the dose of steroids can be increased up to 0.5 to 1 milligram per kilogram of body weight. And if there is no improvement within two weeks or if the steroids cannot be satisfactorily tapered, we recommend early initiation of a disease-modifying antirheumatic drug or a DMARD, such as methotrexate, hydroxychloroquine, or sulfasalazine. We need to understand though that these may take up to two or three months to be effective. Alternatively, we can use biologic agents which have a faster onset of action. Recommended agents include tumor necrosis factor or interleukin 6 receptor inhibitors. In severe cases, immune checkpoint inhibitors may need to be permanently discontinued. But the overall goal is to try to continue therapy while we treat the adverse event. BRITTANY HARVEY: Understood. Appreciate your reviewing that information for inflammatory arthritis. Following that, what are the key recommendations for identification, evaluation, and management of myositis? MARIA SUAREZ-ALMAZOR: Well, myositis is really the most serious of the musculoskeletal toxicities. And it can be life threatening, especially when it's associated with myocarditis and with myasthenia gravis features. It usually presents with proximal weakness of the upper and lower extremities and sometimes with myalgia and even rhabdomyolysis. It usually is very acute in its presentation. Specific testing includes muscle enzymes, creatine kinase and aldolase, and electromyography and muscle biopsy if the diagnosis is uncertain. MRI can be useful as it can show muscle inflammation. And it can also assist in identifying a location for a biopsy if needed. Consultation with rheumatology and neurology should be requested early on. We also recommend that all patients undergo testing of cardiac enzymes such as troponin. And if elevated, a cardiology consultation should be placed right away and further testing performed. For grades 1 and 2, if patient has symptoms, treatment with corticosteroids are 0.5 to 1 milligram per kilogram should be initiated. For patients with grade 3 or 4, checkpoint inhibitors should be discontinued and the patient should be hospitalized. Corticosteroids should be initiated at a dose of 1 milligram per kilogram of prednisone or equivalent. And patients with severe compromise may need intravenous corticosteroid doses at higher doses of 1 or 2 milligrams per kilogram or even higher. For severe disease or if there is myocarditis or concomitant myasthenia gravis, we can consider plasmapheresis. IVIG can also be used, but it has a slower onset of action. And it is important to remember that plasmapheresis can remove immunoglobulins. So if it is to be used, the IVIG should be administered after the plasmapheresis is completed. There are other immunosuppressant therapies such as biologic agents that can also be considered. And sometimes for maintenance, oral immunosuppressants such as azathioprine, methotrexate, or mycophenolate mofetil can also be considered. Patients with severe disease may need to permanently discontinue the checkpoint therapy. BRITTANY HARVEY: OK, those details are helpful for clinicians. So then, for the last category, addressed in this guideline that you mentioned, what are the key recommendations for identification, evaluation, and management of polymyalgia-like syndrome. MARIA SUAREZ-ALMAZOR: Polymyalgia rheumatica syndromes present with marked pain and stiffness of the muscles in the shoulder and hip girdles. But some patients can also present with concomitant inflammatory arthritis. The workup is very similar to that of arthritis. In these patients, it is very important though to obtain a creatine kinase so that the muscle enzyme to be certain that the myalgia is not from myositis, as a treatment would be very different. Although very rare, polymyalgia, in some instances can be associated with giant cell arteritis which, if present, would require more aggressive treatment. For this reason, it is important to ask the patient about symptoms such as headache, visual disturbances, or jaw claudication. The management of polymyalgia-like immune adverse events alone, without any associated vasculitis, is very similar to that of arthritis. So we would use NSAIDs and low-dose steroids for grade 1 and 2. Higher doses of steroids and disease modifying agents, including biologics, might be needed for grades 3 and 4. But overall, very similar management as that of inflammatory arthritis. BRITTANY HARVEY: Great. Thanks for reviewing all of those recommendations for those three different categories. So then, in your view, Dr. Suarez-Almazor, how will these recommendations for the management of musculoskeletal toxicities impact both clinicians and patients? MARIA SUAREZ-ALMAZOR: Thank you, Brittany. For the most common rheumatologic adverse events, such as arthralgia, inflammatory arthritis, or polymyalgia-like syndromes, because they are not life threatening, we may not be as worried. But we need to recognize that they can greatly impair quality of life. So we really hope that these recommendations can assist patients and clinicians in the early recognition of symptoms and also in initiating prompt treatment so our goal to be able to continue checkpoint inhibitor therapy can be achieved by controlling the symptoms that really impair quality of life. Myositis is a much more serious adverse event that can lead to death. Patients may not be able to restart immune checkpoint inhibitor therapy again after they develop myositis. So we hope that these recommendations do highlight the need for very prompt diagnosis, consultation with specialists, and very aggressive treatment early on to control and manage these devastating, life-threatening adverse event. BRITTANY HARVEY: Definitely. Early recognition, treatment, and improved quality of life are key. So I want to thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Suarez-Almazor. MARIA SUAREZ-ALMAZOR: Thank you, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.ASCO.org/supportive-care-guidelines.  You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Jennifer Mammen from Johns Hopkins University, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She discusses the identification, evaluation, and management of endocrine toxicities in patients receiving ICPis, including thyroid-related irAEs, primary AI, hypophysitis, and diabetes in Part 6 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Jennifer Mammen from Johns Hopkins University in Baltimore, Maryland, author on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update and Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. And today, we're focusing on endocrine toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Mammen. JENNIFER MAMMEN: My pleasure, Brittany. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Mammen, do you have any relevant disclosures that are related to these guidelines? JENNIFER MAMMEN: I do not. BRITTANY HARVEY: OK. Thank you. Then, to start us off, what are the immune-related endocrine toxicities addressed in this guideline? JENNIFER MAMMEN: Yeah. So irAEs affect the thyroid and the pituitary most commonly. But we also addressed the possibility of primary adrenal toxicity and also the emerging toxicity of insulin-dependent type 1 diabetes, which, while rare, can present with grade 4 toxicity in the form of diabetic ketoacidosis. BRITTANY HARVEY: Understood. Then, starting with adverse events affecting the thyroid, what are the key recommendations for identification, evaluation, and management of thyrotoxicosis? JENNIFER MAMMEN: So thyrotoxicosis after ICI exposure is almost entirely due to subacute thyroiditis. That's a transient inflammation of the thyroid gland that causes a few weeks of high levels of thyroid hormone, followed by at least several weeks of hypothyroidism as the stores of thyroid hormone are replenished. In the irAE context, many patients do not ever actually recover adequate thyroid function and will remain hypothyroid, requiring thyroid hormone long term. Because the thyrotoxicosis is transient and results from the release of preformed thyroid hormone, anti-thyroid drugs do not help and actually can even make the hypothyroidism phase worse. Therefore, the treatment is really supportive care with beta blockers in particular to control symptoms of the hypothyroidism, such as tachycardia, tremor, or anxiety. BRITTANY HARVEY: In addition to those points for thyrotoxicosis, what are the key recommendations for primary hypothyroidism? JENNIFER MAMMEN: Yeah. So primary hypothyroidism is very common both in the general population and now in this population as a result of thyroiditis. Many patients might actually already be on thyroid hormone when starting immunotherapy. When the pituitary is working, the pituitary hormone thyrotropin or TSH is a reliable indicator of the adequacy of thyroid hormone replacement. And the goal is to use a dose of thyroid hormone that maintains the TSH in the mid reference range, generally between 1 and 3 million international units per liter. When a patient is first presenting or diagnosed with hypothyroidism, for example, in that second phase of thyroiditis, a weight-based dose can be used to estimate the needed replacement dose. For those with higher BMI, generally, an ideal body weight rather than an actual body weight gives a better estimate. And those specific recommendations are in the guidelines. Proton pump inhibitors, calcium/iron supplementation, or GI inflammation can all decrease the absorption of thyroid hormone. And so even the thyroid hormone is really common, and many oncologists are used to managing it, it can be tricky in these patients if there's issues with malabsorption. And so, therefore, an endocrinology consultation can be helpful to titrate and ensure that the dosing is adequate. Once that adequate dose, that stable dose is found, if other factors don't change, dose requirements are generally quite stable and can be monitored annually either by a primary care physician or an oncologist. BRITTANY HARVEY: Great. Those are important points. Then, addressing the immune-related adverse event that impacts the pituitary, what are the key recommendations for identification, evaluation, and management of hypophysitis? JENNIFER MAMMEN: So hypophysitis is inflammation of the pituitary, as you said. And although there are five hormone systems at risk, it's actually most common that the thyroid and the adrenal gland axes are what are affected. The diagnosis is made by a combination of assessing the pituitary hormone and the primary hormone, in this case, the thyroid hormone and cortisol along with the TSH and ACTH, which is the pituitary hormone that regulates the adrenal gland. With primary gland failure, as we said, the pituitary hormones will be elevated. But in hypophysitis, the problem actually comes from the pituitary. And so TSH and ACTH will be low or inappropriately normal for the low primary thyroid hormone level. There are several key points for oncologists who might need to initiate therapy before the patient can see endocrinology. First, thyroid hormone increases the metabolism of cortisol. And so if you've diagnosed central hypothyroidism due to hypophysitis, it's really important to replace cortisol, if needed, before replacing thyroid hormone, because in someone with both deficits, thyroid hormone alone can precipitate an adrenal crisis. Thus, the ASCO Guidelines really emphasize the need to assess both before starting thyroid hormone and also give the option to use steroids empirically, if needed, since the diagnosis can be sorted out later by an endocrinologist. A second important point is that headaches, visual changes, and diabetes insipidus, which is loss of fluid and generally marked by hypernatremia, those are much more common with metastatic disease in the pituitary rather than hypophysitis. And so such symptoms should really prompt a pituitary MRI when they're found in the setting of hormonal losses. The management of central hypothyroidism is similar to that of primary hypothyroidism. But as I said, the TSH is no longer a reliable marker for adequate replacement. So the goal, then, shifts from a TSH in the reference range to a free T4 at the upper half of the reference range. Adrenal insufficiency, as with thyroid hormone insufficiency, is managed by physiologic hormone replacement, and that's best done using hydrocortisone. This is a short-acting steroid that can be given in a way to imitate the natural diurnal rhythm. We use 2/3 of the dose in the morning and 1/3 in the early afternoon, allowing levels to fall as they naturally would overnight. Dose-titration is based on symptoms. And usually, 15 to 25 milligrams of a total daily dose is adequate to control symptoms from adrenal insufficiency. I do think all patients should see endocrinology at some point if they have been diagnosed with hypophysitis because they do need education on sick day rules, otherwise known as stress dosing, and also to be instructed on wearing an emergency alert bracelet or necklace or something. Long-acting steroids can be used for patients who have adherence problems. And of course, those long-acting steroids are more appropriate for the treatment of any other irAE that a patient may develop. While on higher doses of prednisone, patients can discontinue hydrocortisone and then restart it when the prednisone dose is weaned down below 5 milligrams daily. If there's a question about whether the central adrenal insufficiency is from hypophysitis or due to suppression after weaning off high-dose exposure, use of hydrocortisone because of the diurnal rhythm actually allows the adrenal axis to recover normally. And so after weeks, you can test for adrenal recovery using a morning endogenous level 24 hours after the last dose is given, which is another advantage to using the hydrocortisone mode of hormone replacement. BRITTANY HARVEY: Understood. And I appreciate you highlighting those key points for oncologists. Then, following that, what are the key recommendations for primary adrenal insufficiency? JENNIFER MAMMEN: Yeah. So primary adrenal insufficiency, you'll see the ACTH elevated just like in primary thyroid disease, and the cortisol will be low. Again, this situation is actually much more common with metastatic disease, and therefore, imaging is called for if you find that pattern of hormonal changes. It's been case-reported to happen with irAEs, but in general, this is incredibly rare. The management of hydrocortisone replacement for people with primary adrenal insufficiency is really the same as for hypophysitis. We're using hydrocortisone with that diurnal physiologic replacement pattern. Primary adrenal insufficiency, however, also generally results in the loss of mineralocorticoid function. And so most patients also need at least a low dose of fludrocortisone replacement. BRITTANY HARVEY: OK. And then the last adverse event addressed in the endocrine toxicity section of this guideline, what are the key recommendations for identification, evaluation, and management of diabetes? JENNIFER MAMMEN: Yeah. So diabetes in this patient population is very tricky because so many of these patients are getting high-dose steroids as part of their chemotherapy regimens, and this can cause a lot of hyperglycemia. And I think it's actually easy to become complacent about seeing blood glucoses in the 200s. And in fact, most of the hyperglycemia will be just that, secondary to steroid exposure and worsening type 2 diabetes. It can be managed with a titration of routine medications. But they are now increasingly less rare but still rare events of acute loss of pancreatic function, presumably autoimmune, that can be accompanied by life-threatening diabetic ketoacidosis. And the challenge for oncologists, I think, is to have a low enough threshold to investigate a suspicious pattern of hyperglycemia, for example, hyperglycemia with complaints of polyurea or, on physical exam, a more rapid respiratory rate that could indicate compensation for metabolic acidosis. So it's really a question of being a good clinician and taking the diabetes in context and not just assuming that it's due to steroid exposure. This is, I think, important because, like I said, diabetic ketoacidosis can be a grade 4 emergency, and patients can end up in the intensive care unit, needing a lot of intervention, which if we have a higher suspicion in clinic, we might be able to avert by getting rapid communication with endocrinology, starting people on insulin and that kind of an approach. BRITTANY HARVEY: Definitely. A common theme with these toxicities seems to be early identification is key. So thank you for reviewing the high-level recommendations for each of these toxicities. In your view, how will these recommendations for the management of endocrine toxicities impact both clinicians and patients? JENNIFER MAMMEN: Yeah. So I think making diagnoses in the hormonal systems can be complex and does require attention to the interactions, like we were talking about, between the pituitary and the primary gland. It's not something that oncologists necessarily have front of mind. And yet hormone replacement is actually quite straightforward. Once the need for it is recognized, since there's no side effects from replacing a hormone at an appropriate dose, it's just a replacement. And so, therefore, rapid diagnosis and initiation of hormone replacement can really allow patients to continue immunotherapy with a very minimal disruption, even in the face of an endocrine irAE. Although at our institution the close coordination between treating oncologists and endocrinologists is available, that's certainly not true everywhere. And I think that the ASCO Guidelines are designed to try and help oncologists make these diagnoses and initiate therapy to stabilize patients and even allow them to continue treatment while awaiting any necessary consultations, even in the case of thyroiditis, perhaps, managing what's a self-limited event and then moving on, which reduces the burden on patients with other priorities to focus on. BRITTANY HARVEY: Great. Those are very important points. So I really want to thank you for all of your work on these guidelines. And I appreciate you taking the time to speak with me today, Dr. Mammen. JENNIFER MAMMEN: It's my pleasure. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Jarushka Naidoo from Johns Hopkins University, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She discusses the identification, evaluation, and management of lung toxicities in patients receiving ICPis, focusing on pneumonitis in Part 5 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING]   SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network-- a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcast. My name is Brittany Harvey, and today we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Jarushka Naidoo from Johns Hopkins University in Baltimore, Maryland. Author on management of immune related adverse events in patients treated with immune checkpoint inhibitor therapy, ASCO Guideline update, and management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy ASCO guideline. And, today, we're focusing on lung toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Naidoo. JARUSHKA NAIDOO: Thank you. It's my pleasure to share updates on this guideline. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest policy is followed for each guideline. The full Conflict of Interest information for this guideline panel is available online with a publication of the guidelines in the Journal of Clinical Oncology. Dr. Naidoo, do you have any relevant disclosures that are directly related to these guidelines? JARUSHKA NAIDOO: Yes. So I have research funding in the last two years from Merck, AstraZeneca, and Bristol Myers Squibb. And I also have served in a consulting role-- or an advisory board capacity-- for Merck, AstraZeneca, Bristol Myers. And not specifically related to this work, but also Pfizer, Takeda, Daiichi Sankyo, and Kaleido Biosciences. BRITTANY HARVEY: OK. Thank you for those disclosures. Then-- getting into the content of this guideline-- what are the immune-related lung toxicities addressed in this guideline? JARUSHKA NAIDOO: Thanks, Brittany. So the main lung toxicity that is addressed in this guideline is immune checkpoint inhibitor pneumonitis, which-- as this audience knows-- is an uncommon, but potentially fatal toxicity particularly associated with anti-PD-1 or PD-L1 monotherapy, but can also occur with combination immunotherapy approaches. In the guideline, we go through what is known about the natural history, risk factors, and then, of course, our comprehensive approach to identifying, evaluating, and managing this toxicity, which is defined as a focal or diffuse inflammation of the lung parenchyma. We also identify that, while pneumonitis is the quintessential lung toxicity that can occur with immune checkpoint inhibitors, we also note that there are some other lung toxicities that have been reported on, but for which we relatively little. And this includes sarcoid-like granulomatous reactions, including subpleural micronodular opacities and hilar lymphadenopathy, as well as pleural effusions. And these have been associated with both CTLA-4 and the PD-1, PD-L1 immune checkpoint inhibitor therapies. BRITTANY HARVEY: I appreciate that overview. So then, you mentioned the main toxicity here is pneumonitis. What are the key recommendations for identification, evaluation, and management of pneumonitis? JARUSHKA NAIDOO: Thanks, Brittany. So yeah, this is a key focus of the guideline. So, as we're aware, pneumonitis is defined as a focal or diffused inflammation of the lung parenchyma and is a toxicity that was identified as one of the early toxicities in the early clinical trials of the PD-1 inhibitors. The incidence of this toxicity is estimated at anywhere between 0% and 10%, and in large meta analysis, looks to be around 2% to 3% in terms of incidents. In terms of how to evaluate patients with suspected immune-related pneumonitis, the common symptoms would be cough, shortness of breath, fever, and chest pain. And in a patient who has suspected pneumonitis, some of the first tests to be done would be to take a pulse oximetry and to do some chest imaging. Chest imaging is preferable with a CT scan with contrast in order to rule out alternative etiology, such as pulmonary embolus For patients who are symptomatic-- which means CTCAE grade 2 or greater-- we also recommend a standard infectious workup, which is guided by institutional guidelines. But based on our ASCO guideline, we outline that this should include, at a minimum, a nasal swab, sputum culture and sensitivity, blood culture and sensitivity, and urine culture and sensitivity, as well as a standard COVID-19 evaluation. When we come to the diagnosis of pneumonitis, we then evaluate that in terms of CTCAE grade. Where the grade of pneumonitis refers, firstly, to whether a patient has symptoms, and the proportion of the lung parenchyma that may be involved with pneumonitis on chest imaging. Broadly speaking, patients with grade 1 pneumonitis are asymptomatic and usually identified on radiographic imaging almost incidentally. For these patients, we would recommend either holding immunotherapy or proceeding with close monitoring. And we recommend that patients should have weekly physical exams and pulse oximetry offered, and consideration of further chest imaging if the diagnosis is uncertain, or to follow progress-- usually around every three to four weeks-- or, if a patient becomes symptomatic, it may be more often than this. We also recommend that we may consider doing spirometry or DLCO evaluation as a repeat in these patients. Broadly, again, in terms of the evaluation of patients-- if patients are symptomatic from pneumonitis, which means they have a symptom related to radiographic features, then this would be called grade 2. And usually, radiographically, patients have more of the lung parenchyma involved-- greater than 25%-- and require a medical intervention. And the management would be prednisone, 1 to 2 milligrams per kilogram per day, that is then tapered over 4 to six weeks, and immunotherapy is held during that time. Importantly, in order to knuckle down the diagnosis of pneumonitis, we recommend consideration of doing a bronchoscopy with bronchoalveolar lavage sampling in order to truly rule out alternative infectious diagnoses or lymphangitis carcinomatosis. And for this reason, a transbronchial biopsy can also be considered. In some cases, we also consider treating with empiric antibiotics to cover infection if we feel that this remains in the differential diagnosis. If patients do not clinically improve after 48 to 72 hours on prednisone, then we recommend treating at a higher grade, meaning grade 3, where patients have severe symptoms, hospitalization is required, and a larger proportion of the lung parenchyma is involved. For these patients who have grade 3 or greater pneumonitis, we recommend permanently discontinuing immunotherapy, administering a higher dose of steroids at methylprednisolone, 1 to 2 milligrams per kilogram per day. And, once again-- if there is no improvement after 48 hours, we recommend a range of potential additional immunosuppressive approaches, which include either infliximab, mycophenolate mofetil, intravenous immunoglobulin, or cyclophosphamide. And there are currently no recommendations as to which may be the optimum immunosuppressive approach, but there are a number of clinical trials aiming to elucidate the answer to this. Importantly, overall in patients who are symptomatic, it may also be appropriate to consult pulmonary medicine and infectious diseases teams to weigh in on the diagnosis and management going forward. BRITTANY HARVEY: Great. Thank you for that clear, step-wise approach to the evaluation and management of pneumonitis. So then, in your view, Dr. Naidoo-- how will these recommendations for the management of lung toxicities impact both clinicians and patients? JARUSHKA NAIDOO: I think it's very important for both clinicians and patients to be aware of the potential side effects of the treatment that patients are receiving with immune checkpoint inhibitors. We know that some toxicities from immunotherapy tend to be mild and can be managed quite well with corticosteroids or other approaches. What we understand about lung toxicities is that, thankfully-- in the majority of cases-- pneumonitis will be well-controlled with corticosteroids and holding of immunotherapy. However, in a proportion of patients, pneumonitis may become severe and may even lead to treatment-related deaths. And for that reason, both patients and clinicians need to be aware of what to look out for in terms of the symptoms of pneumonitis, and how to diagnose and manage this toxicity quickly and efficiently in order to avoid poor outcomes. BRITTANY HARVEY: Absolutely. Those are excellent points for both clinicians and patients to keep in mind. So I really want to thank you for all of your work on these guidelines and for taking the time to speak with me today, Dr. Naidoo. JARUSHKA NAIDOO: You're very welcome, Brittany. And thank you to the ASCO oncology community for the opportunity to share this important work. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Yinghong Wang from MD Anderson Cancer Center, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She discusses the identification, evaluation, and management of gastrointestinal toxicities in patients receiving ICPis, including colitis and hepatitis in Part 4 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING]   SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey. And today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Yinghong Wang from the University of Texas MD Anderson Cancer Center in Houston, Texas, author on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update and Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. And today, we're focusing on gastrointestinal toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Wang. YINGHONG WANG: Thank you, Brittany. It's my great pleasure to be invited to participate in this education event. I'm happy to share my experience and the knowledge that I learned over all the research studies in this field and share with the readers or the community providers on this specific topic. BRITTANY HARVEY: Great. Thank you. Then, first, before we get into the content, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Wang, do you have any relevant disclosures that are directly related to these guidelines? YINGHONG WANG: I do have consulting services to two pharmaceuticals, but they're not related to the current guidelines that are published from the ASCO. They're Tillotts Pharma and Athenex Pharma. BRITTANY HARVEY: OK. Thank you. Then, let's talk about these gastrointestinal toxicities. So first, what are the immune-related gastrointestinal toxicities addressed in this guideline? YINGHONG WANG: So these particular guidelines have provided very detailed description on the incidence and clinical presentations and also recommendations on the evaluation and treatment for the upper and the lower gastrointestinal adverse events and the liver and even other organ toxicity, including the exocrine pancreas toxicities that are being categorized as GI field related to checkpoint inhibitor treatments. BRITTANY HARVEY: OK. And then what are the key recommendations for the identification, evaluation, and management of colitis? YINGHONG WANG: So colitis is definitely one of the most common organ to be involved in this category of toxicity-related checkpoint inhibitors. And that's why a lot more studies have been studied because the patient volume can allow enough power to run a lot of analysis. I think the summary that I would say-- the recommendations from the current ASCO Guidelines include the early recognition and evaluation with close monitoring for people who had suspicious symptoms for gastrointestinal adverse events and early stool inflammatory marker evaluation even in patients who had grade 1 symptoms. And very important to rule out alternative causes of the symptom presented, like infections or cancer metastases or some other medication-related side effects other than checkpoint inhibitors. And the other important component of evaluation is endoscopy and the pathological evaluation for patients who had a positive stool inflammatory markers or if the patient has a presentation of colitis symptoms like bleeding. And also, the presence of ulcers on the endoscopy usually has been found to predict a steroid refractory disease course. Therefore, the early initiation of more potent treatment like biologic agents, such as infliximab or vedolizumab, is very critical. The other alternative medical treatment, like ustekinumab or tofacitinib or even fecal transplantation for refractory cases, should also be considered in the small portion of patients. The disease monitoring while on the medical treatment is critical via the repeat endoscopy or following the fecal calprotectin level to guide the duration of treatment and the time to resume immune checkpoint inhibitor treatments if indicated. The rechallenge of these checkpoint inhibitors is possible among patients with GI toxicities, and the risk of GI toxicities is completely manageable. That's the brief summary of the GI recommendations. BRITTANY HARVEY: Yeah. Thank you for that summary. And then just in addition to those key recommendations, is there anything additional about the identification, evaluation, and management of hepatitis? YINGHONG WANG: Yeah. The hepatitis-- the incidence is not as common as colitis but can be severe in extreme cases. So it requires the equal attention to recognize and evaluate for liver toxicity after checkpoint inhibitors with close monitoring. We also need to rule out other alternative causes of the symptoms, including the infections, alcohols, iron overload, thromboembolic events, cancer metastases, et cetera. The imaging, on the other hand, is more critical for liver toxicity evaluation. This is a little bit different from using the endoscopy and biopsy for luminal GI tract toxicities. And the liver biopsy should also be considered in certain select cases through all other differential diagnosis and also the other alternative treatment other than corticosteroid, including azathioprine and mycophenolate mofetil, that are mentioned in the small case series and also listed in the current ASCO Guidelines. BRITTANY HARVEY: Great. Thank you for that overview for both colitis and hepatitis. So then, in your view, how will these recommendations for the management of gastrointestinal toxicities impact both clinicians and patients? YINGHONG WANG: Yeah. Given the increasing volume of patients experiencing the GI adverse events related to the checkpoint inhibitor cancer therapies and their related morbidities, so both the clinicians and patients need to be familiar with the clinical presentations and the time frame of onset to ensure early recognition and early diagnosis, especially serious complication and even mortality can occur due to the significant delay in appropriate treatment in extreme cases. So the updated guideline provided by ASCO and also other professional societies in the US or internationally can provide a great resources to the academic and community clinicians when they encounter these cases in their practice. So ultimately, the implementation of appropriate management and future prospective clinical trials in this field for these challenging conditions should improve the patient's outcome of toxicities and also cancer. And that's the goal of our clinicians and academia providers, to be able to serve the patient better in the future. BRITTANY HARVEY: Definitely. Well, thank you for sharing this summary with us today, for all of your work on these guidelines, and for taking the time to speak with me today, Dr. Wang. YINGHONG WANG: Thank you very much for this opportunity. Please let me know if you have any questions. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Milan Anadkat from Washington University & Dr. Aung Naing from MD Anderson Cancer Center, authors on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” They discuss recommendations for cutaneous toxicities in patients receiving ICPis, including rash, bullous dermatoses & SCAR in Part 3 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey. And today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Milan Anadkat from Washington University in St. Louis, Missouri. And Dr. Aung Naing from the University of Texas M.D. Anderson Cancer Center in Houston, Texas, authors on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update and Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. And today, we're focusing on cutaneous toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here Dr. Anadkat and Dr. Naing. AUNG NAING: Thank you for having us. MILAN ANADKAT: Thank you. BRITTANY HARVEY: I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Anadkat, do you have any relevant disclosures that are directly related to these guidelines? MILAN ANADKAT: As listed in the document, I don't have any direct disclosures. I do have a number of indirect disclosures, as I've consulted on similar topics in the past. BRITTANY HARVEY: Thank you. Then Dr. Naing, do you have any relevant disclosures that are related to these guidelines? AUNG NAING: I do not have. BRITTANY HARVEY: Great, then let's get into the content of this guideline and the cutaneous toxicities that we're here today to talk about. So Dr. Naing, what are the immune-related cutaneous toxicities addressed in this guideline? AUNG NAING: Well, with the advancement of immunotherapy, we've seen better response in our cancer patients. However, together with such positive outcomes, we are also seeing side effects caused by the immunotherapy. Disruption of the homeostatic mechanisms include a unique spectrum of side effects or immune related adverse events, commonly called IRAEs. The most common immune related adverse events in patients receiving checkpoint inhibitors are dermatitis, enterocolitis, transmitis, and endocrinopathies. However, if you look at the most commonly reported IRAE of any grade, it is dermatologic toxicity. So here in this guideline, we addressed how to take care of the patients when they are having these side effects, particularly with the cutaneous toxicities. So when you look at that time to median onset of skin toxicities, it ranges from two to five weeks. And using CTCAE criteria for grading is a challenge for skin toxicity, as it may not reflect the true picture. So, therefore, severity may be graded based on body surface area, tolerability, mobility, and durations. Those are the points also we discuss in this guideline. Broadly speaking, they are three groups of cutaneous IRAEs. They are rash inflammatory dermatitis, bullous dermatoses, and finally, Severe Cutaneous Adverse Reactions, SCAR. It is important to have thorough physical exam and rule out any other etiology of skin problems. In general, it's also important to work closely with our colleagues from dermatology. While some of those low grade skin toxicities could be treated in outpatient setting, consulting the cases with dermatologists is important for higher grades of skin toxicities, such as bullous dermatoses and SCAR. My colleague, Dr. Milan Anadkat, will follow with a discussion on the role of dermatologists in taking care of patients with cutaneous toxicities caused by immunotherapy. BRITTANY HARVEY: Thank you, Dr. Naing for reviewing those. So then you just mentioned three categories of toxicity. And I'd like to review the key recommendations for each. So Dr. Anadkat, starting with what is recommended for the identification, evaluation, and management of rash or inflammatory dermatitis? MILAN ANADKAT: Thank you, Brittany. And thank you Dr. Naing for teeing up this discussion. I think, as was mentioned, there are three major categories of cutaneous toxicity that are seen from immunotherapy. By and large, the most common is rash or inflammatory dermatitis, from which there are multiple different phenotypes or looks by which physicians may be seeing. The most common phenotypes within rash or inflammatory dermatitis, which account for over 90% of the cutaneous toxicity seen from immunotherapy, include lichenoid, which is a purple, flat topped bumpy rash that can involve the skin or the mucosal membranes. The psoriasiform, which resembles psoriasis, morbilliform, or oftentimes, maculopapular, which resembles a measles-like pink exanthem over the trunk, or generalized eczema and itching. So what's important is identifying the particular phenotype and categorizing it as an inflammatory dermatosis and excluding the other two phenotypes of cutaneous toxicity, such as bullous dermatoses or Severe Cutaneous Adverse Reactions. BRITTANY HARVEY: Great, and then moving into that second category that you both mentioned, what are the key recommendations for bullous dermatoses? MILAN ANADKAT: And so the key phenotypes for bullous dermatoses, by and large, is bullous pemphagoid, which is the most common phenotype seen in this category. Although other phenotypes resembling autoimmune bullous diseases, such as pemphigus or bullous drug reactions may also be seen. With bullous pemphigoid we see tense blisters, or tense bullae, frequently overlying a bed of erythema on the skin. Patients typically complain of considerable itching, far more than pain, with this category of eruption. BRITTANY HARVEY: Got it. Thank you for reviewing that for bullous dermatoses. So then the third group is Severe Cutaneous Adverse Reactions. So what are the key recommendations there? MILAN ANADKAT: And so the third group, being Severe Cutaneous Adverse Reactions, is a term used worldwide to encompass conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and DRESS or drug reaction with eosinophilia and systemic symptoms. These are, fortunately, rare, but can be life threatening skin eruptions. They account for less than 1% of all skin reactions seen from immunotherapy. When practitioners are approaching a patient who may potentially have one of these conditions, patients typically will exhibit symptoms of malaise, fatigue, fever, and a dramatic cutaneous eruption, which will either present with peeling or sloughing of the top layers of the skin, or a generalized erythema covered with multiple sterile pinpoint pustules. Oftentimes, there are associated symptoms of lymphadenopathy and organ toxicity that is noticed simultaneously, such as hepatotoxicity, or eosinophilia, or acute renal failure. BRITTANY HARVEY: Great, I appreciate you reviewing the identification of all three of those groups. So then I'd like to hear from you both on this last question. But in your view, how will these recommendations for the management of cutaneous toxicities impact both clinicians and patients? AUNG NAING: I would say that recognition of the toxicity is really important, particularly if you can actually catch the toxicity when it is in the mild grade. If you take care of them, then you can actually stop them from being mild to severe toxicity. That's number one. Number 2 is in that way, we may not have to halt or stop the immunotherapy treatment that could be beneficial to the patients. And also, working together with the dermatologists is very important, because as I discussed earlier, some of them, we could take care of as an outpatient. But there will be certain dermatology toxicities, where we need to work closely with our dermatologists. And please also remember that these are the guidelines. You will be seeing the patient in the setting. So I think using that guideline and clinical judgment, that would actually help our patients at large. MILAN ANADKAT: I think that's excellent. One, I think, important aspect of these guidelines is not only to correctly identify the phenotypes of cutaneous toxicity, but as Dr. Naing mentioned, it assists in management of these toxicities. The goal of these guidelines, especially as it pertains to the skin toxicity, is to accurately identify what toxicity is occurring for the patient, but then more importantly, to guide on appropriate management strategies to allow the patient to continue on immunotherapy and minimize or avoid unnecessary treatment interruption or treatment discontinuation. The guidelines assist in management strategies according to the severity by which patients present. And as mentioned, I think ultimate priority will be given to the practitioner directly treating the patient. But consideration towards not only extent of body surface area involved, but severity of cutaneous eruption is thoroughly reviewed. And in addition to phenotype, including such patient reported outcomes, such as degree of pain, itch, or interruption on activities of daily living help guide the degree of management that can be provided. BRITTANY HARVEY: Those are excellent points. I want to thank you so much for your work on these guidelines and for taking the time to speak with me today, Dr. Naing and Dr. Anadkat. AUNG NAING: Thank you. MILAN ANADKAT: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast. And be sure to subscribe, so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Bryan Schneider from the University of Michigan Health System and Dr. Kathryn Bollin from Scripps MD Anderson Cancer Center, co-chairs of the Management of Immune-Related Adverse Events Guideline Expert Panel. They discuss an overview of the “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update” in Part 1 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and I want to introduce you to our series on the Management of Immune-Related Adverse Events. ASCO has developed two guidelines for the management of immune-related adverse events, one for patients treated with immune checkpoint inhibitor therapy and a second for patients treated with CAR T-cell therapy. Today, we'll be focusing on an overview of the Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. And we'll have authors join us for future episodes to discuss the key recommendations for organ-specific management for patients treated with immune checkpoint inhibitor therapy and an episode to discuss the management of immune-related adverse effects in patients treated with CAR T-cell therapy. Today, I am joined by Dr. Bryan Schneider from the University of Michigan Health System in Ann Arbor, Michigan, and Dr. Kathryn Bollin from Scripps MD Anderson Cancer Center in San Diego, California, co-chairs on Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy, ASCO Guideline Update and authors of the Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy, ASCO Guideline. Thank you for being here, Dr. Schneider and Dr. Bollin. BRYAN SCHNEIDER: Thank you, Brittany. KATHRYN BOLLIN: Thank you for having us. BRITTANY HARVEY: I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Schneider, do you have any relevant disclosures that are related to this guideline? BRYAN SCHNEIDER: I have research funding to my institution from Bristol Myers Squibb and Genentech Roche at the time of panel formation. BRITTANY HARVEY: Thank you. And, Dr. Bollin, do you have any relevant disclosures that are directly related to this guideline? KATHRYN BOLLIN: No disclosures. BRITTANY HARVEY: Thank you. Then, let's talk about this guideline. So first, Dr. Schneider, what prompted this update to the Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy Guideline last published in 2018? BRYAN SCHNEIDER: Yeah. The previous guideline was widely used and consistently one of the top read articles of the JCO over the last couple of years. And since the original guideline publication in 2018, new data have emerged on the management of immune checkpoint inhibitor toxicities. So our goal was to build on the original guideline with more treatment options, especially for patients who fail initial steroid treatment. New strategies have developed for the management of many toxicities, especially GI, cardiac, and heme toxicities. And ASCO and the panel felt it was important to present these new options to the providers in the community. We also wanted to add sections that the providers would find valuable, including a table with many of the immunosuppressive agents used with typical dosages and schedules. We also added a table of commonly conducted testing while patients are on high-dose steroids as this is something many medical oncologists may not be used to handling as we typically do not have patients on steroids at high doses for several weeks or even months. BRITTANY HARVEY: Understood. Then, in addition to those updates that Dr. Schneider just mentioned, Dr. Bollin, what is the general scope and purpose of this guideline? KATHRYN BOLLIN: Yes. So the immune-related adverse event management guideline update and the CAR T-cell toxicity guideline serve to provide physicians that are prescribing these therapies with an understanding of the wide range of known potential toxicities of these agents and the best available evidence-based and expert opinion recommendations for their management. So up to 70% of patients treated with immune checkpoints will experience some form of immune-related adverse event, and nearly all patients getting CAR T-cell therapies experience toxicity. So recognition of the occurrence of these toxicities and appropriate management are essential for optimizing patient outcomes. BRITTANY HARVEY: Definitely, those are key points. So then, Dr. Schneider, what are the overarching recommendations for the management of immune-related adverse events irrespective of the affected organ? BRYAN SCHNEIDER: I think early recognition of the side effect is critical. So the guideline has typical signs and symptoms of each toxicity to help clinicians decide if this is occurring in their patients. Second, I think it's critical to grade the toxicity. We often don't do that with side effects related to traditional chemotherapy outside of clinical trials. So for example, if a patient has a platelet count of 75, I can't think off the top of my head what grade that is. I just know I'm going to hold chemotherapy for a week or two. But grading of the toxicity of these immune checkpoint therapies really is very important to decide whether patients can just be watched, whether they need to start steroids or whether they need to be admitted. I think still corticosteroids and dose holds are the first steps that clinicians will do. The majority of these toxicities-- although it would be nice if we could personalize the treatment based on the particular side effect and what we see under the microscope if the particular affected organ is biopsied, I think, in broad strokes, corticosteroids can be implemented easily, and a lot of our oncologists can be comfortable doing this potentially without subspecialty help. Having said that, I think multidisciplinary care is a must for the higher-grade side effects as, in oncology, we can't pretend to also be cardiologists, gastroenterologists, neurologists, dermatologist, and so on. And although there may be varying degrees of comfort from our subspecialists regarding the management of these toxicities, we do need their help for shared decision making, especially for the steroid refractory toxicities. We always want to emphasize a slow steroid taper oftentimes over at least four to six weeks. We get into trouble when we try to get them off the steroid quickly because they do have side effects that the patient may not enjoy. But oftentimes, we try to taper them quickly, and the side effect comes roaring back. And then, finally, to escalate immunosuppression quickly if no improvement with high-dose steroids is observed, oftentimes, that's done even within just a few days. But commonly, in practice, there's still hope that the steroid will kick in two or three weeks down the road, and that's not a good strategy. If the patient's having significant symptoms and steroids aren't helping, they do need to go on to a more important immunosuppressant. BRITTANY HARVEY: Those are important notes on the overarching management, particularly on how the adverse effects are different than those in patients treated with chemotherapy and the importance of multidisciplinary care. So then, Dr. Bollin, in your view, how will this guideline impact clinical practice? KATHRYN BOLLIN: So the impact of this guideline update is actually very broad. As with the previous guideline, as Dr. Schneider alluded to earlier, it's been very frequently accessed by readers since it offers symptom outlines and algorithmic recommendations for early identification and the management of immune-related adverse events based on the severity and organ system involved. What's really important to understand is that while initially, as hematology-oncology physicians prescribing these agents, we're doing so in the setting of early phase clinical trials. We were learning about the toxicities, and those physicians were often managing the toxicities themselves. But now, with the exponential increase and the therapeutic indications for immune checkpoint therapies in cancer, the experience with the toxicities and their management and the questions have also followed suit with an exponential rise. With this guideline update, we have experts among all of the internal medicine subspecialties that are now guiding the hematology-oncology physicians in immune-related adverse event management. We enlisted the experts in crafting this guideline update. So in summary, this serves not only as a tool for the prescribing hematology-oncology physicians but also for all of the subspecialists in the community and within academic centers for optimizing patient outcomes in the setting of immune-related adverse events. BRITTANY HARVEY: Great. Yeah, it sounds like this update will be hugely important for practicing clinicians. So then, in addition to those points raised by Dr. Bollin, Dr. Schneider, what are the implications for patients receiving immune checkpoint inhibitor therapy? BRYAN SCHNEIDER: So we really hope this will be an essential tool to help providers quickly treat patients when these toxicities present. Often, this is unexpected, and busy clinicians may be blindsided by these issues. So these guidelines will provide a quick resource to guide the workup and formulate a treatment plan that will expedite patient recovery. And ultimately, this should help promote quality of life for patients on these therapies and may help reduce trips to the emergency department, hospitalizations, and potentially allow the safe rechallenge of immune checkpoint therapy after resolution of the side effect. Many centers have the advantage of subspecialty support with experience in managing these toxicities. But for providers who may not have immediate access to, say, hepatology or endocrinology, we hope these guidelines will help the oncology providers provide the best treatment to facilitate the optimal clinical outcome. BRITTANY HARVEY: Absolutely, those are key for optimal care. Then, finally, Dr. Bollin, looking toward the future, what are the important outstanding questions and developing areas of research for the management of immune-related adverse events? KATHRYN BOLLIN: So while our recognition of immune-related adverse events, the testing for them, and management strategies have greatly improved with the expanded use of and experience with these therapies, large gaps in our knowledge remain. Translational and basic science research efforts are underway to understand these gaps, such as with the intrinsic and extrinsic drivers of autoimmunity, such as those with HLA allelic variations and the microbiomes interplay with our immune systems. There are also research efforts underway to develop rapid diagnostic tests to deploy early in the onset of irAE signs and symptoms and for the development of biomarkers and modeling tools that will aid us in predicting which patients are likely to experience immune-related adverse events. There have also been some interventional protocols that have attempted to prevent these immune-related adverse events by incorporating immune suppressants along with therapeutic agents. But so far, promising results with this strategy remain elusive. In regard to treatment for immune-related adverse events, investigators are working to learn the best strategies for selective immune suppression rather than just the use of glucocorticoids that will control immune-related adverse events while maintaining the clinical benefit of these incredible anticancer therapies. BRITTANY HARVEY: Thank you for highlighting those research gaps and both of you for your efforts to lead this guideline update. We'll be joined by authors on the guideline over the next episodes to review the key recommendations for organ-specific management in patients treated with immune checkpoint inhibitors and to review the recommendations for patients receiving CAR T-cell therapy. Stay tuned for these episodes highlighting the sections of the guidelines. And thank you for your time today, Dr. Schneider and Dr. Bollin. KATHRYN BOLLIN: Thank you so much. BRYAN SCHNEIDER: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center and Dr. Monalisa Ghosh from the University of Michigan Health System, authors on “Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline.” They discuss recommendations for management of irAEs in patients treated with CAR T-Cell Therapy in Part 2 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network. A collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today we're continuing our series on the management of immune-related adverse events. ASCO has developed two guidelines for the management of immune-related adverse events-- one for patients treated with immune checkpoint inhibitor therapy and a second for patients treated with CAR T-cell therapy. In our last episode, you heard an overview of the Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. Today, we'll be focusing on the Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline, and we'll have authors join us for future episodes to discuss the key recommendations for organ-specific management for patients treated with immune checkpoint inhibitor therapy. Today, I am joined by Dr. Monalisa Ghosh, from the University of Michigan Health System in Ann Arbor, Michigan and Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center in New York, New York, authors on both Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline and Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. Thank you both for being here, Dr. Ghosh and Dr. Santomasso. In addition, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest policy is followed for each guideline. The full Conflict of Interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Ghosh, do you have any relevant disclosures that are directly related to this guideline? MONALISA GHOSH: No. I do not have any relevant disclosures. BRITTANY HARVEY: Thank you. And, Dr. Santomasso, do you have any relevant disclosures that are directly related to this guideline? BIANCA SANTOMASSO: Yes. I'd like to disclose that I've served as a paid consultant for Celgene, Janssen Pharmaceutical, and Legend Biotech for advising them on the topics of CAR T-cell therapy side effects. BRITTANY HARVEY: Thank you. Then, getting into these immune-related adverse events-- first, Dr. Ghosh, can you give us an overview of the scope and purpose of this guideline? MONALISA GHOSH: Sure. The purpose of this guideline is to offer expert guidance and recommendations on the management of immune-related adverse events in patients treated with chimeric antigen receptor or CAR T-cell therapy. This guideline offers guidance on the diagnosis, evaluation, and management of the most common toxicities of CAR T-cell therapy, which includes Cytokine Release Syndrome-- or CRS-- and immune effector associated neurologic syndrome-- or ICANS. As well as other potential, but less common toxicities, such as Hemophagocytic Lymphohistiocytosis-- or HLH-- B-cell aplasia, prolonged and recurrent cytopenias, Disseminated Intravascular Coagulation-- or DIC-- and infections. BRITTANY HARVEY: Great. Thank you. Then, Dr. Santomasso-- looking at this guideline, there's a few overarching recommendations. So, what are those general recommendations for the management of immune-related adverse events in patients receiving CAR T-cell therapy? BIANCA SANTOMASSO: Yes. The overarching recommendations are, really, first to recognize that these side effects exist. And that, as such, it's important to recognize that patients who develop these toxicities or side effects after CAR T-cell therapy need to be evaluated, or managed in, or transferred to a specialty center that has experience with the management of these toxicities. They're new toxicities. This is a new therapy. And patients are increasingly going to be managed in, or treated in, the outpatient setting, and, as such, they need to remain within a short distance of the treating center for about four to eight weeks post-therapy, and they should then return to their treating center upon experiencing any toxicities. Finally, as its flu season and infection season, it is recommended that inactivated influenza and COVID-19 vaccination be performed on patients and also family members as well. And any patient who does have an active infection, the CAR T-cell infusion should be delayed until that infection has been successfully treated or controlled. I often make a final point, which is that the immunogenicity of and efficacy of COVID-19 vaccines is uncertain in these patients with these agents, but the potential benefits outweigh the risks and uncertainties for most patients. BRITTANY HARVEY: Thank you. Those are important points for patients and treating clinicians. So then, Dr. Ghosh-- as you mentioned, this guideline addresses the seven most common CAR-T-related toxicities, and I'd like to review the key recommendations for each of those. So let's start with, what are the key recommendations for identification, evaluation, and management of cytokine-release syndrome? MONALISA GHOSH: Well, Cytokine Release Syndrome is one of the two major toxicities that occur immediately or within a short time period after infusion of CAR T-cells. We have defined Cytokine Release Syndrome, or CRS, as an immune-mediated phenomenon that's characterized by various symptoms that are indicative of immune activation and inflammation. And patients may experience signs and symptoms that could include fever, hypotension, hypoxia, tachycardia, shortness of breath, rash, nausea, headache, and various other symptoms that are a little less common. These symptoms are caused primarily by the release of cytokines. Cytokines are the messengers of the immune system, and most of them are released by bystander immune and non-immune cells. We know that the onset of Cytokine Release Syndrome is variable depending on the CAR T-cell product that's used, as well as the patient population that's treated. But it generally occurs anywhere from two to seven days after infusion of CAR T-cells, and in some rare cases can occur even a little bit later. A standard grading system has been developed and grade CRS, or Cytokine Release Syndrome, based on three parameters-- fever, hypotension, or low blood pressure; and hypoxia or low oxygen levels. CRS is primarily managed with IL-6 antagonists because IL-6 is an inflammatory cytokine that has been shown to mediate a lot of the systemic effects that we see from Cytokine Release Syndrome. And one of the treatments is the monoclonal antibody tocilizumab, which acts against-- or blocks-- the IL-6 receptor. CRS that is refractory to tocilizumab is generally treated with steroids. Then there's limited experience with additional therapies, especially in the setting of CRS, that does not respond to tocilizumab or steroids. There are other anti IL-6 therapies available. For example, siltuximab, which binds to IL-6 itself rather than the IL-6 receptor. However, there have been no direct comparative studies of these agents. Anakinra, which is also an IL-1 receptor antagonist has also been shown to mitigate CRS in some CAR T-cell recipients that have high grade CRS. BRITTANY HARVEY: OK. Thank you for reviewing those management strategies. So, following that-- Dr. Santomasso, what are key recommendations for identification, evaluation, and management of immune effector cell-associated neurotoxicity syndrome? BIANCA SANTOMASSO: Sure. Immune Effector Cell-associated Neurotoxicity Syndrome-- also known as ICANS-- is the second most frequent severe toxicity that can be seen after CAR T-cell therapy. So, what is ICANS? These are transient neurological symptoms that occur in the days after infusion, most commonly with CD19 CAR T-cell therapy. And the clinical manifestations of ICANS include encephalopathy, which is confusion, behavioral changes, expressive aphasia, or other language disturbance, change in handwriting or other fine motor impairment or weakness, and tremor and headache can also be seen. In more severe cases, patients can become obtunded with a depressed level of consciousness or even develop seizures, and they may require a higher level of ICU care, such as intubation for airway protection. And in very rare cases, malignant cerebral edema may develop, which may be fatal. ICANS can occur at the same time as Cytokine Release Syndrome, or can also occur several days after or shortly after CRS resolves, so it's important to have a high index of suspicion even after Cytokine Release Syndrome has resolved, but typically the side effects are self-limited and occur within the one month after infusion. Most symptoms lasts between 5 and 17 days, and the time of onset duration and severity of ICANS may really vary depending on the CAR T-cell product used or the disease state of the patient. So, what do I mean by that? Patients with high disease burden seem to be at increased risk for severe ICANS, so kind of knowing the disease that the patient has and the burden of disease is important. And then also there may be product-specific differences as well, so reviewing the product label is important as well because each may have its own risk evaluation and mitigation strategies that inform both the duration and the frequency of monitoring for ICANS after infusion. For evaluation of ICANS, we recommend, again, the ASTCT ICANS grading system. These allow for monitoring of several different aspects of neurologic function in these patients. Mental status changes are really what define the onset of ICANS. So for CRS, it's fever; for ICANS, it's mental status changes. And the severity of the mental status change can be determined by a standardized score known as the ICE score, which stands for Immune Effector Cell-associated Encephalopathy score. This is a simple 10-point scoring metric where points are assigned for orientation to year, month, city, hospital, ability to name three objects, ability to follow simple commands, write a standard sentence, and count backwards from 100 by tens. And for children younger than age 12 or those with developmental delay, The Cornell Assessment of Pediatric Delirium, also known as the CAPD, can be used in placement of the ICE assessment. Prior to CAR infusion, patients should be evaluated, including with an ICE score, for their baseline neurologic status. And what's nice is that this ICE assessment can be used as a daily screen after CAR infusion for the onset of ICANS during at-risk period. Then, other than the ICE score, there are four other neurologic domains that contribute to ICANS grading, and that's level of consciousness, seizures, severe motor weakness, and signs and symptoms of elevated intracranial pressure or cerebral edema, and patients are graded according to the most severe symptom in any of the five domains. So for patients who develop ICANS, it's recommended that they have workup, including blood work, CRP, CBC, comprehensive metabolic panel, fibrinogen, and coagulation tests. Neuroimaging with a non-contrast CT of the brain should be done and considering MRI of the brain in patients who are stable enough. In addition, electroencephalogram and lumbar puncture should be considered. And the electroencephalogram is really to rule out subclinical seizures, and the lumbar puncture is to assess the opening pressure-- or the pressure within the central nervous system-- and also to send studies to rule out infection. And again, these all have to be considered on an individual case by case basis, but are things to keep in mind. So for treatment of ICANS, the mainstay of treatment is, really, supportive care and corticosteroids. Tocilizumab, while it seems to rapidly resolve Cytokine Release Syndrome and most symptoms, actually does not resolve ICANS and may worsen it, so steroids are really typically used. The typical steroid is dexamethasone at a dose of 10 milligrams, and the interval really depends on the grade of the ICANS. Because of the possibility that tocilizumab may worsen neurotoxicity, ICANS really takes precedence over low grade CRS when the two occur simultaneously. And patients who don't show improvement within 24 hours after starting steroids or other supportive measures should have CSF evaluation and neuroimaging. Often treatment of seizures-- many patients are put on Keppra and levetiracetam or other anti-seizure medicine if they develop ICANS, and patients with grade 3 or greater ICANS may need an ICU level of care and escalation of steroid doses. The steroids are continued until ICANS improves to grade 1 and then tapered as clinically appropriate. And the most important thing to remember is that ICANS just needs to be monitored very closely as patients may worsen as some steroids are tapered. They also may improve rapidly after steroids are started, so steroids should be tapered quickly as patients improve. And, again, as with CRS, there's limited experience with other agents, such as Anakinra and siltuximab, but those could be considered in severe or refractory cases. BRITTANY HARVEY: Understood. I appreciate you going through when and how clinicians should screen for ICANS and those key management points. So, in addition to that-- Dr. Ghosh, what are the key recommendations regarding cytopenias? MONALISA GHOSH: So cytopenias can occur post-CAR T-cell infusion, and they can occur either in the early phase or in the later phase after CAR T-cell infusion. Meaning that they can occur early within the first few days to weeks post-CAR T-cell therapy or could even occur months to years later. These cytopenias include anemia, thrombocytopenia, leukopenia, neutropenia. Many patients may present with fatigue, weakness, shortness of breath, lightheadedness, frequent infections, fevers, bruising, and bleeding, and the symptoms usually are consistent with how they would present otherwise with anemia, thrombocytopenia, or neutropenia. Acute cytopenias within three months of CAR T-cell therapy are more common. This is due to usually the lymphodepleting chemotherapy that is administered prior to CAR T-cell therapy. Most patients receive a combination of fludarabine and cyclophosphamide prior to CAR T-cell infusion, or they may receive another agent, such as bendamustine. Most patients also come into CAR T-cell therapy with low lymphocyte counts from previous therapies. Early cytopenias, as I mentioned, are generally due to lymphodepleting chemotherapy or other recent therapies. There also could be an immune-mediated process due to the CAR T-cells. Usually prolonged cytopenias which occur beyond three months post-CAR T-cell infusion can be seen in a small number of patients. And the mechanism of prolonged cytopenias is really unclear at this time, but likely multifactorial. Most recipients of CAR T-cells who have prolonged cytopenias beyond three months post-CAR T-cell infusion should have a standard workup to rule out other common causes, such as vitamin or nutritional deficiencies. They should also have testing such as bone marrow biopsy and scans to rule out relapse disease-- relapse lymphoma or leukemia, for instance, that could be causing these cytopenias. Other examples would be myelodysplastic syndrome or other bone marrow failure syndromes. So cytopenias are generally managed with supportive care including growth factor and transfusion support. This applies to both cytopenias in the early period post-CAR T-cell therapy or more delayed prolonged cytopenias. In patients who have prolonged cytopenias of unclear cause that could be immune-mediated, other interventions such as high dose IVIG or even steroids could be considered depending on the situation. For those that have cytopenias in the first few months post-CAR T-cell therapy, generally they are monitored and treated with supportive care, and these cytopenias eventually resolve in the majority of patients. BRITTANY HARVEY: Great. Those are important considerations. Then, Dr. Santomasso, what are the key recommendations regarding Hemophagocytic Lymphohistiocytosis? BIANCA SANTOMASSO: The major recommendations for the identification, evaluation, and management of Hemophagocytic Lymphohistiocytosis, or HLH-- this is also known as macrophage activation syndrome. First, let's just start by saying that this is a dysfunctional immune response, and it's basically characterized by macrophages which are revved up and hyperactive and also possibly lymphocytes as well. There are high levels of pro-inflammatory cytokines during this state and tissue infiltration, and hemophagocytosis, and organ damage. This can occur outside of the context of CAR T-cell therapy, either as a primary HLH or secondary HLH that can be either triggered by infections, or autoimmune disease, or cancer-- especially hematological malignancies, but HLH has also been observed as a rare complication of CAR T-cell therapy. And outside of the setting of CAR T-cell therapy, HLH is defined by fever, cytopenias, hyperferritinemia-- or high ferritin level-- as well as bone marrow hemophagocytosis. And what's interesting is that this is very similar to what's seen during Cytokine Release Syndrome, and that can make it difficult for patients who have moderate to severe CRS to distinguish that from HLH. The laboratory results may be very similar. So the key to recognizing HLH is really to have it on your differential even though it occurs rarely after CAR T-cell therapy. It may occur with slightly different timing and may require more aggressive treatment. The lab alterations can include, again, as I mentioned, these elevated levels of several cytokines, such as interferon gamma. We can't normally send those in the hospital or the clinic, but sometimes soluble IL-2 receptor alpha can be sent and serum ferritin can be sent, and that's an especially useful marker. There have been diagnostic criteria for CAR T-cell-induced HLH that have been proposed, and these conclude very high ferritin levels-- over 10,000-- and at least two organ toxicities that are at least grade 3, such as transaminitis, increased bilirubin, renal insufficiency or oliguria, or a pulmonary edema, or evidence of hemophagocytosis in bone marrow or organs. Unlike other forms of HLH that occur outside of the context of CAR T-cell therapy, the patients may not have hepatosplenomegaly, lymphadenopathy, or overt evidence of hemophagocytosis. So just because a patient may not show those yet doesn't mean that HLH shouldn't be considered. If we see patients that have a persistent fever without an identified infection source or worsening fever, we basically should be considering HLH and doing the appropriate workup and treatment. Patients with HLH often have low fibrinogen, high triglycerides, and also cytopenias as well. The treatment-- just as there's an overlap kind of in the signs and symptoms, the treatment and the clinical management overlaps as well with CRS, so tocilizumab is typically administered. But corticosteroids should really be added for these patients, especially if there's clinical worsening or grade 3 or greater organ toxicity. And if there's insufficient response after 48 hours of corticosteroid therapy plus tocilizumab, many centers consider adding another medication such as Anakinra. I'll finally make a comment that, outside of the context of CAR T-cell therapy, HLH is sometimes treated with cytotoxic chemotherapy, such as etoposide. This approach generally is not used as a first line for patients undergoing CAR T-cell therapy due to etopiside's documented toxicity to T lymphocytes. And generally, the corticosteroids, plus the anti IL-6 agent, plus Anakinra is considered the first line of management. BRITTANY HARVEY: Got it. That's an important note on the management of HLH, and a great note on distinguishing CRS and HLH. So in addition, Dr. Ghosh-- what are the recommendations for management of B-cell aplasia? MONALISA GHOSH: B-cell aplasia, it's a disorder that's caused by low numbers or absent B-cells. And this is particularly relevant to CD19 directed CAR T-cell therapy, which is what most of the CAR T-cell therapies that are available right now target. They target CD19, and CD19 is present on normal as well as malignant B-cells. So most patients who receive anti-CD19 CAR T-cell therapy will develop B-cell aplasia at some point, and B-cell aplasia may be temporary or prolonged. It usually does, on one hand, indicate ongoing activity of the CD19 CAR T-cells and can be used as a surrogate marker. And increase in CD19 CAR T-cells could, in some patients, signal impending relapse, or dysfunction, or absence of activity of CD19 CAR T-cells. B-cell aplasia in CAR T-cell recipients is really due to, as I mentioned, an on-target, off-tumor effect. It can be prolonged and there is variability in rates of prolonged B-cell aplasia. The most significant consequence of B-cell aplasia is that it can lead to low immunoglobulin production. And immunoglobulin production is a very important part of the immune response by providing antibody-mediated immunity, so patients may present with frequent infections and low immunoglobulin levels. For most CAR T-cell recipients, this can be managed with infusions of Intravenous Immunoglobulins-- IVIG. However, the presence of B-cell aplasia can also present other challenges-- especially during this current pandemic, as Dr. Santomasso alluded to earlier, that it is unclear if patients will be able to mount a sufficient enough antibody response to the COVID-19 vaccines available since they cannot produce significant amounts of antibodies. This is an active area of research. However, we do advise that all CAR T-cell recipients do get the COVID vaccine and also other seasonal vaccines, such as the influenza vaccine. So it remains to be seen. We need some more long-term follow-up studies on how many people who receive CD19-directed CAR T-cell therapy will have prolonged B-cell aplasia and what the consequences will be. At this time, it is suggested that patients have their IgG levels monitored and-- if possible-- their actual B-cell numbers monitored. And if their IgG levels drop below a certain number, then they may receive IVIG infusions intermittently. We recommend in this guideline using 400 as a possible cutoff for IgG levels prior to administering IVIG. However, if patients have higher IgG levels and they have recurrent or life threatening infections, infusion of IVIG is recommended as a consideration to help boost the antibody response. BRITTANY HARVEY: OK. As you mentioned, those challenges are particularly relevant now. So then, Dr. Santomasso, what are the key recommendations regarding Disseminated Intravascular Coagulation? BIANCA SANTOMASSO: Disseminated Intravascular Coagulation is a disorder that's characterized by systemic pathological activation of blood clotting mechanisms, which results in both clot formation throughout the body and also bleeding. There's an increased risk of hemorrhage as the body is depleted of platelets and other coagulation factors. So it's basically important for clinicians to be aware that DIC-- or Disseminated Intravascular Coagulation-- can occur after CAR T-cell therapy, and it can occur either with or without concurrent Cytokine Release Syndrome. The treatment is primarily supportive care and replacing the factors, such as fibrinogen-- based on the levels-- and also replacing factors based on partial thromboplastin time and bleeding occurrences. But corticosteroids and IL-6 antagonist therapy can be used if there is concurrent CRS or in the setting of severe bleeding complications. There is limited evidence for other interventions. BRITTANY HARVEY: Great. Appreciate you reviewing those. So then, the last category of toxicity addressed in this guideline-- Dr. Ghosh, what are the key recommendations for identification, evaluation, and management of infections? MONALISA GHOSH: So a variety of infections can be seen after CAR T-cell therapy. And there are many factors that can lead to infection after CAR T-cell therapy including the presence of cytokines, such as neutropenia or leukopenia and B-cell aplasia that we earlier discussed-- leading to low immunoglobulin production and protection. As well as the increased risk of infection due to use of high-dose steroids to treat CAR T-cell-related toxicities, such as ICANS or CRS. Early after the infusion of CAR T-cell therapy-- that is, within three months-- patients often develop neutropenia due to lymphodepleting chemotherapy and/or the CAR T-cells themselves. And these patients are particularly susceptible to infection, so most of the infections that occur early on tend to be bacterial infections, and a few fungal infections have been observed as well. Patients who receive high-dose steroids for high grade CRS or ICANS have been shown to have increased serious infectious complications including bacterial infections, fungal infections, as well as viral reactivations. Infectious complications that occur later are often due to hypogammaglobulinemia due to B-cell aplasia and reduced production of immunoglobulins. And treatment is typically directed at the infectious source, as it would be even if these patients did not have CAR T-cell therapy. There are some prophylactic antimicrobials that are recommended for CAR T-cell recipients who have prolonged cytopenias. Especially those with prolonged neutropenia should be on some sort of bacterial and/or fungal prophylactic antimicrobials. Patients should also be monitored for hypogammaglobulinemia long term and should receive intravenous immunoglobulins as needed. As we have mentioned a couple of times already, being very aware that these patients are also more susceptible to seasonal infection, such as influenza, is important, and so vaccinations are very important for this patient population. Vaccinating against influenza and vaccinating against COVID-19. BRITTANY HARVEY: Thank you both for reviewing those key points for the most common CAR T-related toxicities. So, just to wrap us up-- Dr. Santomasso-- in your view, how will this guideline impact both clinicians and patients? BIANCA SANTOMASSO: Well, I think we've seen now that cell therapy is really one of the major advances in cancer treatment in the past decade. And I think it's reasonable to expect more of these cell therapies to be developed, and we'll hopefully see their use extend beyond very specialized centers. But CAR T-cell therapy side effects are manageable if they're recognized, so I think this guideline helps that, and they're reversible with proper supportive care. They can be serious and they require close vigilance and prompt treatment. But, again, we believe this guideline and recommendations will help members of clinical teams with both the recognition and management of all of these toxicities, and that will help patients by increasing their safety. BRITTANY HARVEY: Great. That's important to note that these toxicities can be severe, but are also manageable. So I want to thank you both for your work on these guidelines and for taking the time to speak with me today, Dr. Santomasso and Dr. Ghosh. BIANCA SANTOMASSO: Our pleasure. MONALISA GHOSH: Absolutely. It was my pleasure. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events in patients treated with immune checkpoint inhibitors. To read the full guidelines, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

In our newest segment, one which reflects on our complete lack of judgement and discernment, we present LIVE SINGING, the segment that features various singers "singing" (yes, that word was intentionally placed within quotation marks!) some of your favorite songs! On today's show, "Cannabis Carl" and "Paranoid Pete", came in to sing "HOW DO YOU KEEP THE MUSIC PLAYING?". As Al often says, what could POSSIBLY go wrong??? Enjoy!

(I Do Not Own the Rights to the Music Playing in this Podcast) I remember the first time I started my self-care Journey. I was nervous when I realized that people were leaving my life. I truly felt as if I was on a plane I thought about when the flight attendant begun to give us the safety speech about what to do in the event of an emergency. This was an eye opening for me, as they stated if the plane lose cabin pressure, an oxygen mask would come down in front of us and that we should put the mask on ourselves First. As I thought about this, I was in shock I thought to myself if I'm on this plane with my son I'm going to make sure he is taking care of first. It was a part of who I was to take care of my son first, I could actually see myself bouncing out of my seat to go help my son. It was then that I realized that if I didn't take care of Me first. I would not have any life to give others. I literally had an epiphany when I thought about what you need to do in the event of an emergency on the plane. As a matter of fact that moment I began my self-care journey and realized that before I can commit to taking care of others including my son I have to take care of me. Please follow JS Self-Care on all Social Media Platforms . https://linktr.ee/Jsselfcare Disclaimer: This podcast is for educational purposes only. The host claims no responsibility to any person or entity for any liability, loss or damage caused or alleged to be caused directly or indirectly as a result of use of the application or interpretation of the information presented in this podcast.

Glasses/sunglasses with built-in speakers have been a thing for a shockingly long time now. They've never been particularly popular, mind, but at the very least, they're an interesting enough concept for companies to continue taking a sporadic stab at the category, whose primary appeal seems to be not being forced to purchase both glasses and […]

CT Rowe shares stories about what it was like to work for the National Ballet of Canada Orchestra, how she ended up playing what she did there and what she's playing now - CT is a remarkable person who tells me that she lived her whole live practicing how to live her life here in the country - from the glamorous concert halls of the world to a lovely home on Fraser Lake. We talk about it all. I love that she picketed Carnegie Hall. She'll tell you why. And an added treat, the music at the end is CT playing. Enjoy! #BLACKLIVESMATTER And last week was a hard week for many, especially people of colour who are exhausted from having to explain again and again how their lives are in peril by the police and the system of anti-black racism that is destroying lives. Give a listen to these podcasts - Black people talking about Black Lives. We've been told it will get better - it won't if we don't do anything. I am posting these links in the hope that they will amplify the voices of Black people at a time when we should all be listening. Things have to change. Canadian Podcasts I highly recommend Sandy and Nora Talk Politics Podcast. Sandy Hudson was one of the co-founders of Black LIves Matter Toronto and she and co-host Nora Loreto talk about important issues - they hold no punches and are a refreshing voice and reality check. Sandy and Nora Talk Politics The Globe and Mail's Podcast Colour Code Podcasts from the USA 1. Still Processing Podcast about Colin Kaepernick 2. The Daily Podcast Systems that Protect the Police 3. Code Switch Podcast A Decade of Watching Black People Die --- Send in a voice message: https://anchor.fm/roy-mitchell5/message

[smart_track_player url=”http://traffic.libsyn.com/7figureceo/7CEO_049-Your_Perfect_Day_With_Andy_Levine.mp3″ title=”7CEO 049: Your Perfect Day with Andy Levine” artist=”Casey Graham” social=”true” social_twitter=”true” social_facebook=”true” social_gplus=”true” ] Andy Levine started his company, Sixthman, 15 years ago which takes fans and bands on vacation together on cruise ships. He sold it in 2012 and continued to run it until 2016 when he stepped into the role of Chairman. He was a previous guest of the podcast on episode 28. Today we're taking a different approach to the podcast and talking about some more personal stuff that leaders of an organization deal with. Andy shares about how he has developed a rhythm for his days that is best for him, his family and his leadership. LINKS Andy's first episode on The 7-Figure CEO Podcast: Episode 28 Productive App – Productive habits and daily goals tracker Email your top take-aways and learnings to Casey@CaseyGraham.com Apply for a Breakthrough Call with Casey: CaseyGraham.com/Action   TOP TAKE-AWAYS Andy journaled for a year and logged what he did with his time and what was going on with his family. He started on the journey to help build the optimal day for him and his family. He used his phone to write about 300 words a day to describe what happened during the day, how he spent his time and how the day went. Through this he developed an ideal rhythm for him. YOUR PERFECT DAY IN THREE PARTS 1. MORNINGS FOR ME – Exercise – Crossfit, Yoga, swimming or running – Learning – Listening to a podcast or reading – Music – Playing guitar or piano – Mindfulness – Identify five things, touch four things, pick out three unique sounds, two unique smells and one unique taste (which helps with anxiety) – Nutrition – Make a good food choice first thing in the morning To Business Owners and Entrepreneurs: You CAN take time for you! You don't have to buy into the idea that you have to work so hard that you neglect yourself and those you love! If you're leading people, you're going to do a better job if you show up feeling confident about yourself and ready to connect with and lead people! You don't have to always be the first person in the office! Anxiety is a big issue that entrepreneurs go through and maybe it's a result of a noisier, busy world that our bodies aren't able to process everything that's coming in. Physical exercise is one of the best therapies for anxiety. 2. DAYS FOR OTHERS Each of us have gifts that should be used to help others. As the leader of an organization, you should plan to spend the first hours of your day serving others – helping them achieve their weekly wins. You can also invest in your customers to serve them! If you're investing in yourself first then you will have the energy and bandwidth to serve others for a few hours. It's also very important to expand your network and go out and meet with people. Through getting out of your everyday, office routine to meet with others and go to conferences, you help others, hear of opportunities, and innovate new ideas for your business and life. 3. NIGHTS FOR US This is meeting your family or loved ones in a shared orbit of interest. Ask your loved ones what they enjoy doing just with you? By asking them you take the guess work out of how to best love your family and friends. By showing initiative, you communicate they are important. There are three big relationships we have that should be prioritized. Create a daily rhythm to take care of these relationships and that works well for you! 1. Ourselves
 – This is probably the hardest relationship because we know everything about us. 2. Others – customers, employees, peers 3. Significant relationships – those you love and friends   Feeling Stuck In Your Business? I'm currently offering free 30-minute Breakthrough Calls to help business owners, presidents and CEOs with their current business challenge. If you have over $400K in annual revenue and would like help, schedule your free Breakthrough Call today.

6 AM - 1 - Vincent is meeting the Fair Rebecca's parents manana; Marshall lost his smartphone; Openings. 2 - Early COW; MailBag. 3 - The News with Marshall Phillips. 4 - The Palestinians are really mad right now.