Podcasts about R0

In this JCO Article Insights episode, host Jospeh Mathew summaries Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial, by Palmer, et al published December 5, 2024. Transcript Joseph Matthew: Hello and welcome to the Journal of Clinical Oncology Article Insights. I'm your host, Joseph Matthew, and today we will be discussing the article "Long-Term Survival in Resected Pancreatic Ductal Adenocarcinoma with Adjuvant Gemcitabine plus Capecitabine Compared to Modified FOLFIRINOX from the ESPAC-4 and the PRODIGE 24 Trials" by Dr. Palmer et al. To summarize the relevant evidence, the ESPAC-4 was a European phase 3 multicenter randomized clinical trial published in 2017 comparing adjuvant gemcitabine and capecitabine (GemCap) with gemcitabine monotherapy following macroscopic margin-negative resections for operable pancreatic ductal adenocarcinoma (PDAC). The trial had included non-metastatic patients aged 18 years or older, World Health Organization (WHO) performance scores of 2 or less, creatinine clearance of at least 50 mL/min, and a life expectancy of over three months who had not received any prior anticancer treatment. Patients who had undergone R2 resections were selectively excluded. Eligible participants were randomized 1:1 within 12 weeks of pancreatectomy to one of the two treatment arms, with chemotherapy initiated within two weeks from the date of randomization. The regimens involved six cycles, each lasting four weeks, for an overall duration of 24 weeks. In the monotherapy arm, gemcitabine dosed at 1 g/m² was given as an intravenous infusion once a week for three weeks, followed by one week off. In the GemCap arm, capecitabine dosed at 1660 mg/m² was added to gemcitabine, given daily for three weeks, followed by one week off. Patients were followed up every three months, with the primary endpoint being overall survival (OS). The study showed that at a median follow-up of 43.2 months, GemCap was associated with a significantly longer OS than gemcitabine alone. Subsequently, in 2018, the Phase 3 randomized PRODIGE 24 trial was conducted in centers across France and Canada, comparing adjuvant modified FOLFIRINOX (mFOLFIRINOX) with gemcitabine in a similar subset of patients with resected PDAC and reported longer OS with the mFOLFIRINOX regimen. This study, however, had more restrictive eligibility criteria when compared to ESPAC-4, including patients aged under 80 years, WHO performance status of 0 or 1, with no significant cardiovascular disease, and a postoperative serum CA 19-9 of less than 180 U/mL. There was hence a subset of ESPAC-4 patients who did not meet the eligibility criteria for mFOLFIRINOX as set by the PRODIGE 24. The present study was conducted to estimate the overall 5-year survival rates for patients of ESPAC-4 receiving GemCap and gemcitabine, further stratifying survival in either arm according to the status of the surgical margins (R status) and the resected nodes (N status), and also to investigate whether GemCap retained a survival benefit over gemcitabine in PRODIGE 24-ineligible patients. A total of 732 patients, evenly distributed between both arms, were followed up for a median period of 104 months. Adjuvant GemCap was found to retain its survival advantage over gemcitabine, with a significantly longer median OS of 31.6 months when compared to 28.4 months with gemcitabine alone. Further subgroup analysis was performed with reference to the resection margins and the nodal status. As a reminder, in the ESPAC-4 trial, 60% of patients were found to have microscopically positive margins (an R1 resection), and 80% were node-positive. The difference in survival was greater in patients undergoing microscopic margin-negative resections (R0) who experienced a median OS of 49.9 months with GemCap when compared to 32.2 months with gemcitabine. Node-negative patients also had a significantly greater 5-year OS rate with GemCap of 59% versus 53% with gemcitabine monotherapy. However, it is important to note that no significant difference in survival outcomes was observed in margin-positive (R1) or node-positive patients in the two arms. The investigators also evaluated GemCap in the subgroup of 193 patients (comprising 26.4% of the ESPAC-4 cohort) who were not considered to have met the eligibility criteria for PRODIGE 24. The survival benefit of combination therapy was retained in this group, with patients receiving GemCap experiencing a median survival of 25.9 months compared to 20.7 months with adjuvant gemcitabine. Although cross-trial comparisons have limited validity, good agreement was noted in adverse grade 3 or greater toxicity associated with the control gemcitabine arms of ESPAC-4 and PRODIGE 24, serving as the basis for a qualitative comparison of toxicities between mFOLFIRINOX and GemCap. Neutropenia was more prevalent in the GemCap arm, affecting 40.8% of patients compared to 28.4% with mFOLFIRINOX. However, granulocyte colony-stimulating factor (G-CSF) was administered to 62.2% of patients in PRODIGE 24. Palmar-plantar erythrodysesthesia (PPE) was also more prevalent with GemCap. Patients on mFOLFIRINOX were more likely to observe grade 3 or greater fatigue, diarrhea, nausea and vomiting, sensory peripheral neuropathy, and paresthesias. The investigators concluded that GemCap was the standard adjuvant treatment for patients with PDAC undergoing an upfront resection who were not feasible for mFOLFIRINOX. Further exploratory analysis revealed that patients under the age of 70 who had undergone a microscopic margin-negative (R0) resection for node-negative PDAC were likely to derive an OS benefit from the addition of capecitabine to gemcitabine in the adjuvant setting. In contrast, mFOLFIRINOX would be more effective than gemcitabine in patients with positive margins (R1) or involved nodes, as per the PRODIGE 24 trial. Thank you for listening to JCO Article Insights. Please come back for more interviews and article summaries, and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit ASCO.org/podcasts. 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.

Dr. Ebony Hoskins and Dr. Andreas Obermair discuss the surgical management of gynecologic cancers, including the role of minimally invasive surgery, approaches in fertility preservation, and the nuances of surgical debulking. TRANSCRIPT Dr. Ebony Hoskins: Hello and welcome to the ASCO Daily News Podcast, I'm Dr. Ebony Hoskins. I'm a gynecologic oncologist at MedStar Washington Hospital Center in Washington, DC, and your guest host of the ASCO Daily News Podcast. Today we'll be discussing the surgical management of gynecologic cancer, including the role of minimally invasive surgery (MIS), approaches in fertility preservation, and the nuances of surgical debulking, timing, and its impact on outcomes. I am delighted to welcome Dr. Andreas Obermair for today's discussion. Dr. Obermair is an internationally renowned gynecologic oncologist, a professor of gynecologic oncology at the University of Queensland, and the head of the Queensland Center for Gynecologic Cancer Research. Our full disclosures are available in the transcript of this episode. Dr. Obermair, it's great speaking with you today. Dr. Andreas Obermair: Thank you so much for inviting me to this podcast. Dr. Ebony Hoskins: I am very excited.  I looked at your paper and I thought, gosh, is everything surgical? This is everything that I deal with daily in terms of cancer in counseling patients. What prompted this review regarding GYN cancer management? Dr. Andreas Obermair: Yes, our article was published in the ASCO Educational Book; it is volume 44 in 2024. And this article covers some key aspects of targeted precision surgical management principles in endometrial cancer, cervical cancer, and ovarian cancer. While surgery is considered the cornerstone of gynecologic cancer treatment, sometimes research doesn't necessarily reflect that. And so I think ASCO asked us to; so it was not just me, there was a team of colleagues from different parts of the United States and Australia to reflect on surgical aspects of gynecologic cancer care and I feel super passionate about that because I do believe that surgery has a lot to offer. Surgical interventions need to be defined and overall, I see the research that I'm doing as part of my daily job to go towards precision surgery. And I think that is, well, that is something that I'm increasingly passionate for. Dr. Ebony Hoskins: Well, I think we should get into it. One thing that comes to mind is the innovation of minimally invasive surgery in endometrial cancer. I always reflect on when I started my fellowship, I guess it's been about 15 years ago, all of our endometrial cancer patients had a midline vertical incision, increased risk of abscess, infections and a long hospital stay. Do you mind commenting on how you see management of endometrial cancer today? Dr. Andreas Obermair: Thank you very much for giving the historical perspective because the generation of gynecologic oncologists today, they may not even know what we dealt with, what problems we had to solve. So like you, when I was a fellow in gynecologic oncology, we did midline or lower crosswise incisions, the length of stay was, five days, seven days, but we had patients in hospital because of complications for 28 days. We took them back to the operating theaters because those are patients with a BMI of 40 plus, 45, 50 and so forth. So we really needed to solve problems. And then I was exposed to a mentor who taught minimal invasive surgery. And in Australia he was one of the first ones who embarked on that. And I can remember, I was mesmerized by this operation, like not only how logical this procedure was, but also we did rounds afterwards. And I saw these women after surgery and I saw them sitting upright, lipstick on, having had a full meal at the end of the day. And I thought, wow, this is the most rewarding experience that I have to round these patients after surgery. And so I was thinking, how could I help to establish this operation as standard? Like a standard that other people would accept this is better. And so I thought we needed to do a trial on this. And then it took a long time. It took a long time to get the support for the [LACE - Laparoscopic Approach to Cancer of the Endometrium] trial. And in this context, I just also wanted to remind us all that there were concerns about minimal invasive surgery in endometrial cancer at the time. So for example, one of the concerns was when I submitted my grant funding applications, people said, “Well, even if we fund you, wouldn't be able to do this trial because there are actually no surgeons who actually do minimally invasive surgery.” And at the time, for example, in Australia, there were maybe five people, a handful of people who were able to do this operation, right? This was about 20 years ago. The other concern people had was they were saying, could minimally invasive surgery for endometrial cancer, could that cause port side metastasis because there were case reports. So there were a lot of things that we didn't know anyway. We did this trial and I'm super happy we did this trial. We started in 2005, and it took five years to enroll. At the same time, GOG LAP2 was ramping up and the LACE trial and GOG LAP2 then got published and provided the foundations for minimally invasive surgery in endometrial cancer. I'm super happy that we have randomized data about that because now when we go back and now when people have concerns about this, should we do minimally invasive surgery in P53 mutant tumors, I'm saying, well, we actually have data on that. We could go back, we could actually do more research on that if we wanted to, but our treatment recommendations are standing on solid feet. Dr. Ebony Hoskins: Well, my patients are thankful. I see patients all the time and they have high risk and morbidly obese, lots of medical issues and actually I send them home most the same day. And I think, you know, I'm very appreciative of that research, because we obviously practice evidence-based and it's certainly a game changer. Let's go along the lines of MIS and cervical cancer. And this is going back to the LACC [Laparoscopic Approach to Cervical Cancer] trial.  I remember, again, one of these early adopters of use of robotic surgery and laparoscopic surgery for radical hysterectomy and thought it was so cool. You know, we can see all the anatomy well and then have the data to show that we actually had a decreased survival. And I even see that most recent updated data just showing it still continued. Can you talk a little bit about why you think there is a difference? I know there's ongoing trials, but still interested in kind of why do you think there's a survival difference? Dr. Andreas Obermair:  So Ebony, I hope you don't mind me going back a step. So the LACC study was developed from the LACE trial. So we thought we wanted to reproduce the LACE data/LAP2 data. We wanted to reproduce that in cervix cancer. And people were saying, why do you do that? Like, why would that be different in any way? We recognize that minimally invasive radical hysterectomy is not a standard. We're not going to enroll patients in a randomized trial where we open and do a laparotomy on half the patients. So I think the lesson that really needs to be learned here is that any surgical intervention that we do, we should put on good evidence footing because otherwise we're really running the risk of jeopardizing patients' outcomes. So, that was number one and LACC started two years after LACE started. So LACC started in 2007, and I just wanted to acknowledge the LACC principal investigator, Dr. Pedro Ramirez, who at the time worked at MD Anderson. And we incidentally realized that we had a common interest. The findings came totally unexpected and came as an utter shock to both of us. We did not expect this. We expected to see very similar disease-free and overall survival data as we saw in the endometrial cancer cohort. Now LACC was not designed to check why there was a difference in disease-free survival. So this is very important to understand. We did not expect it. Like, so there was no point checking why that is the case. My personal idea, and I think it is fair enough if we share personal ideas, and this is not even a hypothesis I want to say, this is just a personal idea is that in endometrial cancer, we're dealing with a tumor where most of the time the cancer is surrounded by a myometrial shell. And most of the time the cancer would not get into outside contact with the peritoneal cavity. Whereas in cervix cancer, this is very different because in cervix cancer, we need to manipulate the cervix and the tumor is right at the outside there. So I personally don't use a uterine manipulator. I believe in the United States, uterine manipulators are used all the time. My experience is not in this area, so I can't comment on that. But I would think that the manipulation of the cervix and the contact of the cervix to the free peritoneal cavity could be one of the reasons. But again, this is simply a personal opinion. Dr. Ebony Hoskins: Well, I appreciate it. Dr. Andreas Obermair: Ebony at the end of the day, right, medicine is empirical science, and empirical science means that we just make observations, we make observations, we measure them, and we pass them on. And we made an observation. And, and while we're saying that, and yes, you're absolutely right, the final [LACC] reports were published in JCO recently. And I'm very grateful to the JCO editorial team that they accepted the paper, and they communicated the results because this is obviously very important. At the same time, I would like to say that there are now three or four RCTs that challenge the LACC data. These RCTs are ongoing, and a lot of people will be looking forward to having these results available. Dr. Ebony Hoskins: Very good. In early-stage cervical cancer, the SHAPE trial looked at simple versus radical hysterectomy in low-risk cervical cancer patients. And as well all know, simple hysterectomy was not inferior to radical hysterectomy with respect to the pelvic recurrence rate and any complications related to surgery such as urinary incontinence and retention. My question for you is have you changed your practice in early-stage cervical cancer, say a patient with stage 1B1 adenocarcinoma with a positive margin on conization, would you still offer this patient a radical hysterectomy or would you consider a simple hysterectomy? Dr. Andreas Obermair:  I think this is a very important topic, right? Because I think the challenge of SHAPE is to understand the inclusion criteria. That's the main challenge. And most people simplify it to 2 cm, which is one of the inclusion criteria but there are two others and that includes the depth of invasion. Dr. Marie Plante has been very clear. Marie Plante is the first author of the SHAPE trial that's been published in the New England Journal of Medicine only recently and Marie has been very clear upfront that we need to consider all three inclusion criteria and only then the inclusion criteria of SHAPE apply. So at the end of the day, I think what the SHAPE trial is telling us that small tumors that would strictly fulfill the criteria of a 1B or 1B1 cancer of the cervix can be considered for a standard type 1 or PIVA type 1 or whatever classification we're trying to use will be eligible. And that makes a lot of sense. I personally not only look at the size, I also look at the location of the tumor. I would be very keen that I avoid going through tumor tissue because for example, if you have a tumor that is, you know, located very much in one corner of the cervix and then you do a standard hysterectomy and then you have a positive tumor margin that would be obviously, most people would agree it would be an unwanted outcome. So I'd be very keen checking the location, the size of the tumor, the depths of invasion and maybe then if the tumor for example is on one side of the cervix you can do a standard approach on the contralateral side but maybe do a little bit more of a margin, a parametrial margin on the other side. Or if a tumor is maybe on the posterior cervical lip, then you don't need to worry so much about the anterior cervical margin, maybe take the rectum down and maybe try to get a little bit of a vaginal margin and the margin on the uterus saccals. Just really to make sure that you do have margins because typically if we get it right, survival outcomes of clinical stage 1 early cervix cancer 1B1 1B 2 are actually really good. It is a very important thing that we get the treatment right. In my practice, I use a software to record my treatment outcomes and my margins. And I would encourage all colleagues to be cognizant and to be responsible and accountable to introduce accountable clinical practice, to check on the margins and check on the number on the percentage of patients who require postoperative radiation treatment or chemo radiation. Dr. Ebony Hoskins: Very good. I have so many questions for you. I don't know the statistics in Australia, but here, there's increased rising of endometrial cancer and certainly we're seeing it in younger women. And fertility always comes up in terms of kind of what to do. And I look at the guidelines and, see if I can help some of the women if they have early-stage endometrial cancer. Your thoughts on what your practice is on use of someone who may meet criteria, if you will. The criteria I use is grade 1 endometrioid adenocarcinoma. No myometria invasion. I try to get MRI'd and make sure that there's no disease outside the endometrium. And then if they make criteria, I typically would do an IUD. Can you tell me what your practice is and where you've had success? Dr. Andreas Obermair: So, we initiated the feMMe clinical trial that was published in 2021 and it was presented in a Plenary at one of the SGO meetings. I think it was in 2021, and we've shown complete pathological response rates after levonorgestrel intrauterine device treatment. And so in brief, we enrolled patients with endometrial hyperplasia with atypia, but also patients with grade 1 endometrial adenocarcinoma. Patients with endometrial hyperplasia with atypia had, in our series, had an 85 % chance of developing a complete pathological response. And that was defined as the complete absence of any atypia or cancer. So endometrial hyperplasia with atypia responded in about 85%. In endometrial cancer, it was about half, it was about 45, 50%. In my clinical practice, like as you, I see patients, you know, five days a week. So I'm looking after many patients who are now five years down from conservative treatment of endometrial cancer. There are a lot of young women who want to get pregnant, and we had babies, and we celebrate the babies obviously because as gynecologist obstetricians it couldn't get better than that, right, if our cancer patients have babies afterwards. But we're also treating women who are really unfit for surgery and who are frail and where a laparoscopic hysterectomy would be unsafe. So this phase is concluded, and I think that was very successful. At least we're looking to validate our data. So we're having collaborations, we're having collaborations in the United States and outside the United States to validate these data. And the next phase is obviously to identify predictive factors, to identify predictors of response. Because as you can imagine, there is no point treating patients with a levonorgestrel intrauterine joint device where we know in advance that she's not going to respond. So this is a very, very fascinating story and we got our first set of data already, but now we just really need to validate this data. And then once the validation is done, my unit is keen to do a prospective validation trial. And that also needs to involve international collaborators. Dr. Ebony Hoskins: Very good. Moving on to ovarian cancer, we see patients with ovarian cancer with, say, at least stage 3C or higher who started neoadjuvant chemotherapy. Now, some of these patients are hearing different things from their medical oncologist versus their gynecologic oncologist regarding the number of cycles of neoadjuvant chemotherapy after getting diagnosed with ovarian cancer. I know that this can be confusing for our patients coming from a medical oncologist versus a gynecologic oncologist. What do you say to a patient who is asking about the ideal number of chemotherapy cycles prior to surgery? Dr. Andreas Obermair: So this is obviously a very, very important topic to talk about. We won't be able to provide a simple off the shelf answer for that, but I think data are emerging.  The ASCO guidelines should also be worthwhile considering because there are actually new ASCO Guidelines [on neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer] that just came out a few weeks ago and they would suggest that we should be aiming for R0 in surgery. If we can maybe take that as the pivot point and then go back and say, okay, so what do need to do to get the patient to zero?  I'm not an ovarian cancer researcher; I'm obviously a practicing gynecologic oncologist. I think about things a lot and things like that. In my practice, I would want a patient to develop a response after neoadjuvant chemotherapy. So, if a patient doesn't have a response after two or three cycles, then I don't see the point for me to offer her an operation. In my circle with the medical oncologists that I work with, I have a very, very good understanding. So, they send the patient to me, I take them to the theater. I take a good chunk of tissue from the peritoneum. We have a histopathologic diagnosis, we have a genomic diagnosis, they go home the same day. So obviously there is no hospital stay involved with that. They can start the chemotherapy after a few days. There is no hold up because the chances of surgical complication in a setting like this is very, very low. So I use laparoscopy to determine whether the patient responds or not. And for many of my patients, it seems to work. It's obviously a bit of an effort and it takes operating time. But I think I'm increasing my chances to make the right decision. So, coming back to your question about whether we should give three or six cycles, I think the current recommendations are three cycles pending the patient's response to neoadjuvant chemotherapy because my aim is to get a patient to R0 or at least minimal residual disease. Surgery is really, in this case, I think surgery is the adjunct to systemic treatment. Dr. Ebony Hoskins: Definitely. I think you make a great point, and I think the guideline just came out, like you mentioned, regarding neoadjuvant. And I think the biggest thing that we need to come across is the involvement of a gynecologic oncologist in patients with ovarian cancer. And we know that that survival increases with that involvement. And I think the involvement is the surgery, right? So, maybe we've gotten away from the primary tumor debulking and now using more neoadjuvant, but surgery is still needed. And so, I definitely want to have a take home that GYN oncology is involved in the care of these patients upfront. Dr. Andreas Obermair: I totally support that. This is a very important statement. So when I'm saying surgery is the adjunct to medical treatment, I don't mean that surgery is not important. Surgery is very important. And the timing is important. And that means that the surgeons and the med oncs need to be pulling on the same string. The med oncs just want to get the cytotoxic into the patients, but that's not the point, right? We want to get the cytotoxic into the patients at the right time because if we are working under this precision surgery, precision treatment mantra, it's not only important what we do, but also doing it at the right time. And ideally, I I would like to give surgery after three cycles of neoadjuvant chemotherapy, if that makes sense. But sometimes for me as a surgeon, I talk to my med onc colleagues and I say, “Look, she doesn't have a good enough response to her treatment and I want her to receive six cycles and then we re-evaluate or change medical treatment,” because that's an alternative that we can swap out drugs and treat upfront with a different drug and then sometimes they do respond. Dr. Ebony Hoskins:  I have maybe one more topic. In the area I'm in, in the Washington D.C. area, we see lots of endometrial cancer and they're not grade 1, right? They're high-risk endometrial cancer and advanced. So a number of patients with stage 3 disease, some just kind of based off staging and then some who come in with disease based off of the CT scan, sometimes omental caking, ascites. And the real question is we have extrapolated the use of neoadjuvant chemotherapy to endometrial cancer. It's similar, but not the same. So my question is in an advanced endometrial cancer, do you think there's still a role, when I say advanced, I mean, maybe stage 4, a role for surgery? Dr. Andreas Obermair: Most definitely. But the question is when do you want to give this surgery? Similar to ovarian cancer, in my experience, I want to get to R0. What am I trying to achieve here? So, I reckon we should do a trial on this. And I reckon we have, as you say, the number of patients in this setting is increasing, we could do a trial. I think if we collaborate, we would have enough patients to do a proper trial. Obviously, we would start maybe with a feasibility trial and things like that. But I reckon a trial would be needed in this setting because I find that the incidence that you described, that other people would come across, they're becoming more and more common. I totally agree with you, and we have very little data on that. Dr. Ebony Hoskins: Very little and we're doing what we can. Dr. Obermair, thank you for sharing your fantastic insights with us today on the ASCO Daily News Podcast and for all the work you do to advance care for patients with gynecologic cancer. Dr. Andreas Obermair: Thank you, Dr. Hoskins, for hosting this and it's been an absolute pleasure speaking with you today. Dr. Ebony Hoskins: Definitely a pleasure and thank you to our listeners for your time today. Again, Dr. Obermair's article is titled, “Controversies in the Surgical Management of Gynecologic Cancer: Balancing the Decision to Operate or Hesitate,” and was published in the 2024 ASCO Educational Book. And you'll find a link to the article in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclaimer: 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. Find out more about today's speakers: Dr. Ebony Hoskins @drebonyhoskins Dr. Andreas Obermair @andreasobermair Follow ASCO on social media:       @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn       Disclosures:   Dr. Ebony Hoskins: No relationships to disclose. Dr. Andreas Obermair: Leadership: SurgicalPerformance Pty Ltd. Stock and Ownership Interests: SurgicalPerformance Pty Ltd. Honoraria: Baxter Healthcare Consulting or Advisory Role: Stryker/Novadaq Patents, Royalties, and Other Intellectual Property: Shares in SurgicalPerformance Pty Ltd. Travel, Accommodation, Expenses: Stryker    

Today I want to take a look at the Basic Reproduction Number, or R0 (r-naught). We saw this term become more commonplace in the news and other talk during the COVID-19 pandemic. What is R0 and what does it mean? How do public health officials come up with this number? What are the limitations? And how is it used in everyday public health? Joining me to offer some clarity on R0 is Chandana Bala. Chandy is a science writer for Gideon Informatics. Watch the video at Outbreak News TV

基本資訊請見 麻疹疫苗效期迷思？MMR疫苗接種建議 自費MMR疫苗接種院所 https://linshibi.com/?p=21628 我對於新聞最近不斷的強調麻疹可以1傳18人這件事有點在意。我認為這樣寫過於簡化。來吧，讓我們再上一次R0值的課（我想多半人都忘光了吧）。 "麻疹疫苗覆蓋率九成五，才有群體免疫力。" 這個到達群體免疫力的門檻英文稱為HITs（herd immunity threshold），和這個傳染病的R0值（基本傳染數）有關。R0值指的是在“沒有外力介入，同時所有人都沒有免疫力的情況下”，一個感染到某種傳染病的人，會把疾病傳染給其他多少個人的平均數。 公式：HITs=1-1/R0 wiki百科上幫大家算好了 麻疹R0 12~18，算出是92~95% 流感R0 1.5~1.8，算出是33~44% 04b孔醫師解讀： 1.可空氣傳染的麻疹病毒R0值超高，一個人可以傳給12~18人，疫苗接種率加上有得過的人需要至少達到92-95%以上的高門檻才能有效防治。這可以解釋這麼多年來日本為何一直無法完全根除麻疹，但台灣可以控制的不錯。 2.麻疹疫苗早年在日本施打有出過副作用，讓很多人不敢施打的事件，造成他們一直有一個世代的人是缺口。 3.但請注意，在此刻的台灣，麻疹不太可能平均傳這麼多人，因為我們疫苗施打率超高，顯然不是所有人都沒有免疫力的狀態，動不動就會遇到有防護力的人可以擋住他，讓他傳不下去。 4.另外一個要注意的變數是疫苗的有效性（effectiveness）。上述的公式是假設打疫苗就有100%防感染的保護力，但如果只能部分保護，那需要施打的人數就需要更多。麻疹疫苗非常有效且經過多年的驗證，病毒不會一直突變，自然感染後理論上就是終身免疫，打疫苗也可以維持很長久的效果。流感疫苗每年要猜病毒株，沒完全猜對的那年有效性就會較低。新冠後期我們已經不會談群體免疫這件事了，因為疫苗防止Omicron感染的效果有限且短暫，主要是防重症。 延伸閱讀： 日本流感進入大流行期 要打流感疫苗嗎？可以和新冠疫苗一起打嗎？左流右新？ https://linshibi.com/?p=48579 日本蘋果病大流行 東京還能去嗎？孕婦 慢性貧血 免疫功能不全者請注意 https://linshibi.com/?p=48455 旅平險海外突發疾病 請注意有無給付法定傳染病 美商安達 臺灣產物保險 旺旺友聯 南山人壽 https://linshibi.com/?p=48622

In a two-part discussion, the hosts analyze the movie Contagion from their expert perspectives, focusing on the film's portrayal of epidemiology and genomics. They note that the movie compresses timelines for dramatic effect, speeding up the virus's spread and the response to it, and that decisions about managing a crisis are based on societal values, not just science. In part one, the hosts discuss the movie's depiction of the R0 value. They note that while this explanation is useful for the audience, it is unlikely that an epidemiologist would need to explain this concept to other epidemiologists. The group notes that the MEV1 virus is modeled on the real-life Nipah virus and comment on a scene where the genome of the virus is described as being 15 to 19 kilobases in length with 6 to 10 genes. They also discuss the movie's depiction of virus isolation and the unrealistic speed with which the initial assessment of the virus occurs. The podcasters touch upon the BSL4 lab and how the film depicts how the scientists behave. They also discuss the character of Matt Damon, who is exposed to the virus but does not get sick, and is an example of an asymptomatic carrier. In part two, the bioinformaticians examine the "genome dashboard" scene, noting the software's informative interface, which includes an alignment panel, protein structure, and a recombination map. They also discuss a scene where a phylogenetic tree is used to determine a change in the R0 value. They find this unrealistic because the tree is just a picture that doesn't accurately represent how a virus spreads. The group discusses how the bioinformatician is depicted in the film as moving in and out of the lab, which may have been realistic in 2011 but is less so in the present day. They discuss how the CDC is portrayed in the film, noting scenes that were filmed at the actual CDC, as well as their experiences at the CDC. The podcasters note the movie is very US-centric and that many international partners would be involved in solving a global pandemic.

In der heutigen Folge, die ganz unbeabsichtigt eine Weihnachtsfolge geworden ist (entschuldigt an dieser Stelle die Verspätung, ich werde morgen sehr müde meine Geschenke auspacken :') ) wollen wir uns mit dem ganz umbesinnlichen Thema des internationalen Organhandels auseinandersetzen. Bleibt sicher

In a two-part discussion, the hosts analyze the movie Contagion from their expert perspectives, focusing on the film's portrayal of epidemiology and genomics. They note that the movie compresses timelines for dramatic effect, speeding up the virus's spread and the response to it, and that decisions about managing a crisis are based on societal values, not just science. In part one, the hosts discuss the movie's depiction of the R0 value. They note that while this explanation is useful for the audience, it is unlikely that an epidemiologist would need to explain this concept to other epidemiologists. The group notes that the MEV1 virus is modeled on the real-life Nipah virus and comment on a scene where the genome of the virus is described as being 15 to 19 kilobases in length with 6 to 10 genes. They also discuss the movie's depiction of virus isolation and the unrealistic speed with which the initial assessment of the virus occurs. The podcasters touch upon the BSL4 lab and how the film depicts how the scientists behave. They also discuss the character of Matt Damon, who is exposed to the virus but does not get sick, and is an example of an asymptomatic carrier. In part two, the bioinformaticians examine the "genome dashboard" scene, noting the software's informative interface, which includes an alignment panel, protein structure, and a recombination map. They also discuss a scene where a phylogenetic tree is used to determine a change in the R0 value. They find this unrealistic because the tree is just a picture that doesn't accurately represent how a virus spreads. The group discusses how the bioinformatician is depicted in the film as moving in and out of the lab, which may have been realistic in 2011 but is less so in the present day. They discuss how the CDC is portrayed in the film, noting scenes that were filmed at the actual CDC, as well as their experiences at the CDC. The podcasters note the movie is very US-centric and that many international partners would be involved in solving a global pandemic.

Send us a Text Message.In this episode, we celebrate the 100th edition of the Digital Pathology Podcast!Thank you so much for being part of this journey!You are my Digital Pathology Trailblazers and I prepared a Digital Pathology Trailblazer manifesto for us!This is the 9th edition of DigiPath Digest, and we are attracting more and more people to this series.I am also working on a new YouTube digital pathology course and am offering the first 100 enrollments for free in exchange for feedback. During today's episode, we cover several papers including research on AI for predicting post-operative liver metastasis, validation of AI-based breast cancer risk stratification models, AI applications in clinical microbiology, advances in parasitology diagnostics, AI for retinal assessment, and AI models for detecting microsatellite instability in colorectal cancer. We also unveil a Digital Pathology Trailblazer manifesto emphasizing the ethos and dedication of the community. Join us to stay current with literature, advancements, and insights from the fascinating world of digital pathology.00:00 Introduction and Announcements00:25 Live Podcast Proposal01:40 Welcome and Audience Interaction03:05 Updates and Apologies06:11 YouTube Course Announcement07:23 Technical Difficulties and Solutions10:00 Digital Pathology Club and Vendor Sessions11:28 First Research Paper Discussion17:38 Second Research Paper Discussion20:07 ER Positive and HER2 Negative Patient Subgroup Analysis20:59 Independent Prognostic Value of StratiPath Breast Solution21:59 Challenges and Benefits of Image-Based Stratification22:58 Technical Difficulties and Live Stream Interaction24:22 Introduction to Paper Number Three: AI in Clinical Microbiology28:07 AI in Parasitology Screening and Diagnosis29:30 Physics-Informed AI for Retinal Assessment33:08 AI for Microsatellite Instability Detection in Colorectal Cancer36:42 YouTube Course Announcement and Digital Pathology Trailblazer Manifesto42:25 Celebrating the 100th Episode of the Digital Pathology PodcastTHE ABSTRACTS WE COVERED TODAY

Dr. Shaalan Beg highlights practice-changing studies in GI cancers featured at the 2024 ASCO Annual Meeting, including the ESOPEC trial in esophageal adenocarcinoma and durable responses to PD-1 blockade alone in mismatch repair-deficient locally advanced rectal cancer. TRANSCRIPT Geraldine Carroll: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Shaalan Beg, an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center. Dr. Beg will be discussing practice- changing abstracts and other key advances in GI oncology that were presented at the 2024 ASCO Annual Meeting. His full disclosures are available in the transcript of this episode.  Dr. Beg, thanks for being on the podcast today.  Dr. Shaalan Beg: Thank you for having me. Geraldine Carroll: Let's begin with LBA1, the ESOPEC trial. This was featured in the Plenary Session, and this study compared two treatment strategies for locally advanced esophageal adenocarcinoma that could be treated with surgery. The strategies include the CROSS protocol, which consisted of chemoradiotherapy before surgery, and the FLOT protocol of chemotherapy before and after surgery. Can you tell us about this practice-changing study, Dr. Beg? Dr. Shaalan Beg: Yes. According to this study, perioperative chemotherapy with FLOT was better than neoadjuvant therapy with chemoradiation and carbo-taxol for people with adenocarcinoma of the esophagus. There were 438 patients enrolled on this phase 3 study. R0 resection rates were fairly similar across both groups. The PCR rates were a little higher on the FLOT group. But when you look at the median overall survival difference, 66 months in the FLOT group versus 37 months in the CROSS group, 3-year survival was 57% versus 50% favoring FLOT therapy as well.  So a couple of caveats on this clinical trial, because the first thing to note is that the standard treatment for this disease has evolved because we now don't only give CROSS chemoradiation, we also give immunotherapy after the completion of chemoradiation for this group of patients. And in this study, since it predated that standard of care, patients did not receive immunotherapy. But having said that, the take home for me here is that chemotherapy is better than chemoradiation for this group of patients, recognizing the fact that 1) they only enrolled adenocarcinoma patients, and 2) patients with high T stage were not included. So the folks with high T stage would be those who we would expect would benefit from the radiation aspect. So my take home here is that more chemotherapy is better in the perioperative space. Radiation should be considered for individuals who need more local control. But in general, I think we're going to see us moving more towards chemotherapy-based regimens with FLOT for this group of patients. Geraldine Carroll: Great. So moving on to rectal cancer, in LBA3512, investigators reported durable, complete responses to PD-1 blockade alone in mismatch repair deficient locally advanced rectal cancer. Can you tell us more about the promising durable responses that occurred in this trial?  Dr. Shaalan Beg: On first glance, seeing that immunotherapy has good activity in patients with mismatched repair deficient rectal cancer isn't really headline breaking news anymore. We've known about this activity for this group of patients for many years. Earlier at ASCO, the investigators presented early results of this compound for people receiving six months of dostarlimab therapy for people with mismatched repair deficient, locally advanced rectal cancer, and showed that they had a very high complete response rate. At that time, it generated a lot of interest and there was a lot of curiosity on whether these outcomes will be sustained. We don't know other characteristics of their biologic status and whether this was some sort of reflection of the patients who are selected or not.   So here in this presentation at ASCO 2024, they did come back to present follow-up data for people with mismatch repair deficient colorectal cancer, having received 6 months of dostarlimab. Forty-seven patients had been enrolled, and the 41 patients who had achieved a clinical complete response continued to have disease control with no distant metastases. So that's very compelling information. There were no additional serious adverse events greater than grade 2 that they saw, and they did follow circulating tumor DNA, and those did normalize even before they had their colonoscopy to examine their tumors.  So, again, we're continuing to see very encouraging data of immunotherapy, and the response rate with dostarlimab seems to be very interesting for this disease, and it will be interesting to see how this pans out in larger studies and how this translates into the use of dostarlimab across other diseases where other checkpoint inhibitors are currently being used. Geraldine Carroll: Absolutely. So, moving on to LBA3501. The COLLISION trial looked at surgery versus thermal ablation for small cell colorectal liver metastases. This was an international, multicenter, phase 3, randomized, controlled trial. How will this study change clinical practice?  Dr. Shaalan Beg: Kudos to the investigators here. They looked to understand the difference in outcome in treating people with colorectal cancer with liver only metastases. These clinical trials are extremely difficult to design. They're very difficult to enroll on because of the multidisciplinary aspect of the interventions and patient and provider biases as well. So on this clinical trial, the investigators enrolled people with resectable colorectal cancer, liver metastases so they did not have any metastases outside the liver. Patients were required to have 10 or less known metastases that were less than 3 cm in size. There were other allowances for larger tumors as well. And after an expert panel review, patients were randomized to either resection or ablation. It was up to the physicians whether they performed these laparoscopically or openly or percutaneously, depending on the biology of the patient and the anatomical presentation.  There was a predefined stopping rule at the half-time for this clinical trial, which showed a benefit in the experimental arm of ablation compared to standard of care. The overall survival was not compromised. Progression-free survival was not compromised with local therapy. But there were differences in morbidity and mortality, as we would expect, one being a surgical procedure and the other being ablation, where, according to this study, of the 140 or so patients who received either treatment, 2.1% of people who underwent resection died within 90 days of surgery. The AE rate was 56% in the resection sample compared to 19% in ablation, and the 90-day mortality for ablation was 0.7%. So less morbidity, improved mortality, reduced adverse events with ablation versus surgical resection without compromising local control and overall survival.   And I think for practice here in the United States, this does provide very interesting data for us to take back to the clinic for lesions that are relatively small and could generally be addressed by both surgery and ablation. Historically, there are various non biologic factors that could go into deciding whether someone should have surgery or ablation, and it could be based on who the physician is, who's seeing the patient, what the practice patterns in a specific organization are, and where their expertise lie. But here we're seeing that ablation for the small lesions is a very effective tool with very good local control rates, and again, in this selected group of patients with liver only metastases. And I think it is going to make tumor board discussions very interesting with data backing ablation for these lesions. Geraldine Carroll: Well, let's move onto the MOUNTAINER study. This study created some buzz in the colorectal cancer space. That's Abstract 3509. Can you tell us about the final results of this phase 2 study of tucatinib and trastuzumab in HER2-positive metastatic CRC? What are your thoughts on this treatment option, which seems to be well tolerated? Dr. Shaalan Beg: So, HER2 overexpression or amplification occurs in about 3 to 5% of patients with metastatic colorectal cancer and up to 10% of people who have a RAS/RAF wild type disease. On the previous episodes of the podcast we have covered precision targeted therapy in colorectal cancer, focusing on c-MET, focusing on BRAF, and here we have updated results targeting HER2 for colorectal cancer. And the results of the MOUNTAINEER study have been out for a while. This is a phase 2 study looking at combining tucatinib which is a highly selective HER2 directed TKI with trastuzumab, the monoclonal antibody for HER2 targeting. And what they found on this study is the confirmed overall response rate was 38%. Duration of response was 12 months, overall survival was 24 months and these are the results that have been already released and now we have an additional 16 months of follow up and these results continue to hold on. PFS and overall survival gains were held, which makes it a very interesting option for people with colorectal cancer. You mentioned the tolerability aspect and side effects. I think it's important to know the spectrum of side effects for this disease may be a little different than other TKIs. There's hypertension, but there's also the risk of diarrhea, back pain and pyrexia, with the most common grade 3 treatment related adverse event was an increase in AST level seen in 10% of people of grade 3 and above.  So where does that really leave us? There is a confirmatory randomized first-line trial of tucatinib and trastuzumab in the first line setting, which is currently ongoing. So we'll stay tuned to see where that leads us. And with the HER2 space right now for colorectal cancer with the development of antibody drug conjugates, we may have more than one option for this group of patients once those trials read out. Geraldine Carroll: Excellent. Well, moving on to LBA4008, that's the CheckMate-9DW trial. This trial reported first results looking at nivolumab plus ipilimumab versus sorafenib or lenvatinib as first-line treatment for advanced hepatocellular carcinoma. Can you tell us about this trial? Will there be a potential new standard of care in advanced HCC? Dr. Shaalan Beg: When we think about patients with advanced HCC, the only treatment option that they had for about a decade and a half were just oral track tyrosine kinase inhibitors that had modest to moderate clinical activity. Since then, we've seen that combination therapy is better than TKI therapy, and the combination therapy has taken two different forms. One is a combination of checkpoint inhibitor and antiangiogenic therapy, such as in the combination of atezolizumab and bevacizumab. The other is a combination of dual checkpoint inhibitor therapy. Here we are talking about the results of nivolumab and ipilimumab. Previously, we've talked about the combination of durva and tremi for the treatment of patients with HCC.   So in this study, nivo was given for the first 4 cycles, nivo and ipi were given together, nivo 1 mg per kg, and IPI 3 mgs per kg every 3 weeks for 4 cycles. And then the CTLA-4 inhibitor ipilimumab was stopped. And this was followed by monotherapy nivolumab every 4 weeks until disease progression or up to 2 years. And it was compared to dealers' choice, lenvatinib or sorafenib. The median overall survival of nivo-ipi was 23 months versus 20 months with lenvatinib-sorafenib. The 24-month overall survival was 49% with ipi-nivo versus 39%. And the overall response rate with nivo-ipi was 36% compared to 13%. So again, significantly improved clinical activity.   And when we talk about immunotherapy combinations, the question that comes to mind is how well is this tolerated? There's a lot of work and iteration that took place in figuring out what the right combination strategy of ipi and nivo should be, because some of the earlier studies did demonstrate fairly high adverse events in this group of patients. So on this study, we saw that grade 3 or 4 treatment related adverse events were seen in 41% of people who received nivo-ipi and 42% if they received lenvatinib or sorafenib. So, certainly a high proportion of treatment related adverse events, but probably also reflective of the disease population, which is being tested, because those numbers were fairly similar in the control arm as well.  So we've known that nivo-ipi is active in HCC. There is an approval in the second-line space, so it remains to be seen if this data helps propel nivo-ipi to the first-line space so we end up with another combination regimen for patients with advanced hepatocellular carcinoma.  Geraldine Carroll: Excellent. Well, before we wrap up the podcast, I'd like to ask you about LBA3511. In this study, investigators looked at total neoadjuvant treatment with long course radiotherapy versus concurrent chemoradiotherapy in local advanced rectal cancer with high risk factors. So this was a multicenter, randomized, open label, phase 3 trial. What are your key takeaways here? Dr. Shaalan Beg: Key takeaway here is that total neoadjuvant therapy was better than the conventional chemoradiation followed by chemo. So this clinical trial enrolled people with T4a/b resectable disease with clinical N2 stage, and they were randomized, as you mentioned, to receiving chemoradiation with radiation capecitabine followed by surgery, and then CAPOX or capecitabine versus chemo, short-course radiation, and additional chemotherapy followed by surgery.  And when we compare both arms, the total neoadjuvant therapy led to improved disease-free survival, improved PCR rates compared to standard concurrent neoadjuvant chemo radiotherapy in this group of patients. The two arms were fairly well-balanced. The number of T4 lesions was a little higher in the chemoradiation group. There were 49% in the chemo radiation group versus 46% had clinically T4 disease, but the nodal status was fairly similar. We should keep in mind that the other baseline characteristics were fairly well balanced.  And when we look at the outcomes, the disease-free survival probability at 36 months was 76% in the total neoadjuvant group compared to 67% with chemoradiation. And the metastasis free survival in total neoadjuvant therapy was 81% versus 73%. So a fairly compelling difference between the two arms, which did translate into an overall survival of 89% versus 88% in the two groups. So definitely higher disease-free survival and metastasis free survival, no difference on the overall survival with these groups. And it talks about the importance of intensifying chemotherapy upfront in this group of patients who can have a fairly high burden of disease and may struggle with receiving chemotherapy postoperatively. Geraldine Carroll: Excellent. Well, thank you, Dr. Beg, for sharing your fantastic insights with us on these key studies from the 2024 ASCO Annual Meeting. It's certainly a very exciting time in GI oncology. Dr. Shaalan Beg: Absolutely. Thank you for bringing these studies out, because I think a lot of these are practice-changing and can start impacting the clinical care that we're giving our patients right now. Geraldine Carroll: Thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: 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. 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.   Find out more about today's speakers: Dr. Shaalan Beg   @ShaalanBeg     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures:  Dr. Shaalan Beg:   Consulting or Advisory Role: Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen   Speakers' Bureau: Sirtex   Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics   Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune  

Doctors Vamsi Velcheti, Sandip Patel, and Michael Zervos discuss recent updates on the management of early-stage non-small cell lung cancer (NSCLC), including the optimization of neoadjuvant and adjuvant treatment options for patients and the role of surgery in the era of targeted therapy and immuno-oncology in lung cancer. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I am a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. On today's episode, we'll be discussing recent updates on the management of early-stage non-small cell lung cancer (NSCLC), including the optimization of neoadjuvant and adjuvant treatment options for our patients, and the evolving role of surgery in the era of targeted therapy and immuno-oncology in lung cancer.  Today, I am delighted to be joined by two renowned experts in this space, Dr. Sandip Patel and Dr. Michael Zervos. Dr. Patel is a professor of medicine and a medical oncologist specializing in lung cancer at UCSD. Dr. Mike Zervos is the clinical chief of the Division of Robotic Thoracic Surgery and Director of General Thoracic Surgery at NYU Langone. Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available at asco.org/DNpod. Dr. Patel and Dr. Zervos, it's a great honor to have you on the podcast today. Welcome aboard. Dr. Sandip Patel: Great to be joining you.  Dr. Vamsi Velcheti:  Let's get started with Dr. Patel. As you know, over the last decade we've had dramatic advances in systemic therapy options for patients with metastatic non-small cell lung cancer, in both the realms of targeted therapy and immunotherapy. These have significantly improved outcomes for our patients with metastatic lung cancer. What's exciting is that more recently, we've seen the incorporation of these agents, both targeted therapies and immunotherapies, in early-stage non-small cell lung cancer. Dr. Patel, can you tell our listeners about these exciting recent advances and why do you think it's so important to incorporate these personalized systemic therapy options for our early-stage patients? Dr. Sandip Patel: I think it's a great point and a great question. And so, I think one thing to understand is that non-small cell lung cancer is actually multiple diseases. We give it one name based on how it looks under the microscope, but the vast majority of our advances to improve outcomes for patients have come from our ability to understand specific subgroups.  Many of our therapies have had activity in the advanced setting. We have our patients with metastatic or more widespread disease, which naturally led to the thought that could we utilize these therapies in earlier stage disease and potentially increase the rate of cure for many of our patients, lung cancer being the most common cancer killer worldwide. And so to your point, trying to understand how to best treat a patient really involves personalized medicine, typically driven by understanding the genomic profile of their tumor and two of the genes that have graduated from being tested for in the metastatic setting and now in the localized setting are EGFR and ALK. And these in particular are mutations that confer sensitivity to small molecule inhibitors, EGFR with osimertinib, ALK in the localized setting with alectinib based on the data that we've seen.  And so, one of the areas that's been particularly exciting is our ability to maximize a patient's chance for durable remissions by integrating these therapies after surgery, after chemotherapy when appropriate, and continuing generally for a finite amount of time, two to three years depending on the agent in the study we're discussing for these patients. Additionally, immunotherapy, which has revolutionized our treatment of patients with metastatic disease, may be particularly well-suited for the localized setting of non-small cell lung cancer as well. Dr. Vamsi Velcheti: Excellent points, Sandip. You're absolutely right, in the metastatic setting, we've all come to accept molecular testing, sequencing, and biomarker profiling as a standard, but unfortunately, that hasn't quite yet percolated into the early-stage setting. Can you talk about some of the challenges that we face as we have these therapeutic options available now for more early-stage patients? Dr. Sandip Patel: So, I think there are 3 flavors of localized therapy in non-small cell lung cancer. One is the advanced, unresectable stage 3, for which the approach is often concurrent chemo-radiation followed by some form of consolidated therapy. We're about to hear the results of LAURA, which is the study looking at EGFR-mutated non-small cell lung cancer.  For other patients, historically, the treatment has been durvalumab, an anti-PD-L1 directed immunotherapy. The other two are operative treatment of localized cancer: adjuvant treatment after surgery, or neoadjuvant or perioperative, in which chemoimmunotherapy begins before surgery. And testing depends on the settings. For the stage 3 patient who's likely getting concurrent chemo-radiation, they may have a very small amount of tissue, and so often these are done by pulmonary EBUS biopsies and that's how we pathologically confirm that advanced stage 3B. There may not be a lot of tissue available for molecular testing. In fact, if you look at the PACIFIC analysis, just looking at PD-L1, which is just an IHC off a single slide, a third of patients weren't able to even get a PD-L1, let alone a genomic result. And so, I think that's one of the areas of LAURA that's going to be particularly interesting to see as we try to implement it into our practice after seeing the full data.  I think in the adjuvant setting, we're lucky because our surgeons, Dr. Mike Zervos here, will get us a large amount of tissue in the surgical resection specimen, so we tend to get enough tissue to do genomics while they're under chemotherapy, there tends to be time to wait for their genomic result. Where this really gets complicated is in the neoadjuvant or perioperative setting, where time is everything.  The most important thing we can do for a patient in the localized space is get them to the operating room, get them started on radiation, their curative local modality, and that's where we have a time pressure but also a sample pressure because that is a diagnostic biopsy. It's a very small piece of tissue. Initially, there are multiple stains that have to be done to identify this lung cancer as opposed to another tumor. And so that's an area that I think we're going to need additional approaches given that cell-free DNA tends to have lower yield in lower stage disease in giving us a result. Dr. Vamsi Velcheti: Great points, Sandip. How do you deal with this issue in San Diego? The challenge is now we have a lot of trials, we'll talk about those neoadjuvant immunotherapy trials, but we know that immunotherapy may not be as effective in all patients, especially those with EGFR or ALK or some of these non-smoker, oncogene-driven tumors. So, we don't want to be giving patients treatments that may not necessarily be effective in the neoadjuvant space, especially when there is a time crunch, and we want to get them to surgery and all the complications that come with giving them targeted therapy post-IO with potential risk for adverse events. Dr. Sandip Patel: Absolutely. It is a great point. And so, the multidisciplinary team approach is key, and having a close relationship with the interventional pulmonary oncs, interventional radiology surgery, and radiation oncology to ensure that we get the best treatment for our patients. With the molecularly guided therapies, they are currently more on the adjuvant setting in terms of actually treating. But as you mentioned, when we're making a decision around neoadjuvant or perioperative chemo IO, it's actually the absence of EGFR now that we're looking for because our intervention at the current time is to give chemoimmunotherapy. Going back to the future, we used to use single gene EGFR within 24 hours, which was insufficient for a metastatic panel, but it often required five slides of tissue input. ALK can be done by IHC, and so some of these ‘oldie but goodie' pathologic techniques, and that pathologists, if I haven't emphasized, understanding what we're trying to do at a different context is so key because they are the ones who really hold the result. In the neoadjuvant and perioperative setting, which many of us favor, especially for stage 3A and stage 2B disease, understanding how we can get that result so that we can get the patient to the operating room in an expeditious way is so important. There is a time pressure that we always had in the metastatic setting, but I think we feel much more acutely in the neoadjuvant and perioperative setting in my opinion. Dr. Vamsi Velcheti: Fascinating insights, Dr. Patel.  Turning to Dr. Zervos, from a surgical perspective, there has been an evolution in terms of minimally invasive techniques, robotic approaches, and enhanced recovery protocols, significantly improving outcomes in our patients post-surgery. How do you see the role of surgery evolving, especially with the increasing complexity and efficacy of these systemic therapies? How do you envision the role of surgery in managing these early-stage patients, and what are the key considerations for surgeons in this new era? Dr. Michael Zervos: Thanks, Vamsi. Thanks, Sandip. Thank you for having me on the podcast. Obviously, it's an honor to be a part of such a high-level discussion. I have to say, from a surgeon's perspective, we often listen to you guys talk and realize that there's been a lot of change in this landscape. And I think the thing that I've seen is that the paradigm here has also changed. If we were having this discussion 10 years ago, a lot of the patients that I am operating on now, I would not be operating on. It really has been amazing. And I think the thing that stands out to me the most is how all of this has changed with neoadjuvant chemotherapy checkpoint inhibition. I think, for us as surgeons, that's really been the key. Whether it's CheckMate 816 or whatever you're following, like PACIFIC, the data supports this. And I think what we're seeing is that we're able to do the surgery, we're able to do it safely, and I think that the resectability rates are definitely high up there in the 90% range. And what we're seeing is pretty significant pathologic responses, which I think is really amazing to me.  We're also seeing that this has now shifted over to the oligometastatic realm, and a lot of those patients are also being treated similarly and then getting surgery, which is something that we would not have even thought of ever. When you look at the trials, I think a lot of the surgery, up to this point, has been done more traditionally. There's a specific reason why that happens, specifically, more through thoracotomy, less with VATS, and less with robotic. Sandip, I think you guys have a pretty robust robotic program at UCSD, so I'm sure you're pretty used to seeing that.   As you guys have become so much more sophisticated with the treatments, we have also had to modify what we do operatively to be able to step up to the plate and accept that challenge. But what we are seeing is yes, these treatments work, but the surgeries are slightly more complicated. And when I say slightly, I'm minimizing that a little bit.  And what's complicated about it is that the treatment effect is that the chemo-immune check inhibition actually has a significant response to the tumor antigen, which is the tumor. So it's going to necrose it, it's going to fibrose it, and wherever there is a tumor, that response on the surgical baseline level is going to be significant. In other words, there are going to be lymph nodes that are stuck to the pulmonary artery, lymph nodes that are stuck to the airway, and we've had to modify our approaches to be able to address that.   Now, fortunately, we've been able to innovate and use the existing technology to our advantage. Personally, I think robotics is the way we have progressed with all this, and we are doing these surgeries robotically, mainly because I think it is allowing us, not only to visualize things better, but to have sort of a better understanding of what we're looking at. And for that matter, we are able to do a better lymph node dissection, which is usually the key with a lot of these more complicated surgeries, and then really venturing out into more complicated things, like controlling the pulmonary artery. How do we address all this without having significant complications or injuries during the surgery? Getting these patients through after they've successfully completed their neoadjuvant treatment, getting them to surgery, doing the surgery successfully, and hopefully, with minimal to no morbidity, because at the end, they may be going on to further adjuvant treatment. All of these things I think are super important. I think although it has changed the landscape of how we think of things, it has made it slightly more complicated, but we are up for the challenge. I am definitely excited about all of this. Dr. Vamsi Velcheti: For some reason, like medical oncologists, we only get fixated on the drugs and how much better we're doing, but we don't really talk much about the advances in surgery and the advances in terms of outcomes, like post-op mortality has gone down significantly, especially in larger tertiary care centers. So, our way of thinking, traditionally, the whole intergroup trials, the whole paradigm of pneumonectomies being bad and bad outcomes overall, I think we can't judge and decide on current treatment standards based on surgical standards from decades ago. And I think that's really important to recognize.  Dr. Michael Zervos: All of this stuff has really changed over the past 10 years, and I think technology has helped us evolve over time. And as the science has evolved for you with the clinical trials, the technology has evolved for us to be able to compensate for that and to be able to deal with that. The data is real for this. Personally, what I'm seeing is that the data is better for this than it was for the old intergroup trials. We're able to do the surgery in a better, more efficient, and safer way. The majority of these surgeries for this are not going to be pneumonectomies, they are going to be mostly lobectomies. I think that makes sense. I think for the surgeons who might be listening, it doesn't really matter how you're actually doing these operations. I think if you don't have a very extensive minimally invasive or robotic experience, doing the surgery as open is fine, as long as you're doing the surgery safely and doing it to the standard that you might expect with complete lymph node clearance, mediastinal lymph node clearance, and intrapulmonary lymph node clearance. Really, I think that's where we have to sort of drive home the point, really less about the actual approach, even though our bias is to do it robotically because we feel it's less morbidity for the patient. The patients will recover faster from the treatment and then be able to go on to the next phase treatments. Dr. Vamsi Velcheti: In some of the pre-operative trials, the neoadjuvant trials, there have been some concerns raised about 20% of patients not being able to make it to surgery after induction chemo immunotherapy. Can you comment on that, and why do you think that is the case, Sandip?  Dr. Sandip Patel: Well, I think there are multiple reasons. If you look, about half due to progression of disease, which they might not have been great operative candidates to begin with, because they would have early progression afterwards. And some small minority in a given study, maybe 1% to 2%, it's an immune-related adverse event that's severe. So, it's something that we definitely need to think about. The flip side of that coin, only about 2 in 3 patients get adjuvant therapy, whether it be chemotherapy, immunotherapy, or targeted therapy. And so, our goal is to deliver a full multimodal package, where, of course, the local therapy is hugely important, but also many of these other molecular or immunologically guided agents have a substantial impact.  And I do think the point around neoadjuvant and perioperative is well taken. I think this is a discussion we have to have with our patients. I think, in particular, when you look at higher stage disease, like stage 3A, for example, the risk-benefit calculus of giving therapy upfront given the really phenomenal outcomes we have seen, really frankly starting with the NADIM study, CheckMate816, now moving on into studies like KEYNOTE-671, AEGEAN, it really opens your eyes in stage 3. Now, for someone who's stage 1/1b, is this a patient who's eager to get a tumor out? Is there as much of an impact when we give neoadjuvant therapy, especially if they're not going to respond and may progress from stage 1 and beyond? I think that's a reasonable concern. How to handle stage II is very heterogeneous. I think two points that kind of happen as you give neoadjuvant therapy, especially chemo-IO that I think is worth for folks to understand and this goes to Mike's earlier point, that is this concept if they do get a scan during your neoadjuvant chemo immunotherapy, there is a chance of that nodal flare, where the lymph nodes actually look worse and look like their disease is progressing. Their primary tumor may be smaller or maybe the same. But when we actually go to the OR, those lymph nodes are chock-full of immune cells. There's actually no cancer in those lymph nodes. And so that's a bit of a red herring to watch out for.   And so, I think as we're learning together how to deliver these therapies, because the curative-intent modality is, in my opinion, a local modality. It's what Mike does in the OR, my colleagues here do in the OR. My goal is to maximize the chance of that or really maximize the long-term cure rates. And we know, even as long as the surgery can go, if only 2 or 3 patients are going to get adjuvant therapy then 1 in 10, of which half of those or 1 in 20, are not getting the surgery and that's, of course, a big problem. It's a concern. I think better selecting towards those patients and thinking about how to make these choices is going to be hugely important as we go over. Because in a clinical trial, it's a very selective population. A real-world use of these treatments is different. I think one cautionary tale is that we don't have an approval for the use of neoadjuvant or perioperative therapy for conversion therapy, meaning, someone who's “borderline resectable.” At the time at which you meet the patient, they will be resectable at that moment. That's where our best evidence is, at the current time, for neoadjuvant or perioperative approaches.  Dr. Vamsi Velcheti:   I think the other major issue is like the optimal sequencing of immune checkpoint here. Obviously, at this point, we have multiple different trial readouts, and there are some options that patients can have just neoadjuvant without any adjuvant. Still, we have to figure out how to de-escalate post-surgery immunotherapy interventions. And I think there's a lot of work that needs to be done, and you're certainly involved in some of those exciting clinical trials. What do you do right now in your current clinical practice when you have patients who have a complete pathologic response to neoadjuvant immunotherapy? What is the discussion you have with your patients at that point? Do they need more immunotherapy, or are you ready to de-escalate?  Dr. Sandip Patel: I think MRD-based technologies, cell-free DNA technologies will hopefully help us guide this. Right now, we are flying blind along two axes. One is we don't actually know the contribution of the post-operative component for patients who get preoperative chemo-IO. And so this is actually going to be an ongoing discussion. And for a patient with a pCR, we know the outcomes are really quite good based on CheckMate816, which is a pure neoadjuvant or front-end only approach. Where I actually struggle is where patients who maybe have 50% tumor killing. If a patient has only 10% tumor killing ... the analogy I think in clinic is a traffic light, so the green light if you got a pCR, a yellow light if you have that anywhere from 20%-70% residual viable tumor, and then anything greater than that, you didn't get that much with chemo-IO and you're wondering if getting more chemo-IO, what would that actually do? It's a bit of a red light. And I'm curious, we don't have any data, but my guess would be the benefit of the post-op IO is because patients are in that kind of yellow light zone. So maybe a couple more cycles, we'll get them an even more durable response. But I am curious if we're going to start relying more on MRD-based technologies to define treatment duration. But I think it's a very complicated problem. I think folks want to balance toxicity, both medical and financial, with delivering a curative-intent therapy. And I am curious if this maybe, as we're looking at some of the data, some of the reasons around preferring a perioperative approach where you scale it back, as opposed to a neoadjuvant-only approach where there's not a clean way to add on therapy, if you think that makes sense. But it's probably the most complicated discussions we have in clinic and the discussion around a non-pCR. And frankly, even the tumor board discussions around localized non-small cell lung cancer have gone very complex, for the benefit of our patients, though we just don't have clean data to say this is the right path.   Dr. Vamsi Velcheti: I think that the need for a really true multidisciplinary approach and discussing these patients in the tumor board has never been more significant. Large academic centers, we have the luxury of having all the expertise on hand. How do we scale this approach to the broader community is a big challenge, I think, especially in early-stage patients. Of course, not everyone can travel to Dr. Zervos or you for care at a large tertiary cancer centers. So, I think there needs to be a lot of effort in terms of trying to educate community surgeons, community oncologists on managing these patients. I think it's going to be a challenge. Dr. Michael Zervos: If I could just add one thing here, and I completely agree with everything that has been said. I think the challenge is knowing beforehand. Could you predict which patients are going to have a complete response? And for that matter, say, “Okay. Well, this one has a complete response. Do we necessarily need to operate on this patient?” And that's really the big question that I add. I personally have seen some complete response, but what I'm mostly seeing is major pathologic response, not necessarily CR, but we are seeing more and more CR, I do have to say. The question is how are you going to predict that? Is looking for minimal residual disease after treatment going to be the way to do that? If you guys could speak to that, I think that is just tremendously interesting.  Dr. Vamsi Velcheti: I think as Sandip said, MRD is looking very promising, but I just want to caution that it's not ready for primetime clinical decision making yet. I am really excited about the MRD approach of selecting patients for de-escalation or escalation and surgery or no surgery. I think this is probably not quite there yet in terms of surgery or no surgery decision. Especially for patients who have early-stage cancer, we talk about curative-intent treatment here and surgery is a curative treatment, and not going to surgery is going to be a heavy lift. And I don't think we're anywhere close to that. Yet, I'm glad that we are having those discussions, but I think it may be too hard at this point based on the available technologies to kind of predict CR. We're not there.  Dr. Michael Zervos: Can I ask you guys what your thought process is for evaluating the patient? So, when you're actually thinking about, “Hey, this patient actually had a good response. I'm going to ask the surgeons to come and take a look at this.” What imaging studies are you actually using? Are you just using strictly CT or are you looking for the PET? Should we also be thinking about restaging a lot of these patients? Because obviously, one of the things that I hate as a surgeon is getting into the operating room only to find out that I have multiple nodal stations that are positive. Which really, in my opinion, that's sort of a red flag. And for me, if I have that, I'm thinking more along the lines of not completing that surgery because I'm concerned about not being able to provide an R0 resection or even having surgical staple lines within proximity of cancer, which is not going to be good. It's going to be fraught with complications.  So, a lot of the things that we as surgeons struggle with have to do with this. Personally, I like to evaluate the patients with an IV intravenous CT scan to get a better idea of the nodal involvement, proximity to major blood vessels, and potentially even a PET scan. And though I think in this day and age, a lot of the patients will get the PET beforehand, not necessarily get it approved afterwards. So that's a challenge. And then the one thing I do have to say that I definitely have found helpful is, if there's any question, doing the restaging or the re-EBUS at that point to be particularly helpful.  Dr. Sandip Patel: Yeah, I would concur that having that pathologic nodal assessment is probably one of the most important things we can do for our patients. For a patient with multinodal positive disease, the honest truth is that at our tumor board, that patient is probably going to get definitive chemoradiation followed by their immunotherapy, or potentially soon, if they have an EGFR mutation, osimertinib. For those patients who are clean in the mediastinum and then potentially have nodal flare, oftentimes what our surgeons will do as the first stage of the operation, they'll actually have the EBUS repeated during that same anesthesia session and then go straight into surgery. And so far the vast majority of those patients have proceeded to go to surgery because all we found are immune cells in those lymph nodes.  So, I think it's a great point that it's really the pathologic staging that's driving this and having a close relationship with our pathologists is key. But I think one point that I think we all could agree on is the way that we're going to find more of these patients to help and cure with these therapies is through improved utilization of low-dose CT screening in the appropriate population in primary care. And so, getting buy-in from our primary care doctors so that they can do the appropriate low-dose CT screening along with smoking cessation, and find these patients so that we can offer them these therapies, I think is something that we really, as a community, need to advocate on. Because a lot of what we do with next-generation therapies, at least on the medical oncology side, is kind of preaching to the choir. But getting the buy-in so we can find more of these cases at stage 1, 2 or 3, as opposed to stage 4, I think, is one of the ways we can really make a positive impact for patients. Dr. Vamsi Velcheti: I just want to go back to Mike's point about the nodal, especially for those with nodal multistation disease. In my opinion, those anatomic unresectability is a moving target, especially with evolving, improving systemic therapy options. The utilization for chemo radiation has actually gone down. I think that's a different clinical subgroup that we need to kind of think differently in terms of how we do the next iteration or generation of clinical trials, are they really benefiting from chemo-IO induction? And maybe we can get a subset of those patients in surgery. I personally think surgery is probably a more optimal, higher yield to potentially cure these patients versus chemo radiation. But I think how we identify those patients is a big challenge. And maybe we should do a sequential approach induction chemo-IO with the intent to kind of restage them for surgery. And if they don't, they go to chemo consolidation radiation, I guess. So, I think we need to rethink our approach to those anatomically unresectable stage 3s. But I think it's fascinating that we're having these discussions. You know, we've come to accept chemo radiation as a gold standard, but now we're kind of challenging those assumptions, and I think that means we're really doing well in terms of systemic therapy options for our patients to drive increased cures for these patients. Dr. Michael Zervos: I think from my perspective as a surgeon, if I'm looking at a CT scan and trying to evaluate whether a patient is resectable or not, one of the things that I'm looking for is the extent of the tumor, proximity to mediastinal invasion, lymph nodes size. But if that particular patient is resectable upfront, then usually, that patient that receives induction chemo checkpoint inhibition is going to be resectable afterwards. The ones that are harder are the ones that are borderline resectable upfront or not resectable. And then you're trying to figure out on the back end whether you can actually do the surgery.  Fortunately, we're not really taking many patients to the operating room under those circumstances to find that they're not resectable. Having said that, I did have one of those cases recently where I got in there and there were multiple lymph node stations that were positive. And I have to say that the CT really underestimated the extent of disease that I saw in the operating room. So, there are some challenges surrounding all of these things. Dr. Sandip Patel: Absolutely. And I think for those patients, if upfront identification by EBUS showed multi nodal involvement, we've had excellent outcomes by working with radiation oncologists using modern radiotherapy techniques, with concurrent chemo radiation, followed by their immunotherapy, more targeted therapy, at least it looks like soon. I think finding the right path for the patient is so key, and I think getting that mediastinal pathologic assessment, as opposed to just guessing based on what the PET CT looks like, is so important. If you look at some of the series, 8% to 10% of patients will get a false-positive PET on their mediastinal lymph nodes due to coccidioidomycosis or sarcoidosis or various other things. And the flip side is there's a false-negative rate as well. I think Mike summarized that as well, so I think imaging is helpful, but for me, imaging is really just pointing the target at where we need to get pathologic sampling, most commonly by EBUS. And getting our interventional pulmonary colleagues to help us do that, I think is so important because we have really nice therapeutic options, whether it's curative-intent surgery, curative-intent chemo radiation, where we as medical oncologists can really contribute to that curative-intent local therapy, in my opinion.  Dr. Vamsi Velcheti: Thank you so much Sandip and Mike, it's been an amazing and insightful discussion, with a really dynamic interplay between systemic therapy and surgical innovations. These are really exciting times for our patients and for us. Thank you so much for sharing your expertise and insights with us today on the ASCO Daily News Podcast.   I want to also thank our listeners today for your time. If you value the insights that you hear today, please take a moment to rate, review, and subscribe to the podcast wherever you get your podcasts. Thank you so much. [FH1]   Dr. Sandip Patel: Thank you. Dr. Michael Zervos: Thank you.   Disclaimer: 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.   Follow today's speakers: Dr. Vamsidhar Velcheti @VamsiVelcheti Dr. Sandip Patel @PatelOncology Dr. Michael Zervos   Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Facebook ASCO on LinkedIn   Disclosures:  Dr. Vamsidhar Velcheti: Honoraria: ITeos Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Sandip Patel: Consulting or Advisory Role: Lilly, Novartis, Bristol-Myers Squibb, AstraZeneca/MedImmune, Nektar, Compugen, Illumina, Amgen, Certis, Eli Lilly, Roche/Genentech, Merck, Pfizer, Tempus, Iovance Biotherapeutics. Speakers' Bureau: Merck, Boehringer Ingelheim Research Funding (Inst.):Rubius, Bristol-Myers Squibb, Pfizer, Roche/Genentech, Amgen AstraZenece/MedImmune, Fate, Merck, Iovance, Takeda   Dr. Michael Zervos: No relationships to disclose

Featuring perspectives from Dr Bradley J Monk, including the following topics: Introduction (0:00) Case: A woman (gBRCA1) in her late 40s, 5 months after surgery and adjuvant paclitaxel/carboplatin for Stage II ovarian cancer, now with a single umbilical metastasis — Kellie E Schneider, MD (9:47) Case: A woman (gBRCA2) in her late 60s with Stage IIIC ovarian cancer after surgery and chemotherapy who has received primary olaparib maintenance for 3 years develops acute myeloid leukemia — Swati Vishwanathan, MD (17:21) Case: A woman in her early 60s presents with Stage IV ovarian cancer (BRCA wild-type, homologous recombination deficiency-positive) — Neil Morganstein, MD (22:53) Case: A woman (gBRCA2) in her late 40s with Stage IIIC primary peritoneal cancer receives carboplatin/paclitaxel after R0 debulking surgery; genetic testing results pending — Karim ElSahwi, MD (27:30) Case: A woman in her early 60s with PMH of breast cancer and with limited recurrence of ovarian cancer (BRCA wild-type, homologous recombination deficiency-positive) after chemotherapy and maintenance niraparib refuses to receive chemotherapy — Gigi Chen, MD (33:06) Case: A woman (gBRCA2) in her mid 60s with high-grade serous carcinoma of the fallopian tube undergoes surgery and chemotherapy/bevacizumab but cannot tolerate a PARP inhibitor and refuses to take another agent — Thomas P Morrissey, MD (40:51) Case: A woman (homologous repair deficiency-positive) in her mid 70s with ovarian cancer and disease progression on EPIK-O trial of alpelisib with olaparib tests positive for folate receptor alpha and receives mirvetuximab soravtansine — Lyndsay J Willmott, MD (45:46) Journal Club with Dr Monk (54:13) CME information and select publications

Drs. Shaalan Beg and Rachna Shroff discuss key abstracts on GI cancers that were featured at the 2024 ASCO Gastrointestinal Cancers Symposium, including SKYSCRAPER-08, EMERALD-1, and NEST-1 in esophageal squamous cell carcinoma, hepatocellular carcinoma, and colorectal cancer, respectively. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. Today, we'll be discussing key abstracts and other exciting highlights from the 2024 ASCO Gastrointestinal Cancers Symposium. Joining me to discuss some key takeaways from the meeting is the chair of this year's Symposium, Dr. Rachna Shroff. Dr. Shroff is the division chief of Hematology Oncology and chief of GI Medical Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for clinical and translational research at the University of Arizona College of Medicine – Tucson. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Dr. Shroff, welcome back to the ASCO Daily News Podcast, and congratulations on a great Symposium. The scientific advances and innovative, multidisciplinary approaches that were featured throughout the meeting were really inspiring and reflect the incredible strides we're making in GI cancer research. Dr. Rachna Shroff: Thank you so much for having me back. I am delighted to be here.  Dr. Shaalan Beg: Dr. Shroff, the theme of this year's symposium was "Taking Personalized Care to the Next Level." I'd love to hear your reflections on the sessions that you found most exciting and really resonated with the attendees.  Dr. Rachna Shroff: Yes, thank you. We were really excited about this theme because we really felt that “Taking Personalized Care to the Next Level” translated to thinking through personalized approaches to patient care, not just in the traditional ways that we think of with precision oncology and genomics driving our care, but also how we can think through multidisciplinary approaches and an individualized care plan. Thinking through how artificial intelligence and novel clinical trial designs can and should be implemented to meet the needs of our individual patients. And so we really highlighted that in what was a somewhat new reboot of a session called “Intersections,” which were every day and were really more cross-tumor; they were tumor agnostic but were thematic focused. As I mentioned, those themes were really based on feedback that we had from prior attendees, as well as from the program committee's feeling on what are really the questions that we are dealing with and that are burning in the clinic today and that includes the emerging role of artificial intelligence and machine learning and how we integrate that into our clinical care, approaches to oligometastatic disease, and it's not really just something that we think of in colorectal cancer but haven't fully used that paradigm to really apply it to other GI malignancies. And then the art and science of clinical trial design where, again, traditional randomized phase 3 trials might not be the best and most innovative and most expedient way of bringing novel therapeutics to our patients. And so, I thought that all of those sessions were really highlighting different important topics that we deal with day to day. Additionally, we had a really fantastic keynote lecture from Dr. Kimmie Ng of the Dana-Farber Cancer Institute. She is a world-renowned expert in the early-onset colorectal cancer space, and the timing of her keynote was perfect with the new cancer statistics that came out literally days before GI ASCO that demonstrated this just dramatic rise in early onset GI malignancies as a whole, not just colorectal. And she spoke really in a comprehensive manner not just on clinical approaches, screening approaches, and how to find these patients at an earlier stage, but also kind of gave us a call to action, if you will, in terms of public health initiatives, as well as like I said, clinical care and really thinking outside of the box for how to reach these patients.  And then, of course, we always have what I think is one of my favorite aspects of the meeting, which are the networking opportunities that include the Trainee and Early Career Networking Luncheon, the Women's Networking Reception, and the Meet the Experts Luncheon where, especially as junior career investigators, you have an opportunity to meet what we think of as the “big names” in GI cancer. Dr. Shaalan Beg: Absolutely, I remember my first couple of GI ASCO meetings and those were probably the most memorable sessions that I attended as junior faculty as well.   So let's take a deeper dive into some key abstracts from the meeting. I'd like to begin with Abstract 245. This is the SKYSCRAPER-08 study. It's first-line tiragolumab and atezolizumab with chemotherapy in an Asian patient population with esophageal squamous cell carcinoma. What are your key takeaways from this study?  Dr. Rachna Shroff: Yeah. This was an exciting study in my opinion in the sense that thinking through how we can build on immunotherapy backbones is obviously a pressing question across the GI cancer space. So this was a phase 3 randomized, double-blinded, placebo-controlled trial that looked specifically at patients with esophageal squamous cell carcinomas. And the study was enrolled fully with an Asian population. It looked at taking the traditional chemotherapy backbone and adding to it an anti-PD-L1 with atezolizumab and an anti-TIGIT with tiragolumab. Again, that proof of principle of using anti-TIGIT and PD-L1 has been looked at across a lot of different GI cancer spaces and we know that the esophageal squamous cell cancers tend to be very immunotherapy responsive. So this was a really important question.  This involved a number of patients, a little over 460 patients, who were randomized one-to-one to receive the tiragolumab with atezolizumab with the standard paclitaxel and cisplatin, that's used for esophageal squamous versus chemotherapy alone with placebo. And the primary endpoint was independent review of progression-free survival, and overall survival. And so, out of the 461 patients randomized, there was at the primary analysis, a median improvement in progression free survival, from 5.4 months in the control arm to 6.2 months with a tira-paclitaxel plus chemo arm with a hazard ratio of 0.56, highly statistically significant. Similarly the median overall survival was also improved from 11.1 months to 15.7 months again with a hazard ratio of 0.7 and some of the other key efficacy endpoints were also improved with the addition of the anti-TIGIT PD-L1 approach. And importantly, there was not really safety signals that jumped out at us.  And so, to me, what this means is that, in our patients with esophageal squamous cell carcinoma, we really should be thinking about chemotherapy with immunotherapy as a backbone and how we can build on it. And, you know, I would imagine that it's hard to argue with both the PFS and OS endpoint that adding anti-TIGIT won't necessarily be kind of the new approach to these patients. And importantly, I'll point out that it seems to be a benefit across the subgroups, including PD-1 status, which is always our big question here. I think the only thing to keep in mind is this was an all-Asian population and whether or not that kind of immune profile of the immune responsiveness is different in those patients, but regardless, a positive phase 3 trial. Dr. Shaalan Beg: It's really exciting to see immune checkpoint inhibitors or immunotherapy beyond PD-1 targeted, CTLA-4 targeted treatments making their way into GI Cancers.  Dr. Rachna Shroff: Absolutely. Dr. Shaalan Beg: Sticking with the immunotherapy theme, let's focus on hepatocellular carcinoma. So LBA432, the EMERALD-1 study of transarterial chemoembolization combined with durva with or without bevacizumab looked at people with unresectable hepatocellular carcinoma eligible for embolization. So really a highly anticipated study, I'm wondering what your thoughts are and whether it'll be practice-changing for this field.  Dr. Rachna Shroff: I was excited to see the press release when it showed that the study was positive, and I think it's because now that we're using immunotherapy in the advanced HCC space, our obvious question is, can we integrate it into multimodality approaches? There are a lot of smaller studies looking at neoadjuvant IO approaches, and in this intermediate stage, unresectable hepatocellular carcinoma patients. We wanted to know if there was a utility to liver directed therapy with immunotherapy.  So, this was a large study. It was a global study looking at unresectable HCC with preserved Child-Pugh function. But it was Child-Pugh A and up to B7, importantly. And there were 616 patients randomized in a 1:1:1 fashion, with the control arm being just TACE alone. But then, there was also an opportunity for durvalumab with TACE, as well as durvalumab plus bevacizumab with TACE. The patients would receive durvalumab during their TACE treatments and could receive up to four TACE treatments and then subsequently were either continued on durvalumab alone, durvalumab plus bevacizumab, or the placebo. The primary endpoint was progression-free survival, powered specifically to look at TACE versus durvalumab plus TACE. In this study, the primary endpoint was met with a significant improvement in PFS. Median PFS was 15 months versus 8.2 months, with a hazard ratio of 0.77. Most prespecified subgroups demonstrated this benefit.  Importantly, there was a secondary endpoint looking at durvalumab plus TACE versus TACE alone, and that actually did not show a statistically significant improvement in median PFS from 8.2 months in the control arm to 10.0 months. The overall response rates were slightly higher with the durvalumab plus bevacizumab approach at 43.6%. And importantly in these patients, who oftentimes have a higher burden of disease in the liver, median time to progression is a really important and clinically meaningful endpoint. That was 22 months with the durvalumab plus bevacizumab and TACE versus 10 months for TACE alone. I would just point out that the overall concern we always have with bevacizumab is the increased risk of bleeding and the treatment-related adverse event profile. Overall, there were no safety signals that emerged from this, with nothing that really, especially in that bleeding risk category, jumped out at us. Of course, we haven't seen the overall survival data yet because we have not seen enough follow-up to really see that number.  I do think that this is potentially practice-changing, and I think it just demonstrates that there's probably some synergy between anti-VEGF with anti-PD-1, and then the liver-directed treatments. The obvious question for us in the United States is that the vast majority of people are moving away from TACE and towards more radioembolization and what can we extrapolate from this? Does this really tell us much if people are using more of a Y90-based approach? I think those are a lot of the burning questions that most of us have.  Dr. Shaalan Beg: Yeah, and it's a very interesting direction that the HCC space is taking because we heard in previous meetings, the role of PD-1 inhibition as adjuvant therapy after resection. Now, we have data for local-regionally advanced disease over local-regional treatments. And of course, you already mentioned the data for more advanced disease. So it sounds like immunotherapy may be impacting the management of anyone diagnosed with hepatocellular carcinoma.  Let's talk about the MONET trial, Abstract 249, which compared thoracoscopic esophagectomy and open esophagectomy for thoracic esophageal cancer. Do you think this is a study which may influence the treatment of patients with thoracic esophageal cancer? Dr. Rachna Shroff: So, this was, again, I think, a really important question. It was a randomized, controlled phase 3 trial comparing a more minimally invasive approach with TE — thoracoscopic esophagectomy — versus an open approach. This had patients with clinical stage 1-3, excluding T4 thoracic esophageal squamous cell carcinomas. They were randomized 1:1 to the open versus the TE approach, with a primary endpoint of overall survival and an important secondary endpoint of relapse-free survival. 300 patients were randomized, and at the second planned interim analysis, the median follow-up was a little over two and a half years. The 3-year overall survival was 82% in the TE group versus 70.9% in the open group. The DSMC of this trial actually recommended early termination based on the non-inferiority, which is what they were specifically looking at. There was a very statistically significant one-sided p-value for non-inferiority.  Importantly, the 3-year recurrence-free survival was also markedly better in the TE group versus the open group, with no real notable differences in R0 resection, or a large percentage of patients who needed to be converted from a TE to an open approach, and really not any significant difference in overall postoperative morbidity. I think this just supports the concept that minimally invasive approaches for our patients with GI malignancies can and should be considered. Again, esophageal squamous because they tend to be seen a lot more in Asia, this study was conducted in Japan, but I think that being said, a lot of our surgeons in Europe and in the U.S. are also very amenable to minimally invasive approaches. And I think this just supports the fact that an open approach is not necessary. So, I would think again, that this is something that is implementable and I think will affect the field.  Dr. Shaalan Beg: Moving on to metastatic cholangiocarcinoma, there have been many FGFR inhibitors that have shown activity and promise and are approved for the management of cholangiocarcinoma with FGFR alteration. But at this ASCO GI, we heard the results of the safety and efficacy of an FGFR1, 2, and 3 inhibitor, tinengotinib, as monotherapy for advanced metastatic cholangiocarcinoma (Abstract 434). How do you see this fitting into the broad picture? Dr. Rachna Shroff: Yeah, so this was highly anticipated data, primarily because at this point, the FGFR space in cholangiocarcinoma is quite crowded. And so a lot of us were getting sick of the "me-too" drugs. What is really unique about tinengotinib is that, not only is it a selective multikinase inhibitor, but it also, in preclinical models as well as in early phase one trials, demonstrated potent inhibition of patients with FGFR2 fusions and rearrangements who had acquired resistance mutations. So, as we better understand the first generation of FGFR inhibitors and note the resistance mechanisms, these drugs are now being developed to try to circumvent or overcome those.  This study looked at 4 different cohorts: 1 cohort with FGFR2 fusion patients who had primary progression who never responded to FGFR inhibitors, a second cohort with FGFR2 fusion patients who had progression after primary response, so those with acquired resistance, and then there was non-fusion FGFR alterations because we do know that a number of cholangiocarcinoma patients have other FGFR alterations that are not fusions, and then those with FGFR wild-type. The primary endpoint was objective response rate, with a total of 48 patients enrolled across the four cohorts. And so the 40 patients who were evaluable in the group that had primary resistance, which was the first cohort, there was a response rate was 9.1% and that was partial response, and 31% had tumor reduction with tinengotinib. And similarly in those with acquired resistance, 37.5%, 3 out of 8 patients had a partial response and tumor reductions were noted with an overall disease control rate between those patients with FGFR2 fusions of 94.7%, between those with primary and secondary resistance.  In the patients who had FGFR alterations, there was 3 out of 9 patients with a partial response and again, tumor reductions were notable across the board and the disease control rate was 88.9%. The FGFR wild-type group, not surprisingly, did not see any partial responses, but interestingly, 75% of these patients had at least disease control, and the median progression-free survival was 5.26 months, again, kind of most notably impressive in the 2 cohorts that included FGFR2 fusions. The toxicity profiles are what we come to expect for FGFR inhibitors and we've gotten better at managing those and mitigating some of those so there was really nothing to jump out there. So there is now an ongoing randomized phase III trial specifically looking at tinengotinib versus physician's choice in patients with FGFR2-altered cholangiocarcinoma after having received prior FGFR inhibitors. So that's where I think it's in is for those of us who know that there are multiple drugs in the space, our big question is can we sequence through that? Can we offer multiple FGFR inhibitors in these patients? And I think we are all eagerly anticipating this data as well as the subsequent data to really justify the use of these novel second generation FGFR inhibitors.  Dr. Shaalan Beg: It's been fantastic to see the evolution of these compounds in precision medicine, or precision oncology at its finest, in terms of understanding mechanisms of resistance and treating refractory disease.   Let's focus on colorectal cancer. I'll tell you, there has been a lot of discussion, Dr. Shroff, on social media, on insurance companies sometimes rejecting one biologic or the other based on tumor sidedness. We have talked about tumor sidedness predicting response on this podcast based on data from previous studies. But this year in GI ASCO, Abstract 207 explored the role of tumor genomics and tumor sidedness and they said that it's tumor genomics, that tumor genomics better explains the differences on outcomes, and it explains it better than sidedness. What does this mean to the field? Because a lot of professional organizations have guidelines that are asking people to now incorporate sidedness. So how does that change based on these results? Dr. Rachna Shroff: I really commend these authors on leveraging real-world data, and I think we're getting better and better at recognizing that real world data actually informs our clinical decision making, possibly better than sometimes some of these studies that lead to the guidelines and algorithms that we develop. So this is a perfect example of a little bit cart before horse in trying to understand the way that sidedness and genomics may interplay.   So this was a study that basically leveraged both the Foundation Medicine and Flatiron Health clinical genomic database and looked at patients with microsatellite stable metastatic colorectal cancer. There were a total of 3,845 patients included in a kind of two-thirds one-third split between left sided and right-sided colorectal cancer. And they found the typical genomic alterations that historically have been thought of more with left-sided colorectal cancer like APC and then more of the RAS BRAF alterations in the right-sided patients. But I think what they really thought and what I think was remarkable is they really looked at the patients and how they received chemotherapy with anti-EGFR or bevacizumab therapies, and they did a multivariate analysis to really see what is driving outcomes. And like you mentioned, what they found was patients in the RAS pathway, those classified as having alterations in the RAS pathway, had less favorable outcomes, while those with APC altered group had more favorable outcomes. And that was regardless of treatment received and sidedness.  And so when they did an analysis of what was called a “likelihood ratio test,” they found that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction, but not when sidedness was added to genomics. Like you said, it kind of demonstrates, at least in this mining of real-world data from Flatiron that tumor genomics is probably a better driver and a more important driver in determining outcomes than sidedness.  I totally agree with you. I would push for us to really kind of bring a little bit of noise to this and to make insurance companies and other companies that are looking at this to think through this a little bit more and make sure that we're putting all of the data together in a comprehensive passion before making the treatment plans and determinations. Dr. Shaalan Beg: The last abstract I'd like to ask you about is Abstract 117, the NEST-1 trial. This study looked at neoadjuvant botensilimab and balstilimab for resectable mismatch repair proficient and deficient colorectal cancer, both MSS and MSI. What are your key takeaways from this study?  Dr. Rachna Shroff: This is another study that is demonstrating that there may potentially be a role for immunotherapy in microsatellite stable patients. I will make the caveat that this was a single-arm study that really was looking at feasibility safety, with efficacy as a secondary endpoint. The combination of bot-bal in the neoadjuvant space for colorectal cancer patients, they received one dose of boten and two fixed doses of bal two weeks apart and then were taken to surgery. They limited the number of patients and out of the 12 patients that were enrolled, they limited the number of mismatch repair deficient patients. So to your point, they allowed both, but they wanted to make sure it was not just MSI-high patients. What they basically found is that it was safe and did not delay surgery or increase risks of adverse events. But importantly, there was significant regression of tumor noted. And some interesting spatial biology analyses demonstrated potentially novel mechanisms of action, especially in the MSS population, and that ctDNA reductions correlated with pathologic response. There were a lot of different things that they were looking at, basically suggesting that bot-bal is safe and can be used in both mismatch repair–deficient and proficient patients with colorectal cancer. And now importantly, they've added some additional cohorts and expanding the study. As I mentioned, this is right now just 12 patients, but does definitely have a provocative result.  Dr. Shaalan Beg: Thanks so much, Dr. Shroff.  Finally, the role of cell-free DNA (cfDNA) in GI cancers has been an exciting and important development in our field. There's tremendous data that emerged at the GI meeting, and we have decided to do a separate ASCO Daily News Podcast dedicated to ctDNA. So listeners, please look out for our coverage of key studies on ctDNA in GI cancers very soon here on the ASCO Daily News Podcast.  Many thanks, Dr. Shroff, for sharing your insights with us today and for your great work in building a robust GI meeting this year. Thank you very much. Dr. Rachna Shroff: Thank you so much. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and inform. It is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Our guests on this podcast express their own opinions, experiences, and conclusions. These statements do not necessarily reflect the views of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an endorsement by ASCO.   Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Rachna Shroff @rachnatshroff   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals   Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Giuseppe Caruso to discuss PARPi de-escalation in ovarian cancer. Dr. Caruso is a gynecologist, currently working as a research fellow at Mayo Clinic, Division of Gynecological Surgery, in Rochester (MN, USA) under the supervision of Professor William Cliby. He is also a PhD fellow in “Network Oncology and Precision Medicine” at Sapienza University of Rome in Italy and collaborates with the European Institution of Oncology in Milan (Italy) under the mentorship of Professor Nicoletta Colombo. His main areas of interest are ovarian cancer and precision oncology.   Highlights: Systemic therapy de-escalation is a new frontier in personalizing therapy for advanced ovarian cancer. PARPi are so effective that selected patients may require less systemic therapy to achieve the same outcomes. The fundamental key is to limit de-escalation to BRCAm/HRD-positive patients with R0 after surgery. Several de-escalation attempts are under investigation, but none is currently recommended outside of clinical trials.

El Dr. Luis Alfonso Romero, oncólogo médico de León, Guanajuato, México, en este episodio de “Pase de visita” abordará un caso clínico de una paciente con cáncer de ovario seroso de alto grado. Como invitados al programa se encuentran tres médicos mexicanos, el Dr. Eduardo Cisneros, oncólogo quirúrgico residente en el Hospital Juárez de México; la Dra. Gabriela Castro, ginecooncóloga residente en el Hospital Militar de Especialidades de la Mujer, SEDENA y el Dr. Alfonso Torres Rojo, cirujano oncólogo adscrito al Hospital Ángeles México, los tres de la Ciudad de México. Ellos, con base en evidencia científica y en su experiencia, responderán a varias interrogantes. El caso describe a una mujer de 58 años que recibió el diagnóstico de cáncer de ovario seroso de alto grado en etapa III hace tres años. En ese momento, se le administró un tratamiento que incluyó citorreducción primaria R0, seguida de seis ciclos de quimioterapia con carboplatino y paclitaxel. Después de tres años sin evidencia de enfermedad, la paciente experimenta una recurrencia, evidenciada por un aumento en los niveles de Ca125 hasta 200 y por tomografía se revela una actividad tumoral de 4 cm a nivel pélvico que parece afectar el sigmoides. Las preguntas para los médicos respecto a este caso son las siguientes: ¿Cuál es el beneficio de realizar la citorreducción antes de iniciar la quimioterapia sistémica en casos de recurrencias locales? ¿Se ha evidenciado algún beneficio al combinar la cirugía con quimioterapia hipertérmica intrabdominal (Hipec) en este contexto? ¿Qué seguridad se le ofrece a la paciente con la resección multiorgánica en términos de control de la enfermedad? Fecha de grabación: 6, 12 y 17 de octubre de 2023.     Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.

¡Hola amantes de la montaña y apasionados del entrenamiento al aire libre! Hoy en nuestro podcast, vamos a adentrarnos en un mundo fascinante: la ciencia detrás del entrenamiento en montaña. Y para empezar, vamos a descomponer la carga, ¿qué significa eso? No te preocupes, te lo explicaré de una forma que te resulte interesante y entretenida. Imagina que estás a punto de subir una montaña épica y quieres estar en la mejor forma posible. Para lograrlo, necesitas entender la magia detrás de la carga de entrenamiento. Hay estudios que hablan de cómo la carga se compone y cómo interactúan sus elementos para maximizar tu rendimiento. Es como armar un rompecabezas para convertirte en un atleta de montaña de élite. La carga de entrenamiento se describe a menudo a través de tres variables básicas: el volumen, la intensidad y la frecuencia. Estas tres son como los ingredientes secretos para el éxito en la montaña. Volumen es la cantidad de trabajo que haces, como la distancia que recorres o el tiempo que entrenas. Intensidad se refiere a cuán duro entrenas, ya sea por ritmo, potencia, o frecuencia cardíaca. Y la frecuencia es cuántas veces entrenas en un período de tiempo. Lo emocionante es que la combinación de estas tres variables es lo que te ayudará a optimizar tus entrenamientos para alcanzar tus metas. Entonces, ¿qué te sugiere la ecuación volumen x intensidad x frecuencia? ¡Sí, suena a una fórmula mágica para tu éxito en la montaña! Y si te suena familiar, es porque estas tres variables se relacionan con los métodos de entrenamiento que ya exploramos en episodios anteriores. ¡Todo encaja como un rompecabezas! Esto demuestra la importancia de conocer los procesos y hitos fisiológicos detrás de tu entrenamiento. No se trata solo de cronometrar tiempos y recuperaciones, sino de darle sentido a cada paso que das. Hablemos más a fondo sobre estas magnitudes de carga: volumen, intensidad y frecuencia. El volumen es como la base de tu entrenamiento, la cantidad de trabajo que haces. Puedes medirlo en kilómetros, horas de entrenamiento o desnivel ascendido en el caso del trail running, por ejemplo. El volumen te da números concretos sobre tu esfuerzo. La intensidad, por otro lado, es más escurridiza. Puede ser el ritmo, la potencia, la frecuencia cardíaca, o incluso tu percepción subjetiva del esfuerzo. La intensidad agrega calidad a tu entrenamiento, pero es un poco más difícil de cuantificar. Y luego está la frecuencia, que se refiere a cuántas veces entrenas en un período de tiempo. Esto está estrechamente relacionado con el volumen, ya que si ajustas la frecuencia, puedes aumentar o disminuir el volumen y, a su vez, afectar la intensidad. ¡Es un equilibrio fascinante! Ahora bien, ¿cómo cuantificamos esta carga en la práctica? Tenemos varios métodos, y uno de los más antiguos es el "Banister TRIMP", que se basa en la frecuencia cardíaca. Utiliza una ecuación para asignar valores a diferentes zonas de intensidad basadas en la frecuencia cardíaca. Este método es como un GPS para tu carga de entrenamiento.Este modelo trifásico establece 3 zonas de intensidad (como su nombre indica): - Zona I: para trabajo realizado por debajo del Umbral aeróbico. Le da un valor de 1. - Zona II: para aquel realizado entre umbrales. Le da un valor de 2. - Zona III: para esfuerzos por encima del U. Anaeróbico. Le da un valor de 3. Así pues, Banister establece que la carga o TRIMPs será una sencilla fórmula en la que se multiplica el tiempo de entrenamiento en minutos por la frecuencia cardiaca media y por el factor de ponderación de cada una de las zonas. También tenemos el "ECO" o Equivalentes de Carga Objetiva, que se basa en las zonas de entrenamiento propuestas por expertos españoles como Roberto Cejuela. Este método pondera la intensidad de manera más precisa, evitando el problema de no distinguir entre esfuerzos limítrofes. En este caso en vez de en las zonas de FC, se basa en las zonas de trabajo propuestas por Jesús Garcia Pallarés y su equipo. Que son las que hemos estudiado en módulos anteriores y se dividen de R0 a R6. Este método relaciona como el anterior el volumen con la intensidad, multiplicando también el tiempo en minutos de ejecución por un valor asignado a cada zona de entrenamiento. Por último, no podemos olvidar el "Training Stress Score (TSS)", un indicador que toma en cuenta la duración y la intensidad del entrenamiento. Es muy popular en el ciclismo y se adapta a diferentes deportes. ¡Es como la fórmula secreta para calcular tu estrés de entrenamiento! rTSS = para aquellos deportistas que basan su entrenamiento en ritmo de carrera. - hrTSS = para aquellos deportistas que basan su entrenamiento en frecuencia cardiaca. Así que, queridos oyentes, la próxima vez que estés en la montaña, recuerda que tu éxito se basa en cómo combinas volumen, intensidad y frecuencia. Es como jugar a ser un científico del deporte mientras exploras la naturaleza. ¡Hasta la próxima aventura en la montaña! ________________________________________________________________ ‍♀️ ‍♂️ ¡Motivación en cada paso de tu viaje! Descubre más en: https://www.instagram.com/estrategas.Trail/ ¿Amante de los videos? Suscríbete aquí: https://www.youtube.com/c/XimEscanellasEstrategas/videos Regalo especial: Las 5 claves para un entrenamiento efectivo. ¡Regístrate! https://ximescanellas.com/pagina-registro-5-claves/ Sigue nuestra cuenta personal en: https://www.instagram.com/xim_escanellas/ https://ximescanellas.com/ Alcanza tus de manera inteligente y eficiente. Contáctanos vía WhatsApp: http://ximescanellas.com/hablamos/

Pour écouter l'épisode en format vidéo : https://youtu.be/R0_n_aOwisQ Bienvenue à tous au nouvel épisode du podcast Hypercroissance en mode discussion d'affaires! Cette semaine, Jonathan Léveillé et moi (Antoine Gagné), abordons un des plus grands fléaux dans le monde des affaires... Le manque de ventes constantes! Trop d'entreprises se fient au bouche à oreille pour bâtir leur entreprise. Malheureusement, dépendre des autres pour construire son propre futur est hautement dangereux. On vous donne donc des techniques aujourd'hui afin de bâtir un système de ventes prévisibles. Bonne écoute! Pour avoir un deuxième avis sur vos campagnes publicitaires : j7media.com/hypercroissance Pour en savoir plus Openmind : https://www.openmindt.com/ Pour discuter avec moi sur Linkedin : https://www.linkedin.com/in/antoine-gagn%C3%A9-69a94366/ Notre podcast Social Selling : https://www.j7media.com/fr/social-selling Notre podcast Commerce Élite : https://www.purecommerce.co/fr/podcast-commerce-elite Notre podcast No Pay No Play : https://podcasts.apple.com/es/podcast/facebook-ads-on-parle-de-g%C3%A9n%C3%A9ration-de-leads/id1447812708?i=1000607648614 Le Podcast Pivot : https://www.dev2ceo.com/podcast Suivez-nous sur les médias sociaux : Linkedin : https://www.linkedin.com/company/podcast-d-hypercroissance/ Facebook : https://www.facebook.com/podcastHypercroissance Instagram : https://www.instagram.com/podcasthypercroissance/

Drs. Shaalan Beg and Shiraj Sen discuss notable advances in GI cancers featured at the 2023 ASCO Annual Meeting, including the PROSPECT and PRODIGE-23 trials in rectal adenocarcinoma, the MORPHEUS study in uHCC, and the NORPACT-1 trial in pancreatic head cancer. TRANSCRIPT     Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host for the podcast today. I'm the vice president of oncology at Science 37, and I'm an adjunct associate professor at UT Southwestern Medical Center. My guest today is Dr. Shiraj Sen. He is a GI medical oncologist and the director for clinical research at NEXT Oncology in Dallas.   Today, we'll be discussing practice-changing studies and other key advances in GI cancers that were featured at the 2023 ASCO Annual Meeting.   You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the podcast are available on our transcripts at asco.org/DNpod.   Shiraj, it's great to have you on the podcast today.  Dr. Shiraj Sen: Thanks so much for having me today, Shaalan.  Dr. Shaalan Beg: We saw exciting new data and great progress in GI oncology at the ASCO Annual Meeting. I was hoping we could talk about LBA2. This was the PROSPECT study that was presented during the Plenary Session. It's a randomized, phase 3 trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemo, followed by the selective use of chemoradiation, followed by TME or total mesorectal excision for the treatment of locally advanced rectal cancer. This is the Alliance N1048 trial. What are your thoughts on this study?  Dr. Shiraj Sen: Thanks, Shaalan. It was great to see another GI study presented in a Plenary Session, and I thought this was a great trial that really took us back to thinking about why we do chemoradiation as well as chemotherapy perioperatively in locally advanced rectal cancer. And asking the important question of is there a select patient set or subset where we might be able to safely omit the chemoradiation piece.  To me, the impressive part was this study enrolled from 2012 to 2018. In 2012, when this treatment really started enrolling, the standard of care was long-course chemoradiation for five and a half weeks, followed by surgery, followed by adjuvant chemotherapy with FOLFOX or CAPOX. During this time, a lot of the practices of these patients have shifted from that to giving total neoadjuvant therapy, where we bunch the chemotherapy and chemotherapy upfront prior to the patient undergoing surgery. And this study really asked us to take a look at both practices and ask the question of which one is better and is it possible to de-escalate care for patients who get upfront chemotherapy and omit the chemoradiation and still have similar outcomes.   I thought it was very interesting that this was done in a non-inferiority-type manner, and we can talk more about that in a few minutes as well. But taking that all into context, the fact that in this study, that the non-inferiority endpoints were met for both disease-free survival as well as overall survival in the patients who were able to omit chemoradiation, I think in the big picture sense told us that there truly might be a patient subset where—this is in patients with T2 node-negative disease or T3 node-negative or T3 node-positive disease—where we might be able to safely exclude the chemoradiation and still have similarly effective outcomes for these patients.  Dr. Shaalan Beg: Those are great points, especially when we have started to think about colon cancer and rectal cancer as many different diseases based on their location. And we know that in some instances their biology can be different as well.   Can you talk a little bit about who those patients are that were enrolled on this trial? Because when I think about the German rectal study that led to us using neoadjuvant chemoradiation, the data was really around pelvic control of disease and sphincter preservation. So how did the patients who enrolled in this trial relate to the typical person with rectal cancer who walks through your doors?   Dr. Shiraj Sen: Yeah, great point. I think we should point out the inclusion-exclusion criteria for this study. These patients were only those who were, again, T2 node-positive or T3 node-positive or negative, patients for whom chemoradiation would be indicated in the setting, and patients for whom they'd be good candidates for sphincter-sparing surgeries. So, tumors that are quite up high. These are not for individuals who have tumors requiring an APR. These are not for patients who have clinical T4 tumors. And this is not applied, again, to those high-risk patients who have 4 or more pelvic lymph nodes that are 1 cm in size or larger in the short access. And so, patients who need essentially an APR and the high-risk T4 tumors who are, I think, better suited by something like we'll talk about later in the PRODIGE study.   I think one last point that might be worth making here on the PROSPECT trial is that it was a non-inferiority trial. And in my opinion, this was really a great use of a non-inferiority study. I believe that when there's a new treatment under consideration used in a non-inferiority study, it should be because that therapy or modality of treatment is safer, more cost-effective, or could help increase access to care without compromising efficacy, and ideally maybe more than one of the above. And in this case, I think really all of those checkboxes are met.   In urban settings where we work, we think about access to radiation being quite plentiful, but when we get to more rural areas, or parts of the world where they may not have access to radiation like we may, I think this data can help drive care for a number of patients there. It can certainly be more cost-effective as it allows the omission of radiation. And certainly, from some of the PRO data that they presented, it certainly can be felt to be safer and help omit some toxicities as well.  Dr. Shaalan Beg: Yeah, you mentioned a total neoadjuvant therapy and we seem to be entering this space in rectal cancer where the decision on which modalities an individual person will need for the management of their disease and what sequence they will need is all up for debate, whether that's chemotherapy or radiation, long-form, short-form radiation. And we also heard some results at earlier ASCO meetings around the omission of surgery in people who've had complete clinical responses as well.   And you mentioned total neoadjuvant therapy and at ASCO this year we heard the results from LBA3504, which is a PRODIGE-23 trial. The investigators reported 7-year results of this phase 3 study from the UNICANCER group in France. This study is really pushing the envelope. What are your key takeaways here?   Dr. Shiraj Sen: Great point. I think this study, especially when taken in conjunction with the PROSPECT trial, highlights the fact that these patients really can have heterogeneous diseases and ones that really require careful consideration and discussion at multidisciplinary tumor boards. Unlike the patient population in the PROSPECT trial, the PRODIGE study did treat patients with higher-risk disease. So these were patients with clinical T3, T4 tumors and so higher risk, and asked the question now with more mature 7-year follow-up of, when compared to receiving the standard of care at the time, which was a chemoradiation followed by TME, followed by adjuvant FOLFOX for 12 cycles or the capecitabine, does TNT giving again now modified full FOLFIRINOX for six cycles followed by chemoradiation followed by TME and then adjuvant FOLFOX, do the improvements in both disease-free survival, overall survival, and metastatic relapse rate, do they hold up, and/or are there any differences in local control?   And again, here they demonstrate that even with longer-term follow-up, that the improvements in OFS, DFS, and metastatic relapse rate, really do hold up even with longer-term follow-up. And so, for these patients with higher risk disease, it does seem that giving induction chemotherapy with modified FOLFIRINOX before chemoradiotherapy really might be kind of best practices. The safety profile, even with longer-term follow-up was unchanged. There was not any increase in local recurrences. And again, looking at quality of life metrics there seemed to be similar or maybe improved quality of life for patients who receive the TNT approach. And now again, I think the next step is, as the presenter mentioned, investigating this even in a more tailored fashion, as was done with the PROSPECT study.  Dr. Shaalan Beg: Let's change gears and talk about liver cancer. Abstract 4010 showed the results of the MORPHEUS-liver study. This was a phase 1b/2 randomized trial of tiragolumab in combination with atezolizumab and bevacizumab for people with unresectable locally advanced or metastatic hepatocellular cancer. It's really exciting to see innovations with immune therapy changing how we've managed hepatocellular cancer in the last few years. And here, we're seeing an addition of a third agent to an already approved regimen of atezolizumab and bevacizumab. I was really curious to hear what your take-home message is from this study.   Dr. Shiraj Sen: Yeah, this was another very interesting abstract that was presented at ASCO this year. It's hard to believe that it was only 3 years ago that we first got the approval of atezo plus bev, and that it took more than a decade to really have us as a field improve on outcomes for patients with liver cancer above and beyond giving sorafenib. And here we are just 3 years later, already launching new phase 3 studies from these sorts of early-phase adaptive signal-seeking studies. The investigators as a whole should be commended for the speed at which new drug development has really progressed in liver cancers after, again, quite a lull we had in the pre-I/O days.   It's encouraging to see that in just 3 years that there's another phase 3 study now being launched in HCC on the heels of this data combining the atezo-bev backbone to the anti-TIGIT molecule tiragolumab. Now, I know there was a lot of discussion and some criticism of this study and what the real effects of adding tiragolumab to atezo-bev might be because of the underperformance of the control arm. In this study, the atezo-bev control arm, it should be noted that was only 18 patients, had a response rate of only 11%. And of course, with longer-term follow-up of the IMbrave150 study, we know that with the atezo-bev, we expect a response rate of about 30%. And so how a real-world population of individuals receiving atezo-bev would compare to those receiving tiro-atezo-bev has been discussed. But I think the only real way to answer that question would be with a large, randomized phase III study. And it's encouraging to see that one is being launched to ask that question.    Dr. Shaalan Beg: Absolutely. Let's change gears and talk about pancreatic cancer. LBA4005 explored short-course neoadjuvant FOLFIRINOX versus upfront surgery for people with resectable pancreatic head adenocarcinoma in the NORPACT-1 study. This is a multicenter randomized phase 2 trial and we're starting to see the reporting of clinical trials evaluating the sequencing of systemic therapies for resectable disease. We've heard studies for neoadjuvant therapy for borderline resectable as well as resectable trials in previous meetings. But there's a lot of discussion around the NORPACT-1 trial which may be causing some people to pause on our current understanding of treatment sequencing for resectable disease. I'm curious to hear what your take homes are.   Dr. Shiraj Sen: Thanks. Yes, I thought this was a very interesting study as well. Depending on which institution one practices in, in recent years, many have shifted their practice for individuals with resectable pancreatic cancer from administering full FOLFIRINOX or adjuvant therapy only after surgery to giving it in the neoadjuvant setting based on, again, a number of smaller studies, some that are single institution. This is one of the first studies that in a randomized fashion has asked the question in just resectable pancreatic cancer. So we're not talking about borderline resectable or other patients.    But in resectable pancreatic cancer, whether there are differences now comes if patients receive surgery first, followed by FOLFIRINOX-only adjuvant setting or essentially getting perioperative FOLFIRINOX and so neoadjuvant, followed by surgery, followed by, as tolerated, four cycles of adjuvant FOLFIRINOX. And I was a little surprised by some of the results and to me some of these data were a little intriguing.  Specifically, I think if we take a deeper look like the discussant had after the presentation, there are, I think, some unanswered questions. Specifically, half the patients were randomized to receive neoadjuvant FOLFIRINOX and half of them received upfront surgery. But in the group of individuals who received neoadjuvant FOLFIRINOX, it looked like only half of them completed neoadjuvant chemotherapy. And some answers into kind of why that was, and what it was about those patients then who were in the neoadjuvant arm, is one thing that comes to mind.    Secondly, what I thought was interesting was this study was that it was designed very well to try to take out as much heterogeneity as possible. However, in both arms, there was actually quite a substantial number of individuals who ended up receiving gemcitabine-based chemotherapy. And that's even in the patients who received neoadjuvant FOLFIRINOX, and individuals who received neoadjuvant FOLFIRINOX, only 25% post-op went on to receive adjuvant FOLFIRINOX. And 75% almost received gemcitabine-based therapy. And again, why so many patients received off-protocol adjuvant therapy is something that kind of struck me.  I think the third and final thing that really struck me was, in the patients that received neoadjuvant FOLFIRINOX, there was a higher rate of R0 resections. 56% of patients had an R0 resection compared to those who got upfront surgery, where there was only a 39% rate and similarly kind of higher levels of N0 resection. And yet, despite all of this, again, the authors did show quite clearly that there were not any significant improvements in outcomes for patients that received neoadjuvant therapy, but kind of how improved surgical endpoints do not translate to overall survival and overall endpoints; I think there are still some questions there.    However, I do agree overall that despite these limitations with the conclusions of the author, that at this time at least, it's not clear; the results don't support the widespread use of neoadjuvant FOLFIRINOX as a standard of care for resectable pancreatic cancer. Fortunately, there are studies ongoing, like the Alliance [for Clinical Trials in Oncology] study and the PREOPANC-3 study that hopefully will kind of help settle this verdict.    Dr. Shaalan Beg: Yeah, it's a stark reminder that we need better treatments. I think we've been shifting the sequencing of these treatments and slicing them in as many ways as we can. And the core challenge is in finding better systemic therapies that have been found to be effective in advanced stage as well as in curative stages like this. And one of the points that bothered me about this trial was the drop-off that they saw at the beginning when the biliary system was being drained, or they were getting biopsies because folks who went for surgery upfront didn't always require those procedures. They didn't require histologic diagnosis either. But as is standard practice, before we give systemic therapy, we require psychologic confirmation. And that may have introduced a delay of a couple of days or a couple of weeks, which could have resulted in some imbalances in how survival is measured and how folks were doing. Because, as you know, a lot of times people diagnosed with this disease can be fairly sick, and a matter of a couple of days or weeks can make a big difference in terms of treatment with those.  I'm really excited to wait and hear how the Alliance study and the PREOPANC follow-up trials pan out and as a very important cautionary note for everyone, both the folks who have adopted neoadjuvant therapy and those that have not followed the data. And kudos to the investigators for completing that trial.  Dr. Shiraj Sen: Yeah, I fully agree. I'm glad to see that these trials are being run. I think we should not take anything away from the fact that these are very challenging trials to run. I think we certainly owe a big kudos to the patients who enroll in these studies who have resectable disease, but they're still willing to go through the process of an extra consent form, an extra kind of screening process, additional testing required to go into a clinical trial. And it's only because of them that we're able to run these studies and, as a field, get some answers on how to best take care of our patients.   Dr. Shaalan Beg: Shiraj, thank you so much for coming to the podcast today and sharing your valuable insights on the ASCO Daily News Podcast.   Dr. Shiraj Sen: Thank you so much for having me, and to all of the ASCO staff for having this podcast.  Dr. Shaalan Beg: And thank you to our listeners for your time today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review and subscribe wherever you get your podcasts.    Disclaimer:   The purpose of this podcast is to educate and 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.    Find out more about today's speakers:   Dr. Shaalan Beg  @ShaalanBeg  Dr. Shiraj Sen  @ShirajSenMDPhD     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn     Disclosures:    Dr. Shaalan Beg:   Consulting or Advisory Role:  Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen   Speakers' Bureau: Sirtex   Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics   Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune     Dr. Shiraj Sen:   Employment: Roche/Genentech  Stock and Other Ownership Interests: Roche/Genentech  Research Funding (Institution): ABM Therapeutics, Zentalis Pharmaceuticals, Parthenon Therapeutics, Pyxis Oncology, Georgiamune Inc.      

Brett Crozier grew up in California, graduated from the United States Naval Academy, and embarked on a thirty-year career in the Navy, flying dozens of combat missions over Iraq and leading at the highest levels of operational command. He served as the commanding officer of a combat F/A-18 strike fighter squadron, the world's largest and most advanced communications ship, and ultimately the USS Theodore Roosevelt before retiring from the Navy in 2022. Surf When You Can is his first book. Please visit: https://surfwhenyoucan.com/2019 Navy feature on Brett Crosier:  https://www.youtube.com/watch?v=87EEPZ5mf1A&authuser=1Brett's Retirement Ceremony: https://www.youtube.com/watch?v=R0-xkk-ooxk&t=7s&authuser=1

Greetings Glocal Citizens! Kicking off the midway point between the Spring Equinox and Summer Solstice--the reason behind the ancient observation of May Day (https://en.wikipedia.org/wiki/May_Day), we have a two-part conversation that likewise offers interesting perspectives on the contemporary observation of May Day - International Workers' Day (https://en.wikipedia.org/wiki/International_Workers%27_Day) and the difference that mindset can have on the fruits of one's labor. My guest for these discussions is Dr. Juleen Christopher. A dual citizen of the United States (by way of the US Virgin Islands) and the British Virgin Islands, in 2018 Juleen firmly reset her roots in the BVI with the purchase of St. Bernard's Hill House, a 5-star luxury villa experience in Tortola, British Virgin Islands. In her other world, she is the Founder and Inspiration Strategist of Beyond The Fork, a consultancy aimed at helping companies, their leaders and their employees navigate interpersonal challenges and work more effectively as teams.  Since arriving in the mainland US from her native St. Croix, she has become a cognitive-behavioral research scientist because she is passionate about working with tools to help guide and empower individuals to become accountable for their holistic health and well-being through education, understanding, and personal growth. This work has taken her from the American south to the East Coast and now to the midwest where she calls now calls Minneapolis, Minnesota home. There is so much more to get to know about this dynamic Glocal Citizen so be sure to tune in and check out the links below! Where to find Juleen? www.stbernardshillhouse.com On LinkedIn (https://www.linkedin.com/in/juleenchristopher/) On Instagram (https://www.instagram.com/stbernardshillhouse_bvi/) On Facebook (https://www.facebook.com/profile.php?id=100084768841373&sk=about) What's Juleen reading? Alphabet Murders Series (https://www.amazon.com/stores/Sue-Grafton/author/B000APENIA?ref=ap_rdr&store_ref=ap_rdr&isDramIntegrated=true&shoppingPortalEnabled=true) by Sue Grafton Works by Zadie Smith (https://www.amazon.com/s?k=zadie+smith&i=digital-text&crid=1MRNRHH8L63S9&sprefix=zadie+smith%2Cdigital-text%2C255&ref=nb_sb_noss_1) What's Juleen watching? African Folktales Reimagined (https://www.unesco.org/en/articles/unesco-netflix-global-launch-short-films-african-folk-tales-reimagined-29-march?TSPD_101_R0=080713870fab20008864d80ce7383c4893d809f05d7a0cc853c2c287bc7c41f306e6521d836bb1a108f58a915e143000e30b8eb185b53dda103d858cd9aea26024549206dadf1eef55bb635960dcf480b8b9877b1bf69c4e05d3ce0cf90257fe) Kim's Convenience (https://en.wikipedia.org/wiki/Kim%27s_Convenience) Never Have I Ever on Netflix (https://www.netflix.com/title/80179190) La Reina del Sur (https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjmrKia09X-AhXcV6QEHcwuD_EQFnoECEoQAQ&url=https%3A%2F%2Fwww.netflix.com%2Ftitle%2F80107369&usg=AOvVaw0jEr7WbLQcQTF8Z9ghIbeD) What's Juleen listening to? Angelique Kidjo (https://en.wikipedia.org/wiki/Ang%C3%A9lique_Kidjo) Biggest Afrobeats Artists (https://www.schooldrillers.com/biggest-afrobeats-artist/) Bossa Nova (https://en.wikipedia.org/wiki/Bossa_nova) Other topics of interest: About my Ayurveda Treatments in Ghana (http://ayushghana.com/#:~:text=Ayurveda%20is%20a%20wholistic%20way,deceases%2C%20but%20to%20prevent%20ailments) About the British Virgin Islands (https://en.wikipedia.org/wiki/British_Virgin_Islands) Governance in the BVI (https://en.wikipedia.org/wiki/British_Virgin_Islands) Who is a Belonger? (https://en.wikipedia.org/wiki/Belonger_status) About Jerry Blackwell (https://en.wikipedia.org/wiki/Jerry_W._Blackwell) Redemption Botanicals (https://redemptioncanna.com/our-story/) Minnesota Equity & Justice Project (https://www.mnhum.org/program/minnesota-equity-justice-project/?utm_source=rss&utm_medium=rss&utm_campaign=minnesota-equity-justice-project) Positive Intelligence (https://www.positiveintelligence.com) Special Guest: Juleen Christopher.

Greetings Glocal Citizens! Kicking off the midway point between the Spring Equinox and Summer Solstice--the reason behind the ancient observation of May Day (https://en.wikipedia.org/wiki/May_Day), we have a two-part conversation that likewise offers interesting perspectives on the contemporary observation of May Day - International Workers' Day (https://en.wikipedia.org/wiki/International_Workers%27_Day) and the difference that mindset can have on the fruits of one's labor. My guest for these discussions is Dr. Juleen Christopher. A dual citizen of the United States (by way of the US Virgin Islands) and the British Virgin Islands, in 2018 Juleen firmly reset her roots in the BVI with the purchase of St. Bernard's Hill House, a 5-star luxury villa experience in Tortola, British Virgin Islands. In her other world, she is the Founder and Inspiration Strategist of Beyond The Fork, a consultancy aimed at helping companies, their leaders and their employees navigate interpersonal challenges and work more effectively as teams.  Since arriving in the mainland US from her native St. Croix, she has become a cognitive-behavioral research scientist because she is passionate about working with tools to help guide and empower individuals to become accountable for their holistic health and well-being through education, understanding, and personal growth. This work has taken her from the American south to the East Coast and now to the midwest where she calls now calls Minneapolis, Minnesota home. There is so much more to get to know about this dynamic Glocal Citizen so be sure to tune in and check out the links below! Where to find Juleen? www.stbernardshillhouse.com On LinkedIn (https://www.linkedin.com/in/juleenchristopher/) On Instagram (https://www.instagram.com/stbernardshillhouse_bvi/) On Facebook (https://www.facebook.com/profile.php?id=100084768841373&sk=about) What's Juleen reading? Alphabet Murders Series (https://www.amazon.com/stores/Sue-Grafton/author/B000APENIA?ref=ap_rdr&store_ref=ap_rdr&isDramIntegrated=true&shoppingPortalEnabled=true) by Sue Grafton Works by Zadie Smith (https://www.amazon.com/s?k=zadie+smith&i=digital-text&crid=1MRNRHH8L63S9&sprefix=zadie+smith%2Cdigital-text%2C255&ref=nb_sb_noss_1) What's Juleen watching? African Folktales Reimagined (https://www.unesco.org/en/articles/unesco-netflix-global-launch-short-films-african-folk-tales-reimagined-29-march?TSPD_101_R0=080713870fab20008864d80ce7383c4893d809f05d7a0cc853c2c287bc7c41f306e6521d836bb1a108f58a915e143000e30b8eb185b53dda103d858cd9aea26024549206dadf1eef55bb635960dcf480b8b9877b1bf69c4e05d3ce0cf90257fe) Kim's Convenience (https://en.wikipedia.org/wiki/Kim%27s_Convenience) Never Have I Ever on Netflix (https://www.netflix.com/title/80179190) La Reina del Sur (https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjmrKia09X-AhXcV6QEHcwuD_EQFnoECEoQAQ&url=https%3A%2F%2Fwww.netflix.com%2Ftitle%2F80107369&usg=AOvVaw0jEr7WbLQcQTF8Z9ghIbeD) What's Juleen listening to? Angelique Kidjo (https://en.wikipedia.org/wiki/Ang%C3%A9lique_Kidjo) Biggest Afrobeats Artists (https://www.schooldrillers.com/biggest-afrobeats-artist/) Bossa Nova (https://en.wikipedia.org/wiki/Bossa_nova) Other topics of interest: About my Ayurveda Treatments in Ghana (http://ayushghana.com/#:~:text=Ayurveda%20is%20a%20wholistic%20way,deceases%2C%20but%20to%20prevent%20ailments) About the British Virgin Islands (https://en.wikipedia.org/wiki/British_Virgin_Islands) Governance in the BVI (https://en.wikipedia.org/wiki/British_Virgin_Islands) Who is a Belonger? (https://en.wikipedia.org/wiki/Belonger_status) About Jerry Blackwell (https://en.wikipedia.org/wiki/Jerry_W._Blackwell) Redemption Botanicals (https://redemptioncanna.com/our-story/) Minnesota Equity & Justice Project (https://www.mnhum.org/program/minnesota-equity-justice-project/?utm_source=rss&utm_medium=rss&utm_campaign=minnesota-equity-justice-project) Positive Intelligence (https://www.positiveintelligence.com) Special Guest: Juleen Christopher.

Featuring perspectives from Drs Robert L Coleman, Matthew A Powell and Brian M Slomovitz, moderated by Dr Shannon N Westin, including the following topics: Immune Checkpoint Inhibitors for Patients with Advanced Microsatellite Instability (MSI)-High/Mismatch Repair (MMR)-Deficient Endometrial Cancer — Dr Powell  Introduction (0:00) Case: A woman in her early 60s with MSI-high recurrent endometrioid adenocarcinoma of the uterus experiences progression after minimal response to carboplatin/paclitaxel — Lyndsay J Willmott, MD (2:25) Case: A woman in her early 50s with MSI-high metastatic endometrial adenocarcinoma after rapid, highly symptomatic progressive disease on paclitaxel/carboplatin — Kellie E Schneider, MD (8:21) Faculty presentation: Dr Powell (14:35) Immunotherapy-Based Strategies for Patients with MMR-Proficient (pMMR) Endometrial Cancer — Dr Coleman  Case: A woman in her early 60s with a 10-cm right ovarian mass and right pelvic adenopathy; total abdominal hysterectomy with bilateral salpingo-oophorectomy and para-aortic lymph node dissection reveal microsatellite stable (MSS) carcinosarcoma of the endometrium with right ovary and pelvic lymph node involvement (R0); adjuvant paclitaxel/carboplatin administered — Thomas P Morrissey, MD (24:46) Case: A woman in her late 60s with Stage IB, Grade 1 endometrial cancer after hysterectomy/sentinel lymph node biopsy — Dana M Chase, MD (30:11) Faculty presentation: Dr Coleman (35:54) Diagnosis and Management of Adverse Events Associated with Immune Checkpoint Inhibitors Alone and in Combination for Endometrial Cancer — Dr Westin  Case: A woman in her early 60s with a family history of breast cancer — Dr Morrissey (46:05) Case: A woman in her mid 70s who underwent hysterectomy, lymphadenectomy, omentectomy and 6 cycles of carboplatin/paclitaxel for a Stage IB MSS serous endometrial cancer; develops metastatic disease to the lungs 11 months later and is started on lenvatinib/pembrolizumab — Dr Chase (51:36) Faculty presentation: Dr Westin (57:09) Novel Investigational Agents and Strategies Under Evaluation for Patients with Endometrial Cancer — Dr Slomovitz  Case: A woman in her early 70s with HER2-positive serous carcinoma of the uterus receives adjuvant carboplatin/paclitaxel and trastuzumab, now no evidence of disease and receiving maintenance trastuzumab — Dr Willmott (1:07:34) Case: A woman in her early 80s with MSI-high metastatic endometrial cancer who receives talazoparib on the TAPUR clinical trial after experiencing progressive disease on pembrolizumab after 4 cycles — John K Chan, MD (1:13:01) Faculty presentation: Dr Slomovitz (1:18:53) CME information and select publications

JCO PO author Dr. Brandon Huffman shares insights into his JCO PO article, “Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients With Esophageal and Gastric Cancers” and discusses the article's findings of ctDNA levels in the preoperative, postoperative, and surveillance settings in patients with EGC. Host Dr. Rafeh Naqash and Dr. Huffman discuss ctDNA assessments, treatment paradigms and interventions, and tumor-informed assays. TRANSCRIPT Dr. Abdul Rafeh Naqash: Hello, and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, social media editor for JCO Precision Oncology, and I'm also an Assistant Professor in Medical Oncology at the OU Stephenson Cancer Center. Today, I am excited to be joined by Dr. Brandon Huffman. Dr. Huffman is a gastrointestinal medical oncologist, and he's also an instructor in medicine at the Dana-Farber Cancer Institute at the Harvard Medical School. He's the lead author on today's JCO Precision article, "Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients with Esophageal and Gastric Cancers."   Our guest's disclosures will be linked in the transcript.   Dr. Huffman, welcome to our podcast and thanks for joining us today. Dr. Brandon Huffman: Of course. Thanks for having me. Dr. Abdul Rafeh Naqash: For the sake of this discussion, we'll refer to each other using our first names. So, Brandon, exciting to have you today. We're going to talk about this very interesting topic on circulating tumor DNA and how your team used the ctDNA assessment in patients with esophageal and gastric cancers. For the sake of the listeners, could we start by asking you what are the current treatment paradigms for early-stage esophagogastric cancers? Since you practice this on a daily basis, what is the current approach, briefly, which will play into how this study looked at ctDNA in the context of early-stage esophagogastric cancers? Dr. Brandon Huffman: Yes, definitely. Thanks first for having me. Thanks for highlighting our work, and I'm really excited to talk with you about our manuscript and research today. To answer your question about how to treat localized esophagogastric cancer, it's a little bit more specific depending on where in the esophagus, GE junction or stomach where the tumors arise. For instance, we treat esophageal and upper gastroesophageal junction cancers with, often, chemoradiation, neoadjuvantly, and that is followed by surgery. And if there's a pathologic incomplete response, then many patients will get Adjuvant Nivolumab, a PD-one inhibitor, whereas the lower the tumor is in the upper GI tract, most often, perioperative chemotherapy is used for the lower GEJ and gastric cancers. Dr. Abdul Rafeh Naqash: Thank you so much. And I know, I think to some extent, if I remember correctly, immunotherapy has been incorporated into this paradigm. Is that a fair assessment? Dr. Brandon Huffman: That's exactly right. So, excitingly, we treat patients with neoadjuvant chemo or chemoradiation, and surgery is really the crux of the treatment paradigm for esophagogastric cancers in general. However, recently the CheckMate 577 clinical trial for the use of adjuvant Navolumab showed an improvement in disease-free survival in patients who had an incomplete path response. They used one year of Nivolumab compared to placebo. So it has recently become a standard of care where I practice, and I feel like a common practice around the country. Dr. Abdul Rafeh Naqash: Thank you so much. Now, going to the premise of this paper where you and your team basically looked at circulating tumor DNA as a prognostic marker in these patients that had early-stage esophagogastric cancers, was there a specific reason why you wanted to look at the early stage? What was the rationale for evaluating this biomarker in this patient population? Dr. Brandon Huffman: So, esophageal and gastric cancers affect a large number of patients every year. And unfortunately, despite our best efforts with curative intent therapy, over 50% recur within three years. So we know that there are pre surgical risk factors such as a larger bulky primary tumor or lymph node-positive disease that increase the risk for progression or recurrence after surgery. And we know, in addition, in other GI malignancies and other malignancies such as colorectal cancer, for instance, that the presence of circulating tumor DNA after surgical resection of localized tumors is associated with an increased risk of recurrence. So this has actually led to clinical trials investigating whether or not ctDNA can be integrated into the decision-making for adjuvant colorectal cancer treatment, such as ongoing trials such as the BESPOKE trial, COBRA, DYNAMIC trials that have recently been reported. The use of ctDNA is being used in other malignancies. And to give you a little bit of background, this project started when I was seeing patients with Dr. Sam Klempner at Mass General during my fellowship, where I was in the combined Dana-Farber/Mass General program. And he and others had begun collecting serial plasma samples on every patient we saw with esophagus, gastroesophageal junction and gastric cancers to assess for the presence or absence of ctDNA. And we used the tumor-informed ctDNA assay from Signatera, which, for those who aren't familiar, this is a ctDNA platform where a panel is built from the results of whole exome sequencing on the patient's FFPE tumor. The panel includes 16 patient-specific somatic single nucleotide variants for each patient, and it's new for each patient. Once that panel is built, the cell free DNA is tested from a plasma sample. And if there are two or more of the tumor-specific variants present, then they're considered ctDNA positive. So some of those colorectal cancer trials that I mentioned before are using this assay, and we wanted to investigate whether or not this high-risk population could be further assessed for risk of recurrence. Dr. Abdul Rafeh Naqash: Excellent. Thank you so much. And I know that a lot of these ctDNA based assessments have made inroads into the GI malignancy space, lesser in the other tumor types. I think we are all trying to catch up to what you guys are doing in the early-stage colon cancer space or the early-stage esophagogastric cancer space. So it's definitely very a interesting avenue to assess minimal residual or molecular residual disease. Now, going back to the methodology, I found it very interesting, and I think it's very important for listeners especially to understand the context of ctDNA assessments because I think a majority of oncologists are used to the liquid biopsy aspect. But this is not necessarily the liquid biopsy. It's somewhat different. So what I've understood, and I'd like to ask you to explain in the context of tumor-informed and tumor uninformed assays, what are the assays that are available, and how do they differ in terms of serial monitoring? And why is this ctDNA-based assessment somewhat different or more patient-customizable than our regular liquid biopsy assays, which are also blood based but not tumor-informed? Dr. Brandon Huffman: That is the question of the hour. And many different research projects are ongoing to try and identify which one is better, if one is better. I know that there are some commercial assays, for instance, that are not tumor-informed. They take a blood sample and then test for cell free DNA. The risk behind that is it's testing for common genetic mutations from a next-generation sequencing panel platform. And it may also detect CHIP variants or clonal hematopoiesis of indeterminate potential variants that aren't related to the underlying solid tumor malignancy. So a tumor-informed assay, for instance, such as the one that we used in this study, uses the patient's tumor and sequences it with whole exome sequencing and identifies very specific variants within the tumor that are only present within the tumor because they compare it also with a normal blood sample from the patient at the same time. And so they pick tumor-informed specific variants that then they test for on their assay. And that increases the sensitivity of the ctDNA assay so that you can really try to understand, is this cell free DNA that we are detecting related to the tumor or can we ignore it potentially? I don't know if we can necessarily ignore it in all honesty because it could affect- there's a lot of ongoing work that is looking at the risk of CHIP. But overall, this is specific for the primary tumor that we were investigating. Dr. Abdul Rafeh Naqash: I definitely agree with you there. I think the important point, as you mentioned, is that using the whole exome approach, in the blood and the tumor, you're able to eliminate the CHIP variants or the germline variants that may not be contributing. And that way you're able to specifically look at certain genetic alterations that eventually, I think using PCR-based approaches, you identify the same and quantify the same in the blood serially. And that's how this tumor-informed assay is somewhat unique and different. Now, going to the crux of this study, could you tell us a little about the patient population? I think you stratified patients. You had a pre-operative cohort, you had an MRD cohort, you had a surveillance cohort, and you had a cohort where you assessed ctDNA positivity at any time point. So, several different cohorts, and you assess recurrence-free survival in those cohorts. Could you tell us a little bit more about how you evaluated these cohorts? What were the selection criteria, and how many patient samples did you have for these different cohorts? Dr. Brandon Huffman: Absolutely. So, we aimed to determine the feasibility of testing ctDNA in patients with gastroesophageal cancer. And so, there were several clinicians from over 70 institutions across the United States who began prospectively collecting serial plasma samples for the presence or absence of the tumor-informed ctDNA. And they included patients from stages one through stage four, gastroesophageal cancer specifically, they included patients who were stages one through four with gastroesophageal cancer. They were collected at the discretion of the ordering clinicians and then incorporated into their routine clinical care as they saw fit. Within this dataset, we have a subset, a large number of patients that is unique to this dataset, specifically in that we have clinical outcomes, treatment, and follow-up data for the patients that were reported on the main findings in the paper. So, overall, we collected and analyzed over 900 plasma samples in almost 300 patients with gastroesophageal cancer, esophageal, gastroesophageal junction and gastric cancers. And in many of the analyses, we lumped them all together. But then we also wanted to separate it out because, as I mentioned before, the treatment paradigm does differ amongst a more proximal esophageal tumor compared to a distal gastric cancer. So, we focused a majority of our analyses on the detection of ctDNA and localized disease, which included 212 patients with stages one through three gastroesophageal cancer. And I would say we had three major findings. Most of the patients who were tested beforehand, which was a small subset, as I mentioned, this was pragmatic at the discretion of the ordering clinician, but most of the patients who were tested beforehand had positive preoperative ctDNA present. Of the patients who were tested for postoperative ctDNA at any time point, and then specifically within the different subsets of populations that we talked about, postoperative ctDNA was associated with at least a tenfold increased risk of recurrence in all subsets. And ctDNA detection postoperatively was independently associated with recurrence when controlling for age, sex, tumor location, and microsatellite status. So, a few of the populations that we wanted to test for, one in particular was the molecular residual disease, or MRD window. We labeled this MRD window as the time from surgical resection until 16 weeks. So, if patients were ctDNA positive within that window, we counted that in the primary outcome. And the reason that we chose the MRD window, in addition to this time point of 16 weeks - I should say that the 16 weeks is without any therapy postoperatively, so they have not been treated with any chemo or immunotherapy in this window. We thought that this MRD window was an interesting research topic because the CheckMate 577 Adjuvant Nivolumab clinical trial identified that 16 weeks was the window in which patients could be enrolled up until that timepoint to receive adjuvant nivolumab. So, we're thinking from a future project standpoint, a future clinical trial, perhaps, that if we have identified that patients who are ctDNA positive within this timepoint window, is there an increased risk for recurrence? Because if there is, then perhaps nivolumab intervention will decrease that risk or something that is escalated further. And that's a question that we don't have the answer for, a question that our data can't answer adequately. But it's an interesting one that I see the future questions that can be answered from these data. Dr. Abdul Rafeh Naqash: Thank you so much. And I agree with you there that this is a very intriguing approach of finding out whether treatment escalation has to be done based on ctDNA positivity, but also, conversely, treatment de-escalation, which there is a lot of emphasis being laid on, especially in the early phase trial in lung cancer, especially in the early setting when targeted therapies or immunotherapies are approved for one to three years, depending on what kind of therapy you're looking at. In those individuals that perhaps have negative ctDNA after one year, maybe therapy de-escalation would be a reasonable approach. So, definitely more interesting clinical trial ideas in this space focusing on ctDNA assessments. Now, one of the questions that comes to my mind is, when you use ctDNA-based assessments, initially, the patient gets biopsied, and it usually takes four to six weeks for ctDNA-based assessments to come back--I'm talking about tumor-informed assay results to come back, in my personal experience. So, could that potentially, or in your practice, how do you mitigate those delays? If you're trying to schedule a patient for surgery, for example, does that cause any delays in any care because you're trying to get the assessment done, or does your workflow proceed as planned and then you get the results and then subsequently you perhaps make a decision based on their ctDNA assessment? Dr. Brandon Huffman: At the present time, we are trying to gather more data to understand what we should do with the results that we're receiving. And I think the starting point of collecting serially to just understand the process is helpful. One of the questions we wanted to know that we weren't able to answer with this dataset was: is there lead time? In many cases, ctDNA detection can occur even a year prior to radiographic recurrence. In our case, because this was a pragmatic, clinically at the discretion of the investigators when they decided to test patients for ctDNA, there is heterogeneity among those who are ctDNA positive, and when they get their radiographic imaging, maybe they were moved up. I know in our practice with Dr. Klempner, when I was seeing these patients with him, it was a flag for us to order scans earlier in a patient that we might not have historically ordered so that we could then see, is there something intervenable? Maybe there was a positive lymph node on PET imaging that we could radiate or that wasn't included in the neoadjuvant radiation, for instance. So, we could not predict the lead time from positivity to radiographic recurrence, but I think that that's the hope is that we detected micrometastatic disease, my hope is that we can intervene in the future. But these data aren't able to quite answer that question perfectly. Dr. Abdul Rafeh Naqash: Sure. And there's definitely caveats to doing this in a pragmatic manner based on investigator assessments. Now, another question I was thinking of is, when you do do these ctDNA based assessments, and since these are tumor-informed, meaning you biopsy the tumor initially, you identify certain single nucleotide variants and those are the ones that you basically barcode and do PCR assessments using blood. We've learned time and again that tumors can change based on the kind of therapy that you give the patient. So, if your tumor is seeing FOLFOX nivolumab, or all the other novel therapies that you guys give in the setting, is there a chance that the tumor changes over time and you may not be able to capture those newer single-nucleotide variants that are coming up? It's just a provocative question, but I wanted to see what your thoughts are on that. Dr. Brandon Huffman: It's a great question. I don't entirely know the answer. I'll just be forthright about that. I do think that when designing these assays, they try to choose the more clonal rather than subclonal variants. And so the hope is that, despite the heterogeneity that we know occurs in esophagogastric cancers, we can eliminate that possibility. But you're right, there's no perfect way of knowing that. Dr. Abdul Rafeh Naqash: I really appreciate you using that word subclonal versus clonal. I think that perhaps makes a difference there. But again, more to do in this field to understand how the tumor evolves and whether it's the clonal mutation, subclonal mutation that needs to be followed. But definitely a lot of interesting work in this space that's ongoing, and, like you mentioned, there are ongoing trials, and both in the neoadjuvant adjuvant space, this field is definitely moving fast in the right direction. I briefly want you to highlight that one patient case study example that you had. And this was a patient with oligometastatic disease recurrence where you used the ctDNA assessment. And I do some of this in my daily practice, and I really found it useful to have this sort of a patient case example that elaborates in the bigger picture of how this kind of assessment works in a real-life scenario. So it's not just data, it's a patient's trajectory over the course of time where the treating physician was able to use this assay. Could you tell us a little bit more about this individual example here? Dr. Brandon Huffman: Yeah, absolutely. So this was a 56-year-old man that we saw in clinic with stage three esophageal adenocarcinoma, and was treated with the standard neoadjuvant cross chemoradiation, had an R0 resection with residual disease with a significant treatment effect. And there were lymph nodes that were positive on surgical resection with 39 lymph nodes removed. The patient recovered well and was followed with the standard of care radiographic and clinical surveillance. We also were looking for ctDNA, and what we noted was that there were, often you find these undulating pulmonary nodules that come and go, and they may or may not be infectious, and maybe there's one that's sub-centimeter that slowly grows, and what we found was that at about five months post-surgery, there was a positive ctDNA MRD, and we repeated it at short interval and noted a rising value, which this assay will give you a quantitative value. Once we did that, we ordered imaging and saw a nine-millimeter pulmonary nodule and ultimately biopsied it. It was there in the right upper lobe, and it was positive for metastatic adenocarcinoma. So we treated the patient with the standard FOLFOX plus Nivolumab and actually did SBRT, stereotactic body radiotherapy, to the lung metastasis. And his ctDNA became undetectable. So because FOLFOX is toxic, we transitioned to a maintenance of Nivolumab and he was on maintenance therapy for several months and had no radiographic evidence of disease and remained ctDNA negative for twelve months. So we biopsied the right upper lobe lung lesion. It was positive for metastatic adenocarcinoma, and then after a multidisciplinary discussion, we treated him with SBRT and then FOLFOX and Nivolumab and then dropped down to Nivolumab maintenance once his ctDNA was undetectable. That highlights the fact that this was an isolated recurrence, which we continued to monitor, and then he had another site of disease a few months later, and we did SBRT to that area while he maintained on just Nivolumab, and the ctDNA came down as well.   So I think, although it doesn't prove anything necessarily, other than demonstrating there is a correlation with the newly diagnosed metastatic disease, it does note that you can use this in dynamic ways, and if it really helps patients live longer, although this is anecdotal--who knows? If we hadn't done SBRT to that area, it was 9 mm. We could have waited until it grew, but then maybe some subclonal, more aggressive metastasis could have really put this patient in a much tougher situation. So it's an interesting case example, and there are several others that we could have put in here that are pretty similar. Dr. Abdul Rafeh Naqash: Thank you so much for highlighting that case. I couldn't agree more that there is a certain aspect to the ctDNA assessment, where in individuals like the example that you've highlighted here, this can provide lead time potentially and help with earlier management of perhaps more like oligometastatic disease rather than diffuse disease burden. And in that context, one of the questions that I was going to ask you, based on your data, was there any correlation of tumor burden preoperatively and ctDNA positivity after surgery that you guys were able to identify or thinking of identifying? Dr. Brandon Huffman: Unfortunately, with our data set, we weren't able to look at that assessment of comparing the overall tumor burden to the quantitative value. But it's an interesting one because we know that in other malignancies, for instance, if there is a correlation of overall disease burden, it also depends on the tumor type, but we also know that perhaps patients will respond differently to chemo or immunotherapy if they have a lower tumor burden, if they have a lower ctDNA value, potentially. I think that's an interesting question for a future project. Dr. Abdul Rafeh Naqash: Thank you so much, Brandon. We do like to talk a little bit about the person behind the work. So tell us a little bit more about yourself, your training, your interests, and some little advice for other early-career investigators who might be looking into a similar space and hopefully get inspired by the kind of work that you've done or are planning to do. Dr. Brandon Huffman: Sure. So, as I mentioned, when I started this project, I was in fellowship. I was seeing patients with Dr. Sam Klempner at Mass General, where I saw patients with him for a year, and as part of my clinical training in the Dana-Farber/Mass General HemOnc Fellowship. Since that time, I have graduated fellowship. I'm a GI Medical Oncologist at Dana-Farber Cancer Institute, and in the GI division, I see patients with all GI malignancies, and I focus on the development of clinical trials in upper GI malignancies, along with investigating the use of circulating tumor DNA as a biomarker, hopefully, we can understand whether it's a predictive biomarker that we can intervene upon in the future. I think the greatest advice that I received and that I will give to all future trainees; I'm not sure that I'm qualified to tell this to all the junior investigators, but here it is: Find yourself a mentor who really cares and invests in you and your ideas. I have that with Sam, and this project was an incredible part of my development as a junior investigator. I've asked really interesting questions. There are more questions that can be answered from this data set, and I'm excited for the opportunity. Dr. Abdul Rafeh Naqash: Thank you so much, Brandon. Thanks for taking the time to speak with us today and thank you for choosing JCO Precision Oncology as a destination for your work. Hopefully, we'll see more of this subsequently in the years to come. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating, a review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts  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. Guest Bio Dr. Brandon Huffman, MD, is a gastrointestinal medical oncologist and Instructor in Medicine at Dana-Farber Cancer Institute and Harvard Medical School.  Guest Disclosures Brandon M. Huffman Stock and Other Ownership Interests: Doximity

Featuring perspectives from Drs Mansoor Raza Mirza, Amit M Oza and Richard T Penson, moderated by Dr Joyce F Liu, including the following topics: •      Optimal Genomic Evaluation of and Targeted Therapies for Newly Diagnosed Advanced Ovarian Cancer — Dr Mirza o   Introduction (0:00) o   Case: A morbidly obese woman in her mid 40s who is a Jehovah's Witness with ovarian cancer and a germline BRCA2 mutation — Lyndsay J Willmott, MD (1:10) o   Case: A woman in her early 50s with BRCA wild-type, homologous recombination repair deficiency (HRD)-negative Stage IV ovarian cancer, a large pleural effusion and ascites — Kellie E Schneider, MD (7:16) o   Faculty presentation: Dr Mirza (13:51) •      PARP Inhibitors for Relapsed/Refractory Ovarian Cancer — Dr Oza o   Case: A woman in her mid 60s with recurrent BRCA wild-type ovarian cancer in ongoing and durable remission with paclitaxel/carboplatin followed by maintenance niraparib — John K Chan, MD (26:13) o   Case: A woman in her early 50s with a germline BRCA2 mutation and recurrent platinum-sensitive ovarian cancer who received paclitaxel/carboplatin/bevacizumab and maintenance olaparib/bevacizumab — Thomas P Morrissey, MD (32:09) o   Faculty presentation: Dr Oza (36:55) •      Rationale for and Available Data with PARP Inhibitors in Combination with Other Anticancer Therapies for Advanced Ovarian Cancer — Dr Liu o   Case: A woman in her early 20s with newly diagnosed Stage IV, low-grade serous carcinoma of the ovary with pleural effusions — Dana M Chase, MD (48:55) o   Case: A woman in her late 40s with high-grade serous ovarian cancer who received neoadjuvant chemotherapy on the Phase III FIRST trial and undergoes R0 debulking surgery — Dr Schneider (52:51) o   Faculty presentation: Dr Liu (57:39) •      Novel Agents for the Treatment of Ovarian Cancer — Dr Penson o   Case: A woman in her mid 60s with multiregimen-refractory metastatic ovarian cancer who receives paclitaxel/tumor treating fields on the INNOVATE-3 trial and develops dermatologic toxicity — Dr Chan (1:07:19) o   Cases: A woman in her early 70s with multiple comorbidities and extensively treated recurrent, platinum-resistant BRCA wild-type, HRD-negative, PD-L1-positive, FR-alpha-mutant ovarian cancer and a woman in her mid 40s with a germline BRCA1 mutation and multiregimen-recurrent FR-alpha-mutant carcinomatosis — Dr Chase and Dr Willmott (1:11:00) o   Faculty presentation: Dr Penson (1:18:20) CME information and select publications

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: R0 Is Not Counterfactual, published by jefftk on April 13, 2023 on LessWrong. Someone who helps organize an N95-required dance recently wrote to a group of organizers: R0 is the number of people that an infected individual is likely to infect. R0 was 5.4 in Dec 2022. ... People who assume increased risk for themselves are also assuming increased risk for 5.4 other people. This is wrong in two main ways, and I responded on the list, but I wanted to share my response here as well because the claim illustrates two common misconceptions. The first issue is that R0 is for an entirely "susceptible" population, one in which no one has any gained any immunity from exposure or vaccination. What an R0 of 5.4 would mean is that if it had suddenly appeared in 2019, each infected person would on average infect 5.4 others. This is very different from the current situation where most people have had several shots, plus most people have had covid at least once. The term for the expected number of people an infected person will directly infect given current conditions is Rt, currently about 1. Which is really just another way of saying that covid levels have been changing relatively slowly: if Rt were 5.4 we'd have rapid growth tearing through the population. The other issue is that even Rt doesn't tell you how many infections you getting sick would cause. You may know various things about your behavior that make the expected number of people you'd directly infect higher or lower, but that's not the main issue. Instead it's that (a) people you infect can go on to infect other people and (b) people you infect might otherwise have been infected by other people. These two factors push in opposite directions, but both can be quite large. Here are a pair of toy situations showing how, holding Rt fixed, one infection can lead to either very many or almost no counterfactual infections: A new epidemic is starting, and Rt (which is R0 in this case) is 5.4. There are very clear symptoms, and people are just starting to catch on. Very soon there will be massive behavior changes to suppress Rt, and at this stage those might or might not be enough. One more person getting infected could have a 5% impact on the chance that this becomes a pandemic infecting ~half the world. In which case the expected number of additional infections is ~200M people. Here (a) is the main factor. An new pandemic is well under way, and it has easily missed symptoms. Even with lots of precautions in place, Rt is still a very high 5.4. There are so many paths by which a person can get infected that one additional infection has almost no effect on how many people eventually get infected. Here (b) is the main factor. Now, "how many counterfactual infections would I cause if I got sick", and "how would my getting sick shift the distribution of when other people get sick" are really valuable questions to know the answers to if you're trying to understand the social impacts of more risky behavior, and it would be great if we did know these. But the progress epidemiologists have put into estimating R0 is not most of what you'd draw on in trying to get better answers. Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.

In this episode of the IJGC podcast, Editor-in-Chief, Dr. Pedro Ramirez, is joined by Dr. Janos L. Tanyi to discuss intraoperative imaging with OTL38 in ovarian cancer. Dr. Tanyi is an associate professor in the Department of Obstetrics and Gynecology at The University of Pennsylvania. He developed an advanced immunotherapy program that allows patients' own immune cells to recognize and kill their tumor; a gene-engineered T cell approach. Dr. Tanyi has a broad background in immunotherapy, cancer immunology, molecular genetics and clinical expertise in gynecologic oncology. He has the frontline experience in ovarian cancer immunotherapy as he is the primary PI for both the ovarian cancer vaccine and adoptive T cell transfer trials at University of Pennsylvania. At Penn, he has fostered the establishment of a rich translational research environment focused on ovarian cancer. Furthermore, Dr. Tanyi led the Phase 2 and 3 trials evaluating the efficacy and safety of Pafolacianine Sodium combined with intraoperative molecular imaging during cytoreductive surgery of ovarian cancer. Highlights: - It is well known that the extent of residual disease after surgery is negatively correlated with patient survival in ovarian cancer. To achieve R0 complete cytoreduction remains the goal of surgery. In this phase III study, it was evaluated whether Cytalux, would identify cancer lesions not identified by the surgeon by white light visual inspection or palpation. - During this phase 3 trial, one or more additional cancer lesions were identified in approximately 33% of patients using of Cytalux with near-infrared imaging which was not detected by white light visual inspection and manual palpation. - The intraoperative use of Cytalux with near-infrared imaging can be a good adjunct to current surgical approaches in identifying additional cancer lesions during cytoreductive surgery.

Trung Quốc nay đã từ bỏ hoàn toàn chính sách “zero-Covid”, mở cửa trở lại với thế giới bên ngoài, cụ thể là kể từ ngày 08/01/2023 sẽ không còn áp dụng biện pháp cách ly bắt buộc đối với những người nhập cảnh vào Trung Quốc, đồng thời người dân Trung Quốc sẽ được tự do ra nước ngoài.  Tác động kinh tế Việc Trung Quốc, nền kinh tế lớn thứ hai thế giới, sẽ mở cửa trở lại hoàn toàn vào quý 2/2023 là một thông tin tích cực cho toàn thế giới nói chung và cho Việt Nam nói riêng, nhất là các doanh nghiệp xuất khẩu sản phẩm sang Trung Quốc với số lượng lớn sẽ được hưởng lợi. Việc nới lỏng các biện pháp chống Covid-19 của Trung Quốc sẽ có tác động tích cực đến thương mại toàn cầu và giúp tái khởi động chuỗi cung ứng bị gián đoạn. Nhiều hãng hàng không đã thông báo nối lại đường bay giữa Trung Quốc và Việt Nam, thúc đẩy ngành du lịch của Việt Nam cũng như giao thương giữa Việt Nam và Trung Quốc. Theo tập đoàn quản lý đầu tư VinaCapital, việc Trung Quốc mở cửa trở lại sẽ giúp kích thích tăng trưởng của Việt Nam vào năm 2023, vì nước này là đối tác thương mại lớn nhất của Việt Nam và là thị trường du lịch  lớn nhất của Việt Nam. Trong báo cáo mới công bố, ông Michael Kokalari, Chuyên gia Kinh tế trưởng của VinaCapital, dự báo việc Trung Quốc mở cửa trở lại sẽ thúc đẩy tăng trưởng GDP của Việt Nam hơn 2% vào năm tới, do lượng khách du lịch Trung Quốc trở lại vào nửa cuối năm 2023. Riêng về mặt giáo dục, theo tờ vnExpress, nhiều sinh viên Việt Nam du học ở Trung Quốc đã thở phào nhẹ nhõm khi nghe tin Trung Quốc sắp mở cửa trở lại, bởi vì trong gần 3 năm qua, nhiều người trong số họ đã phải học trực tuyến với rất nhiều khó khăn, áp lực, còn những ai vẫn sang Trung Quốc để tiếp tục học thì phải gánh những khoản chi phí rất lớn cho vé máy bay, cho cách ly tập trung … Tuy nhiên, phải chờ thêm một thời gian để thấy rõ hơn tác động của việc Trung Quốc mở cửa trở lại đối với nền kinh tế thế giới và hiện vẫn chưa biết các chính sách của Trung Quốc sẽ như thế nào sau thời kỳ hậu "zero- Covid". Lo ngại dịch lây lan Nhưng Trung Quốc mở cửa trở lại đúng vào lúc mà tại quốc gia 1,4 tỷ dân này số ca nhiễm Covid-19 đang bùng nổ, có thể đã lên đến hàng chục triệu, thậm chí hàng trăm triệu ca. Trước tình hình đó, nhiều nước trên thế giới, như Hoa Kỳ, Nhật Bản, Ấn Độ, Hàn Quốc, Ý… đã thông báo những biện pháp hạn chế đối với các hành khách đến từ Trung Quốc, cụ thể là xét nghiệm Covid-19 và cách ly bắt buộc đối với họ, nhằm ngăn chặn dịch bệnh từ Hoa lục lây lan sang.  Riêng đối với Việt Nam, về mặt kinh tế, Trung Quốc mở cửa trở lại có nghĩa là giao thương giữa hai nước sẽ dần trở lại bình thường, nhất là ngành du lịch sẽ đón tiếp trở lại lượng du khách Trung Quốc, vốn chiếm đông nhất trong tổng số du khách quốc tế.  Nhưng vấn đề đặt ra là với lượng du khách Trung Quốc sẽ ồ ạt đổ sang, có nguy cơ là dịch Covid sẽ lại bùng phát mạnh ở Việt Nam hay không? Theo các chuyên gia dịch tễ học, như bác sĩ Trương Hữu Khanh, nguyên Trưởng khoa Nhiễm thần kinh, Bệnh viện Nhi đồng 1, Phó chủ tịch Liên chi hội truyền nhiễm TP Hồ Chí Minh, Việt Nam có một mức độ miễn dịch cao, nên không lo ngại lắm. Theo thống kê chính thức, cho đến nay Việt Nam đã tiêm gần 265,5 triệu liều vac-xin Covid-19, chích đủ ba mũi cho gần 80% dân số trên 18 tuổi: “ Quan trọng là mức độ miễn dịch của Việt Nam. Độ miễn dịch ở Việt Nam khi làm xét nghiệm thử một vài vùng đã đạt được đến hơn 90%. Việt Nam cũng đã trải qua một thời gian ứng phó với Omicron. Nếu Omicron biến thể mà vẫn là trong một nhánh của Omicron thì không đáng lo đối với một nước có mức độ miễn dịch cao như vậy.   Còn sự xuất hiện của một biến thể khác theo tôi thì rất là khó, tại vì Trung Quốc tuy họ đóng cửa, nhưng họ cũng có bị nhiễm, họ cũng có Omicron. Tác nhân của dịch bệnh hiện nay ở Trung Quốc cũng là một nhánh của Omicron thôi. Nếu một biến thể nhẹ của Omicron xâm nhập vào Việt Nam, với mức độ miễn dịch của Việt Nam, tỷ lệ chích mũi 3 cao, thì cũng không đến nổi phải quá sức lo lắng như những nước khác. Với một nền miễn dịch như vậy thì cũng không cần thiết phải làm một cái gì thật dữ dội. Chỉ những nước nào mà nền miễn dịch còn kém và đặc biệt là dân số lớn tuổi mà miễn dịch nền  cũng kém, thì mới đáng lo ngại.” Nguy cơ xuất hiện biến thể mới Sự bùng nổ số ca nhiễm ở Trung Quốc hiện nay chính là do biến thể BF.7, một biến thể của Omicron BA.5. Theo các chuyên gia, BF.7 có chỉ số R0 (tỷ lệ sinh sản của virus) từ 10 đến 18,6, có nghĩa là một người bị nhiễm sẽ truyền virus cho từ 10 đến 18,6 người khác. Đây là một tỷ lệ lây nhiễm cực cao, so với mức R0 từ 6 đến 7 của biến chủng Delta, 5,08 đối với biến thể Omicron hay 3 của chủng   gốc SARS-CoV-2.  Do có tốc độ lây lan nhanh chóng như vậy, biến thể BF.7 có thể gây ra mối đe dọa mới trên toàn thế giới hay không? Đáng lo ngại hơn nữa, từ Trung Quốc có sẽ xuất hiện một biến thể nào khác với Omicron hay không? Đối với bác sĩ Trương Hữu Khanh, trước mắt, biến thể mới ở Trung Quốc chưa đáng ngại lắm: “ Nếu nói về một tỷ lệ lây mà có thể dẫn đến một biến thể lạ hơn nữa, thì tốc độ lây lan ở những nước khác hiện nay vẫn là do Omicron, ví dụ như hiện nay có một vài nước, sau khi có Omicron cũng có những đợt sóng với số ca bệnh rất cao, nhưng vẫn không có biến thể khác với Omicron, tức là một bậc cao hơn Omicron, với những thay đổi cấu trúc. Với cách lây như vậy và với tốc độ lây như vậy mà cũng không xuất hiện biến thể cao hơn Omicron, thì có lẽ với tốc độ lây ở Trung Quốc, nó cũng khó mà thay thế Omicron.  Biến đổi một thể sang một cái khác cho tới hiện nay, theo nhận định của tôi, rất là khó. Bởi vì Omicron đã xuất hiện cả một năm nay rồi, thậm chí hơn nữa, những chỉ có những biến thể nhánh, tức là chỉ có khác về tốc độ lây thôi, chứ không gây bệnh nặng. Nguy cơ đó rất là thấp. Thứ hai là mình có tìm nguy cơ cao hơn thì phải tìm thêm nó là một biến chủng như thế nào. Không chỉ riêng Việt Nam mà cả tất cả các nước đều phải tìm biến chủng đó, nếu nó xuất hiện.  Theo tôi cái quan trọng nhất là có một biến thể nào sớm hay không, có nghĩa là có biến thể nào khác với những biến thể đang xuất hiện ở những nơi khác ngoài Trung Quốc hay không, để mình có thể dự đoán cho tất cả các nước trên thế giới. Tuy nhiên, nếu nó đã lây ra một nước ngoài Trung Quốc thì nó sẽ lây khắp thế giới. Mình cũng phải chuẩn bị tư thế để tìm xem có biến thể nào mới không. Nhưng nếu nó vẫn là biến thể trong dòng của Omicron thì nó không đáng ngại.”  Không cần xét nghiệm du khách Trung Quốc? Trong khi một số nước đã thông báo áp dụng xét nghiệm Covid với hành khách Trung Quốc, thì những nước khác như Úc, Đức, Thái Lan thì không ban các quy định gì mới đối với những người đến từ Hoa lục. Riêng Việt Nam thì cho đến cuối tuần qua chưa có thông báo gì. Nhưng đối với các chuyên gia như bác sĩ Trương Hữu Khách, chưa cần thiết áp dụng xét nghiệm toàn bộ du khách Trung Quốc vào Việt Nam:   “ Kiểm soát thì cũng có lợi hơn một chút thôi, tức là khi có kết quả dương tính thì chúng ta phải phân tích, chạy sequencing, để coi nó thuộc biến thể nào. Nhưng đòi hỏi phải lấy mẫu cho tất cả những người từ bên Trung Quốc sang thì tương đối là khó, bởi vì giao thương giữa Việt Nam với Trung Quốc khá là nhiều. Chắc chắn là Việt Nam sẽ nghe ngóng, sẽ phân tích các số ca nhiễm sau khi giao thương lại với Trung Quốc để xem nó thuộc biến thể gì, chứ còn làm xét nghiệm với tất cả mọi người thì hơi phí, trong khi nền miễn dịch của mình đã đạt được như vậy. Họ sang đây, nếu họ có biểu hiện bệnh mà tình cờ mình xét nghiệm hoặc mình chủ động tìm những ca điển hình và mình nghe ngóng xem là khi nó lây ra ngoài cộng đồng của Việt Nam thì mình cũng phân tích nó loại biến thể nào thì mình mới ứng phó kịp thời, chứ nếu mình làm từ đầu thì rất là tốn kém, mà cũng làm mất đi một cơ hội để làm ăn kinh tế với Trung Quốc.” Theo báo chí trong nước, bộ Y Tế hiện chưa có ý kiến đánh giá tình hình dịch sau khi Trung Quốc thông báo sắp mở cửa trở lại. Tuy nhiên, tại phiên họp thứ 19 Ban chỉ đạo quốc gia phòng chống Covid-19 ngày 23/12, bộ trưởng Y Tế Đào Hồng Lan đã cảnh báo về nguy cơ bùng phát các làn sóng Covid-19 do biến chủng mới. Dịp Tết dương lịch, Tết Nguyên đán với nhu cầu giao thương, du lịch tăng cao, là điều kiện thuận lợi cho các bệnh truyền nhiễm lây lan, có thể làm gia tăng số ca nhiễm Covid-19. Tháng 8, Bộ Y tế đề xuất Thủ tướng chưa công bố hết dịch, chưa xem Covid-19 là bệnh lưu hành tại Việt Nam. Bộ cũng cho rằng hiện Việt Nam "cơ bản đáp ứng" những điều kiện cần thiết để chuyển tiếp từ phòng chống đại dịch sang quản lý bền vững, nhưng vẫn cần cảnh giác với các biến chủng mới của virus.

Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we round out our discussion of early stage lung cancer treatment!* When deciding if a patient can get surgery upfront or not, remember the three “Fellow on Call” criteria for early stage lung cancer: - Mass invading other structures or mediastinum- Central lymph nodes (single digit)- Tumor >7 cm* If surgery is NOT an option at this time, where do we go from here?- Treat with upfront concurrent definitive chemoradiation- Treat with “induction” chemotherapy or induction concurrent chemoradiation**If surgery is/may be possible***What are the goals of “induction” treatments? - Eradicate microscopic disease- Improved local control, possibly shrinkage- Adding radiation may allow you to downstage tumor or lymph nodes to have a possible improvement in surgical outcomes* What sorts of discussions are being had a thoracic tumor board in patients with newly diagnosed early stage NSCLC? - Is the patient a surgical candidate?- If the patient is not a surgical candidate, then what are the options:--Definitive concurrent chemoradiation (usually) followed by immunotherapy---Pearl 1: Always choose this if surgeon thinks the patient is unresectable in general even with an induction approach---Pearl 2: Always choose this if 2 out of 3 criteria we discussed above are met---Pearl 3: Always choose this if N3 disease- “Induction” regimen with either chemotherapy alone or concurrent chemoradiation followed by surgery * What's the idea behind “induction” chemo or chemoradiation? - There is a chance that patients with these high risk features may already have micrometastatic disease, so treatment upfront can help address that- There is a chance that after surgery, patient may suffer deconditioning, which may preclude the use of chemo +/- radiation (up to 90% of patients are often eligible for chemoradiation before surgery; this drops to ~60% after surgery)- Local disease control to achieve the best possible surgical outcome (R0 resection) and also prevent any microscopic residual disease from then having the opportunity to spread systemically, especially in areas where the mass may be adjacent to many blood vessels or lymph nodes* What to treat with in the neoadjuvant setting?- Platinum containing regimens (“platinum doublets”):-- Carboplatin + paclitaxel-- Cisplatin + etoposide-- Cisplatin + gemcitable-- Cistplain + pemetrexed- Can combine this with radiation* How does the data about chemotherapy+IO in the neoadjuvant setting fit in here (CHECKMATE 816)?- In patients with Stage IIB to IIIA (8th edition) WITHOUT EGFR or ALK mutation, treatment with NEOADJUVANT chemotherapy q3w x3 cycles (most got cisplatin based therapy) + nivolumab 360mg q3w x3 cycles resulted in improved event free survival (31.6 months vs. 20.8 months) AND pathological complete response was 24.0% vs. 2.2%- Current NCCN guidelines state that if nivolumab is used in neoadjuvant setting, it should not be used in adjuvant setting- There is still uncertainty about how this fits into treatment compared to “traditional” neoadjuvant approaches with chemo+/-radiation*So after neoadjuvant treatment, does everyone go to surgery?- Always re-assess the status of the disease; if there is progression of disease, then will go to definitive chemoradiation- Discuss with surgeons to confirm if the patient is still a surgery candidate* If patient undergoes surgery, then what?- If patient got neoadjuvant therapy and an R0, then they are done with treatment- If R0 resection was not able to achieved, then either radiation “boost” to the area (if they previously got radiation), a course of radiation (if they just got induction chemo) or re-resection- We discuss the adjuvant setting in more detail in Episode 026 (https://www.thefellowoncall.com/tfocpodcast/episode-001disclaimer-wfhgf-ml3b6-9m66a-8rrc4-k8w87-x7xdd-wrzye-4xg8x-t73gt-cxc5s-nmg8f-cfyd6-hgs35-5pcwx-tf6dh-trggt-xzkt7-923gg-rpjzx-6s36p-hk27n-bbpgx-jymml-9lfam-76m4s)** If surgery is not possible*** If patient cannot go through to surgery Definitive chemoradiation:- Same chemotherapy agents as above, but treatment course is longer.- For instance, for NSCLC, total 60Gy in 2Gy divided fractions (5 days/week, 6 weeks of treatment) with chemotherapy* Additional therapy after chemoradiation (PACIFIC Trial) - Found that “consolidation” durvalumab 44% PFS 18 months vs 20% 5year survival benefit 40% vs. ~30% without treatmentReferences:https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450 - NCCN Lung Cancer guidelines https://www.nejm.org/doi/full/10.1056/nejmoa1709937 - PACIFIC Trial (NEJM 2017)https://www.nejm.org/doi/10.1056/NEJMoa2202170 - CHECKMATE 816 (NEJM 2022) Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Covid 8/18/22: CDC Admits Mistakes, published by Zvi on August 18, 2022 on LessWrong. Two Covid-related things happened this week that I did not expect. The CDC admitted that it had failed us during the pandemic, withdrew at long last many of its remaining recommendations and promised reforms to be less academic and otherwise do better. A new paper found potential biological markers for Long Covid, claiming it can be identified via tests that match patient self-reports almost all the time. This points towards potential progress in treatment, and more generally in Long Covid being much more concretely A Thing that might exist and could be reasoned about. There are still flaws, and even without flaws there is still much work to do here. Most of the reasons not to be concerned remain, so up front: I do not think that this should substantially change anyone's level of Covid precautions. Executive Summary CDC finally fully gives up on six foot social distancing and other measures. CDC admits some failure, promises reforms that seem potentially promising. New study finds potential biological markers for Long Covid. Also I think someone said something about over the counter hearing aids? Let's run the numbers. The Numbers Predictions Prediction from last week: 650k cases (-5%) and 3,200 deaths (+0%). Results: 602k cases (-12%) and 3,183 deaths (-1%). Prediction for next week: 560k cases (-8%) and 3,200 deaths (+1%). I do not know why cases declined more than expected but result seems robust so I see no reason to expect it not to continue at least somewhat. There won't be enough time for the decline to impact deaths yet, so I'm mostly going with the null prediction there. There is not much meaningful uncertainty here. Deaths Cases Decline cuts across all four regions. We are fully into the BA.5 era with nothing on the near-term horizon to replace it, so things should be quiet for a few months at least. Physical World Modeling A guide to buying the right HEPA air filter. Bob Wachter sees no sign of anything that might replace BA.5. Thread also reminds us that it is a common mistake not to take into account the correlation between the Covid status of people who choose to be together in a group. Trevor Bedford however sees logistic growth in BA.2.75, although only with R0 ~ 1.3 (versus ~1 for BA.5) which isn't that much of an advantage for a new strain taking over. My guess is Trevor is right and BA.2.75 will displace BA.5 over time, but that we will barely even notice. Some sad news. I opened a Manifold market on whether she'll experience a rebound, to see how common people think such events are. This also brings up the question, what happens when you're against actual physical world modeling and instead blindly follow CDC rules? They do know he had Covid-19 plus a rebound within the last few weeks? That it is absurd to think that being a ‘close contact' puts him at relatively high risk for Covid-19 given that timeline? No. Of course not. This is not a man to concern himself with whether or not an action makes physical sense. Almost no children under 5 are getting vaccinated, even weaker ‘than experts feared.' Doses are being discarded due to lack of demand. This should not be a fear so much as a revealed preference. If we had approved these doses sooner, I am guessing we would have had much higher uptake, although still nothing that would have satisfied experts. At this point, people don't care enough, especially given the logistics are frequently annoying. This raises the question of why we insisted in so many crazy precautions for these same young children for so long, in ways that I strongly believe did serious damage to their development and well-being. They were never at risk and everyone knew this well enough not to bother doing much about it when finally given the oppo...

1.WHO國際衛生條例突發事件委員會在6月25日開會後，一致建議世衛組織總幹事現階段應確定疫情不構成「國際關注公共衛生緊急事件」（PHEIC，Public Health Emergency of International Concern）。 2.報告中討論了五月以來在47個國家已經有了3040例通報。目前主要在歐美流行的猴痘和在非洲觀察到的病程表現通常不典型，可能僅有少數疹子，侷限在生殖器，鼠蹊部，肛門周圍，而不會到全身。他也可以在發燒，淋巴結腫大，疲勞前就有疹子。 3.多半都是輕症，極少數需要住院。目前僅通報一例免疫不全的患者死亡。似乎致死率也和之前有所改變。病毒有可能突變到比較會傳染，但致死率也降低。起碼不像非洲看到的1%甚至到10%的致死率。 4.一些初步的研究估計此波R0值是0.8，但在高風險族群比方說和患者從事高危險性行為者，則會大於1。荷蘭研究平均潛伏期是8.5天，但可以在4.2到17.3天之間。目前只有10位醫護人員染疫，不過9位都是非職場感染。 5.WHO委員會決定目前不構成國際關注公共衛生緊急事件PHEIC，但需要繼續關注後續發展。如果有以下狀況發生，可能都要重新評估： a.接下來的 21 天內報告的病例大為增長，在目前受影響的人群中和之外，比方說在性工作者中發生的比例。 b.有證據表明在更多國家造成明顯傳播，或在已流行國家還產生了更多傳播。 c.在弱勢群體的病例數量增加，比方說免疫不全族群，包括控制病況不佳的HIV帶原者，孕婦和兒童。 d.若有報告臨床嚴重程度增加的證據，比方說死亡率或是住院率增加。 e.若有證據表明在歐美反向感染到動物。 f.若有證據表明病毒有明顯突變導致其傳染力、致病力或免疫逃逸特性增強，對病毒藥物有抗藥性等等。 g.若在西非和中非國家以外的地方發現致病力更強的病毒株流行的證據。 p.s.PHEIC指的是「通過疾病的國際傳播構成對其他國家的公共衛生風險，以及可能需要採取協調一致的國際應對措施的不同尋常事件」；該事件狀態在「情況嚴重、突然、不尋常或意外」、「公共衛生影響超出了受影響國家的邊界​​」、「可能需要立即採取國際行動」時啟用。 自2009年以來，共計有六次國際關注的突發公共衛生事件，分別是：2009年H1N1新型流感疫情、2014年小兒麻痺疫情、2014年西非伊波拉疫情、2015年至2016年茲卡病毒疫情、2018年至2019年剛果伊波拉疫情，以及於2020年1月31日宣布的2019新型冠狀病毒疫情。 04b解讀： 1.此波猴痘疫情已經超過3000例，八成都在歐洲。多半都有性行為密切接觸史。WHO報告中表示此次病毒有不典型表現，不會像傳統上先發燒然後起疹子，從臉部開始，然後到身體其他部位這樣的病程。這次滿多病患可能僅有少數疹子，甚至只有一顆。他可以侷限在生殖器或是鼠蹊部，肛門周圍，而不會到全身。他也可以在發燒前就有疹子。我個人猜測這樣的不典型表現，似乎代表病毒本身已經有突變了。和之前在非洲看到已經不同。這樣輕症的表現，可能讓這個病較難診斷，且已經在歐美傳播一陣子了。 2.目前僅通報一例奈及利亞案例死亡，似乎致死率也和之前有所改變。病毒有可能突變到比較會傳染，但致死率也降低。起碼不像非洲看到的1%甚至到10%的致死率。 3.目前不是很確定性行為體液是否會傳染。但確定的是透過直接接觸受感染的皮膚疹子是會傳染的。 4.在非洲比較常見的傳染途徑是囓齒類傳染人，但這波歐美疫情顯然主要應該是人傳人，且多半是親密接觸。 5.我個人目前不會特別擔心猴痘，至少威脅不會有新冠病毒高，主要有以下原因： a.目前看來飛沫甚至空氣傳染應該不是主要傳播途徑。不然我們看到的案例數理當更多。且在戴口罩勤洗手的新冠防疫習慣之下，應該不太容易傳播。主要要提醒的是，不要進行不安全的性行為。 b.此疾病已經有疫苗也有藥物。且絕大多數都會自己好。 c.這是DNA病毒，不會像RNA病毒一樣這麼容易突變。 別被新聞嚇到了！我不會理解猴痘為下一個大魔王。新冠對於全人類的威脅目前還是大很多啦。 來複習一下猴痘懶人包。 https://linshibi.com/?p=40187 歡迎追蹤前台大感染科醫師。04b的發聲管道！ 我的電子名片 https://lit.link/linshibi 希望大家當我的種子教師，推廣正確的新冠衛教。科學防疫，不要只以恐懼防疫！ 歡迎贊助林氏璧孔醫師喝咖啡，讓我可以在這個紛亂的時代，繼續分享知識努力做正確新冠相關衛教。 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

What is monkeypox and how did it get here?We're talking about the monkeypox virus: its incubation period, symptoms, transmission, how contagious it is, treatment and mortality rate. It's similar to smallpox, which only two countries are officially in possession of WHO authorized smallpox repositories of. Iraq, North Korea and France are also believed to possess “illegal” stockpiles. If you enjoy our content, become a patron and unlock our premium episodes. 1 We discuss how Russia produced tons of biological weapons using similar plagues. As Pulitzer Prize winner Ed Yong of The Atlantic said, “The US has spent decades thinking about how to handle smallpox bioterrorism. The two cases of monkeypox in 2021 provided handy test runs for those plans.” The State Centre for Research on Virology and Biotechnology in Novosibirsk called Vector is in possession of smallpox and anthrax, as well as more recent pathogens like Ebola. 2 Smallpox had a 30% fatality rate at its peak. Monkeypox is between 1-10% depending on the strain and care available. The COVID SARS 2 R0 is 8. Monkeypox's R naught is less than 1 (average) so far. R0 is the average number of people who will contract a disease from one person with that disease. Although it's rare, if you have swollen lymph nodes, fever, headaches, pustules, puss filled blisters, or lesions on your hands and feet, extremities, and face you should probably head to the ER... Monkeypox is transmitted by bodily fluids. It is not an airborne virus like COVID, monkeypox is also a DNA virus so it doesn't mutate easily. The virus is mostly carried by rodents. In 2003 USA had a monkeypox outbreak in Illinois after an import of rodents from Ghana. What's different now is so many cases without a clear prime source. Rarely, monkeypox makes away from it's endemic areas in Nigeria, Ghana, and Congo. When it does,outbreaks are usually in the single digits, not this time. On May 20th confirmed cases were in the US, UK, Spain, and Portugal. As we record on May 24, monkeypox is in all NATO countries plus a few. Those first affected were men who have sex with men. It is important to not stigmatize any group of people. Early narratives about a disease can become lore. And narratives turned stigma can stop people from reporting symptoms. Stigma and disinformation is exactly what evangelical Republicans and the Russian orthodox church will likely do, though. We discuss Russian experiments with Marburg, Ebola, bubonic plague, anthrax, HIV, and camelpox. Catherine the Great was the first Russian vaccinated for smallpox, and all these years later this outbreak has the stocks of companies with an interest in vaccines like TPOXX and TEMBEXA such as Siga, Tonix Pharmaceuticals, Emergent BioSolutions, and Bavarian Nordic soaring. We discuss Vektor Labs in Koltsovo, Siberia (as well as its predecessor, Biopreparat) where Putin's doctors work on the latest vaccines... they say... maybe also bioweapons. Ilya Drozdov was in charge of Vector, but he's now the world's most famous missing scientist, either accidentally or on purpose. If there is still a Russian bioweapons program they're in volation of the Biological Weapons Convention. Vector is the second largest such facility in the world behind the Wuhan Institute of Virology in China. Our Russian bioweapons history knowledge mostly comes from defector Ken Alibek who testified about his time in Russian bioweapons research before Congress. 1. Mary G. Reynolds et al. ...Risk Factors for Human Monkeypox.... Emerging Infectious Diseases. Vol 13, November 2007. ⇤2. Ed Yong. So Have You Heard About Monkeypox?. The Atlantic. May 2022. ⇤

This week Sam is joined by Shannon Fox, education and training coordinator at Lowes Financial Management. Whilst going through her own financial planning exams it dawned on Shannon that there should be more support for candidates. In 2020 Shannon co-led the launch of the Lowes Financial Academy who have an impressive 85% pass rate on getting candidates through the R0 exams at the first time of asking. Today Shannon tells us all about the academy, who it's for and how they can help you pass your R0 exams to become a level 4 qualified financial planner. For more information or if you would like to join the academy, you can follow this link: https://lowesacademy.co.uk We cover: Shannon's career journey What is the Lowes Financial Academy?  A deep dive into the academy programme. What you can expect. Financial education in schools Advice for anyone who wants to become a financial planner. How long does it take? Be sure to follow financial planner life on YouTube for extra content about a career within financial Planning HIT THAT SUBSCRIBE BUTTON! below are some excellent links from our sponsor Recruit UK for any aspiring or experienced financial planners looking for new job opportunities or looking to get ahead in their career.   Financial Planning Qualifications guide https://recruitukltd.co.uk/whats-the-true-cost-of-becoming-a-financial-planner-or-paraplanner-a-definitive-guide/  2021financial planner salary guide    Financial planning Salary Guide https://recruitukltd.co.uk/recruit-uk-salary-survey-2020/  If you are an experienced financial planning candidate looking for a new job opportunity please reach out directly to sam@financialplannerlife.com or call 07854778712 he covers all roles within the profession across the UK.   if you hold level 4 qualification and looking for an entry role into financial planning please also reach out!  

Time to talk about the most widespread infection in the world, Helicobacter pylori. Following the accidental abandonment of incubated plates, H. Pylori colonies were discovered, launching a larger investigation into the microbiology of the human stomach. More research is needed on this disease-causing gram-negative bacterium, but our hosts provide the basics of its characteristics, transmission routes, and prevention in this episode.   More about Helicobacter pylori: Persistence strategies of the bacterial pathogen Helicobacter pylori Gastroenteritis and Transmission of Helicobacter pylori Infection in Households Nobel prize is awarded to doctors who discovered H pylori Pathogen Safety Data Sheets Trends in Hospitalizations for Peptic Ulcer Disease H pylori finds its home  Stay tuned for more episodes, posting on the first Thursday of each month. Subscribe to our show wherever you get your podcasts and find more info at weebeastiespodcast.com   The Wee Beasties podcast is a production of Nephros, Inc., a company committed to improving the human relationship with water through leading, accessible technology. ***   SHOW TRANSCRIPT: Christian: I am back with Dr. Kimothy Smith. Kimothy, welcome back!  Kimothy: Thanks, Christian.  Christian: All right…how are we doing today Kimothy? How's life?  Kimothy: I'm feeling a lot of stress, and I've got a pain in my stomach. I think I'm getting an ulcer.  Christian: Today's the right day to have this conversation, I think. We're talking about pathogens on this podcast, so I hear?  Kimothy: Cool! Let's go.  Christian: I was watching that documentary, Human Nature, last night. Have you seen it yet? It's about genomics, personalized medicine using CRISPR cas9 and the scope of genetic and molecular engineering to cure disease, but also do wild projects like bringing back a wooly mammoth. Cool stuff. Worth a watch if you have some time.  Kimothy: I'll check it out, but I tend to be a bit old school. And, I don't mean to go too deep on the old school stuff here, but, have you seen Jurassic Park? Do you really want to bring back a wooly mammoth?  Christian: What is that line from Jeff Golblum in Jurassic Park? “Your scientists were so preoccupied with whether or not they could, they didn't stop to think if they should?”  Kimothy: Yeah, definitely.  Christian: Well, what's our next waterborne pathogen?  Kimothy: Apropos to my ulcer generation, it is Helicobacter pylori.  Christian: H. pylori, I'm not super familiar with this one, but if memory serves this is spiral-shaped bacteria that makes a home in your stomach and can cause ulcers and even stomach cancer in some cases, right?  Kimothy: Yeah, you're on the right track, Christian. According to a 2013 report1 in Nature, H. pylori is the most widespread infection in the world, infecting at least half of the global population. The World Health Organization (WHO) recognized H. pylori as a group 1 carcinogen in 1994, but the backstory on this little bug isn't that straight forward.  H. pylori was discovered more recently, in comparison to the other microorganisms we've discussed – it was discovered in 1983 – and, interestingly enough, it was first found as a colony in the human stomach in a really unexpected stroke of luck after two doctors were trying to demonstrate a connection between the severity of gastric distress experienced by their patients and the number of bacteria present. In part, this discovery prompted scientists to begin a larger investigation into the microbiology of the human stomach using 16S rRNA analysis – and now we know that the stomach and the rest of the human gut has an extraordinarily diverse microbiome of bacteria which is critical to our immune response and other autonomic faculties. And I must tell you, Christian, as a side note, I've heard an urban legend that your microbiome can determine if you have a sweet tooth or not. Have you heard that?  Christian: I have not, but I've got a horrible sweet tooth. I'm always wanting sweets. So, I'm sort of wondering if we should run a 16S rRNA analysis of my gut biopsy.  Kimothy: Keep your microbiome to yourself, please.  Christian: Yeah, so this was part of what catalyzed the gut microbiome frenzy in the 90's. But wait, what was the stroke of luck? And, if good bacteria is so critical to our gut and immune response how is H. pylori, a pathogenic bacterium, able to stay alive in there?  Kimothy: Yeah, Christian, I'm glad you asked. So, the stroke of luck was in the successful culture. The two Australian doctors credited with the discovery just mistakenly left a plate in the incubator a lot longer than they had intended, and they just happen to get H. pylori colonies on it.  Those that have worked with H. pylori before will know just how persnickety the bacteria is – it is exceedingly difficult to grow outside of its habitat.  Christian: And why is that?  Kimothy: Well, let me get into the weeds a bit here. So, like many of the other pathogens we've discussed, H. pylori is a gram-negative bacterium, which means it has that extra LPS (lipopolysaccharide) barrier on its outer membrane. So, for starters, its more protected simply by its composition as a gram-negative bacterium. However, H. pylori has a really cool mechanism that allows it to transform its shape when it's under stress – examples of stress may include a change in pH or salinity, or an increase in the gases present – like nitrogen, carbon dioxide, and oxygen.    Christian: Uh huh…so what does it change its shape to?  Kimothy: Well, as I was saying a moment ago, H. pylori is hard to grow on a plate outside its ideal habitat.  It turns out that even in its ideal habitat, the stomach, the bacterium only thrives in these really specific conditions of pH and gas and any deviation from those conditions will cause the cells to become dormant and actually change shape. So check this out: H. pylori is spiral or helix-shaped (that's where the name comes from, Helico-bacter) and form follows function here, so it needs to burrow into the epithelium in the stomach lining in order to survive, so it uses its spiral shape and several flagella to literally corkscrew itself into our stomach to take residence. But, if the cell becomes stressed because a change in any of those conditions – pH, salt, gas, or temperature – it will slow down its metabolic machinery and change from its spiral shape and into a coccoid form.  It's still unclear if this transformation under stress is a selected adaptation or something else.  Several studies point to H. pylori's transformation as an evolutionary adaptation to cope with stress and others show no relationship.  There need to be more experiments to tease this out, but it is clear that a VBNC state is common with H. pylori, which again makes this a very, very difficult organism to culture from biopsies.  Christian: OK, we did get pretty deep there, let me just recap real quick: H. pylori is a gram-negative pathogen that is spiral (helix-shaped) with several flagella, which make it very motile; it is really selective about its environment (which is the stomach) and it doesn't grow well at all outside of that environment, in fact it usually enters a VBNC state if it becomes stressed in any way and when it's stress it changes shape into a coccoid form – this is a smaller spherical shape, right? I think the etymology of coccoid is actual berry in Greek, right? So, it transforms from a rod-spiral to a berry-shape? Lastly, and most importantly H. pylori results in the host ultimately getting stomach ulcers and even cancer, right?  OK, but we've been talking a lot about this pathogen living in stomachs, H. pylori is also in bulk water, though.   Kimothy: Yes, so the route of infection for H. pylori is still a bit mysterious and not always well-characterized to researchers. Contaminated water sources are certainly a means of infection, but so is fecal-oral and mucous-oral routes. This can result from living in close quarters with a large community and just not have access to proper disinfectants on touchable surfaces.  Once one person in a close-quarters household acquires H. pylori the R0 in that sample size will increase over time according to a Stanford Medical School manuscript in 2006.  R0 is just a term we use to describe the rate of infection to other individuals.    Christian: So the good news, if there is good news, is that educating people on transmission routes and increasing access to disinfectants can likely really disrupt or lower the R0.  Kimothy: That's right, Christian.  I'd like to come back to bulk water and liquid biopsies though if I may for a moment. Because H. pylori is so challenging to culture one of the best and most reliable ways to detect and study H. pylori is by using molecular diagnostic tools such as NGS using 16S rRNA and qPCR. We've talked about pathogens that cause pneumonia and acute respiratory infections, we've talked about pathogens that infect the blood, and now we have a pathogen that infects your gut with little to no indication of infection in most patients.  And although worldwide infection rates are going down, largely because of what you mentioned – access to clean water and surface disinfectants, the best way we can track and surveil this bug is by using these new diagnostic tools. Culturing for this bug is just too time consuming, unreliable, and not specific enough. It's analog in a digital world.  Christian: All right, well H. pylori…the peptic ulcer disease-causing gram-negative bacterium.  One more thing before we go – I know you're not a medical doctor, but how is H. pylori usually treated? Just a super dose of antibiotics?   Kimothy: Yeah, bacterium is very susceptible to antibiotic regimens, so it can usually be eradicated with a high-powered antibiotic.    Christian: Well, cool deal. We'll put some links in the show notes to some of these manuscripts we've mentioned in case you're interested. Kimothy, as always, thanks so much for the chat today.  Kimothy: You bet, Christian.

A recent Canadian study found that music download patterns are very similar to the epidemic curve of infectious diseases.加拿大最近一项研究发现，音乐的下载模式与传染病的流行曲线非常相似。Dora Rosati, lead author of the study and former graduate in maths and statistics at McMaster University in Ontario, Canada along with colleagues, wondered whether they could learn anything about how songs become popular using mathematical tools that are more usually applied to study the spread of infectious diseases.这项研究的主要作者是加拿大安大略省麦克马斯特大学数学和统计专业的多拉·罗萨蒂，他和他的同事们想知道，是否能用常用于研究流行病传播的数学工具来研究歌曲是如何流行起来的。The team turned to a database of almost 1.4bn individual song downloads from the now-discontinued music streaming service MixRadio. Focusing on the top 1,000 songs downloaded in the UK between 2007 and 2014, they measured how well a standard model of epidemic disease, called the SIR model, fitted trends in song downloads over time.说干就干！这个团队以现已停产的音乐流媒体服务MixRadio中的近 14 亿首单曲下载量作为数据库，集中研究从2007年到2014年间在英国下载的前1000首歌曲，测量了流行病的标准模型（以下简称为 SIR 模型）与歌曲下载量随时间变化趋势的拟合程度。The research, published in Proceedings of the Royal Society A: Mathematical and Physical Sciences, found the model performed just as well when describing song download trends as it did when describing the spread of a disease through the population.这项发表在《皇家学会会刊 A：数学和物理科学》上的研究指出，流行病标准模型不仅能描述疾病在人群中的传播，还能准确地描述歌曲的下载趋势。Rosati said: "It implies that a lot of the social processes that drive the spread of disease, or analogues of those processes, might also be driving the spread of songs. More specifically, it supports the idea that both music and infectious diseases depend on social connections to spread through populations."罗萨蒂说：“我们的研究说明了许多推动疾病传播的社会过程也可能推动了歌曲的传播。具体来说，它印证了音乐和传染病在人群中传播都依赖社会联系。”"With a disease, if you come into contact with someone who is ill, then you have a certain chance of catching that disease. With songs, it looks very similar. The big difference is that for songs, it doesn't necessarily have to be physical contact – it could be that my friend used this cool new song in their Instagram story, so now I'm going to go and find it."“如果你接触到生病的人，那你就有可能感染这种疾病。音乐的传播也是这样。最大的不同点是，歌曲不一定需要身体接触——可能我的朋友在Ins里用了一首很酷的新歌，我也会去找到这首歌听听看。”Dr Thomas Rawson, a disease modeller at Imperial College London, said: "It's something that makes complete sense, when you consider that word of mouth is something that, much like disease, it will carry on via other people. The main difference is that there are more ways for music to spread."帝国理工学院的一位疾病模型学家托马斯·罗森博士提到：“口碑就像疾病一样可以人传人，这完全不难理解。至于音乐，它最大的不同是传播途径更多了。”罗萨蒂的团队还计算了不同音乐类型的基本繁殖数 (R0)——一种流行病学度量，用于描述传染性因子的传染性或传播性。Although this varied substantially within genres, they found that dance and metal had the lowest median R0 scores at 2.8 and 3.7. Pop music was more transmissible, but it was vastly outstripped by genres such as rock and hip-hop, while electronica – a form of electronic music intended for listening, rather than dancing – had the highest R0, at 3430. This makes it roughly 190 times more transmissible than measles, which has an R0 of about 18.研究者们发现不同音乐类型的R0值差异很大，舞曲和金属乐的R0中位数最低，分别为2.8 和3.7；相比之下流行乐更具传播性，不过要是拿流行乐和摇滚乐、嘻哈音乐比，那它的传播性又远远不如后两者了。而电子乐（用来听而非跳舞的电子乐形式）的 R0 最高，为3430。要知道，麻疹的R0仅为18，那也就是说，电子乐的感染力是麻疹的 190 倍！"The reason why we might see some really sky-high R0s for songs is that you can just make a tweet and you have already infected a hundred people. You can spread a song disease far quicker than you could an infectious disease." said Rawson.看到这里你可能会问：既然电子音乐传播力那么强，为啥我感觉它们还是挺小众的？没错，电子音乐的R0高，并不一定意味着它就变得大众化了，而是说明它会在易受影响的粉丝群体中更快地传播。简单理解，就是更容易“圈地自萌”。Rosati said: "Maybe what those numbers are telling us is that electronica fans tend to be more passionate about their favourite songs … Or maybe the social network of electronica fans is more strongly connected."罗森提到：“我们可能会看到一些歌曲的R0非常高的原因是，你只需发一条推特，就已经感染了100人。歌曲的传播速度比传染病的传播速度要快得多。”"The biggest changes are likely to be in these more niche genres that wouldn't necessarily have been getting the radio play. I think they have a much better chance of spreading in our current situation of streaming and social media platforms," Rosati said.“对于小众的流派，以前可能没那么多电台播放它们，但在我们目前的流媒体和社交媒体平台中，他们有更好的传播机会。”If song popularity really is driven by the same contagious processes as disease, it could open new ways of predicting how new music releases could take off, and present opportunities to boost their spread.如果歌曲的流行真的是由与疾病一样的传染过程驱动的，那么这个研究可能会为预测新音乐的发行开辟新的途径，并极大促进音乐传播。

我說過多次總有一天Delta會進來，我們總要對他做好最壞的打算，最好的準備。這篇就來整理一下目前對Delta的認識吧。 網頁版請見此 https://linshibi.com/?p=39717 五月被WHO宣告為高關注變異株（Variants of Concern, VOC）之後，短短兩三個月，Delta病毒幾乎席捲全球，成為了最新的主流病毒株。 1.Delta變種病毒株比英國Alpha變種病毒的傳染力多5成，R0值估計高達5~9。也就是沒有疫苗和NPI的狀況下，一個人可以傳給5~9個人。 2.由於其傳染力大增，可能疫苗覆蓋率+自然感染者需要到九成才能抑止大量流行。甚至更高。 3.不管有沒有打疫苗，得到感染後鼻咽的病毒量似乎差不多高，都有機會傳染給他人，這發現讓美國CDC重新發出口罩令。後續有研究打疫苗者其病毒量還是下降的比較快，傳給他人的機率也會較低。但已經沒有之前Alpha可看到顯著下降。 4.有研究顯示Delta主要症狀是頭痛，再來是喉嚨痛、流鼻水和發燒，症狀相當類似「重感冒」，相比之下之前比較典型的咳嗽和嗅覺味覺改變則變得比較少見。 5.Delta在沒打疫苗的成人造成重症，住院的機率是Alpha的2倍左右。兒童和青少年的話，根據美國資料感染後重症住院機率沒有增加。但因為其傳染力增加，染疫的分母增加，所以美國兒童青少年總住院人數是增加的。12～17歲沒打疫苗者，住院機率是有打疫苗者10倍。 6.新冠疫苗對Delta的防護力的確較差一些。根據英國公衛部資料，完整施打兩劑疫苗，能對Delta提供81%的防護力，但如果只有接種一劑疫苗，則防護力降為33％。不過世界各地陸續看到在疫苗在施打兩劑後隨時間過去對Delta的保護力在下降，因此正在研究是否需要在6~8個月後注射加強針booster。 7.對於防止Delta的重症和死亡，各種疫苗都還很有效，且是打一劑就已經有一定的效果。這也是個人認為台灣追求第一劑覆蓋率還是有其意義的理由。但在Delta的時代，打疫苗的意義比較重要的還是防止注射者本人不容易重症。之前期待的會比較不容易傳給他人，在Delta上看來已經不是這樣的故事了。 8.在美國和英國，主要造成此波疫情的還是沒施打疫苗的人，特別是重症和死亡者。根據英國研究，打疫苗後還發生的突破性感染較多無症狀，症狀較輕，也較少後遺症和住院。 參考資料： WHO：Tracking SARS-CoV-2 variants https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ 美國CDC：Delta Variant: What We Know About the Science https://www.cdc.gov/coronavirus/2019-ncov/variants/delta-variant.html 英國公衛部： Confirmed cases of COVID-19 variants identified in UK https://www.gov.uk/government/news/confirmed-cases-of-covid-19-variants-identified-in-uk BBC報導：Covid: Is there a limit to how much worse variants can get? https://www.bbc.com/news/health-57431420 報導者：COVID-19病毒變身全解析 從Alpha到Delta，19個月內4大重要變異怎麼發生？疫苗保護力追得上嗎？ https://www.twreporter.org/a/sars-cov-2-variants 各國分年齡的新冠致死率 https://linshibi.com/?p=35732 混打疫苗可行嗎？AZ混打輝瑞/BNT AZ混打莫德納等等 https://linshibi.com/?p=39613 給長輩的AZ疫苗懶人包 https://linshibi.com/?p=39590 高端 聯亞 國產疫苗懶人包 第二期結束就緊急授權可行嗎？ https://linshibi.com/?p=39547 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi Powered by Firstory Hosting

男神瑽寧又來了喔！和上次對談時相比，台灣疫情趨緩，但Delta燒遍全球。這次我們回到黃醫師的本業小兒科，談談Delta是否在兒童會比較嚴重？ 以下是大概的訪綱： 1.可否很快的和大家描述一下，Delta這隻變種病毒你怎麼看？冠狀病毒一變再變，R0值越來越高，在你預期中嗎？ 2.近日很多美國報導描述兒童和青少年的住院數創新高。就您觀察，Delta在兒童會比較容易重症嗎？ Fauci專訪提到目前沒有確切答案，但在英國有看到在大人可能比較嚴重導致住院，如果真是這樣，沒有理由不相信在兒童也會看到類似情形。你同意嗎？ 3.英國和美國對於兒童和青少年的疫苗施打政策不太一樣。你認為在開學前，兒童也該施打疫苗才叫安全嗎？你認同BNT疫苗如果來到台灣，應該有部分要優先給12~18歲的青少年施打嗎？ 4.近來在幾個真實世界疫苗有效性的研究還有臨床三期的追蹤研究，看到BNT疫苗保護力似乎有下降，而莫德納似乎沒有怎麼下降。你怎麼解讀？ 5.台灣目前採取多半人盡量先打到第一劑，把第二劑延後施打的策略。你贊同嗎？延後第二劑是否有保護力下降的風險？你覺得到了什麼程度，應該回頭來追第二劑的覆蓋率？ 6.英國美國目前在期末考中似乎考得不太一樣。你覺得英國是否獲致了一定程度與病毒共存的成功？英國和美國差在哪裡？ 黃瑽寧醫師健康講堂 YT頻道 https://www.youtube.com/channel/UCkha3wg7As4t9duOzre5HcQ 黃瑽寧醫師健康講堂 粉絲專頁 https://www.facebook.com/Dr.TN.Huang 混打疫苗可行嗎？AZ混打輝瑞/BNT AZ混打莫德納等等 https://linshibi.com/?p=39613 給長輩的AZ疫苗懶人包 https://linshibi.com/?p=39590 高端 聯亞 國產疫苗懶人包 第二期結束就緊急授權可行嗎？ https://linshibi.com/?p=39547 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi 歡迎贊助我喝咖啡 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

這集感謝網友幫我做筆記，讓我很快的可以整理好內容！大感謝！ 1.幸琪：加拿大已經兩個星期都沒有公開變種病毒數據，昨天報紙講到加拿大各省政府解封速度都很快，看亞洲韓國澳洲，delta都一直在爬，加拿大也有，但數據沒有公開。記者就問怎麼跟民眾解釋即使有打疫苗，變種病毒還是有第四波？如果真的有打過疫苗，重症機率就比較小，因為還有30%的人還沒打，可以猜的到會不會有第四波的發生。 04b：Delta R0 比較高，達到群體免疫門檻就較高，群體免疫是用R0值算的，還有一個變數是打什麼疫苗，delta目前估的R0值是7.6，算起來要打到將近九成覆蓋率。不只是實際打疫苗還要加上自然感染，自然感染有一定保護率，這兩個加起來要九成，幾乎所有國家目前都沒達到。英國目前打的不錯，美國每州都不一樣，只打完第一劑五成是全國平均，有些州高有些低，美國現在暑假大解放，會來一波delta兇猛疫情。不過雖然數字變高，但住院率和死亡率沒有上去。疫苗有防重症功效，不能防感染，至少不前為止的疫苗是可以防delta，只是病毒會不會繼續變，變到連疫苗都沒有用，就很難說。 2.幸琪：要怎麼跟一般人解釋打完疫苗還是會得，但是得到重症機率不高？ 04b：重點就是這個，如果多半人打完疫苗都比較不會重症，就不用把病毒視為毒蛇猛獸，因為不會癱瘓醫療，2009 H1N1 新型流感，墨西哥當地死亡率1-3%，很高，跟現在新冠一樣，要趕快開始做疫苗，美國首當其衝，逐例通報，當時美國說什麼就做什麼，當年 H1N1 傳遍世界，可是馬上就發現中看不重用，傳染力高，但出了墨西哥死亡率是千分之一，這跟一般季節性流感死亡率一樣，雖是個新的流感病毒，卻沒有引起很大災情，幾個月後美國就宣布這個大流行已經過去了。我一直在等這件事，就是看成一個流感，只要定點通報，不用逐例通報，不用隔離匡列，就是可以走出疫情的時候。 3.幸琪：加拿大衛生長官已經不開記者會了，從去年暑假開始一星期開兩次，上星期就是最後一次，現在每天三四十例。12歲以上78%接種，現在是全世界打第一劑最多的國家，兩劑都打超過35%。 04b：前幾個月加拿大還在抱怨疫苗打不到，但事情可以變得很快，大家要有信心，先進國家都打差不多了。 04b：之前幸琪教授有說過加拿大是巴西變種病毒比例漸增的地方，最近似乎看到Delta會壓制其他病毒的現象。在細菌學上常常看到這種現象，例如細菌抗藥性很重，但抗藥性跟毒性是兩回事，細菌很小沒幾個基因，基因要拿來產生抗藥性，就不會非常毒，很容易致死的就是沒什麼抗藥性的野生種一樣。病毒更小，更沒有幾個基因，假如變種到對於疫苗沒效或是某個機制容易重症，其實都是門檻，現在的beta、gamma都被delta、alpha打敗，因為傳染力有優勢，幸好是這樣，假如主流流行的病毒是疫苗沒效的，就很頭痛。 2.一歷百憂解：柯市長控制疫情上似乎有點急了，但在疫情當口，大家都慢下來比較好，慢新聞的價值在於用慢一點的速度看這個變化的世界。除了台灣疫情外，現在大家在看歐洲盃，無論是歐洲盃還是MLB比賽，大家都不戴口罩，韓國今天還有勞工團體上街遊行。台灣下一步如果降回二級，在聚集活動還是要有所限制，還是要自由一點？ 04b：早安新聞有一次有提到英國試驗，叫做ERP，英國公衛部官方做的實驗，4/17開始規劃各種市內室外活動人數的規劃，打完兩劑、不戴口罩進場群聚，前後都要做快篩，這是用臨床實驗方法驗證可不可以開放，六月發表初步結果，目前大型的活動沒有major outbreak，總共累積五萬八千人，九個活動，只有28例確診，覺得可以繼續做下去。但這是四到六月，delta沒有這麼嚴重，這是alpha之下，R0值沒這麼高，疫苗覆蓋率是夠的。英國舉行三場足球賽，兩萬多人只發生八例，實驗覺得這是可行的，只要大家都有打過疫苗，群聚不戴口罩是可以的，法國也有類似的事。台灣現在不是，疫苗覆蓋率不高，要參考的是過去一年他們沒有疫苗的時候怎麼做的，經濟跟防疫並存，這很困難沒有標準答案，如果防疫至上零容忍，現在都說只等台北市，但一定要等到清零才往下走嗎？真的要到清零，可能要到九月前繼續三級，真的三級下去一定清得了嗎，很多人已經自我解封，生意已經撐不下去。真的要清零，理想可以這樣，現實上很難回去。嘉玲已經嫁人了，很難回來了，想法要改變。 Events Research Programme https://www.gov.uk/government/publications/guidance-about-the-events-research-programme-erp-paving-the-way-for-larger-audiences-to-attend-sport-theatre-and-gigs-safely-this-summer/guidance-on-the-events-research-programme Events Research Programme: Phase I findings https://www.gov.uk/government/publications/events-research-programme-phase-i-findings/events-research-programme-phase-i-findings 3.Shuman：mRNA疫苗保存：莫德納要在2-8度解凍保存，日本關西大學說發現機器壞掉高了0.5-1.4度，這樣疫苗就不行了嗎？疫苗都報廢了。 04b：理論上是，目前三種平台疫苗最脆弱就是mRNA，核糖核酸本來就很脆弱，所以保存條件很麻煩。可能是比例問題，沒有隔太久可能不會怎樣，可是無法檢查出來疫苗是否有效，要回原廠才知道有沒有變質，所以只能當他真的是沒有用報廢掉。 Shuman：BNT保存條件更嚴格，台灣很多疫苗施打站，不是在疫苗院所，可能是醫護人員帶冰桶帶過去，保存上是否有疑慮？ 04b：不用想太多，他們會解決，理論上他們一定要非常注意這些溫度條件。兩種mRNA美國已經打一億計以上，要發生在美國早就發生了，擔心發生問題，美國也有安全性報告，要不就是失效變質，要不就是成分變了會有奇怪副作用，真的發生美國就知道了。 給長輩的AZ疫苗懶人包 https://linshibi.com/?p=39590 高端 聯亞 國產疫苗懶人包 第二期結束就緊急授權可行嗎？ https://linshibi.com/?p=39547 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi 歡迎贊助我喝咖啡 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

今天談談高雄鳳山大樓防疫動作是否過大問題，還有屏東Delta疫情的後續。陳秀熙老師預估的Delta R0值7.6，是從英國目前看到的R0值大概4點多，然後去掉英國目前NPI還有疫苗覆蓋率的因素，回估完全沒有NPI和疫苗因素下R0值應該是多少。而在這種設定之下，理論上已經傳到三代的這次屏東群聚，最嚴重可能會到75人被傳染。但目前顯然沒這麼多，老師認為最大的可能是我們的三級警戒下NPI有效的證明。 屏東應有75人感染Delta病毒 陳秀熙曝確診數低於模型2大原因 https://www.storm.mg/article/3785182 對於屏東縣政府快速封村，陳秀熙讚「做出隔離與篩檢決定，避免影響鄰近區域與其他縣市，這與國外控制有很大不同。」陳秀熙指出，屏東果農夫婦應是感染Delta病毒，經過詳細疫調之後，很快會釐清感染源，找到感染的拼圖。 陳秀熙分析，以Delta病毒基礎再生數與社區流行規模R0值為7.6來推算，屏東應會有75人感染，但現加上2個境外才共14人。陳秀熙推測有2個原因，一為可能隱性感染者還未找到，但未來會陸續出現；另一可能為台灣實施三級警戒，社交距離、口罩實施皆很嚴格。陳秀熙直言，第二種可能性較高，目前屏東疫情已經有受到控制。 給長輩的AZ疫苗懶人包 https://linshibi.com/?p=39590 高端 聯亞 國產疫苗懶人包 第二期結束就緊急授權可行嗎？ https://linshibi.com/?p=39547 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi 歡迎贊助我喝咖啡 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

這集感謝網友幫我做筆記，讓我很快的可以整理好內容！大感謝！ 1.新北疫苗殘劑：長者因為新聞接種踴躍度下降，一開始很緊張疫苗浪費，好險有殘劑預約，但因為好心肝很容易被誤會也是有特權疫苗。目前新北的殘劑是 65 歲以上，但中央說 18，也只能跟民眾講，但民眾還是一直有在預約。殘劑是每天最後一瓶，診所只能約滿十個才能領，如身體有狀況不適合或是不來，才有殘劑，每天殘劑才一到三劑左右，但現在預約的人很多，到七八百或一千。基層人力為了接排殘劑電話，會排擠掉原本要預約施打的人的電話，殘劑真的沒有這麼好排。預約要滿十個才能領，會增加診所的負擔，實務上會有麻煩，要一直打電話溝通，希望中央可以開放一點不需要抽滿十個才去領。殘劑的認定 65 歲是不會有弊端，如果快點開放 65 歲，有可能會像去年流感一樣大家都搶翻打不到又罵翻，所以不敢一下開到 65，可以理解政府，但如果可以不要約滿十個，不夠的就 65-70 歲或一到三類資格確定的，但現在只能打在 65 以上的，如果要打到不是 65 以上應該是陪長輩來打，如果長輩因為身體因素不能打，其他候補都來不及來，那就會打在民眾身上。目前診所的規範下，打到 65 以下非常低，因為 65 以上就非常多，新北的政策是 65 以上，對診所也好，只要看年齡。不是不想開放打，只是有很嚴格的限制。殘劑的名額真的很少，又要預約，大家都忙瘋了，民眾蠻配合的是都有用表單填寫。 看英國和以色列的狀況，以色列人口是台灣一半，英國是三倍，台灣相較起來還是比英國來得好，英國現在連日破萬，除下來三千多例，台灣相對來說安全。但現在即使是打得很好的國家，案例還是上升，更何況是台灣沒有打疫苗打這麼多的國家。但英國的死亡人數不高，應證疫苗有效。目前是要普遍施打一劑？ 04b：防住院，一劑就可以。 AZ打一劑還比輝瑞好？ 04b：防住院率輝瑞一劑94%，AZ 71%。但韓國AZ一劑就有86%（針對英國變種，防有症狀感染），不同研究不一樣，要多看看。 AZ吃虧的是，打得都是老人，老人自然死亡率高，就被污名化，不過這樣也好，長者待在家，出外的年輕人打到殘劑。莫德納進來大家都會打，不會有殘劑，除非是 75 歲以上，現在不打AZ，就有機會等到。莫德納應該不會有人不來打。 2.幸琪：UN的報告，巴勒斯坦加薩走廊新冠致死率5% 04b：總致死率5%，的確偏高，但這可能要拿出PCR檢測陽性率來一起看。台灣目前致死率到4.2%了，比全球平均高，柯P說有黑數，可能是篩檢量不足，分母漏掉輕症和無症狀。祥祥記者會上回應說致死率的變化，每個國家都是往上增再往下降，再來是一直沒公布的PCR陽性率，現在祥祥也說出來了，每個國家一開始疫情嚴重，陽性率破 10%，一個是真的案例很多，第二是檢查做不夠多，如果只在這群人檢查就是 10%，如果往外擴散檢查就會降下來。陽性率標準是如果降到 5% 或 4%，就代表檢查量是足夠的，祥祥說台灣一直都沒有這麼高，所以 PCR 量能還是夠的，這個問題要看PCR陽性率多高。（中間提到巴勒斯坦醫護陽性率8%-24%）要不真的很嚴重要不測的不夠多，祥祥說我們沒有這麼多黑數，難免會漏，但沒有這麼多，那是說我們的致死率就這麼高嗎？亞東醫院邱冠明副院長26日早上演講有提到，亞東的致死率是5%。我覺得收這麼多重症，只有5%蠻了不起的。但邱冠明學長也說，如果不是檢測量能不足那就是醫療量能的問題，那這是說醫療量能不足嗎？有點尷尬。 台灣致死率4.2%偏高？指揮中心：發生率死亡率仍較低 https://www.cna.com.tw/news/firstnews/202106250217.aspx 莊人祥說，各國在疫情初期，染疫致死率皆偏高，英國曾一度超過18%，次高是義大利，致死率破10%的「高原期」維持一段時間，美國、加拿大與韓國亦同，在疫情初期時致死率上升。 台灣最近疫情剛開始，致死率也有上升跡象，莊人祥說，致死率4.2%確實較高，可能與確診者年齡偏高相關，60歲以上確診者占35%，死亡個案60歲以上更占9成，希望透過公共衛生措施將致死率壓下來。 至於外界質疑是否有確診數被低報、確診有黑數，莊人祥以檢驗陽性率說明，依照歐盟與世界衛生組織（WHO）標準，只要檢驗陽性率低於4%至5%，就較不受黑數影響。 莊人祥說，許多國家在疫情初期檢驗陽性率偏高，顯示通報確定病例似乎有低估，而台灣一直都相當低，即便是今年5月，檢驗陽性率最高僅2.8%，仍低於4%至5%，因此通報病例應無低估。 指揮官陳時中也說，各國初期都是針對疫情重點發生地區檢驗，因此檢驗陽性率相對較高，之後擴大檢驗範圍，陽性率就下降。他以雙北市熱區快篩站為例，起初快篩陽性率破10%，隨著檢驗人數漸多，就慢慢下降，目前台灣平均檢驗陽性率為0.7%。 幸琪：把每個年齡層的死亡率拉出來看會差很多。 3.Shuman：日本的莫德納不夠，在重新檢討要不要用AZ，不要再說日本不要AZ了，只是一開始覺得輝瑞莫德納夠，所以就先送人。關於殘劑：就算有預約名單，要臨時跟預約名單的人聯繫，護理師還要一直打電話，拖到下班時間。可以就給陪病者打，陪病者應該也是主要照護者，比較密切接觸的主要照護者先打，也是保護老人。這樣比較不會造成基層負擔。有些長輩可能不會出門，平時也只會接觸到主要照顧者，先打給照顧的人也是對長輩一種保護。 4.恩典護理站：孕婦施打狀況：23 週很想打，但預約不到，朋友就說週數不足，不鼓勵，決定到 30 週打。19 週：有施打，手臂腫脹會痛，沒有其他不舒服。24 週：有打，覺得想吐，因為沒有孕吐症狀，不知道是不是副作用，休息一天就好了。36 週：快生了，已經預約施打。 04b：孕婦是高風險族群，第二孕期再打，第一孕期還不穩定。 恩典護理站：有婦產科醫師都還搞不清楚疫苗的利弊。 5.Luke：討論伊維菌素。 04b：這個是抗寄生蟲藥，抗寄生蟲的療程不會很久，長期吃是沒有安全性資料。主流醫學都覺得資訊不夠充分，問所有臨床試驗人太少，劑量不一樣，沒有好的結論。 6.YT Lu：上課或 guideline 跟實際一線治療上的差距：大家都知道抗生素不用用到這麼高，但還是有很多地方是這樣做，讓人很無力，上課跟實務上聽到都不一樣。上課跟在一線還是有落差。 04b：我在台大的加護病房學習時，記得余忠仁老師說過，supportive care要有信心我們是最強的。這其實是病人預後差距拉開的主因。 7.Charlotte：LA 洛杉磯加大 (UCLA) 發表在「化學學會月刊:奈米領域」(ACSNano) 的最新論文顯示，完成輝瑞 (Pfizer) 或莫德納 (Moderna) 兩劑式新冠疫苗接種的人，抗體數量將在 85 天後減少 90%，凸顯追加疫苗以增加免疫力的必要性。很害怕的是抗體減少 90%。加州重新開放後，都還在適應期，這兩天的新聞說美國的接種率超過 56%，大家都在報復性旅遊，都在外面。除了抗體減少以外，還有 4100 多個案例，依然有重症和死亡，還有 delta 席捲全球。經歷一年半封鎖後，open 能開多久，藥廠大家都在研究怎麼加強疫苗。 https://pubs.acs.org/doi/10.1021/acsnano.1c03972 04b：研究人數有多少？輝瑞追蹤到六個月還是有九成保護力，莫德納也是沒怎麼降。這幾天看到 NBA 季後賽，觀眾進場也沒戴口罩。 https://www.nejm.org/doi/full/10.1056/nejmc2103916 charlotte：棒球場 99% 都沒戴口罩，本來有戴也會拿下來，剩工作人員有戴。 yebin：實際上的抗體下降很正常，CDC 周三有談到什麼時候打第三劑。不能光看抗體變化，前半年會迅速下降，不代表有效性下降。莫德納的研究是有下降，輝瑞沒有。需要打第三次是有效性下降，不是抗體下降，人體的抗體，如果沒碰到病毒，就不用一直產生沒有遇到病毒的抗體。打疫苗會促成記憶細胞，當遇到病毒會促使抗體產生，平常不用產生抗體。抗體下降不代表疫苗失效， mRNA 六個月後還是有抗體，會下降，但不代表沒有保護作用。抗體最容易測也容易跟蹤，可以繼續關注，目前時間還沒到要打第三劑。 8.印度變種在美國的狀況？ yebin：無法避免成為主流，就像重演英國變種。有明顯不好的地方，但也有慶幸的地方，從免疫逃逸看，至少不是Beta突變，之前Alpha傳播起來，Beta沒流行起來。對重症也有很好的保護，但傳播性很強，病例還是會增加，沒辦法。會暴露地區不平衡，在接種率低的地方造成局部危險，造成當地疫情反覆。一定要打完兩針不要覺得打完一針就那裡都可以去。年輕人感染病例越來越高，因為 12 以下不能打，12-17 剛開始打，19-30 打得意願很低，現在病例往 30 歲以下衝。 04b：有些人解讀印度變種專門挑沒有打疫苗的人感染。要提醒大家的是群體免疫需要達到的施打率，一個是看病毒的R0值，這是變動的，比如社區有沒有做好 NPI。要做到群體免疫，R0如果是5-8，疫苗覆蓋率要更高，原來的Alpha可能壓得住，Delta可能就壓不住了，還要看打得是哪一種疫苗。 yebin：美國成年人打一劑有 60%，total 50 多。覺得印度變種估計 R0 5-8 有點誇張，4-5 就差不多了。 04b：防疫久了就會放鬆受不了，想想看國外一年都開開關關，我們現在才一個半月，大家有點耐心，國外燒一年了，我們跟全世界比，我們的下半場第一次段考還可以，大家要有點信心。不管是檢查量能和重症處理，都有上軌道，有控制下來，藉由三級，大家待在家裡。印度變種來了，不知道會怎樣，大家再撐一下，不是 14 天，而是長期。 9.Nobuhiro： 今天去奧運會場研修，會擔心但也希望活動可以順利做完。今天發的一件衣服，有個小口袋，口袋有個 chip，會偵測溫度，手機會提醒你要喝水或很熱擔心會中暑。 國外已經很久了，如果今天政府說停下來，你敢衝出去玩嗎？（04b：很多人出去玩了）可以理解在國外待過的，心情很難受，大家要以保護自己為優先，觀察狀況。 10.Gaston補充關於抗體下降，但有 T細胞的免疫反應，兒科在打疫苗都會跟家長說只要記憶還在，細胞會不斷幫你打疫苗，中和抗體夠，身體就會自己訓練。 04b：美國很常不戴口罩，很容易再度接觸到病毒，抗體應該也會上來才對@@ 給長輩的AZ疫苗懶人包 https://linshibi.com/?p=39590 高端 聯亞 國產疫苗懶人包 第二期結束就緊急授權可行嗎？ https://linshibi.com/?p=39547 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi 歡迎贊助我喝咖啡 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

很興奮第一次有機會和李秉穎老師在有話好說同台！雖然老師是在遠端視訊，溝通隔了一層，但還是很感謝可以直接和老師有提問的機會。在主持人也首肯的狀況下，我把握機會問了老師三個問題。老師很詳細的回答了我關於疫苗施打政策是否可能改動，還有關於陳培哲老師所提次單位蛋白疫苗是保護力最差疫苗的評論。 可惜最後一個問題：如果在我們審查國產疫苗EUA時，WHO還沒有訂出免疫橋接的標準，我們該如何解套？ 因為節目時間卡掉了，沒聽到老師的完整答案。希望還有機會繼續和老師請教！ 影片在此：https://youtu.be/MP71PzCGYC8 感謝網友整理的時間軸： 疫情趨勢 (211新增個案代表什麼) 06:37 李秉穎：疫情要看連續變化，今天延長三級反映1-2週前的狀況，措施產生效果也需要1-2週。目前沒有封城，雙北病例難免擴散，但是如果三級有做好，擴散病例應該不會太多。 14:47 林氏璧：個案數較少可能只是PCR在假日檢測數量較少。校正回歸解決後應公告PCR陽性率；一周陽性率平均數較能清楚呈現疫情趨勢。 苗栗移工 17:16 曾玟學：目前只有京元電的移工全面停班且進行一人一室隔離。其餘苗栗移工在上班之外禁止外出。 對移工而言，防疫旅館可能負擔過重、快篩偽陰性的移工可能進入社區、停工和長期管制可能導致移工逃竄；科技廠外的移工形成黑數。 對本國籍勞工而言，可能在疫情爆發前就存在交叉感染。 行政方面苗栗有翻譯不足致疫調時間過長、隔離宿舍消毒不徹底等問題需要中央和外縣市協助。 疫苗分配和廣篩問題 32:30 林氏璧：理論上群體免疫必須推算R0值和疫苗有效性，但是部分研究顯示，小比例施打就能一定程度的控制疫情。疫苗不夠可以參考英國全面施打第一劑或學習德國混打疫苗。 34:59 李秉穎：混打已納入考慮，但是國外案例顯示副作用升高、有效性研究不足；英國全面打一劑的背景是全國性的社區流行，台灣各區疫情有明顯差異，狀況不同。 44:10 李秉穎：目前應「針對」有接觸史、有疑似接觸史、有呼吸道症狀者進行快篩。但是快篩很難找到潛伏期患者，試劑敏感性較低(偽陰偽陽問題)、各款試劑特異性又過大。全面快篩有困難且存在成本效益問題。 回應陳培哲教授對次單位蛋白疫苗的質疑 46:45 李秉穎：這大概有點誤解，蛋白疫苗是最成熟最傳統的技術，B型肝炎跟子宮頸癌疫苗都是次單位蛋白疫苗，非常安全且有效。 安全性方面，可能會有不預期不良反應的風險，比方說 mRNA 的過敏性休克和腺病毒載體疫苗的血栓問題。 有效性方面，國產疫苗一期試驗和國外Novavax 疫苗的試驗血清抗體效價均「超過」肺炎痊癒者和腺病毒疫苗接種者、「類似」 mRNA 疫苗。次單位蛋白疫苗應該不會是保護力最差的疫苗。 高端 聯亞 國產疫苗懶人包 第二期結束就緊急授權可行嗎？ https://linshibi.com/?p=39547 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi 歡迎贊助我喝咖啡 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

這集感謝網友幫我做筆記，讓我很快的可以整理好內容！大感謝！ 也感謝Dr.Leanne Wu 吳凌安醫師一起回答問題！ 1.吳醫師：在東森節目王世堅議員說，現在國產疫苗尚未解盲，但已簽約，說不定簽約內容是有提到解盲結果若不符合 EUA 標準就不購買？ 04b：歐美訂單也是很早的時候就訂購，第二期都還沒做完就在搶，然後金額很清楚，但今天部長被問的時候就說是商業機密。像日本若有獲得 EUA 才成立（訂單），若沒有就取消。其他國家搶著下訂單是因為其他疫苗是很多國家在搶，國產疫苗又沒人搶，的確可能引發爭議。 2.Nobuhiro：對疫苗有看法是很好，往好處想我們已經比其他國家幸運，請大家再忍耐一下。以日本為例子：去年第一波三月，叫大家不要出門，四月到達最嚴格標準（自肅），五月降低後就稍微解嚴，結果六月就一直起起伏伏，如果當初能夠延長就有機會穩定疫情。我們還有機會做到比日本更好。醫療還是很緊繃，不要覺得跟自己沒關係，其實很多緊急醫療都無法治療。例如在日本有發生過出車禍的小孩本來有機會治療，但因為 covid 造成醫療量能不足，沒有醫院可以收治。 九成的人都很努力，但如果只有一成的人不努力，就很難降低感染力。請把現在的生活不方便當作平常。學習擁抱難受的感覺（日文是：辛抱）。 3.各廠牌第二期實驗人數的爭議： 莫德納第二期 660，第三期三萬。吳醫師：輝瑞（pfizer）是二三期寫在一起，初步查起來有點難界定。我們再確認一下。 4.小孩什麼時候才能打？目前只有輝瑞可以打，但台灣沒有。若有機會打，18 歲以下會優先嗎？ 吳醫師：莫德納也快了，九月有機會 2～11 歲緊急授權。 孩童重症機率比年輕人和老人低。 5.在5月11日 WHO 找了疫苗廠測中和抗體，是否可以準確預測保護力做預測模型，取代傳統第三期。這會有什麼差異，能幫助國產疫苗做第三期嗎？ 轉述何美鄉老師的意見：贊成擴大第二期，應該可以用中和抗體比例來預測有效性，並訂出標準。另外是安全性，三千人的安全性，不能看出五千或一萬的又怎樣，安全性本來就是要透過大量施打才會知道結果（等同於大量施打後的第四期）。 04b：這是非常有可能的方向（有效性可藉由中和抗體判定），就像流感疫苗。但不確定是否有這麼快能趕上國產疫苗的審核。 6.鯨豚爸：AZ 三千多人，國產擴大二期，人數都多於其他廠牌疫苗。三家國產是否要做變異病毒株的疫苗？國家是否要做衛教宣導？以免民眾對於疫苗不信任。 04b：同意要有疫苗的自製能力，疫苗即為國防能力。但全世界這麼多國家，目前有這麼快做出來的，也就中國、美國（ft. 德國）、英國，歐洲這麼多先進大國，也都沒有做，疫苗不是這麼容易的，需要長久的培植，也需要錢。日韓主力也不是自己發展疫苗，也是去搶訂單。畢竟這最快，而且也走代工路線，韓國 AZ、莫德納，日本第一三共代工AZ、武田代工Ｎovavax。我們不是疫苗輸出大國，如果現在想要就做出自己的疫苗，整體的策略可能需要思考一下。 7.何老師說雙北沒辦法清零，中南部有機會，怎麼看？ 04b：同意，中南部就像過去一年的台灣，有機會藉由傳統疫調匡列清零。但雙北可能回不去了，不是每一國都可以像紐西蘭澳洲一樣順利。但這是第一次社區感染，總要努力試試看，努力待在家。就算無法清零也不是世界末日，只是要學著跟病毒共存，等到疫苗打上來。看其他國家打這麼久，現在也就以色列、英國、美國有打到接近群體免疫，想要群體免疫沒這麼簡單，日韓也要到今年 11 月才有機會。目前把 R0 直降下來才是最重要的，我們離群體免疫還很遠。 8.陳秀熙老師說，NPI 要 90 才有辦法降到雙位數： 04b：再兩周，到6月14日，看能不能降到雙位數，就能大概回推NPI是否有到 90。目前是否有做到90分了，我不確定。希望大家繼續努力。 9.企業個別引進疫苗及快篩可行性及風險？ 國外有很多企業需要自我檢測，陰性才能進公司，但快篩有一定偽陽性，可能引發種種問題。美國主要要做 PCR，民眾較多人自己做快篩，自己想知道就會買來測。接受 PCR 較多，但吳醫師表示回美國的陰性報告用抗原快篩檢測也可以。 10.關於各界採購疫苗： 轉述何美鄉老師的意見：大家常類比王永慶捐贈肺炎鏈球菌的疫苗，但這是已上市的商品。目前的肺炎疫苗是緊急授權EUA，並非完全上市的商品。世界各國都是政府來接洽購買，若有不良反應需要照顧施打民眾，甚至國賠，施打順序也都是國家來掌控。 04b：如果有多方管道引進疫苗，就要努力爭取。來源沒問題就ok。 11.建議呼籲恐慌的民眾，宅在家才是有效的？ 04b：目前較擔心看到疫情趨緩就想出門放風的人（抖）（阿公阿罵不要再去菜市場了） 12.吳醫師：英國長期追蹤保護力資料有更新。即使相隔八週再打輝瑞，打完第二劑兩周後對印度變種病毒有88%的保護力，對英國變種病毒則有93%的保護力。 AZ打完第二劑兩周後對印度變種病毒有60%的保護力，對英國變種病毒則有66%的保護力。 兩個疫苗僅施打一劑的三周後，對印度變種病毒僅有33%的保護力，對英國變種病毒則有50%的保護力。 https://www.gov.uk/government/news/vaccines-highly-effective-against-b-1-617-2-variant-after-2-doses https://www.reuters.com/business/healthcare-pharmaceuticals/uk-analysis-finds-two-doses-astrazeneca-covid-19-vaccine-85-90-effective-2021-05-20/ 13.Pauline：AZ 更新的數值主要針對印度變種，目前改成40歲以下不打 AZ。 老人家對疫苗的知識吸收有限，希望媒體不要報導太多不確定的新聞，老年人就是想知道打或不打。 英國 R value，有些地區較低 0.8，高的 1.0~1.1 14.韓國出現第一例TTS，接種 AZ 出現血小板減少症，韓國已打 327 萬劑才出現第一例。台灣是三十萬人出現第一例。 https://newtalk.tw/news/view/2021-06-01/582178 15.shih hwa lai：AZ 想要申請 full market。若正式上市而非僅是EUA，台灣各方想要購買疫苗應該相對簡單。 高端 聯亞 國產疫苗懶人包 第二期結束就緊急授權可行嗎？ https://linshibi.com/?p=39547 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi 歡迎贊助我喝咖啡 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

今天看到記者會公布Rt值的圖，並用紅字寫著本波本土疫情已逐漸趨緩，一則以喜，一則以憂。很怕大家開始放鬆。老話一句，高興五秒鐘就好，這只是說明14天的努力是有效的，但要維持一樣的強度繼續把Rt值壓低呀！你是想和去年的紐西蘭，還是和澳洲一樣？還是其他國家？這要靠大家繼續努力！ Rt值是什麼？反正就是加上時間變化的R0值，這是會隨公衛措施變動的數字。小於1，疫情就會逐漸趨緩。 祥祥說，這張圖是用判讀日估算的，不是基於發病日或是校正回歸。若用發病日估，其實Rt值可能已經低於1了。但我覺得理論上應該用校正回歸那張估，因為判讀日這張中間幾天高峰明顯，所以Rt值可能算來比較好看。 以下是記者會內容： 今日新增274例本土確診，校正回歸剩73例。陳時中指出，經過這兩週的全國人民努力，Rt值已降至1.02，本土疫情已逐漸趨緩。大家的犧牲和努力都是有成效的，呼籲民眾出門仍要記得全程戴口罩並勤洗手，避免外出聚會。 莊人祥解釋，疫情剛開始爆發時說的R0值就是基本再生數，意思是當病毒進入到沒有相關抵抗力的人口族群時，平均可以傳染給多少人的估計值，不過後期不是所有人都沒有抵抗力，這時病毒再生數稱為Rt值，代表一個病人可以傳染給多少人的平均值。 只要Rt值低於1，表示疫情就會開始反轉，而台灣的Rt值已經在陸續下降，目前估算數字是1.02，透過Rt值下降的趨勢來看，明後天沒太大意外的話，Rt值就有可能小於1，代表傳染力有反轉的跡象。 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi 歡迎贊助我喝咖啡 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

到達群體免疫力的門檻英文稱為HITs（herd immunity threshold），和這個傳染病的R0值（基本傳染數）有關。R0值指的是在沒有外力介入，同時所有人都沒有免疫力的情況下，一個感染到某種傳染病的人，會把疾病傳染給其他多少個人的平均數。 https://linshibi.com/?p=37901 公式：HITs=1-1/R0 wiki百科上幫大家算好了 麻疹R0 12~18，算出是92~95% 新冠R0 2.5~4，算出是60~75% 流感R0 1.5~1.8，算出是33~44% 04b解讀： 1.空氣傳染的麻疹病毒R0值超高，一個人可以傳給12~18人，疫苗接種率加上有得過的人需要達到92%以上的高門檻才能有效防治。這可以解釋這麼多年來日本為何一直無法完全根除麻疹，但台灣可以。麻疹疫苗早期在日本施打有出過副作用，讓很多人不敢施打的事件。 2.要注意R0值是會變動的數字。如果這個冬天多數人力行防疫新生活，戴口罩洗手維持社交距離之下，R0值就會越低。當R0值小於1，一個人平均傳給不到一個人，那疾病就無法流行起來。台灣從疫情以來流感的流行曲線也同時躺平，就是這個原因。這個冬天，我相信很大機會應該也是如此。 3.另外一個要注意的變數是疫苗的有效性（effectiveness）。上述的公式是假設打疫苗就有100%的保護力，但如果只能部分保護，那需要施打的人數就需要更多。流感疫苗每年要猜病毒株，沒完全猜對的那年有效性就會較低。 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi 歡迎贊助我喝咖啡 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

The transition from Australia being pretty much free of COVID to reopening the border and allowing it in, is a complicated and fraught issue.The country will eventually have to rejoin the world so people can see family, travel for pleasure or business and go overseas again - but according to experts, there's a list of things that have to happen before then.The most obvious is a very high level of vaccination, so that when coronavirus does arrive again, it won't result in an overburdened hospital systemAnd on today's Coronacast, there's also the big issue of possible vaccine resistant variants.Also on today's show:* More cases of blood clots and low blood platelets* A clarification and refinement of the R0 value discussion from last week

The transition from Australia being pretty much free of COVID to reopening the border and allowing it in, is a complicated and fraught issue. The country will eventually have to rejoin the world so people can see family, travel for pleasure or business and go overseas again - but according to experts, there's a list of things that have to happen before then. The most obvious is a very high level of vaccination, so that when coronavirus does arrive again, it won't result in an overburdened hospital system And on today's Coronacast, there's also the big issue of possible vaccine resistant variants. Also on today's show: * More cases of blood clots and low blood platelets * A clarification and refinement of the R0 value discussion from last week

Harvard Epidemiologist, Dr. Stephen Kissler and John Houghton discuss data modeling for diseases with special consideration of SARS-CoV-2 variants, including B.1.1.7 (UK), P.1 (Brazil), and B.1.351 (South Africa).  This is a deep dive on the nuts and bolts of COVID-19 modeling including insightful definitions of R0, generation interval, start date, and population size. How R0 as a measure becomes substituted with Rt as an outbreak progresses Review data model created by John at the beginning of the epidemic The SIR model (Susceptible, Infectious, or Recovered) How does reinfection change the SIR model? Introducing SIRS (or SIS) Probabilistic vs deterministic modeling The explosiveness of exponential growth Can new variants be introduced at an exponential rate? Discussion of Lancet paper: Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence - The Lancet Math check: If a variant is 40% more infectious than an R0 3.0 wild type-virus, what is the new R0? Check out Dr. Kissler's podcast: Pandemic: Coronavirus Edition.

在大多数普通人看来，疫情能否彻底结束，取决于疫苗的有效率，更专业点儿的说法是“保护率”。但是，这个认知其实很浅，因为在流行病学家看来，疫情能否彻底结束，并不只取决于疫苗的保护率，还有三个极为关键的变量，也就是：感染者基本繁殖数R0值、无症状患者的传染率、疫苗的接种率。

在大多数普通人看来，疫情能否彻底结束，取决于疫苗的有效率，更专业点儿的说法是“保护率”。但是，这个认知其实很浅，因为在流行病学家看来，疫情能否彻底结束，并不只取决于疫苗的保护率，还有三个极为关键的变量，也就是：感染者基本繁殖数R0值、无症状患者的传染率、疫苗的接种率。

在大多数普通人看来，疫情能否彻底结束，取决于疫苗的有效率，更专业点儿的说法是“保护率”。但是，这个认知其实很浅，因为在流行病学家看来，疫情能否彻底结束，并不只取决于疫苗的保护率，还有三个极为关键的变量，也就是：感染者基本繁殖数R0值、无症状患者的传染率、疫苗的接种率。

Episode Topic: Epidemiology of COVID-19The topic of this session will be epidemiology in general and the epidemiology of COVID-19. General concepts like R0 and Rt will be explained and how models work, the assumptions behind them, and what they tell us will also be a topic of discussion.Featured Speakers: Heidi Beidinger-Burnett, Director, Eck Institute for Global Health Masters Program; Associate Professor of the Practice, Department of Biological Sciences, University of Notre Dame; President of the St. Joseph County Board of HealthMary Ann McDowell, PhD, Associate Professor of Biological Sciences and Member of the Eck Institute for Global Health, University of Notre DameAlex Perkins, Associate Professor, Department of Biological Sciences, University of Notre DameJenna Coalson, Assistant Professor of the Practice, Department of Biological Sciences, University of Notre DameRead this episode's recap over on the University of Notre Dame's open online learning community platform, ThinkND: go.nd.edu/4c9bcc.This podcast is a part of the Consider This! ThinkND Series titled “Consider This! Simplifying the COVID-19 Conversation”.

Professor Ken Strain is an experimental physicist, a Fellow of the Royal Society of Edinburgh and the Institute of Physics and is the deputy director of the Institute for Gravitational Research at the University of Glasgow here in Scotland. He was part of the international collaboration that successfully discovered gravitational waves. And on the side there is a large interest in nutrition science. Understanding and thoughts on coronavirus Some headlines from the C19 data and walk through of the analysis of the data so far Lockdown effectiveness Early positive results from Sweden What the R0 value is Cytokines and lung function and/or blood disorders Why might viral evolution favour hypoxia? The Diamond Princess Mitochondria and C19 What do we know so far about people's existing medical conditions and C19, and what could be done about it? Ken can be found at: Twitter - https://twitter.com/Ken__Strain Ally can be found at: Twitter - https://twitter.com/paleocanteen Twitter - https://twitter.com/paleoally Instagram - https://www.instagram.com/paleocanteen YouTube - https://www.youtube.com/c/AllyHouston