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Dr. Allison Zibelli and Dr. Rebecca Shatsky discuss advances in breast cancer research that were presented at the 2025 ASCO Annual Meeting, including a potential new standard of care for HER2+ breast cancer, the future of ER+ breast cancer management, and innovations in triple negative breast cancer therapy. Transcript Dr. Allison Zibelli: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Allison Zibelli, your guest host of the podcast today. I'm an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Comprehensive Cancer Center at Jefferson Health. There was a substantial amount of exciting breast cancer data presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Rebecca Shatsky today to discuss some of these key advancements. Dr. Shatsky is an associate professor of medicine at UC San Diego and the head of breast medical oncology at the UC San Diego Health Moores Cancer Center, where she also serves as the director of the Breast Cancer Clinical Trials Program and the Inflammatory and Triple-Negative Breast Cancer Program.  Our full disclosures are available in the transcript of this episode. Dr. Shatsky, it's great to have you on the podcast today. Dr. Rebecca Shatsky: Thanks, Dr. Zibelli. It's wonderful to be here. Dr. Allison Zibelli: So, we're starting with DESTINY-Breast09, which was trastuzumab deruxtecan and pertuzumab versus our more standard regimen of taxane, trastuzumab pertuzumab for first-line treatment of metastatic HER2-positive breast cancer. Could you tell us a little bit about the study? Dr. Rebecca Shatsky: Yeah, absolutely. So, this was a long-awaited study. When T-DXd, or trastuzumab deruxtecan, really hit the market, a lot of these DESTINY-Breast trials were started around the same time. Now, this was a global, randomized, phase 3 study presented by Dr. Sara Tolaney from the Dana-Farber Cancer Institute of Harvard in Boston. It was assessing essentially T-DXd in the first-line setting for metastatic HER2-positive breast cancer in addition to pertuzumab. And that was randomized against our standard-of-care regimen, which was established over a decade ago by the CLEOPATRA trial, and we've all been using that internationally for at least the past 10 years. So, this was a large trial, and it was one-to-one-to-one of patients getting T-DXd plus pertuzumab, T-DXd alone, or THP, which mostly is used as docetaxel and trastuzumab and pertuzumab every three weeks for six cycles. And this was in over 1,000 patients; it was 1,159 patients with metastatic HER2-positive breast cancer. This was a very interesting trial. It was looking at the use of trastuzumab deruxtecan, but patients were started on this treatment for their first-line metastatic HER2-positive breast cancer with no end date to their T-DXd. So, it was, you know, you were started on T-DXd every 3 weeks until progression. Now, CLEOPATRA is a little bit different than that, though, as we know. So, CLEOPATRA has a taxane plus trastuzumab and pertuzumab. But generally, patients drop the taxane after about six to seven cycles because, as we know, you can't be really on a taxane indefinitely. You get pretty substantial neuropathy as well as cytopenias, other things that end up happening. And so, in general, that regimen has sort of a limited time course for its chemotherapy portion, and the patients maintained after the taxane is dropped on their trastuzumab and their pertuzumab, plus or minus endocrine therapy if the investigator so desires. And the primary endpoint of the trial was progression-free survival by blinded, independent central review (BICR) in the intent-to-treat population. And then it had its other endpoints as overall survival, investigator-assessed progression-free survival, objective response rates, and duration of response, and of course, safety. As far as the results of this trial, so, I think that most of us key opinion leaders in breast oncology were expecting that this was going to be a positive trial. And it surely was. I mean, this is a really, really active drug, especially in HER2-positive disease, of course. So, the DESTINY-Breast03 data really established that, that this is a very effective treatment in HER2-positive metastatic breast cancer. And this trial really, again, showed that. So, there were 383 patients that ended up on the trastuzumab plus deruxtecan plus pertuzumab arm, and 387 got THP, the CLEOPATRA regimen. What was really interesting also to note of this before I go on to the results was that 52% of patients on this trial had de novo metastatic disease. And that's pretty unusual for any kind of metastatic breast cancer trial. It kind of shows you, though, just how aggressive this disease is, that a lot of patients, they present with de novo metastatic disease. It's also reflecting the global nature of this trial where maybe the screening efforts are a little bit less than maybe in the United States, and more patients are presenting as later stage because to have a metastatic breast cancer trial in the United States with 52% de novo metastatic disease doesn't usually happen. But regardless, the disease characteristics were pretty well matched between the two groups. 54% of the patients were triple positive, or you could say hormone-positive because whether they were PR positive or ER positive and PR negative doesn't really matter in this disease. And so, the interim data cutoff was February of this year, of 2025. So, the follow-up so far has been about 29 months, so the data is still really immature, only 38% mature for progression-free survival interim analysis. But what we saw is that T-DXd plus pertuzumab, it really improved progression-free survival. It had a hazard ratio that was pretty phenomenal at 0.56 with a confidence interval that was pretty narrow of 0.44 to 0.71. So, very highly statistically significant data here. The progression-free survival was consistent across all subgroups. Overall survival, very much immature at this time, but of course, the trend is towards an overall survival benefit for the T-DXd group. The median durable response with T-DXd plus pertuzumab exceeded 3 years. Now, importantly, though, I want to stress this, is grade 3 or above treatment-emergent adverse events occurred in both subgroups pretty equally. But there were 2 deaths in the T-DXd group due to interstitial lung disease. And there was a 12.1% adjudicated drug-induced interstitial lung disease/pneumonitis event rate in the T-DXd group and only 1%, and it was grade 1-2, in the THP group. So, that's really the caveat of this therapy, is we know that a percentage of patients are going to get interstitial lung disease, and that some may have very serious adverse events from it. So, that's always something I keep in the back of my mind when I treat patients with T-DXd. And so, overall, the conclusions of the trial were pretty much a slam dunk. T-DXd plus pertuzumab, it had a highly statistically significant and clinically meaningful improvement in progression-free survival versus the CLEOPATRA regimen. And that was across all subgroups for first-line metastatic HER2-positive breast cancer here. And so, yeah, the data was pretty impressive. Just to go into the overall response rate, because that's always super important as well, you had 85.1% of patients having a confirmed overall RECIST response rate in the T-DXd plus pertuzumab group and a 78.6 in the CLEOPATRA group. The complete CR rate, complete response was 15.1% in the T-DXd group and 8.5 in the CLEOPATRA regimen. And it was really an effective regimen in this group, of course. Dr. Allison Zibelli: So, the investigators say at the end of their abstract that this is the new standard of care. Would you agree with that statement? Dr. Rebecca Shatsky: Yeah, that was a bold statement to make because I would say in the United States, not necessarily at the moment because the quality of life here, you have to think really hard about. Because one thing that's really important about the DESTINY-Breast09 data is that this was very much an international trial, and in many of the countries where patients enrolled on this, they were not able to access T-DXd off trial. And so, for them, this means T-DXd now or potentially never. And so, that is a really big difference whereas internationally, that may mean standard of care. However, in the US, patients have no issues accessing T-DXd in the second- or third-line settings. And right now, it's the standard of care in the second line in the United States, with all patients basically getting this second-line therapy except for some unique patients where they may be doing a PATINA trial regimen, which we saw at San Antonio Breast Cancer in 2024 of the triple-positive patients getting hormonal therapy plus palbociclib, which had a really great durable response. That was super impressive as well. Or there is the patient that the investigator can pick KADCYLA because the patient really wants to preserve their hair or maybe it's more indolent disease. But the quality of life on T-DXd indefinitely in the first-line setting is a big deal because, again, that CLEOPATRA regimen allows patients to drop their chemotherapy component about five to six months in. And with this, you're on a drug that feels very chemo-heavy indefinitely. And so, I think there's a lot more to investigate as far as what we're going to do with this data in the United States because it's a lot to commit a patient in the first-line metastatic setting. These de novo metastatic patients, some of them may be cured, honestly, on the HER2-targeting regimen. That's something we see these days. Dr. Allison Zibelli: So, very interesting trial. I'm sure we'll be talking about this for a long time.  So, let's move on to SERENA-6, which was, I thought, a very interesting trial. This trial took patients with ER positive, advanced breast cancer after six months on an AI (aromatase inhibitor) and a CDK4/6 inhibitor. They did ctDNA every two to three months, and when they saw an ESR1 mutation emerge, they changed half of the patients to camizestrant plus CDK4/6 and kept the other half on the AI plus CDK4/6. Can you talk about that trial a little bit, please? Dr. Rebecca Shatsky: Yeah, so this was a big trial at ASCO25. This was presented as a Plenary Session. So, this was camizestrant plus a CDK4/6 inhibitor, and it could have been any of the three, so palbo, ribo, or abemaciclib in the first-line metastatic hormone-positive population, and patients were on an AI with that. They were, interestingly, tested by ctDNA at baseline to see if they had an ESR1 mutation. So, that was an interesting feature of this trial. But patients had to have already been on their CDK4/6 inhibitor plus AI for at least 6 months to enroll. And then, as you mentioned, they got ctDNA testing every 2 to 3 months. This was also a phase 3, double-blind, international trial. And I do want to highlight again, international here, because that's important when we're considering some of this data in the U.S. because it influences some of the results. So, this was presented by Dr. Nick Turner of the Royal Marsden in the UK. So, just a little bit of background for our listeners on ESR1 mutations and why they're important. This is the most common, basically, acquired resistance mutation to patients being treated with aromatase inhibitors. We know that treatment with aromatase inhibitors can induce this. It makes a conformational change in the estrogen receptor that makes the estrogen receptor constitutively active, which allows the cell to signal despite the influence of the aromatase inhibitor to decrease the estrogen production so that the ligand binding doesn't matter as much as far as the cell signaling and transcription is concerned. And camizestrant, you know, as an oral SERD, just to explain that a little bit too; these are estrogen receptor degraders. The first-in-class of a selective estrogen receptor degrader to make it to market was fulvestrant. And that's really been our standard-of-care estrogen degrader for the past 25 years, almost 25 years. And so, a lot of us are just looking for some of these oral SERDs to replace that. But regardless, they do tend to work in the ESR1-mutated population. And we know that patients on aromatase inhibitors, the estimates of patients developing an ESR1 mutation, depending on which study you look at, somewhere between 30% to 50% overall, patients will develop this mutation with hormone-positive metastatic breast cancer. There is a small percentage of patients that have these at baseline without even treatment of an aromatase inhibitor. The estimates of that are somewhere between 0.5 and up to 5%, depending on the trial you look at and the population. But regardless, there is a chance someone on their CDK4/6 inhibitor plus AI at 6 months' time course could have had an ESR1 mutation at that time. But anyway, so they got this ctDNA every 2 to 3 months, and once they were found to develop an ESR1 mutation, the patients were then switched to the oral SERD. AstraZeneca's version of the oral SERD is camizestrant, 75 mg daily. And then their type of CDK4/6 inhibitor was maintained, so they didn't switch the brand of their CDK4/6 inhibitor, importantly. And that was looked at then for progression-free survival, but these were patients with measurable disease by RECIST version 1.1. And the data cut off here was November of 2024. This was a big trial, you know, and I think that that's influential here because this was 3,256 patients, and that's a lot of patients. So, they were all eligible. And then 315 patients ended up being randomized to switch to camizestrant upon presence of that ESR1 mutation. So, that was 157 patients. And then the other half, so they were randomized 1:1, they continued on their AI without switching to an oral SERD. That was 158 patients. They were matched pretty well. And so, their baseline characteristics, you know, the two subgroups was good. But this was highly statistically significant data. I'm not going to diminish that in any way. Your hazard ratio was 0.44. Highly statistically significant confidence intervals. And you had a median progression-free survival in those that switched to camizestrant of 16 months, and then the non-switchers was 9.2 months. So, the progression-free survival benefit there was also consistent across the subgroups. And so, you had at 12 months, the PFS rate was 60.7% for the non-treatment group and 33.4% in the treatment group. What's interesting, though, is we don't have overall survival data. This is really immature, only 12% mature as far as overall survival. And again, because this was an international trial and patients in other countries right now do not have the access to oral SERDs that the United States does, the crossover rate, they were not allowed to crossover, and so, a very few patients, when we look at progression-free survival 2 and ultimately overall survival, were able to access an oral SERD in the off-trial here and in the non-treatment group. And so, that's really important as far as we look at these results. Adverse events were pretty minimal. These are very safe drugs, camizestrant and all the other oral SERDs. They have some mild toxicities. Camizestrant is known for something weird, which is called photopsia, which is some flashing lights in the periphery of the eye, but it doesn't seem to have any serious clinical significance that we know of. It has a little bit of bradycardia, but it's otherwise really well tolerated. You know, I hate to say that because that's very subjective, right? I'm not the one taking the drug. But it doesn't have any serious adverse events that would cause discontinuation. And that's really what we saw in the trial. The discontinuation rates were really low. But overall, I mean, this was a positive trial. SERENA-6 showed that switching to camizestrant at the first sign of an ESR1 mutation on CDK4/6 inhibitor plus AI improved progression-free survival. That's all we can really say from it right now. Dr. Allison Zibelli: So, let's move on to ASCENT-04, which was a bit more straightforward. Sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab in PD-L1-positive, triple-negative breast cancer. Could you talk about that study? Dr. Rebecca Shatsky: Yeah, so this was also presented by the lovely Sara Tolaney from Dana-Farber. And this study made me really excited. And maybe that's because I'm a triple-negative breast cancer person. I mean, not to say that I don't treat hundreds of patients with hormone- positive, but our unmet needs in triple negative are huge because this is a disease where you have got to throw your best available therapy at it as soon as you can to improve survival because survival is so poor in this disease. The average survival with metastatic triple-negative breast cancer in the United States is still 13-18 months, and that's terrible. And so, for full disclosure, I did have this trial open at my site. I was one of the site PIs. I'm not the global PI of the study, obviously. So, what this study was was for patients who had had at least a progression-free survival of 6 months after their curative intent therapy or de novo metastatic disease. They were PD-L1 positive as assessed by the Dako 22C3 assay of greater than or equal to a CPS score of 10. So, that's what the KEYNOTE-355 trial was based on as well. So, standard definition of PD-L1 positive in breast cancer here. And basically, these patients were randomized 1:1 to either their sacituzumab govitecan plus pembrolizumab, day 1 they got both therapies, and then day 8 just the saci, as is standard for sacituzumab. And then the other group got the KEYNOTE-355 regimen. So, that is pembrolizumab with – your options are carbogem there, paclitaxel or nab-paclitaxel. And it's up to investigator's decision which upon those they decided. They followed these patients for disease progression or unacceptable toxicity. It was really an impressive trial in my opinion because we know already that this didn't just improve progression-free survival, because survival is so poor in this disease, of course, we know that it improved overall survival. It's trending towards that very much, and I think that's going to be shown immediately. And then the objective response rates were better, which is key in this disease because in the first-line setting, you've got a lot of people who, especially your relapsed TNBC that don't respond to anything. And you lose a ton of patients even in the first-line setting in this disease. And so, this was 222 patients to chemotherapy and pembro and 221 to sacituzumab plus pembro. Median follow-up has only been 14 months, so it's still super early here. Hazard ratio so far of progression-free survival is 0.65, highly statistically significant, narrow confidence intervals. And so, the median duration of response here for the saci group was 16.5 months versus 9.2 months. So, you're getting a 7-month progression-free survival benefit here, which in triple negative is pretty fantastic. I mean, this reminds me of when we saw the ASCENT data originally come out for sacituzumab, and we were all just so happy that we had this tool now that doubled progression-free and overall survival and made such a difference in this really horrible disease where patients do poorly. So, OS is technically immature here, but it's really trending very heavily towards improvement in overall survival. Importantly, the treatment-related adverse events in this, I mean, we know sacituzumab causes neutropenia, people who are experienced with this drug know how to manage it at this point. There wasn't any really unexpected treatment-related adverse events. You get some people with sacituzumab who have diarrhea. It's usually pretty manageable with some Imodium. So, it was cytopenias predominantly in this disease in this population that were highlighted as far as adverse events. But I'm going to be honest, like I was surprised that this wasn't the plenary over the SERENA-6 data because this, in my mind, there we have a practice-changing trial. I will immediately be trying to use this in my PD-L1 population because, to be honest, as a triple-negative breast cancer clinical specialist, when I get a patient with metastatic triple-negative breast cancer who's PD-L1 positive, I think, "Oh, thank God," because we know that part of the disease just does better in general. But now I have something that really could give them a durable response for much longer than I ever thought possible when I started really heavily treating this disease. And so, this was immediately practice-changing for me. Dr. Allison Zibelli: I think that it's pretty clear that this is at least an option, if not the option, for this group of patients. Dr. Rebecca Shatsky: Yeah, the duration of responses here was – it's just really important because, I mean, I do think this will make people live longer. Dr. Allison Zibelli: So, moving on to the final study that we're going to discuss today, neoCARHP (LBA500), which was neoadjuvant taxane plus trastuzumab, pertuzumab, plus or minus carbo(platin) in HER2-positive early breast cancer. I think this is a study a lot of us have been waiting for. What was the design and the results of this trial? Dr. Rebecca Shatsky: I was really excited about this as well because I'm one of those people that was waiting for this. This is a Chinese trial, so that is something to take note of. It wasn't an international trial, but it was a de-escalation trial which had become really popular in HER2-positive therapy because we know that we're overtreating HER2-positive breast cancer in a lot of patients. A lot of patients we're throwing the kitchen sink at it when maybe that is not necessary, and we can really de-escalate and try to personalize therapy a little bit better because these patients tend to do well. So, the standard of care, of course, in HER2-positive curative intent breast cancer with tumors that are greater than 2 cm is to give them the TCHP regimen, which is docetaxel, carboplatin, trastuzumab, and pertuzumab. And that was sort of established by several trials in the NeoSphere trial, and now it's been repeated in a lot of different studies as well. And so, that's really the standard of care that most people in the United States use for HER2-positive curative intent breast cancer. This was a trial to de-escalate the carboplatin, which I was super excited about because many of us who treat this disease a lot think carbo is the least important part of the therapy you're giving there. We don't really know that it's necessary. We've just been doing it for a long time, and we know that it adds a significant amount of toxicity. It causes thrombocytopenia, it causes severe nausea, really bad cytopenias that can be difficult in the last few cycles of this to manage. So, this trial was created. It randomized patients one to one with stage 2 and 3 HER2-positive breast cancer to either get THP, a taxane, pertuzumab, trastuzumab, similar to the what we do in first-line metastatic HER2-positive versus the whole TCHP with a carboplatin AUC of 6, which is what's pretty standard. And it was a non-inferiority trial, so important there. It wasn't to establish superiority of this regimen, which none of us, I think, were looking for it to. And it was a modified intent-to-treat population. And so, all patients got at least one cycle of this to be assessed as a standard for an intent-to-treat trial. And so, they assumed a pCR rate of about 62.8% for both groups. And, of course, it included both HER2-positive triple positives and ER negatives, which are, you know, a bit different diseases, to be honest, but we all kind of categorize them and treat them the same. And so, this trial was powered appropriately to detect a non-inferiority difference. And so, we had about 380 patients treated on both arms, and there was an absolute difference of only 1.8% of those treated with carbo versus those without. Which was fantastic because you really realized that de-escalation here may be something we can really do. And so, the patients who got, of course, the taxane regimen had fewer adverse events. They had way fewer grade 3 and 4 adverse events than the THP group. No treatment-associated deaths occur, which is pretty standard for- this is a pretty safe regimen, but it causes a lot of hospitalizations due to diarrhea, due to cytopenias, and neutropenic fever, of course. And so, I thought that this was something that I could potentially enact, you know, and be practice-changing. It's hard to say that when it's a trial that was only done in China, so it's not necessarily the United States population always. But I think for patients moving forward, especially those with, say, a 2.5 cm tumor, you know, node negative, those, I'd feel pretty comfortable not giving them the carboplatin here. Notes that I want to make about this population is that the majority were stage 2 and not stage 3. They weren't necessarily your inflammatory HER2-positive breast cancer patients. And that the taxane that was utilized in the trial is a little different than what we use in the United States. The patients were allowed to get nab-paclitaxel, which we don't have FDA approval for in the first-line curative intent setting for HER2-positive breast cancer in the United States. So, a lot of them got abraxane, and then they also got paclitaxel. We tend to use docetaxel every 3 weeks in the United States. So, just to point out that difference. We don't really know if that's important or not, but it's just a little bit different to the population we standardly treat. Dr. Allison Zibelli: So, are there patients that you would still give TCHP to? Dr. Rebecca Shatsky: Yeah, great question. I've been asked that a lot in the past like week since ASCO. I'd say in my inflammatory breast cancer patients, that's a group I do tend to sometimes throw the kitchen sink at. Now, I don't actually use AC in those because I know that that was the concern, but I think the TRAIN-2 trial really showed us you don't need to use Adriamycin in HER2-positive disease unless it's like refractory. So, I don't know that I would throw this on my stage 3C or inflammatory breast cancer patients yet because the majority of this were not stage 3. So, in your really highly lymph node positive patients, I'm a little bit hesitant to de-escalate them from the start. This is more of a like, if there's serious toxicity concerns, dropping carbo is absolutely fine here. Dr. Allison Zibelli: All right, great.  Thank you, Dr. Shatsky, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Rebecca Shatsky: Thanks so much, Dr. Zibelli and ASCO Daily News. I really want to thank you for inviting me to talk about this today. It was really fun, and I hope you find my opinions on some of this valuable. And so, I just want to thank everybody and my listeners as well. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you learn things from it, please take a moment to rate, review, and describe because it helps other people find us wherever you get your podcasts. Thank you again. 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. More on today's speakers Dr. Allison Zibelli Dr. Rebecca Shatsky @Dr_RShatsky Follow ASCO on social media:  @ASCO on Twitter  @ASCO on Bluesky  ASCO on Facebook  ASCO on LinkedIn   Disclosures: Dr. Allison Zibelli: No relationships to disclose Dr. Rebecca Shatsky: Consulting or Advisory Role: Stemline, Astra Zeneca, Endeavor BioMedicines, Lilly, Novartis, TEMPUS, Guardant Health, Daiichi Sankyo/Astra Zeneca, Pfizer Research Funding (Inst.): OBI Pharma, Astra Zeneca, Greenwich LifeSciences, Briacell, Gilead, OnKure, QuantumLeap Health, Stemline Therapeutics, Regor Therapeutics, Greenwich LifeSciences, Alterome Therapeutics  

BELIEVING IN HOPE WITHOUT COMPROMISE. Dr Virgilio Sacchini is dedicated to caring for people with breast cancer at the Memorial Sloan Kettering Cancer Center in New York. He originally trained at Universita degli Studi di Milano (UNIMI, Milan, Italy) where he is Professor of Surgery, and cooperates with the European Institute of Oncology in Milan (IEO, Milan, Italy). Dr Sacchini is a 2023 and 2024 Castle Connolly America's Top Doctor, the peer nominated group of the top 7% of all US practicing physicians. His goal is to achieve the best possible cancer outcomes and cosmetic results for his patients. “The new concept is to target only cancer cells.” “To cure someone and give him or her a miserable life is terrible, so the target in this moment is both better survival and better quality of life, less side effects.” “Once we prove that the combination of the medication with the Avacta technique works, of course it is approved and you can be cured everywhere in the world.”

As part of Oncology On the Go, CancerNetwork® spoke with Andrew M. Evens, DO, MBA, MSc, about developments in the treatment landscape for adolescents and young adults (AYA) with lymphoma. He highlighted collaboration between adult and pediatric oncologists that may better standardize treatment for this population.  Evens is the deputy director for clinical services at the Rutgers Cancer Institute and system director of medical oncology and oncology lead at RWJBarnabas Health Medical Group. Of note, Evens discussed an effort to “harmonize” efforts between adult and pediatric oncologists in treating AYA patients who may receive different treatment regimens, despite being similar in age. Furthermore, he highlighted 2 prominent trials that illustrated collaborative efforts from both adult and pediatric oncologists: the phase 3 SWOG S1826 trial (NCT03907488) and the phase 3 AHOD2131 trial (NCT05675410). Regarding the SWOG trial, Evens highlighted the greater efficacy and tolerability of nivolumab (Opdivo) with doxorubicin hydrochloride (Adriamycin), vinblastine sulfate, and dacarbazine (AVD) vs the standard of care brentuximab vedotin (Adcetris) plus AVD.  “You could say it was, generally speaking, a double winner. [The nivolumab combination] was more effective at 2 years; the progression-free survival [PFS] was greater than 90%, [which was] a remarkable output. When I say a double winner, it was also largely better tolerated. There was less neuropathy, [fewer] infections, and less sepsis [vs brentuximab vedotin plus AVD]. Surprisingly, to a certain extent, [there were] not many immune-related adverse events outside of thyroid [events],” Evens said. Furthermore, Evens discussed how collaboration between adult and pediatric oncology has impacted developments in the AYA lymphoma sphere. He placed a particular emphasis on the efforts of the Lymphoma Research Foundation, which convened multiple AYA lymphoma symposiums and established an AYA consortium. He then outlined unmet needs for this patient population, which included mitigating late toxicities following treatment and addressing inconsistencies in guidelines for lymphoma treatment in the AYA group. Evens then discussed mitigating disparities and addressing barriers to care, underscoring a need to navigate the complexities of treatment for a patient population with a myriad of stressors. He concluded by highlighting resources available to AYA lymphoma groups, which include educational, medical, and psychosocial resources to best educate patients and express to them that they are not alone.  “At the end of the day, be an advocate. Be an advocate for yourself. Be an advocate for others and know that there are [many] resources and people out there to help. We want to make sure nobody has to go through this alone, and that they have the medical and other psychosocial resources available to them,” Evens concluded.

Chest pains and severe fatigue drove Valerie David to seek medical attention, which led to a diagnosis of Stage 3B Cell Diffuse Large Cell Non-Hodgkin's Lymphoma.  A chemotherapy regimen helped her achieve survivorship.  However, years later, she discovered a lump under her armpit.  After getting it checked out, she was diagnosed with Stage 2 Invasive Lobular Carcinoma, a form of breast cancer. Again, aided by a chemotherapy regimen, Valerie survived this diagnosis, but not long after that, she was diagnosed with Stage 4 metastatic breast cancer.  Despite the staging, Valerie was prescribed a less aggressive form of chemotherapy, and survived.  Inspired by her cancer journey, she written and starred in an award-winning one-woman play, “The Pink Hulk,” seen through the United States and in Europe.

In 2018, Beth Brubaker was clobbered by a double whammy.  First, she was diagnosed with breast cancer, then four days later, she learned she was pregnant.  Her initial diagnosis was Stage Zero Ductal Carcinoma In Situ; however, after a lumpectomy, further tests revealed Beth had HER2+ Invasive Ductal Carcinoma, presenting as Paget's Disease.  This required an immediate mastectomy to get rid of the cancer in her left breast, following by an aggressive chemotherapy regimen.  While she was carrying a child and dealing with chemotherapy, Beth continued working as a schoolteacher.  Through all this, she achieved survivorship, and had the blissfully uneventful birth of a daughter, Harper.  

 “What you teach patients about that the side effects may be somewhat different, because it's more of a regional treatment with less systemic toxicities, so it's teaching patients about the drugs, the side effects, and the actual procedure itself,” Lisa Hartkopf-Smith, MS, RN, AOCN®, CHPN, advanced practice nurse at OhioHealth Center in Columbus and ProMedica Cancer Institute in Toledo, OH, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a discussion about the oncology nurse's role in intra-arterial chemotherapy administration. This episode is part of a series about chemotherapy administration, which we'll include a link to in the episode notes. You can earn free NCPD contact hours after listening to this episode and completing the evaluation linked below. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Earn 0.5 contact hours of nursing continuing professional development (NCPD), which may be applied to the nursing practice, oncology nursing practice, or treatment ILNA categories, by listening to the full recording and completing an evaluation at myoutcomes.ons.org by February 2, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of NCPD by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: The learner will report an increase in knowledge about the nurse's role in intra-arterial chemotherapy administration. Episode Notes Complete this evaluation for free NCPD. Oncology Nursing Podcast: Episode 252: Intraperitoneal Administration: The Oncology Nurse's Role Episode 285: Transarterial Chemoembolization: The Oncology Nurse's Role Additional episodes about chemotherapy administration Clinical Journal of Oncology Nursing article: Evaluation of a Chemotherapy and Medication Education Process for Patients Starting Cancer Treatment ONS Huddle Card: Chemotherapy ONS Courses: ONS Fundamentals of Chemotherapy and Immunotherapy Administration ONS/ONCC Chemotherapy Immunotherapy Administration Certificate™ ONS books:  Access Device Guidelines: Recommendations for Nursing Practice and Education (fourth edition) Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) To discuss the information in this episode with other oncology nurses, visit the ONS Communities.   To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library.   To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.   Highlights From Today's Episode  “Intra-arterial chemotherapy has actually been in existence over 70-plus years. It's been around for a long time. There are case reports in the literature as early as 1950 of intra-arterial chemotherapy, one specifically being giving nitrogen mustard, of all things, interactively through a catheter for the treatment of Hodgkin lymphoma.” TS 1:43  “Retinoblastoma is a common indication at this point in time for intra-arterial chemotherapy and has very good success rates. Intra-arterial chemotherapy is also used in liver cancers, whether it's an unresectable liver metastasis from adenocarcinoma of the colon or it's unresectable intrahepatic cholangiocarcinoma, as an another example where it's used. And it can also be used in hepatocellular or HCC carcinoma.” TS 6:36  “Some of the things, like pretreatment, things that the nurse has to look for in any of those are labs and particularly clotting times. You know, to make sure that a PT and an INR and a platelet count was drawn because this patient is going to have a catheter in their artery and frequently will have heparin, so we need to make sure you know what that is.” TS 8:22  “When you're pulling your drug information, your patient drug information sheets, it may not be appropriate to give the Adriamycin® teaching sheet from OncoLink or ChemoCare or ONS because that's generally the side effects of systemic treatment. Whereas if it's going to be given intra-arterially, they are probably not going to have hair loss and mouth sores, and their blood counts may not be affected.” TS 10:36  “In some cases, the nurse may be actually administering the medication, and in other cases they're not going to be actually administering it. So, if you have the situation where that intra-arterial procedure is done, like within the operating room or interventional radiology, then typically the radiologist or another physician will be administering it, but the RN may be in the room. It's often not a chemotherapy-qualified RN, it's often interventional radiology RN, so this is really a group effort between oncology nurses and those interventional radiology nurses and operating room nurses.” TS 12:03  “But in that case, as far as administration, again, it will probably be the physician, but where the nurse can play the role is with all those steps of verification. So, the dual verification process for chemotherapy needs to not just apply when you're giving it ID and an infusion center or inpatient. But it needs to happen in those off sites like interventional radiology in the operating room. So, the nurse in this suite can work and be part of that dual verification process, you know, comparing the orders with the drug and the patient identifiers. The nurse in that type of situation, in interventional radiology or operating room, can help ensure that safe handling occurs because those employees and physicians may not be as familiar with it. So, making sure that you have the PPE gowns the gloves goggles in the correct ways to dispose of it in those suites.” TS 12:43  “With time, just as it would with a venous port, that catheter can move out of place. So, even with the implanted pumps I was mentioning before, those catheters can move, and so we don't routinely check placement of the tip. What can happen is if the tip moves into another place, the patient will have those high doses of chemotherapy going systemic and will experience more side effects.” TS 19:22  “Some part of the adverse reactions could be related to the catheter or the pump itself, and then some of the adverse reactions are related to the drug itself.” TS 20:06  “So, other things that can happen with catheters and pumps, whether they're temporary or permanent, is always the risk for hemorrhage because it's in an artery. So, if something breaks or some tubing becomes disconnected, then the patient could hemorrhage. So, it's important that everything is always lured locked, connections taped, and that is being checked frequently to make sure that everything is tight and secure so that there's not that risk for hemorrhage from a catheter, an IV tubing, or needle becoming disconnected.” TS 21:11  “I honestly think this entire topic is something that's not discussed much, and I wish people knew more about it. I also wish people knew more about one of the areas of this topic—hepatic chemoembolizations, also called TACE [trans-arterial chemoembolization]. There are a lot of patients out there that are getting this in different locations, different hospitals, parts of the country, but because we typically are working in infusion centers are impatient areas, we are often not that knowledgeable about it because it happens somewhere else in interventional radiology or the OR. But our patients are affected by it, and we need to know more about it.” TS 26:55 

HEALTH NEWS   ·         Fermented red clover extract stops menopausal hot flushes and symptoms ·         Resveratrol, quercetin could provide new options for cancer therapy ·         World's largest study shows the more you walk, the lower your risk of death, even if you walk fewer than 5,000 steps ·         Brains of overweight people 'ten years older' than lean counterparts at middle-age ·         Soy protein found to deplete testosterone in men ·         Study shows endometriosis is linked to higher risk of depression, anxiety, eating disorders   Fermented red clover extract stops menopausal hot flushes and symptoms Aarhus University (Denmark), July 24, 2023 The vast majority of women in the menopause are familiar with the status of Red Clover as an herbal medicine that soothes hot flush symptoms and hormonal fluctuations. This holds true, new research shows, if the red clover is taken in a fermented form. Fermented Red Clover extract is demonstrated to decrease significantly both the number and severity of daily hot flushes. The study also found that the extract prevents the normally accelerated menopausal bone loss affecting one in three women over the age of 50 (e.g. results showed treatment blunted bone loss in the spine completely). These findings are very promising as the benefits take place without any of the side effects of traditionally proscribed hormone therapies that increase the risk of cancers and cardiovascular diseases. "It is the fermentation process of the Red Clover extract that makes the difference, as the lactic acid fermentation increases the bioavailability of the bioactive estrogen-like compounds (known as isoflavones or phytoestrogens) that Red Clover has in abundance," explains Max Norman Tandrup Lambert. "The challenge with isoflavones is that they can be difficult to digest as they naturally occur in the plant bound to sugar molecules which prevent absorption. Hence, a large proportion of the isoflavones that are consumed (e.g. as a pill or capsule) can pass through the intestine without entering circulation. This problem is bypassed when the Red Clover extract undergoes a fermentation process. To be technical the process separates the sugar molecules from the isoflavones, thereby increasing bioavailability," explains Max Norman Tandup Lambert. A studyrecruited 130 women with menopause symptoms, of which 60 were selected based on criteria of at least five severe hot flushes per day and blood tests (including FSH, that indicates the "stage" of menopause). "The women were separated into two groups of 30, so 30 drank 150ml Red Clover extract per day for 12 weeks, whilst the other 30 drank a masked placebo product. After 12 weeks we tested again and were speechless about the data. There was a much greater effect than we had hoped for." Says Max Norman Tandrup Lambert.   Resveratrol, quercetin could provide new options for cancer therapy Oregon State University, July 16, 2023 Resveratrol and quercetin, two polyphenols that have been widely studied for their health properties, may soon become the basis of an important new advance in cancer treatment, primarily by improving the efficacy and potential use of an existing chemotherapeutic cancer drug. In laboratory experiments, researchers at Oregon State University have developed a system to increase the bioavailability of these compounds in the body by using "copolymers" that make them water soluble and allow their injection into the blood stream, creating levels that are far higher than could ever be obtained by diet or oral intake. The resveratrol and quercetin then appear to reduce the cardiac toxicity of a very widely used cancer drug, Adriamycin. Although highly effective in the treatment of lymphomas, breast, ovarian and other cancers, Adriamycin can only be used for a limited time in humans because of its cardiotoxicity. The co-administration of these polyphenols might allow much more extensive use of this drug, while at the same time improving its efficacy and demonstrating the polyphenols' own anti-cancer properties, scientists said. Findings on this research have been published in the Journal of Controlled Release, by scientists from the College of Pharmacy at Oregon State University and the School of Pharmacy at Pacific University. Both institutions supported the research. "The co-administration of high levels of resveratrol and quercetin, in both in vitro and in vivo studies, shows that it significantly reduces the cardiac toxicity of Adriamycin," Alani said. "And these compounds have a synergistic effect that enhances the efficacy of the cancer drug, by sensitizing the cancer cells to the effects of the drug." It's possible, Alani said, that after further research it could be demonstrated that use of these compounds can completely eliminate the cardiotoxicity of Adriamycin, as they scavenge the toxic free radicals produced by use of this drug. It's also possible, he said, that administration of these natural polyphenols could have value in cancer therapy by themselves, or in combination with a wider range of other chemotherapeutic drugs.   World's largest study shows the more you walk, the lower your risk of death, even if you walk fewer than 5,000 steps Medical University of Lodz (Poland) & Johns Hopkins University School of Medicine, August 8, 2023 The number of steps you should walk every day to start seeing benefits to your health is lower than previously thought, according to the largest analysis to investigate this. The study, published in the European Journal of Preventive Cardiology, found that walking at least 3967 steps a day started to reduce the risk of dying from any cause, and 2337 steps a day reduced the risk of dying from diseases of the heart and blood vessels (cardiovascular disease). However, the new analysis of 226,889 people from 17 different studies around the world has shown that the more you walk, the greater the health benefits. The risk of dying from any cause or from cardiovascular disease decreases significantly with every 500 to 1000 extra steps you walk. An increase of 1000 steps a day was associated with a 15% reduction in the risk of dying from any cause, and an increase of 500 steps a day was associated with a 7% reduction in dying from cardiovascular disease. The researchers, led by Maciej Banach, Professor of Cardiology at the Medical University of Lodz, Poland, and Adjunct Professor at the Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, found that even if people walked as many as 20,000 steps a day, the health benefits continued to increase. They have not found an upper limit yet. "Our study confirms that the more you walk, the better," says Prof. Banach. "We found that this applied to both men and women, irrespective of age, and irrespective of whether you live in a temperate, sub-tropical or sub-polar region of the world, or a region with a mixture of climates. In addition, our analysis indicates that as little as 4,000 steps a day are needed to significantly reduce deaths from any cause, and even fewer to reduce deaths from cardiovascular disease." There is strong evidence that a sedentary lifestyle may contribute to an increase in cardiovascular disease and a shorter life. Studies have shown that insufficient physical activity affects more than a quarter of the world's population. More women than men (32% versus 23%), and people in higher income countries compared to low-income countries (37% versus 16%) do not undertake a sufficient amount of physical activity. The studies analyzed by the researchers followed up participants for a median (average) of seven years. The mean (average) age was 64, and 49% of participants were female. In people aged 60 years or older, the size of the reduction in risk of death was smaller than that seen in people aged younger than 60 years. In the older adults, there was a 42% reduction in risk seen in those who walked between 6,000 and 10,000 steps a day, while there was a 49% reduction in risk in younger adults who walked between 7,000 and 13,000 steps a day.   Brains of overweight people 'ten years older' than lean counterparts at middle-age University of Cambridge, August 4, 2023 From middle-age, the brains of obese individuals display differences in white matter similar to those in lean individuals ten years their senior, according to new research led by the University of Cambridge. White matter is the tissue that connects areas of the brain and allows for information to be communicated between regions.   Our brains naturally shrink with age, but scientists are increasingly recognising that obesity - already linked to conditions such as diabetes, cancer and heart disease - may also affect the onset and progression of brain ageing; however, direct studies to support this link are lacking.   The team studied data from 473 individuals between the ages of 20 and 87, recruited by the Cambridge Centre for Aging and Neuroscience.  The researchers divided the data into two categories based on weight: lean and overweight. They found striking differences in the volume of white matter in the brains of overweight individuals compared with those of their leaner counterparts. Overweight individuals had a widespread reduction in white matter compared to lean people.   They discovered that an overweight person at, say, 50 years old had a comparable white matter volume to a lean person aged 60 years, implying a difference in brain age of 10 years. Strikingly, however, the researchers only observed these differences from middle-age onwards, suggesting that our brains may be particularly vulnerable during this period of ageing.   "As our brains age, they naturally shrink in size, but it isn't clear why people who are overweight have a greater reduction in the amount of white matter," says first author Dr Lisa Ronan from the Department of Psychiatry at the University of Cambridge, "We can only speculate on whether obesity might in some way cause these changes or whether obesity is a consequence of brain changes."       Soy protein found to deplete testosterone in men University of Connecticut, July 27, 2023  The health detriments of soy consumption are reiterated in a new study out of the University of Connecticut that highlights the importance of avoiding soy at all costs. Researchers from the school found that men who consume soy protein rather than whey protein for muscle recovery and growth experience considerable reductions in their testosterone levels, as well as marked increases in levels of the stress hormone cortisol. Published in the Journal of the American College of Nutrition (JACN), the randomized, placebo-controlled crossover study looked at how soy supplementation affects testosterone, cortisol and sex hormone-binding globulin (SHBG) levels in men who engage in resistance exercises and training. They compared these effects to those brought about in men who supplement with whey. For the research, 10 resistance-trained men in their early 20s had their hormones evaluated in conjunction with an assigned supplemental diet. The men were divided into three groups: one receiving whey protein isolate, one receiving soy protein isolate and the last receiving a maltodextrin-based placebo control. The men were not allowed to take any other supplements, and vegetarians, vegans and individuals who were consuming high-protein diets were excluded. For two weeks, the men were told to ingest 20 grams of their assigned supplement every morning at the same time. The participants were then instructed to perform six sets of heavy resistance squats at 10 reps each, exerting 80 percent of their maximum lifting weight. At the end of the 14-day period, the researchers collected hormone profiles from each of the men and made comparisons. They found that, compared to the men who supplemented with whey, those taking soy did not necessarily produce more estrogen. They did, however, experience decreased testosterone levels and elevated cortisol levels, a deadly combination that can leave men at risk of disease and weight gain. Lowered testosterone levels and elevated cortisol levels are also generally attributed to the feminization phenomenon occurring in men that sometimes leads to disorders like nipple discharge, breast enlargement and hot flashes. It can also lead to inhibited thyroid function, bone loss, sleeping disorders, decreased sex function and reproductive problems.     Study shows endometriosis is linked to higher risk of depression, anxiety, eating disorders Yale University, August 7, 2023 Endometriosis is not just a condition that affects the pelvis, but a systemic disease that involves the entire body. Now, the largest epidemiological study to date on the psychiatric factors that can accompany endometriosis has demonstrated that depression, anxiety, and eating disorders are not only a result of the chronic pain endometriosis generates, but also have their own underlying genetic mechanisms. The team published its findings in JAMA Network Open. "The relationship between endometriosis and mental health is more complicated than we expected," says Renato Polimanti, Ph.D., associate professor of psychiatry and the study's principal investigator. "The biological basis is not just chronic pain, and there is much more that we need to understand." Endometriosis is an extremely painful condition in which tissue similar to the lining of the uterus (endometrium) grows outside the uterus. The disease manifests in a wide array of symptoms including pelvic, abdominal, and low back pain, heavy bleeding, painful sexual intercourse, painful urination and bowel movements, constipation or diarrhea, bloating, nausea, fatigue, and infertility. In this new study, the Yale research team obtained data from the UK Biobank which included more than 8,200 patients with endometriosis and 194,000 healthy controls. First, they investigated if depression, anxiety, and eating disorders were more prevalent in those with endometriosis, accounting for chronic pain, socioeconomic status, age, body mass index, various medications, and co-morbid conditions. They found that having endometriosis significantly increases the odds of having these three psychiatric conditions. through running a genetic correlation analysis, they found a significantly high genetic correlation between endometriosis and each of the three disorders. 

Dr. Shannon Westin, Dr. Rajendra Badwe, and Dr. Alastair Thompson discuss the JCO paper "Effect of Peritumoral Infiltration of Local Anesthetic Before Surgery on Survival in Early Breast Cancer." TRANSCRIPT The guests on this podcast episode have no disclosures to declare.  Dr. Shannon Westin: Hello, and welcome to another episode of JCO After Hours, the podcast where we get in-depth on manuscripts that are published in the Journal of Clinical Oncology. I am your host, Shannon Westin, gynecological oncologist by trade, but serve as our JCO Social Media Editor. And I'm super excited to talk to you about a paper that was just published online, April 6, 2023, entitled “The Effect of Peritumoral Infiltration of Local Anesthetic Before Surgery on Survival in Early Breast Cancer.”   Before we start, I just note that our guests have no conflicts of interest.   And so I'm accompanied by two greats in the field. First is the principal investigator on this trial, Dr. Rajendra Badwe, who is the Director and Head of Surgical Oncology Division at the Tata Memorial Center in Mumbai.  Welcome. Dr. Rajendra Badwe: Thank you. Dr. Shannon Westin: And then, of course, I'm joined by Dr. Alastair Thompson, Co-Director of the Lester and Sue Smith Breast Center and the Section Chief for Breast Surgery at Baylor College of Medicine here in Houston, Texas. We should have met in person. Dr. Alastair Thompson: Great to be with you today, both of you. Thank you. Dr. Shannon Westin: So this is an exciting topic, and of course, as a surgeon, I'm super intrigued. So let's get started. First, I would love for you all to tell me about the rationale for modulating events at the time of surgery to improve survival in any cancer, but specifically in breast cancer as it was in this study. Dr. Rajendra Badwe: So we have been working on events at the time of surgery for quite some time. And for the first time, when I walked through the gynae OPD in Guy's Hospital, there was this cartoon of the cell being extruded for ovulation, and I felt a cell moving from one organ to the other is actually metastasis. And that's how we started working on it. And in the past few years, we have been—a decade or so, we have been publishing changes induced by event of surgery.   So what we did earlier before beginning this trial is picking up a core biopsy before I start surgery. So it's normoxic, well-ventilated as well as well-nutrition-provided tumor, and I do a core biopsy and send it for expression profile on next-generation sequencing. Then, when 50% of the tumor surface is denuded from the opposite side, which is not denuded, I do other core biopsy. And the third core biopsy is when the tumor is in my hand in breast conservation surgery.  So first was normoxic, second was hypoxic, and the last was completely anoxic tumor. And we found that the middle sample, which has never been studied, all our understanding of biology of breast cancer is based on the first core biopsy or the whole tumor sample post-surgery. The middle sample had approximately 800 genes going up and down on the next-generation sequencing mRNA, and majority of these were epithelial-mesenchymal transition, proliferation, invasion, motility. You name the hallmark of metastases, and they were up in the middle of surgery at least in 30% of the tumor. Now, if the cell surface on one side in a three-centimeter tumor ring to the cell at the other end of the tumor as to some invasion has happened, how quickly can it happen? The difference between the two biopsies was just about five minutes.  Obviously, it was some kind of an electrical stimulus that went across the tumor. That's what our assumption was. And if it was to happen through the voltage-gated channels, the downstream effect of voltage-gated channel being depolarized was the same channels that I mentioned, the hallmarks of metastases that I mentioned. And if we were to block it, it was easiest possible by local anesthetic. So that's how this trial was originated. And we did in 1600 patients local anesthetic, half of them randomly allocated to receive lidocaine 0.5% versus not. Dr. Shannon Westin: That is so intriguing. I have to look up this work. I definitely agree with you. We do a lot of pre-biopsies and post-biopsies, but the intra-tumor biopsy is so novel with being able to study the anoxic tissue. I'm so interested. And you kind of started to get into this. Can you dig in a little bit more around that role or how the mechanism of action of this peritumoral anesthetic infiltration might work in preventing metastasis and preventing some of the changes that you were able to see? Dr. Rajendra Badwe: So if adequate amount of local anesthetic injected would paralyze or block the voltage-gated channels, sodium channels, and if the sodium is not allowed to get inside the cell as a gush, the first depolarization does not happen. And the downstream effect of such voltage-gated channels being stimulated is induction of proliferation, induction of invasion, and increased motility of the cell, everything that is necessary for metastases to set in. In fact, somewhere close to about 200 genes that belong to the pathway that allows a cell to express epithelial-mesenchymal transition were upregulated during this hypoxic episode. And hypoxia also is known to produce these changes. So we now, out of these 1583 patients, in about 100 patients, we also have the middle sample. And that's being looked at on the third-generation—next-generation expression profile to see whether the effects that I mentioned just now, are they abrogated by local anesthetic as the underlying mechanism of reducing the metastatic potential or upregulating pro-metastatic pathways in cancer cells. Dr. Shannon Westin: It's so intriguing. I guess I wonder if you or Dr. Thompson can speak a little bit about the results of any studies looking at peritumoral anesthetic infiltration prior to the work that we're going to discuss today. Were there smaller studies that looked at this? Dr. Alastair Thompson: There have been a number of studies over the years, particularly some small studies from the Republic of Ireland, which have suggested that the use of local anesthetic in breast surgery might be beneficial. And then there have been some other larger studies really more thinking about the block of the surgical stimulus to the surgical site, for example, using paravertebral blocks. And we are aware that what is given as an anesthetic, whether it's an agent, intravenous agent, like propofol, or a gaseous agent, may also have some effect on the metabolic response to the trauma of surgery. So there's quite a building logical background to this particular trial. But to my knowledge, this is a unique trial which a group of surgeons have been able to implement a fairly simple technique, taking a very short period of time, but with almost as much impact as some of the major drug trials in terms of disease freedom and overall survival.  Dr. Shannon Westin: Great. So, yeah, let's get into—do you want to take us through the design of the study, Dr. Badwe? Dr. Rajendra Badwe: Yes, thank you. We had 1583 patients who were randomly allocated. These are women with early breast cancer, so essentially, T1, T2 breast cancer with or without lymphadenopathy in the armpit, and metastatic, disease-wise, M0. And these individuals, these patients, were randomly allocated on table to receive local anesthetic versus not. 796 women received local anesthetic, and 804 women did not receive local anesthetic. The adequacy of this local anesthetic was 0.5% of lidocaine being injected on all surfaces of the tumor as if from one pole of the tumor, I would open an umbrella, a needle going in all directions all around the tumor from one side and then from the other side. And if the tumor was larger than being covered by these injections, additional points of injections were done on all surfaces of the primary tumor. The adequacy was tested by inability of the surgeon to use electrical diathermy for dissection. So the surgeon had to use knife to get the tumor out. Because of so much of water content in the tissues, the diathermy would not work. And if it worked, that would mean the amount of local anesthetic injected was inadequate. So that was the quality control parameter.  Postoperatively, patients received standard treatment. We had assessment of the hormone receptors, HER2 receptors. And postoperatively, they received standard chemotherapy, which is—in great majority, was epirubicin or Adriamycin with cyclophosphamide, four cycles, followed by 12 weekly paclitaxel injections. And those who were hormone receptor-positive, premenopausal received tamoxifen, and postmenopausals received either letrozole or Arimidex. All patients who were more than four centimeter positive in tumor size or had lymph nodes positive received postoperative radiotherapy, irrespective of whether they had conservation or mastectomy. And all individuals who had conservation received postoperative radiation, which was the standard protocol.  Talking about those with HER2 positive or triple-negative or ER/PR positive, their distribution on either side was identical, very, very close, no different at all. 35% of those who were HER2 3+ or FISH positive received trastuzumab for a year on either side, but two-thirds of them did not receive trastuzumab because of the cost constraints in India. But the distribution of those who received versus not was identical on both sides. So that's the kind of general demographics of the women who were on the study. Dr. Shannon Westin: Great. I think now—I think everyone's ready for the good news. So how did the infiltration impact outcomes in these patients? Dr. Rajendra Badwe: The primary endpoint was disease-free survival. There were a total of 255 events, 109 events in local anesthetic arm and 146 events in the no local anesthesia arms. That gave us a 26% reduction, a relative reduction of 26%, which reached statistical significance at P 0.01. And at the same time, for overall survival, which was the secondary endpoint, there was a 29% relative reduction in deaths related to breast cancer, and majority of the patients who died died of breast cancer. The other cause of mortality was very little—to be precise, less than 1.5%, and that was also equally distributed on—identically distributed on both sides. So approximately 4% reduction in disease-free survival absolute and a similar 4% reduction in overall survival and the number of deaths. So this was the first trial that looked at preventing metastases than treating micrometastases. Dr. Shannon Westin: Yeah, and I think I would just call on Dr. Thompson here because I think you already started saying this. I mean, when you look at the simplicity of the intervention and the low-cost nature of the intervention and the impact as opposed to some of our “incremental benefits” that we see with different very expensive targeted therapies and immunotherapies, I'd love just to get your thoughts on that. Dr. Alastair Thompson: So, of course. I think this is an extraordinarily well-designed, very balanced trial. Yes, you can say that not all patients are treated the same way around the world. But there's been a rigor about this which is very attractive, and I think it's one of the reasons the Journal of Clinical Oncology has published it.  What is perhaps astonishing is that if we try to first do no harm, we're actually doing a very simple intervention, low cost, relatively easy. The patient is asleep, so it's not painful in any way. It's not toxic at the sort of levels of local anesthetic being administered. And yet we're managing that for every 25 patients who have this addition to their procedure, one of them is going to be disease free and one of them is going to be alive as a consequence in the relatively short term. So, in terms of balancing the issues of trying to implement something versus the benefits to a patient population, the balance is very much in favor of this really quite minor change in practice to give us quite a major, by modern standards, difference in outcomes.  Dr. Shannon Westin: Yeah, I think it's incredibly exciting, and I think, to your point around is it applicable, is it generalizable, I'd love to hear what you all think. I mean, is this something that we should be implementing across the globe? Dr. Alastair Thompson: Well, I think sometimes, we don't always do in our own practices what has been led and demonstrated to be effective elsewhere. And we need to really pause and, I would suggest, think hard whether such a simple intervention could be implemented on our next working day.  Now, many of us do use local anesthesia in the setting of breast surgery, whether it's mastectomy, axillary lymph node surgery, or lumpectomy. But the difference might be that instead of putting this local anesthesia towards the end of the operation, thinking about doing things up front and maybe, therefore, having an even bigger impact than simply good quality pain control and good quality patient care.  Dr. Shannon Westin: I would love also, just as we're kind of coming to a close here, to get both of your thoughts about how we might implement this. And again, this is coming from a somewhat selfish standpoint. How could we implement this in other solid tumors? So is there a way to replicate? Obviously, breast has a very local disease spread pattern. Is there a way to potentially replicate this in other cancer types?  Dr. Rajendra Badwe: So we have begun a similar study in my hospital for squamous cell carcinoma, as well as lung cancer. And I'm sure there will be efforts to replicate in many other cancers where it is possible to inject local anesthetic all around before we start the resectional procedure. But at the same time, we need studies to confirm that this is actually happening. If I were to take a step further and wait for the expression profile of those who have received local anesthetic versus not in this trial, and if it shows that the abrogation of effects related to the downstream stimulation of VGSC, the voltage-gated sodium channels, then it might just be a good idea to use something else. Because if local anesthetic is effective to the extent, say, about x amount, cannabis has about 200x effect on stabilization of voltage-gated channels. So that could be another intervention that can be explored in trials in any site. Dr. Alastair Thompson: So that's a good point. Where do we go from here? And I would suggest that perhaps thinking about which local anesthetic to inject—would a longer-acting local anesthetic be just as effective from a prevention of shedding of metastatic cells, would that give longer additional pain relief? Would it be possible to think about other tumor sites where we're doing a local reception, for example, in the gastrointestinal tract, elsewhere in the body, including lung, for resections? There's just a huge amount of potential which this landmark, practice-changing trial has really pointed us to. And I would envisage that in future podcasts, Shannon, you're probably going to have a lot of people talking with you about other trials that have followed on from this. Dr. Shannon Westin: I hope so because that will mean we're impacting our patients in a positive way. I'm just so thrilled to have the two of you here. This was such a fascinating discussion. It went by so fast, and I hate to bring it to a close. But I encourage our listeners to definitely read this incredibly important manuscript and communicate with us online on how we can move this forward.   Again, this has been JCO After Hours, and we've been discussing “The Effect of Peritumoral Infiltration of Local Anesthetic Before Surgery on Survival in Early Breast Cancer,” published online April 6, 2023. I'm so thrilled that you joined us today on the podcast, and I hope you'll check out our other podcast offerings. Have a wonderful day. 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.      

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. 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. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. At the 2022 ASCO Annual Meeting, registered nurse, breast cancer survivor, and patient advocate Stephanie Walker presented the results of the BECOME Research Project, which looked at Black patient participation in metastatic breast cancer clinical trials. In this podcast, Ms. Walker shares her story with Dr. Manali Patel, a medical oncologist and Assistant Professor of Medicine at Stanford University, as well as the Cancer.Net Associate Editor for Health Equity. They discuss Ms. Walker's experience with metastatic breast cancer, how she became involved with patient advocacy and research, and the work being done within the oncology community to make cancer clinical trials more equitable and inclusive. View disclosures for Ms. Walker and Dr. Patel at Cancer.Net. Dr. Manali Patel: Hello, I'm Manali Patel. I'm a thoracic lung cancer doctor at Stanford University and the VA in Palo Alto. And I'm a researcher that's focused on trying to improve and overcome health disparities and really trying to achieve health equity. I'm also the Cancer.Net Associate Editor for Health Equity. And today it's my great pleasure to talk with Ms. Stephanie Walker. Stephanie is a registered nurse, a survivor of metastatic breast cancer, and a leading patient advocate. She's the lead author of the BECOME Research Project on increasing Black patient participation in metastatic breast cancer clinical trials, which she presented beautifully at the 2022 ASCO Annual Meeting. Stephanie, we can't thank you enough for talking with us today. I'm going to first start off by saying that I am from North Carolina. And Stephanie, I read so much about you over the past few years and noticed that you are living in Tarboro, North Carolina. Is that correct? Stephanie Walker: That is correct. I currently live there. We moved here originally in 2012, but this is my, I think, third or even fourth time living in North Carolina, moving back and forth between Thomasville and Durham and now permanently in Tarboro. Dr. Manali Patel: Well, I love that we share our Tar Heel roots. I am a Tar Heel born, Tar Heel bred. When I die, I'm a Tar Heel dead. So I can't thank you enough for sharing those roots and then also for sharing your story with us today. You were first diagnosed with metastatic breast cancer in 2015. Can you tell us a little bit about your experience with that diagnosis and what it was like to be diagnosed? Stephanie Walker: Well, actually the diagnosis in 2015 was my first diagnosis. I was not an early stager that had a recurrence, so I guess I could say breast cancer was never on my radar regarding family history. I thought maybe kidney disease or hypertension or those kind of things, but never breast cancer. So to say my life derailed at that time, it had. And I don't know if I ever grieved when I was told that I had metastatic breast cancer, I took it and just ran with it. I did not really fall off until many years later when I had to stop working. At the time I was diagnosed, I was working as an on-call nurse for a hospice company. So I was working 7 days on, 7 days off. So on my 7 days on is when I received a call and during my nap time. But yeah, it was very hard. But like I said, I didn't think bad of it. When I did finally look it up and see that the life expectancy was like 36 months, that kind of kicks your butt into gear to do things. But I didn't do anything. I just continued to work. [laughter] I didn't stop working. So yeah, it went through the basic standard of care treatment of Adriamycin, Cytoxan, and Taxol. But I didn't get through my whole series of Taxol due to neuropathy and increased falls. So I stopped at 9 out of 12. Dr. Manali Patel: Still 9 out of 12, it's difficult. And that's a difficult therapy and difficult regimen. You talked about how it derailed your life. And I know I've had the pleasure of reading your story online. I think what's also really interesting is that you had a role as a hospice nurse and over 40 years as a hospice nurse. Stephanie Walker: No, most of my years of nursing was critical care. The last 14 years were hospice care, palliative life care. But, yeah, I just rolled with that. Even taking care of patients that had the same diagnosis kind of brought-- seeing death and dying every day. But then to see somebody with metastatic breast cancer dying was really hard. Dr. Manali Patel: Yeah. And I'm sure that your experience at nursing on the other side and the flip side, and then when you became a patient, is quite different and maybe challenging in and of its own. Stephanie Walker: A lot of people expected or said that. I think I got left out of a lot of things that could have helped my journey in the beginning, like a patient navigation and that kind of thing was kind of not given to me. And I guess it was because being a nurse. But I had no experience other than pediatric oncology. I knew what those children went through. And actually, it actually did help going through my treatment because I would remember this one little girl that was going through chemo, and she got up one morning and her pigtails started falling out, and then she wanted to get on the IV pole and go to the playroom. And I'm thinking to myself, if she can do it-- and I called her by name, if she can do it, what the hell am I complaining about? So it's like, just get up and go to the playroom. [laughter] So I kept going back to that, you know what I mean? These kids that are innocent and have not even started to live their life going through this, and they never complained. So being an old lady at 56, being diagnosed, hell, who was I to complain about it? So just pick your hair up and keep going. [laughter] Dr. Manali Patel: That's right. Get your IV pole and go to the playroom. Stephanie Walker: That's right. Dr. Manali Patel: It's interesting that you mentioned that being from the nursing field and from the medical field kind of excluded you from a lot of what we hope other people receive, which is good education about their diagnosis. And like you mentioned, a patient navigator. Do you think that being a Black woman in any way, shape, or form shaped your experience with cancer, and if so, how? Stephanie Walker: It didn't in the beginning. Like I said, from 2015 up until 2018 when I found myself suddenly without a job or insurance, I had no idea. I didn't know anybody else with metastatic breast cancer. I didn't know what was out there. I guess I didn't have a need that was not met. I had insurance that was paying the bills. I had a husband that helped care for me, 2 adult children that looked in on me, a job that I didn't consider a job, it was a calling, and I had no needs at that time that weren't met. So I didn't have the desire or the need to look outside my little tiny world, I guess, until I found myself in 2018. In 2017, we moved late in the year back to North Carolina from Louisiana and started a new job as a hospice nurse, same kind of a schedule and was out shopping with my husband one day, and I kept saying, "I'm really short of breath." And I said, "All this weight I've gained since treatment, it's horrible. I'm just fat and can't breathe." And he just kind of laughed at me and said, “No, you're fine, you're fine." Well, then I started experiencing chest pain and I said, "I think I need to go to the ER." And for me to say I need to go to the ER, then my husband kicked it into gear and thinking, "Oh gosh, maybe so." Went to the ER, thought I was having an MI [myocardial infarction, a heart attack], ruled that out, and sat back in the lobby for a couple of hours and then they came and got me again and, in a hurry, said that they'd seen that I had a blood clot in my left lung. So it's like, great, here I am now with the PE [pumonary embolism] and having to be on blood thinners. And then I had a TIA [transient ischemic attack, sometimes called a ministroke] on an oral blood thinner. So obviously that failed me. So that's when I had to stop work. And then that's when I went into a deep depression. And people say it's like just because you have to stop work, you get depressed and it's like, yeah, I mean, I had always told myself in the very beginning of my diagnosis, I'm going to work up until the very end. And then not to have that-- and I felt like if I don't do anything, I'm going to die quicker. So I did not know what I didn't know until I found myself trying to figure out how I was going to live, pay bills, eat, pay for treatment. You know, when you don't have that comfort, then I started looking for ways to help provide until I could figure out a plan. And that's when I found the world of metastatic breast cancer and advocacy that I went to my first metastatic breast cancer conference: Living Beyond Breast Cancer, actually in April of 2018. And I don't remember the weekend because I was just in awe that all these women around me had metastatic breast cancer and were thriving. And more than that is I've seen a whole lot of Black people that were like me. So I wanted to know more, learn more, do more. So that's when my whole-- I tell people that was my coming out party of metastatic breast cancer. So I did research trying to find funding and I spent 8 hours a day, 5 days a week looking for that since I didn't have a job, I didn't know what else to do. And luckily, I found enough resources to stop the bridge until I got my first disability check. Nobody told me there was a 5-month waiting period, right? And I found the insurance, thank you to my cancer center, provided ways for me to continue treatment because I made an appointment to tell them I'm going to stop treatment. I can't afford to pay you. But they came through, and I'm thankful for that. So that's when the world of advocacy opened up. It was in 2018, about 3 years after my diagnosis. Dr. Manali Patel: I love that you think and were part of the calling and your identity of being a nurse, and then of course as a hospice nurse, especially, but losing that identity, but then channeling and refocusing and helping other people and really advocating has given me a lot of inspiration as a daughter of a mother that also faced similar challenges. Stephanie Walker: I'm so sorry. Dr. Manali Patel: I really want to thank you for all that you've done on behalf of all women with breast cancer, and especially for Black and Brown community members who have breast cancer. We've read your story and know about you and so are really just thankful for you and the research that you've been doing, especially the research that you presented this past summer at our ASCO Annual Meeting 2022, where you presented the results of the BECOME Research Project. I was hoping that you could give us some background on the study and why you wanted to do research in this particular area? Stephanie Walker: First and foremost, I'm not a researcher. I don't like research, [laughter] and I didn't plan on doing research. So with that being out of the way, I am a nurse. I am a critical care nurse. I am a hospice nurse. I am an advocate. Researcher, not. So actually, it was done because there was another metastatic breast cancer huge advocate, Marina Kaplan, who is no longer with us. I met her at the San Antonio Breast Cancer Symposium in 2019, and she had done a poster presentation regarding patient-centered outcomes as well. And she noticed that the Black respondents to her survey was less than optimal. She only had like 8% return. And she said, "Stephanie, I don't understand, why so low?" And it was like, "Marina, I don't know. I did your survey, so I can't tell you." So she said, "There's got to be a reason." And she said, "Let's delve into trying to find out why." And she said, "How about this? You do the survey. You gear it to the Black population, men and women with metastatic breast cancer, and I'll help you." And I said, "You're definitely going to have to help me. I'm not a researcher. I don't do statistics either. I found that I didn't need that when calculating medication doses." Anyway, so with that being said, she said, "I'll do it. I'll do that part for you." And I thought, me being simplistic, how hard can it be to do a survey, right? You have questions, you put them on a piece of paper, you print them off, you make 100 million copies, and you send them out to people or you ask people in one of your Facebook groups or something, and you just write down the answers. That is not how it's done in the research world. So, unfortunately, before we could get it off the ground, she passed away. And actually, she was very sick at the conference. So she passed away actually the following January-- February. So I kind of put it on the shelf in the back of my mind because I just assumed that was just between me and her. Nobody else knew. She had told somebody else, and they came back to me. It was actually someone at Living Beyond Breast Cancer, Janine. She came back to me. She said, "Hey, do you remember when Marina talked to you about X, Y, Z?" And it's like, "Here it comes." And I said, "Yeah, sure." And I told her I would get it done. I told her I would do it. I told her I would do it. And people said, "She's gone. You don't have to do it." And it's like, "My word is my word." So she introduced me to a group at the Metastatic Breast Cancer Alliance, the information task force, and they looked at it and thought it was a great idea and picked it up as one of their projects. And there I was starting my research problem with being the project lead of people that I didn't know, with an idea that I didn't know how it was going to be done. So I am thankful for a bunch of people, man, I am telling you. So it got done. It was partnered with a marketing and strategic group, CB White, and they actually got it off the ground to which way it needed to go. I didn't realize it cost a lot of money either. [laughter] It started off, we did literature search. We found some ASCO literature that would support our survey. Then we did interviews with the patients, the clinicians, researchers, payers, and they asked the questions -- we formulated questions because we had a subcommittee and someone else did the interviews. And after those were all done, that's how the survey was formed. And the survey went out-- it basically went out via social media. And the subcommittee, it was a bunch of patients and industry people and from the Alliance that pushed us out and was supportive of it and really believed in it. And my goal was to get 500 respondents. I wanted 250 Black and 250 of everybody else. I didn't care who, but I say I didn't reach my mark, and it was a little disappointing. I only had like 420-some people that responded. But everybody said that was really good because I didn't offer them anything. I didn't offer you money. I didn't offer you a gift card. I didn't offer you a cup of coffee. But it was done, and I'm proud of the responses. It was all done -- this whole project was done during the pandemic. And you have to realize that a lot of people in the subcommittee that I had that actually worked really hard, I had never met. So this is a group of people that you only know a face like on Zoom or something. So the results were some of them were -- I kind of expected that. But the biggest shocker for me was -- the number one thing that we're focusing on is a general ask, right? No one asked us, as Black men and women with metastatic breast cancer, talked to us about clinical trials. Dr. Manali Patel: I think that that finding, can you briefly tell us the numbers for the readers? I've read through and also saw the presentation kind of what you found in terms of that being the biggest and then some of the other outcomes that you looked at. Stephanie Walker: Well, some of the other outcomes were like, other than the 4 that we're focusing on, is to better inform, you know what I mean? We need Black patients to know about and to get the information to make informed decisions about clinical trials. That's first. Then the second one was to inspire trust. We all know about all the stuff in the past and the distrust of the Black community with health care providers. So we need to build that, and it has to start in a community in which the person lives. And we also found that more Black than non-Black, when questioned, would try a clinical trial only if they were asked to, but they weren't. So to ensure access -- there were barriers, obviously, to people wanting to participate in a clinical trial. And some of those were the travel time, the difficulty in finding the trials, worrying about the financial burden. And a lot were like, if I go to another facility, is my insurance going to cover it? So that's a big thing. And the final was to address the concerns, legitimate concerns. We need the health care provider to communicate in a clear language that we understand, and also understand the reasons that motivate us to participate in a clinical trial. So with those 4 things, we came up with some actions to do. But those were the 4 big ones that I found out that needed to be addressed. Because when doing this, I didn't do it just to be doing it. I wanted to do it to find out what the barriers were and then to come up with actionable steps. And as a physician or anybody, there's all those surveys people want you to do, and then they stop there. They don't go on. And I'm one of these people, like, don't waste my time. Let's do something that's actionable that we can act upon or help other people to act upon. Dr. Manali Patel: I think those of us in the health equity space, right, are not surprised that a lot of what you found does really play in terms of what the health care provider and what the health system can do. The health system can do things to engender trust rather than putting the blame on the patient, saying that patients don't enroll in clinical trials. Well, maybe we aren't asking patients equitably if they're enrolling. And we need to take a hard look at our own selves and our own practices and think about what we can do similar to a checklist, right? When a patient comes in, how can we make this part of standard of care to make sure that everybody gets asked, and we've got all these fancy decision support tools and our electronic health record that turn up poppers of, "Did you ask the patient about this?" But making this part of the rubric of what we do, I think was really nicely highlighted in your study and your findings. Stephanie Walker: Yeah. And I truly agree. Rubric metric, however you want to say it, people are like, "Well, how are you going to get them to change it?" Like, first of all, with education, and second of all, man, if I could figure out a way to attach a dollar sign to that rubric or that metric, it would be great.  Dr. Manali Patel: I think for our readers, you and I know and really want to get the messaging out for equitable and accessible clinical trials. Can you explain from your perspective why it's so important to be inclusive and to have clinical trials that are accessible and equitable for all patients with cancer? Stephanie Walker: Well, the statistics speak for themselves. Only like 6% of participants in a clinical trial for a metastatic breast cancer are, like 6%. But it's important that the clinical trials are inclusive for everybody, all people, because you want the medications to work for quote-unquote "all people.” And we find that, speaking from just my experience and what I know and have heard, that there are treatments out there that don't actually work on Black people. And one of the big general ones is one of the blood pressure meds we have found recently that does not work or do not work very well with people of color. So we have to include everybody in these clinical trials to be able to have effective treatments to work for everybody, no matter where they are, where they live, who their doctor is, what hospital they go to. All people need to be included. And we find that 80% of the patients are treated in community cancer centers, and those are the patients that are usually left out just due to the fact they're not associated with a teaching medical institution/NCI facility. Dr. Manali Patel: I think this is so important and really appreciate you highlighting that important fact is that making sure that our treatments are effective and feasibly can be provided to all patients in our quest for achieving health equity. What work is currently being done to make clinical trials more inclusive? Stephanie Walker: Everybody is working on that. Even Stephanie is working on that. With a new subcommittee, a little branch out from BECOME, we found that -- we had just spoken of education. And so we came up with an idea of an actionable step. How do we do that, and how do we educate the health care providers regarding all of these facts that we found? And we are going to have a symposium. We came up with a symposium, a 1-day event. And we are going to attach it to the San Antonio Breast Cancer Symposium. We're actually going to have it the day before the symposium starts and hopefully, that will attract health care providers who we're targeting this to come and just listen to see what the patient has to say. We have it broken into 3 sections. The first section is about the health care provider, how to communicate with your patients. What does it look like on the other side? And then the other is broken down into the pharmacy or pharma industry section. What are they doing to help include all people in clinical trials? And a lot of them have jumped on that bandwagon to be inclusive. But really, what are you working on? I want to know. So that's the second session. And the third session is about the patient and the caregiver. From the patient's point of view, how they did with clinical trials, and also a clinical navigator, what their role is to help patients find out about the trials and be that support person and as well the caregiver. A lot of people forget the caregiver goes through this as well. And to get the view of what the caregiver had, what they had, what they needed, what they didn't receive, to find out that so we can provide those things for them, hopefully. But yeah, that's what we're doing now. We're still in the planning phase. Dr. Manali Patel: That's amazing. I love the action-orientedness of really moving to the next step, taking the findings that you found, moving towards really action, and bringing all of the partners together. I know that all the industry partners and really holding people accountable for what they are planning on doing. I love that. What actually are you doing and coming up with a plan for moving forward? Stephanie Walker: Yeah, you have to start holding people accountable, get rid of the biases. And I've been blessed that I had not experienced any kind of biases in my care until the pandemic. And that was when I wanted to get my cancer treatment at a community center closer to home because it was a simple treatment of fulvestrant injection, and I wanted to get it closer to home. And we all agreed. We found a physician that would accept me closer to home. And it was going great until I started having complications, and he totally blew me off, actually. He told me that I needed psychiatric help, but he didn't know I was already getting it. But anyway, after contacting several patients that see this physician, they experienced the same thing. So that's the first time I had experienced anything based on my race and who I am. And that happens when a physician walks into a patient's room, sometimes that's what they see. They don't see Stephanie, they see a Black woman, and they start thinking in their head ticking off things like, "Oh, she's Black. She doesn't understand. She doesn't even know what a clinical trial is. She's going to be non-compliant. She's going to quit. And then she's going to become this angry Black woman that I'm going to have to deal with." So all of that before it is, "Hi, my name is." So, yeah. That experience made me want to do a little bit more to try to get rid of the biases that patients experience. Dr. Manali Patel: Yeah, I think what you're doing to advocating, not only us clinicians, I'm so sorry that you have to experience that. Unfortunately, we've heard and know that it's sometimes the norm of what people experience or the systemic biases that then play into the role with implicit biases and then, unfortunately, lead to delays in care and also mistreatment or even lack of evidence-based treatment for people just based off of their skin color or from what community they may be from, or even how much income they may have or education level. I think what you said about what the work that you're doing and educating us clinicians, number one, first and foremost, what we can do with the health care system and looking at our own practices and our own policies and trying to reduce and remove some of the biases that are baked into the system. But then also what you're doing on the ground with other patients and advocating for patients. I want to close with 1 last question, and you've highlighted some of it, but if you were to give advice to people with cancer who are faced with needing to advocate for themselves, be it for care like you described, or for clinical trials, what advice would you give them? Stephanie Walker: It's almost like having to put burden on the patient to learn. But you do. You have to become Ph.D.-certified with your own illness. You got to go out there and know what you got and know what you need, what the standard of care is, and that is the truth. When you get that diagnosis, I believe you should, first of all, take somebody with you with a notepad to be able to write down things. When you hear the word “cancer,” you don't hear nothing after that. And you're only going to probably absorb a fourth of what you're told at the office. So have somebody to write down what the doctor says, suggestions, and research your plan of care. Find out what the standard of care is. I tell people, don't go to Dr. Google, but you're going to have to Google some things. But try to find vetted sites, reputable sites to do that. And there's lots of organizations out there that you can get the information from. And I don't want to say use Facebook, but believe it or not, there are great groups on Facebook that offer support, information, suggestions, "Hey, I'm getting ready to start this treatment. What happened to you? Or what do you think?" So always arm yourself with questions when you go in. Ask the questions. Don't be afraid to ask. If that doesn't work, of course, with the pandemic, I would have people that want to go with me, and I couldn't go, but I could sit out in the lobby on my cell phone and listen in and encourage them to ask this question or ask the doctor a question. Of course, that has to be given with permission from the physician as well. But arm yourself with as much information as you can. And if you are finding that you're not getting that feeling of, “This doctor has my best interest,” seek a second opinion, third opinion, a fourth opinion. Don't let a doctor railroad you into doing something that you don't understand. If you don't understand, speak up. I tell people all the time, they may know about cancer, but you know about yourself, so hold firm to that. I've told several doctors. I've fired several. So, I mean, they're out there. And I tell people all the time, don't be scared. Be comfortable and always know there's somebody out there. You're not alone to talk to. And being depressed or down sometimes, it's normal. You go there, but don't live there. If you find yourself living there, reach out for help. Because I'm one that thought that nurses don't reach out for help, but I finally did. So don't be afraid to ask for help and know that there's somebody out there with you. Call me. I'm available. Dr. Manali Patel: Ms. Walker, I can't thank you enough for sharing your story with us and telling us more about your experiences and the work that you've been doing-- the important work you've been doing in this area. It was really wonderful to have you, and I hope that we get to meet in person at some point. Stephanie Walker: I really thank you for the opportunity to share and hopefully the information that we both have provided, people will get it and understand it, and it will help somebody, because the work you done while you were at ASCO was amazing, too. So read that. [laughter] So I really do, and I really appreciate the opportunity. Dr. Manali Patel: We are very grateful. And thank you for Cancer.Net, for hopefully being that source of trust and source of information for all of our patients. ASCO: Thank you, Ms. Walker and Dr. Patel. You can find more stories from people with cancer at the Cancer.Net Blog, at www.cancer.net/blog. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

First trial to prove a diet supplement can prevent hereditary cancer Newcastle University (UK), July 25, 2022 A trial in people with high hereditary risk of a wide range of cancers has shown a major preventive effect from resistant starch, found in a wide range of foods such as oats, breakfast cereal, cooked and cooled pasta or rice, peas and beans, and slightly green bananas. An international trial—known as CAPP2—involved almost 1000 patients with Lynch syndrome from around the world, and revealed that a regular dose of resistant starch, also known as fermentable fiber, taken for an average of two years, did not affect cancers in the bowel but did reduce cancers in other parts of the body by more than half. This effect was particularly pronounced for upper gastrointestinal cancers including esophageal, gastric, biliary tract, pancreatic and duodenum cancers. The astonishing effect was seen to last for 10 years after stopping taking the supplement. "We found that resistant starch reduces a range of cancers by over 60%. The effect was most obvious in the upper part of the gut," explained Professor John Mathers, professor of Human Nutrition at Newcastle University. "This is important as cancers of the upper GI tract are difficult to diagnose and often are not caught early on. "Resistant starch can be taken as a powder supplement and is found naturally in peas, beans, oats and other starchy foods. The dose used in the trial is equivalent to eating a daily banana; before they become too ripe and soft, the starch in bananas resists breakdown and reaches the bowel where it can change the type of bacteria that live there. "Resistant starch is a type of carbohydrate that isn't digested in your small intestine; instead it ferments in your large intestine, feeding beneficial gut bacteria—it acts, in effect, like dietary fiber in your digestive system. This type of starch has several health benefits and fewer calories than regular starch. We think that resistant starch may reduce cancer development by changing the bacterial metabolism of bile acids and to reduce those types of bile acids that can damage our DNA and eventually cause cancer. However, this needs further research."   New study finds lowest risk of death was among adults who exercised 150-600 minutes/week Harvard School of Public Health, July 25, 2022 An analysis of more than 100,000 participants over a 30-year follow-up period found that adults who perform two to four times the currently recommended amount of moderate or vigorous physical activity per week have a significantly reduced risk of mortality, according to new research published today in the American Heart Association's journal Circulation. The reduction was 21-23% for people who engaged in two to four times the recommended amount of vigorous physical activity, and 26-31% for people who engaged in two to four times the recommended amount of moderate physical activity each week. In 2018, the United States Department of Health and Human Services' Physical Activity Guidelines for Americans recommended that adults engage in at least 150-300 minutes/week of moderate physical activity or 75-150 minutes/week of vigorous physical activity, or an equivalent combination of both intensities.  The analysis also found: Participants who met the guidelines for vigorous physical activity had an observed 31% lower risk of CVD mortality and 15% lower risk of non-CVD mortality, for an overall 19% lower risk of death from all causes. Participants who met the guidelines for moderate physical activity had an observed 22-25% lower risk of CVD mortality and 19-20% lower risk of non-CVD mortality, for an overall 20-21% lower risk of death from all causes. Participants who performed two to four times above the recommended amount of long-term vigorous physical activity (150-300 min/week) had an observed 27-33% lower risk of CVD mortality and 19% non-CVD mortality, for an overall 21-23% lower risk of death from all causes. Participants who performed two to four times above the recommended amount of moderate physical activity (300-600 min/week) had an observed 28-38% lower risk of CVD mortality and 25-27% non-CVD mortality, for an overall 26-31% lower risk of mortality from all causes. In addition, no harmful cardiovascular health effects were found among the adults who reported engaging in more than four times the recommended minimum activity levels. Previous studies have found evidence that long-term, high-intensity, endurance exercise, such as marathons, triathlons and long-distance bicycle races, may increase the risk of adverse cardiovascular events, including myocardial fibrosis, coronary artery calcification, atrial fibrillation and sudden cardiac death.   Treating dementia with the healing waves of sound Ultrasound applied to the brain could help treat patients with dementia. Tohoku University (Japan), July 20, 2022 Ultrasound waves applied to the whole brain improve cognitive dysfunction in mice with conditions simulating vascular dementia and Alzheimer's disease. The research, conducted by scientists at Tohoku University in Japan, suggests that this type of therapy may also benefit humans. The team, led by cardiologist Hiroaki Shimokawa, found that applying low-intensity pulsed ultrasound (LIPUS) to the whole brain of the mice improved blood vessel formation and nerve cell regeneration without having obvious side effects. "The LIPUS therapy is a non-invasive physiotherapy that could apply to high-risk elderly patients without the need for surgery or anaesthesia, and could be used repeatedly," says Shimokawa. The Tohoku University team found that cognitive impairment markedly improved in mice with conditions similar to vascular dementia and Alzheimer's disease when LIPUS was applied to the whole brain three times a day for 20 minutes each time.    Study: ADHD drugs do not improve cognition in healthy college students University of Rhode Island, July 19, 2022 Contrary to popular belief across college campuses, attention deficit hyperactivity disorder (ADHD) medications may fail to improve cognition in healthy students and actually can impair functioning, according to a study by researchers at the University of Rhode Island and Brown University. Study co-investigators Lisa Weyandt, professor of psychology and a faculty member with URI's George and Anne Ryan Institute for Neuroscience, and Tara White, assistant professor of research in behavioral and social sciences at Brown University, had anticipated different findings. "We hypothesized that Adderall would enhance cognition in the healthy students, but instead, the medication did not improve reading comprehension or fluency, and it impaired working memory," she said. "Not only are they not benefitting from it academically, but it could be negatively affecting their performance." This first-ever multisite pilot study of the impact of so-called "study drugs" on college students who do not have ADHD comes at a time when use of prescription stimulants such as Adderall, Ritalin and Vyvanse is common among young adults who believe the drugs will improve their academic performance.  Results of the study, published in the journal Pharmacy, show that the standard 30 mg dose of Adderall did improve attention and focus -- a typical result from a stimulant -- but that effect failed to translate to better performance on a battery of neurocognitive tasks that measured short-term memory, reading comprehension and fluency. Weyandt has a theory about why working memory would be adversely affected by the medication. Brain scan research shows that a person with ADHD often has less neural activity in the regions of the brain that control executive function -- working memory, attention, self-control. For people with ADHD, Adderall and similar medications increase activity in those regions and appear to normalize functioning. "If your brain is functioning normally in those regions, the medication is unlikely to have a positive effect on cognition and my actually impair cognition. In other words, you need to have a deficit to benefit from the medicine," Weyandt said.         Guanabana: the cancer killer big pharma doesn't want you to know about Northeastern University, July 16, 2022  Guanabana is known by a variety of names -- including soursop, cherimoya, custard apple, Brazilian paw paw and graviola. As far back as the 1970s, the National Cancer Institute (NCI) investigated the merits of guanabana, and discovered the stems and leaves of the tree were successful in destroying cancer cells. "Inexplicably, the results [of the NCI research] were published in an internal report and never released to the public. Since 1976, guanabana has proven to be an immensely potent cancer killer in 20 independent laboratory tests, but as of now, no double-blind clinical trials," reports Christopher Lane, Ph.D., in Psychology Today. Moreover, this study found that a compound derived from the leaves of guanabana was "selectively cytotoxic for the lung (A-549), colon (HT-29), and pancreatic (PACA-2) cell lines with potencies equal to or exceeding those of Adriamycin." And research in the Journal of Natural Products discovered that extracts of guanabana demonstrated pesticidal, antimalarial, antiviral and antimicrobial properties. Likewise, Memorial Sloan Kettering Cancer Center states that guanabana shows anti-inflammatory and anticancer effects in vitro and in vivo. Revered for centuries in South America and Southeast Asia, the bark, leaves, root, seeds and fruit have been used to tame heart disease, asthma, liver issues and arthritis. Guanabana is also helpful for treating sleep disorders, fevers and cough. According to the article, "Guanabana--Medicinal Uses?" extracts of the plant: Attack cancer safely and effectively with an all-natural therapy that does not cause extreme nausea, weight loss and hair loss. Protect the immune system. Boost energy and outlook on life. Effectively target and kill malignant cells in 12 types of cancer -- including colon, breast, prostate, lung and pancreatic cancer. Proved to be up to 10,000 times stronger in slowing the growth of cancer cells than Adriamycin, a commonly used chemotherapeutic drug. Selectively kill only cancer cells, unlike traditional chemotherapy treatments.  *A word of caution: Excessive consumption of guanabana can lead to neuronal dysfunction and degeneration with symptoms similar to Parkinson's disease. Consult with a qualified practitioner before taking guanabana on a daily basis.     High-strength cannabis linked to addiction and mental health problems University of Bath (UK), July 25, 2022 As the strength or potency of cannabis products has increased internationally over the years, so have rates of people being treated for cannabis addiction, say the authors of a new study. Researchers from the Addiction and Mental Health Group at the University of Bath (UK) have systematically analyzed the relationship between the types of cannabis people use and their addiction and mental health problems. Their work draws on 20 studies involving almost 120,000 people. The new study, published in The Lancet Psychiatry, suggests that people who use high-potency cannabis are more likely to experience addiction than those using low-potency products. It also suggests that people using high-potency cannabis are more likely to experience a psychotic disorder, such as schizophrenia. These findings may help to explain why more people have received treatment for cannabis problems over recent years. Data from the European Monitoring Centre for Drugs and Drug Addiction show a 76% increase in people entering treatment for cannabis addiction in the past decade.

Rosalina and Shauna take you through the beginning stage of their chemotherapy treatments. This was recorded at the beginning of their chemotherapy journey of May/June 2021. They discuss conversations with their doctors about treatment plans and their struggle to cope with the reality of undergoing chemotherapy. They also explain their decisions and the reasons they chose to Cold Cap. Both Rosalina and Shauna decided to undergo chemotherapy, where Rosalina's treatment is Taxotere and Cyclophosphamide (TC), and Shauna's treatment is Adriamycin and Cyclophosphamide plus Taxol (AC-T).If you enjoy this episode, please share it with your friends. Help us reach more women by subscribing and rating us on Apple Podcast and Spotify.You can follow us on Instagram @TYFTSpodcast and email us at tyftspodcast@gmail.comResources below:Fast Mimicking Diet:-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190229/-DIY FMD https://www.quantifiedbob.com/fasting-mimicking-diet/-https://www.breastcancer.org/research-news/intermittent-fasting-may-help-cancer-treatments-work-better-https://www.aacr.org/about-the-aacr/newsroom/news-releases/fasting-mimicking-diet-is-safe-may-modulate-metabolism-and-boost-antitumor-immunity-in-cancer-patients/Chemotherapy:-(AC)https://breastcancernow.org/information-support/facing-breast-cancer/going-through-breast-cancer-treatment/chemotherapy/ac-chemotherapy-Taxotere https://breastcancernow.org/information-support/facing-breast-cancer/going-through-treatment-breast-cancer/chemotherapy/docetaxel-taxotere-Cold Cappinghttps://www.breastcancer.org/treatment/side_effects/hair-loss/cold-caps-scalp-cooling

Commentary by Dr. Michelle Kittleson

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. The 2019 ASCO Annual Meeting, held May 31 to June 4, brought together physicians, researchers, patient advocates, and other health care professionals from around the world to present and discuss the latest research in cancer treatment and patient care. In the annual Research Round Up podcast series, Cancer.Net Associate Editors share their thoughts on the most exciting scientific research to come out of this year’s ASCO Annual Meeting and what it means for patients. First, Dr. Lynn Henry will discuss 3 studies that explored new treatment options for women with breast cancer, including a study on immunotherapy for triple-negative breast cancer and 2 studies on treatment for hormone receptor positive, HER2-negative breast cancer. She also discusses research on the effects of a low-fat diet in women diagnosed with breast cancer, and a study on whether pregnancy after breast cancer increased the risk of recurrence.   Dr. Henry is an Associate Professor and Interim Division Chief of Oncology in the Department of Medicine at the University of Utah and Director of Breast Medical Oncology at the Huntsman Cancer Institute. She is also the Cancer.Net Associate Editor for Breast Cancer. Dr. Henry: Hi. My name is Dr. Lynn Henry. I'm a medical oncologist who specializes in treating breast cancer at the University of Utah. Today, I'm going to discuss research on breast cancer that was presented at the 2019 ASCO Annual Meeting in Chicago. In particular, I'm going to focus on the results of some clinical trials that directly impact how oncologists treat patients with breast cancer. First, I'm going to give just a very brief overview of the types of breast cancer and then talk about some research that was presented on triple-negative and hormone-receptor-positive breast cancer. Then I'm going to briefly review findings related to diet and breast cancer as well as pregnancy after breast cancer in women with BRCA mutations. As a quick reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone-receptor positive or estrogen-receptor positive, and those are stimulated to grow by estrogen. We treat those cancers with anti-estrogen treatments or anti-hormone treatments to block estrogen or lower the estrogen level in the body. Other breast cancers are called HER2-positive. These are often more aggressive cancers. But because they have extra copies of HER2, they often respond to treatments that block HER2. And finally, there are breast cancers that don't have hormone receptors or HER2, and these are called triple-negative breast cancer. So first, I'm going to focus on this type, triple-negative breast cancer. Until recently, most of the time, we treated triple-negative breast cancer with chemotherapy because we hadn't found other drugs that worked very well. There's a new type of drug, however, called immunotherapy that tries to use a patient's immune system to help fight the breast cancer. Early in 2019, the FDA approved a new treatment for triple-negative breast cancer that is a combination of a chemotherapy called Abraxane and a new immune drug called atezolizumab or Tecentriq. The combination increased the length of time until cancer progressed or grew. Overall, the treatment was fairly well tolerated. But we did learn that in order for the treatment to work, the cells surrounding the cancer have to have at least a small amount of a very specific protein called PD-L1. So at this recent ASCO meeting, we heard an update about this treatment. In the trial, the patients whose cancers had the PD-L1 protein and who got the combination treatment lived 7 months longer than those who got just the chemotherapy, which was an increase from 18 months to just over 2 years. This is an important first step towards finding a better treatment for this difficult type of triple-negative breast cancer. And this treatment is currently available to patients. Additional clinical trials are going on now to try to find even better combinations of chemotherapy and immune therapies to treat this type of cancer. So next, I'm going to talk about hormone-receptor-positive breast cancer. There were two trials of this type of cancer that had important results presented at the ASCO meeting. First, I'll focus on the treatment of early-stage node-negative breast cancer that is hormone-receptor positive and HER2 negative. The Oncotype DX test is a test we commonly run on tumors of this type to help determine whether treatment with chemotherapy is likely to be helpful. For this test, if your tumor has a score over 25, then chemotherapy is generally recommended in addition to anti-hormone therapy. If you have a score under 11, then chemotherapy is not recommended and a patient should receive only anti-hormone therapy. But for those with scores between 11 and 25, it was unclear how beneficial it was to receive chemotherapy. Last year, the results of the TAILORx trial were reported. And that showed that for women over the age of 50, if their tumor had a score between 11 and 25, they were not likely to get benefit from chemotherapy. However, it turned out it was a bit more complicated for women aged 50 and under. For those with scores between 11 and 15, chemotherapy was not likely to be beneficial. However, for those who score 16 to 25, chemotherapy might be beneficial. So we got some answers but not everything. At this recent ASCO meeting, additional information was reported to help guide treatment decision making for this middle group of women aged 50 and under. So for women whose scores were at the higher end, 21 to 25, chemotherapy was found to be likely to be beneficial. However, in that middle group, the 16 to 20 group, chemotherapy might be beneficial but generally only for women with higher risk cancers, meaning larger cancers or higher grade. This information is helpful because it provides more information for oncologists and for patients when they are discussing whether or not chemotherapy should be included as part of their treatment. So switching gears a little, still staying with premenopausal women and hormone-receptor-positive HER2-negative cancer, but now thinking about metastatic breast cancer, so cancer that has spread. We now have additional information about treatment with an anti-hormone therapy plus an additional drug called the CDK4/6 inhibitor. We've routinely been recommending this treatment combination because it leads to a longer time before the cancer progresses. But until now, we didn't know if it actually allows women with this type of cancer to live longer. The results of the MONALEESA-7 trial, which looked at the combination of an anti-hormone therapy plus the drug called ribociclib, showed that women who received the combination instead of anti-hormone therapy alone live almost 30% longer. So looking at women 3 and a half years after they started treatment, just over 70% of the women who were treated with ribociclib plus anti-hormone therapy were alive compared to just under half of women treated with anti-hormone therapy alone. So these results reinforce that this is an excellent first approach to treatment of premenopausal women who have newly diagnosed, hormone-receptor-positive HER2-negative metastatic breast cancer. So in addition to studies looking at these specific types of breast cancer, there were 2 other interesting studies that were applicable to breast cancer more generally. So there was a large study that was reported that looked at whether having a low-fat diet reduced the likelihood of developing triple-negative breast cancer. So in this study, postmenopausal without cancer were randomized to either a low-fat diet or their usual diet and followed for many, many years. Over time, some of these women developed breast cancer with no difference between those who followed the low-fat diet or the regular diet. However, in this new report, they looked specifically at the women who developed breast cancer who were enrolled in this trial. Fewer women died from their breast cancer if they ate the low-fat diet, especially if they had preexisting high cholesterol, diabetes, and obesity. These findings suggest that having a low-fat diet may actually reduce the risk of dying overall and also specifically from breast cancer. Now, these need to be validated, and we don't quite understand why this would be the case. But in general, it seems like having a low-fat diet, avoiding high cholesterol, diabetes, and obesity is a good thing. And then finally, 1 question that comes up often is whether it is safe to have a baby after the diagnosis of breast cancer. This is especially concerning for patients who have a mutation in genes called BRCA1 or BRCA2 since those mutations greatly increase their risk of developing both breast and ovarian cancer and also leads to the diagnosis of breast cancer at an early age. In addition, patients with these mutations are often recommended to have their ovaries removed at a young age. So in this study, patients who became pregnant did so about 4 and a half years after they were diagnosed with breast cancer. There was no apparent increase in miscarriage, preterm birth, or birth defects compared to what would be expected in women without cancer. And in the patients, there was no increase in the risk of breast cancer recurrence compared to those who did not become pregnant. And in fact, those who became pregnant were slightly less likely to have their cancer return, especially those who had mutations in BRCA1. So while there are some limitations to the study, the findings are reassuring that there does not appear to be an increase in risk of breast cancer returning in these patients with BRCA mutations who become pregnant after breast cancer diagnosis. So overall, as you can see, there's a lot of exciting research going on across all the different subsets of breast cancer. The results of many important clinical trials were reported at the recent ASCO meeting, and there are many more trials ongoing that will hopefully result in the approval of multiple new effective treatments for breast cancer. In addition, there's research going on examining the impact of treatment on patients with breast cancer and trying to improve the lives of those living with breast cancer. Clinical trials are critical for the development of these new treatments. Well, that's it for this quick summary of this important research from ASCO 2019. Overall, we continue on a fast track in breast cancer, with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you very much. ASCO: Thank you, Dr. Henry. Next, Dr. Ezra Cohen will discuss several studies that looked at using immunotherapy and targeted therapy to treat different types of head and neck cancer. Dr. Cohen is Associate Director of Translational Science and leads the Solid Tumor Therapeutics research program at Moores Cancer Center at UC San Diego Health. He is the Cancer.Net Associate Editor for Head and Neck Cancer. Dr. Cohen: Hi. I'm Dr. Ezra Cohen from UC San Diego Moores Cancer Center. Today, I'm going to talk about research on head and neck cancer that was presented at the 2019 ASCO Annual Meeting. I think the most impactful presentation at the meeting was a follow-up on the KEYNOTE-048 study, which implemented the drug pembrolizumab, an anti-PD-1 antibody in first-line recurrent metastatic head and neck cancer. These were patients who were treated with curative intent or presented with metastatic disease, and either way, either had recurrence or eventually developed metastases. The first-line standard of care for these patients used to be the so-called extreme regimen, which involved platinum, 5-FU, and cetuximab. This was validated in an earlier phase III study that was conducted about 10 years ago and was the approved first-line regimen for these patients. In KEYNOTE-048, this extreme regimen was tested against either pembrolizumab alone or pembrolizumab, platinum, and 5-FU, in other words, substituting cetuximab for pembrolizumab in one of the experimental arms. We'd initially seen the interim analysis data at last year's ESMO meeting, but this year, we have the final analysis presented at ASCO. And what we saw was that both experimental arms actually achieved an improvement in overall survival compared to the extreme regimen. Interestingly, for pembrolizumab alone, this occurred in patients whose tumors expressed some level of PD-L1. That was evaluated by something called the composite score and takes into account both stromal and tumor cell staining of PD-L1. In fact, even at a very low level—that is CPS greater than or equal to 1—pembrolizumab monotherapy was superior to the extreme regimen with respect to overall survival. For all patients, the regimen of pembrolizumab plus chemotherapy was superior to the extreme regimen irrespective of PD-L1 staining. What we saw at this year's ASCO meeting was that, in fact, first, the higher the expression of PD-L1, the greater the benefit one derived from pembrolizumab either as monotherapy or in combination with chemotherapy. And in patients who had higher levels of PD-L1 and received both pembrolizumab and chemotherapy, the overall survival was quite remarkable with a hazard ratio of just higher than 0.6. In fact, we now have FDA approval in the United States for pembrolizumab monotherapy with tumors that have some expression level of PD-L1—that is CPS greater than or equal to one—or for all comers in patients who either the CPS status is unknown or patients whose tumors don't express PD-L1. Beyond KEYNOTE-048, we saw interesting data in first-line recurrent metastatic using a regimen of taxane, platinum, and 5-FU compared to the same extreme regimen that we just mentioned. That regimen turned out to be much better tolerated with fewer adverse events but with no improvement in overall survival, giving us a regimen that we could substitute for the extreme regimen if one wanted to, realizing that it does not involve immunotherapy, and for some patients, this may still be an appropriate treatment. Beyond the first-line recurrent metastatic studies, we saw a few interesting trials looking at targeted therapy in head and neck cancer but specific subsets. The first was in patients whose tumors expressed HER2 at very high levels—that is HER2 amplified—and had salivary ductal carcinoma. We've known that a proportion of salivary ductal carcinoma patients' tumors amplify this gene, HER2, similar to breast cancer and some other malignancies and that trastuzumab may, in fact, be effective. Well, in this study conducted by the Memorial Sloan Kettering Group, an antibody-drug conjugate trastuzumab emtansine was employed as a single agent in these patients whose, again, tumors amplified HER2. And what they saw was a remarkable 90% response rate. Now, this was only in 10 patients, so the study is small, but I think it's safe to say that this drug appears to be quite effective in patients with HER2-amplified salivary ductal carcinoma. Along those lines, in the subset of thyroid cancer patients whose tumors either mutate or have a RET fusion, the gene RET, there appeared to be very high efficacy for a novel agent that targets the RET oncogene. This was in both patients with medullary thyroid cancers that often have a RET mutation or in papillary thyroid cancers whose tumors often have a fusion of the same RET gene. Again, underscoring the idea that if we can target a driver even in a relatively small subset of patients, the benefit may be quite large. Along those lines, we had seen prior data for track inhibitors in patients who have in track fusions. And again, this applies to subsets of head and neck cancer patients that have either salivary gland cancers or thyroid cancers. Lastly, we continue to see emerging promising data of combinations with immunotherapy, and 2 highlights from ASCO were pembrolizumab with cetuximab showing a response rate of over 40% in a small group of patients and pembrolizumab with a TLR9 agonist called SD-101 showing about a 30% response rate. Of course, these data are very early and uncontrolled, and so we have to follow these stories further along to see if, indeed, these early signs of efficacy turn out to validate. But the idea that further combinations of immunotherapies eventually making their way to larger studies and hopefully approval is now well enforced in head and neck cancer. Thank you very much for your attention and hope you enjoyed the ASCO 2019 Annual Meeting. ASCO: Thank you Dr. Cohen. Next, Dr. Charles Loprinzi will discuss new research on ways to prevent or treat nausea and vomiting caused by cancer treatment. Dr. Loprinzi is a medical oncologist and the Regis Professor of Breast Cancer Research at the Mayo Clinic. He is also the Cancer.Net Associate Editor for Psychosocial Oncology. Dr. Loprinzi: Hello, I'm Charles Loprinzi, Regis Professor of Breast Cancer Research at Mayo Clinic. I'm going to be talking today about chemotherapy-induced nausea and vomiting. Now, chemotherapy can cause a lot of nausea and vomiting. That's well known, for years and years, by many people. It's not all types of chemotherapy, but some chemotherapy drugs cause a lot of nausea and vomiting, and others cause little to none. It's not as big a problem now as it was decades ago when we didn't have good drugs to try to prevent nausea and vomiting. Many drugs over the time have been developed for trying to prevent this nausea and vomiting problem. Examples of the drugs that cause a lot of nausea and vomiting are Cisplatinum, and Adriamycin and cyclophosphamide is a combination that is oftentimes used for patients with breast cancer. So in the past, we have developed many, many drugs for this. Three of the drugs that have commonly been used for the last many, many years for treatment or prevention of nausea and vomiting associated with chemotherapy are corticosteroid medications like Dexamethasone. It's quite cheap. It's got some side effects, but relatively cheap. Then there's a group called 5-HT3 receptor antagonists. I didn't make up that name, but that's the long name for it. They're relatively expensive, some more expensive than other ones. And then there's another group called NK1 receptor antagonists, and they can be quite expensive, sometimes being hundreds of dollars for each dose that's given to try to prevent nausea and vomiting related to chemotherapy. So a couple years ago, 2016, there was a report in the New England Journal of Medicine, which is a prominent journal for us in the business, that looked at a drug called olanzapine. It's a relatively cheap drug. It's a drug that was developed for psychosis-type problems, given for long term in those patients. But it had been noted that if it's given for just a few days, it seems to markedly improve or decrease the instance of nausea and vomiting, or if people were having nausea and vomiting, it appears actually to help and reverse that particular problem. So this trial looked at 10 milligrams of this drug for 4 days, given before chemotherapy, and then for 3 more days after that. Patients who were on this study got the 3 drugs that I talked about before with the olanzapine or with the placebo. And it noted that it improved things by quite a bit. The patients who had what we call a complete response, which means no vomiting and no need to take extra medications because of nausea and vomiting, improved from 41% of the patients who were on the placebo, to 64% who were on the olanzapine, a 23% improvement. And if we looked at a different endpoint there, the number of patients who had no nausea during the five days after chemotherapy, it was 22% in the group that got the placebo and improved to 37% in the group that didn't. So it was a good result in that area. One of the problems with this drug is that it can cause some sedation, cause some drowsiness for some patients. Most patients, not much, but some patients, it's a problem. So most trials that have been done in the past use this 10-milligram dose. And what we learned at ASCO in 2019, our main meeting that we have once a year, was that people looked at a 5-milligram dose and had looked at 5 milligrams instead of the 10 milligrams. And what it showed is that the results seemed to be quite similar to what was seen with 10 milligrams. They did the study quite the same as what had been reported in the previous trial and the results looks similar. They didn't compare 5 milligrams versus 10 milligrams, which would've been nice because then we would have better information along that line. They did note that there was drowsiness that some patients had, and it looks similar to what was seen with the 10-milligram dose. But these data support, but don't prove, that giving 5 milligrams does look like it's good in this particular setting. So data from this year also supported that instead of giving the drug during the day when getting the chemotherapy, sometimes, people take it at bedtime, and there, the drowsiness is not as big a problem because you want to be drowsy at bedtime. So it's not proven that it works as well at bedtime, but it suggests that that actually is the case. Data from this year also supported that if you looked at those 3 drugs I mentioned before and just took out that 1 really, really expensive one, the NK1 receptor antagonist, and put the olanzapine in there instead, that very cheap medication, that that looked like that one with the olanzapine did better than the very expensive one. Not a whole lot better; they looked similar, but a little bit better in that setting, and it was a whole lot cheaper. This was also seen in a publication that came out a couple of years ago which showed the same sort of result. Again, not proof that it's beneficial, that it's okay to do that, but it looked better. So the next obvious question that comes up then is when you have these 4 drugs that you give, the 3 drugs I mentioned before and this fourth one, what about if you take away that more expensive one and see how they do there? So there was a trial at the ASCO meeting that suggested that the addition of that expensive medications didn't provide a whole lot more benefit. Right now, there is a trial going on across the United States, with about 800 patients who are scheduled to go on this trial, and it's approving about 30 patients a month, which is a pretty good accrual rate, which is looking at this particular question where people would get the 4-drug regimen versus 3 drugs where they take away the expensive intravenous medication. So, in summary, 35 to 40 years ago, when I started my cancer career, when I was about 10 years old, most patients had a lot a trouble with nausea and vomiting with drugs like Cisplatinum. Now, this a minority of patients who have a lot of problems, and we're continuing to find new things that will make things better along this line. Thank you for your attention. ASCO: Thank you Dr. Loprinzi. Learn more about these topics and other research presented at the 2019 ASCO Annual Meeting at www.cancer.net. If this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. And stay tuned for additional Research Round Up podcasts coming later this summer. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

When you think of lemons and cancer, the organization “Alex’s Lemonade Stand” may come to mind. But more than just a way to raise funds for cancer research, lemons can fight cancer by eating them too. Today we will be talking about the real, physical benefits lemons have on the body, and the most effective way to get the most out of this amazing fruit! Lemons vs Cancer Everything people choose to eat either contributes to disease or helps to fight it. Disease cannot live in an alkaline body where it actually feeds disease in an acidic state. Lemons are one of the most alkalizing foods you can consume. It may seem counterintuitive because of it’s sour taste, but it turns alkaline once ingested. Lemons are a citrus fruit, high in vitamin C, which is great for giving our body the immune boost it needs to stay in check. When vitamin C levels are low, little to no repair happens in the body. Lemons are also high in potassium, which stimulates brain and nerve function. Potassium helps reduce free radicals, increases red blood cell production and controls blood pressure. What does all this mean in real-talk? More energy, clearer skin, anti-aging properties, less sickness, less stress, and more focus! Um, yes please! One very simple and inexpensive way I tell my clients to help detoxify their system is to drink warm or hot lemon water throughout the day for a period of two weeks. The trick here is of course not to drink any other beverages during that time. So no juices, coffee, alcohol or ice teas, hot cocoa etc, just sip lemon water throughout the day. This is especially helpful after the holidays or any other time of year you may have overdone the cookies and made a little “too merry”! Make sure the lemon is not from a container of lemon juice, but from a piece of whole lemon. So what’s this about cancer? Well, the compounds found in lemon peels are a thousand times more powerful than Adriamycin, a common drug used in chemotherapy. In fact, Lemons contain 22 anti-cancer compounds, including limonene, citrus pectin and flavonol glycosides which stop the division of cancer cells. Limonene seeks to destroy the malignant cells while leaving behind the healthy cells, undamaged. Let me be clear. I am not suggesting that anyone stop chemotherapy and just eat lemons. This is definitely one more simple way to help fight the disease. In fact, according to The Commonwealth Scientific and Industrial Research Organization of Australia, citrus fruits redice the risk of some cancers by 50 percent. These scientists report that citrus fruits are most protective against stomach, mouth, larynx and pharynx cancers. One of the best ways to consume this superfood is to first rinse, then freeze the fruit whole. Once completely frozen, grate the entire lemon along with its peel. Then feel free to use the shredded lemon as a salad topper, in your morning smoothie, in a cup of hot water or tea, or in various other recipes. Check out my website recipes for one of my favorites: broccoli, avocado and lemon salad, at www.supersimplehealthy.com/recipes. And keep an eye out for the collection of my favorite “Super Simple, Healthy Holiday” recipes on sale for a limited time! As always, feel free to add comments and questions and share this episode with your loved ones. Until next time: Keep it simple. Be Healthy.

Furry-Muscle Cast – 40 – Big Stuff 1.      Introductions ·         Maximus Ursis – Really A Bear?!, No Butt A Cat! (Picture - Max) ·         Tiptoe – Dressing Up, Racing All In Suite. ·         Beastly Bahamut – Bad Jokes And All That. ·         Syn – Snuggling, Fluffing, Following ·         Jazz Wolf – Coding To The Break Of Dawn! ·         Snowheart –  N/A ·         Tiberious – Sick, Gym, Told Ya, Sicker ·         Schredded Wolf – If It’s Not Heavy For Him, It’s Not Heavy For You. ·         Zak – Always Something Else, This Year Sucks.   2.      Programing Note: Interview With Mega-Panda -  Added In Post Progressing   3.      Topics a.      Tiptoe Progress: ·         Pictures – Tiptoe1, Tiptoe2   b.      Crossfit WTF?: ·         Video – “Gym Over Bitches”   c.       Hendo Hoverboards: ·         The world's first REAL hoverboard. ·         Source: https://www.kickstarter.com/projects/142464853/hendo-hoverboards-worlds-first-real-hoverboard   d.      Lemon & Baking Soda Miraculous Combination: ·         Lemon has already been proven to have strong anti – carcinogenic properties. In addition to this there are many other useful properties. Lemon has a strong effect on cysts and tumors. ·         Recent studies have shown that consuming citrus fruits, specifically lemons have prevented and in some cases cured cancer.  And by adding baking soda you will normalize the pH of the body which does not allow the cancer to continue to spread. ·         Lemon destroys carcinogenic cells in 12 types of cancers. Lemon prevents the spread of carcinogenic cells and has 10,000 times stronger effect then drugs like Adriamycin, chemotherapy and narcotic products ·         Source: http://www.healthy-holistic-living.com/lemon-baking-soda-miraculous-combination.html#   e.      The Best Time To Eat A Banana – (Picture Banana) ·         Interestingly, the nutritional profile of bananas changes as they ripen ·         There may be some benefit to eating the ripe banana. Japanese researchers have shown that the antioxidant and anti-cancer properties of the banana surge as it ripens. ·         Yellow skin banana with dark spots on it is 8x more effective in enhancing the property of white blood cells than green skin version. ·         Source: http://positivemed.com/2014/09/16/best-time-eat-banana/   f.        After-School Exercise Yields Brain Gains: Study ·         Regular daily exercise appears to improve children's attention and multi-tasking skills. ·         The researchers randomly assigned 221 children, aged 7 to 9, to either the after-school program or a wait-list for the program. The after-school program occurred for nearly all of the school year (150 days). Over two hours, physical activity alternated with rest periods, resulting in about 70 minutes of moderate to vigorous exercise every weekday. ·         Because the study directly compared two similar groups of children, the findings support the idea that the physical activity actually caused the brain improvements, though it's less clear how physical activity improves thinking skills, the experts said. ·         Source: http://www.webmd.com/fitness-exercise/news/20140929/after-school-exercise-yields-brain-gains-study   4.      Emails A.      From: Sextext Wolf @Max Question: With all the lifting do you plan to work on your thighs more to fill them out to your frame?   B.      From: BlackWolf @Tiptoe Question: I have been following your progress on FurAffinity for a while and like to, say that your journals and progress have been more positive than what they been in the pass, keep moving forward. *Two Furry Thumbs Up*   C.       From: FlexingWolves @Schred Question: When you do shrugs on the bench do you lift from heavy to light, like a pyramiding.   D.      From: FireFoxy To: Tiberious Question:  What are some points of getting into power lifting vs just working out?   5.      Closing Out:  §  We can’t do the show without you, the listeners! §  Please take the time to rate us on iTunes or Thumbs us up at Stitcher Radio. §  You can email us at FMC@furry-muscle.org §  Have any questions or comments? Drop us a line at 571-208-BUFF (2833). §  Follow us on Twitter @FurryMuscleCast §  You can find show notes, pictures, links and many other materials at our main website http://www.furry-muscle.org §  Next Furry-Muscle Cast: December 12th.  

Obwohl die immunstimulatorischen Effekte viraler Nukleinsäursen, wie auch IFN -α und IFN-β, während Virusinfektionen eine wichtige Rolle spielen, ist wenig über ihre Funktion bei viraler Glomerulonephritis, wie beispielsweise HIV Nephropathie, bekannt. Virusinfektionen aktivieren, vor allem mittels IFN-α und IFN-β Produktion eine systemische antivirale Immunantwort. Es wurde gezeigt, dass diese inflammatorischen Zytokine einen pleiotropen immunmodulatorischen Effekt auf renale Mesangialzellen ausüben, was direkt zu glomerulären Krankheiten führt. Aber es ist bisher nicht bekannt, ob die viralen Nukleinsäuren und Typ I IFN einen Effekt auf die glomerulären Epithelzellen haben. (z.B. Podozyten und PECs). Um den Effekt von Nukleinsäuren auf Podozyten und PECs zu erforschen, stimulierten wir diese Zellen mit synthetischen dsDNA-(poly-dAdT) Komplexen mit lipofectamine, um eine virale Infektion zu imitieren. Wir haben herausgefunden, dass dsDNA stetig viele IFN-stimulierte Gene in Podozyten und PECs induziert. Desweitern haben wir herausgefunden, dass dsDNA die PECs Proliferation mindert und die CD24+/CD133+PECs Differenzierung zu ausgereiften Podozyten inhibiert. Um unsere Hypothese, dass deis aufgrund von der Sekretion von IFN-α und IFN-β passiert ist, zu bestätigen, haben wir den Effekt von diesen anitviralen Zytokinen auf PECs- und Podozyten-Homöostase etabliert. Wir haben herausgefunden, dass beide IFNs stetig Podozyten und PECs dazu anregen, stetig mehrere IFN-stimulierte Gene zu exprimieren. Trotzdem hat nur IFN-β das Podozytensterben induziert und die Permeabilität der Podozyten-Monolayer erhöht. In der Adriamycin-induzierter Nephropathie bei SCID Mäusen haben Injektionen mit IFN-α oder IFN-β die Proteinurie, den Makrophagen Influx und die Glomerulosklerose verstärkt. Trotzdem induziert nur IFN-β das mitotische Podozytensterben (katastrophale Mitose), welches zu einer reduzierten Podozytenanzahl führt. Wir haben führt, dass IFN-α einen Zellzyklusarrest in-vivo bei PECs induziert, der zur glomerulären Schädigung führt. Balb/c Mäuse, die Adriamycin gespritzt bekommen haben und täglich mit IFN-α und IFN-β behandelt wurden zeigten einen aggravierten Phänotyp mit vermehrter Proteinurie. Im Gegensatz zu dem, was an Studien in SCID Mausen gezeigt wurde, war der Effekt auf die Proteinurie nach IFN-α Behandlung prominenter bei Balb/c Mäusen, verglichen mit IFN-β. Deshalb haben Typ I IFNs einen deutlichen Effekt auf Podozyten und Parietalzellen. Zusammen fördern die Typ I IFNs die Glomerulosklerose durch verstärkten Untergang der Podozyten sowie durch Unterdrückung ihrer Regeneration aus Vorläuferzellen.

Maligne Lymphomerkrankungen stellen lebensgefährliche Krankheitsbilder dar. Auch wenn mit der ersten Therapie nach Diagnosestellung bis zu 50 % der Patienten geheilt werden können. Patienten mit Rezidiverkrankungen haben eine deutlich niedrigere Überlebensrate. Daher kommen bei diesen Patienten, auch in der Ära der monoklonalen Antikörper, intensivere Therapieformen wie die PBSCT zum Einsatz, um die Überlebensraten zu erhöhen. Seit den ersten Transplantationen von PBPC bei Menschen in den Jahren 1985 und 1986, und damit dem Beweis der Durchführbarkeit dieser Therapieform, haben sich die Forschungsziele rasch geändert (Körbling et al., 1985); (Kessinger et al., 1986); (Juttner et al., 1985). Wenn auch keine Verbesserung der Überlebenszeiten im Vergleich zur ABMT nach¬gewiesen werden konnte, waren die klinischen und finanziellen Vorteile der PBSCT für die weitere Verbreitung Ausschlag gebend. Somit rückten die Einflüsse auf die Mobilisation, die Apherese und die Transplantation selbst in den Mittelpunkt des Interesses. In dieser Arbeit wurde vor allem die Auswirkung der zytostatischen Vortherapie auf die Mobilisation der PBPC untersucht. Aber es wurden auch andere, zumeist patientenunabhängige Parameter bezüglich ihres Einflusses auf die PBPC sowie die Beurteilung des Mobilisierungsschemas hinsichtlich Verträglichkeit und Ausschwemmung von BPC, analysiert. Die Untersuchung des Salvageschemas IEV mit Ifosfamid, Etoposid und Epirubicin ergab sehr gute Ergebnisse hinsichtlich der Mobilisierung von PBPC und der Aktivität gegenüber den Tumorzellen. Es wurden 37 Patienten evaluiert. Vier Patienten hatten ein T-Zell-Lymphom, acht ein centroblastisches NHL, vier Patienten hatten ein centroblastisches NHL nach Transformation aus einem centroblastisch/centrocytischem NHL, zwölf Patienten hatten centroblastisch/centrocytische NHL, vier Patienten hatten ein centrocytisches NHL, ein Patient hatte ein lymphocytisches NHL, zwei Patienten ein Plasmozytom und zwei waren am M. Hodgkin erkrankt. 14 Prozent der Patienten, d.h. fünf Patienten erreichten nach dem IEV-Schema eine komplette und 68 Prozent, d.h. 25 von 37 Patienten, eine partielle Remission.. Dies bedeutet eine Ansprechrate von 82 Prozent was 30 Patienten entspricht. Bei 7 Patienten, d.h. 18 Prozent wurde eine Progression festgestellt. Nur ein Patient verfehlte die vorgegebene Mindestanzahl an PBPC nach Mobilisierung mit IEV. Trotzdem konnte dieser Patient erfolgreich transplantiert werden und überlebte mindestens 51 Monate. In 29 % der Fälle mußte die IEV-Dosis reduziert werden, was die hämatologische Toxizität von 77% verdeutlicht. Von den fünf Todesfällen, was 12 Prozent der Patienten entspricht, verstarben vier der Patienten an den Folgen der Tumorprogression und ein Patient an einer Sepsis. Aufgrund der hohen Rate an Todesfällen sollte eine Dosisreduktion des IEV-Schemas vor allem bei Patienten über 60 Jahren erfolgen. Der signifikante Zusammenhang zwischen Überlebenszeit nach der Transplantation und der Anzahl der PBPC belegt die Wichtigkeit der Einflußfaktoren auf die Stammzellmobilisierung . Statistisch signifikante Zusammenhänge konnten wir in Bezug auf den zeitlichen Abstand zur Erstdiagnose sowie zur letzten Chemotherapie vor Salvagetherapie beobachten. Je größer die zeitlichen Abstände waren, umso höher war die Anzahl der PBPC. In Bezug auf die Vortherapie zeigten sich für Vincristin, Cyclophosphamid und Ifosfamid signifikante Korrelationen. Cyclophosphamid und eventuell auch Vincristin als Vortherapie verminderten die Stammzell¬ausbeute. Patienten, mit Ifosfamidgabe in der Anamnese, erzielten, sogar dosisbezogen, signifikant mehr PBPC als Patienten ohne diese Vortherapie. Tendenzielle Zusammenhänge konnten wir bei dem Geschlecht, Knochenmarksbefall, Stadium der Erkrankung, der Diagnose sowie vorheriger Bestrahlung und Gabe von Methotrexat erkennen. Männer erzielten eine doppelt so hohe Mobilisierung von CFU-GM als die Frauen unserer Studie. Auch Patienten mit Knochenmarksbefall wiesen tendenziell niedrigere Ergebnisse an PBPC auf als die ohne Knochenmarksbefall. Bei Erkrankten mit niedrigem Ann Arbor Stadium (A im Rezidiv bis B) konnten wir ebenfalls mehr als doppelt so hohe periphere BPC feststellen als bei Erkrankten mit fortgeschrittenem Tumorleiden (VA und B). Patienten mit niedrigmalignen Non-Hodgkin-Lymphomen erzielten weniger PBPC als jene mit M.Hodgkin, Plasmozytom oder hochmalignen NHL. Auch die Patienten, die eine Bestrahlung in der Vortherapie erhalten hatten, erreichten im Vergleich mit Patienten, die keine Bestrahlung erhalten hatten, weniger als die Hälfte an PBPC. Patienten nach Methotrexatgabe wiesen von der Tendenz her mehr PBPC auf als jene ohne anamnestische Methotrexatgabe. In Bezug auf das Alter, Überleben, Anzahl der Rezidive und Höhe der Laktatdehydrogenase des Patienten konnten wir keine Beziehungen zwischen der Anzahl der PBPC und den untersuchten Parametern erkennen. Auch die, vor der Salvagetherapie verabreichten Anzahl der Chemotherapieschemata oder der Chemotherapiezyklen sowie die Gabe und Dosis an Adriamycin, Procarbazin, Mitoxantron, Melphalan, Chlorambucil, Bleomycin und Etoposid hatten keinen Einfluß.

Background. Immigration of leukocytes into inflamed tissue is mediated by CC chemokines. Blockade of the CC chemokine receptor CCR1 was shown to reduce interstitial inflammation and fibrosis in murine obstructive nephropathy. However, it is not known whether CCR1 blockade is protective in progressive renal injury associated with severe proteinuria. This study therefore examines the effect of the small-molecule CCR1 antagonist BX471 in a mur-ine model of adriamycin-induced focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome and progressive interstitial inflammation and fibrosis. Methods. Adriamycin (ADR) nephropathy with persistent proteinuria was induced in male BALB/c mice by two intravenous injections of ADR (13 mg/kg) at day 0 and 14. BX471 treatment was started at day 14 when proteinuria had developed. At 6 weeks, renal histology was studied by morphometry and immunohistochemistry. The expression of chemokines was localised by immunohistochemistry and quantified by RNAse protection assays. The expres-sion of CCR1 in different leukocyte subsets was quantified by PCR. Results. At week 6, ADR-treated mice showed focal segmental glomerular sclerosis, associ-ated with tubulointerstitial injury consisting of tubular dilation and atrophy, interstitial leuko-cyte infiltration and fibrosis. The mRNA expression of CCR1 and CC chemokines, including the CCR1 ligands CCL3/MIP-1 and CCL5/RANTES, was upregulated in diseased kidneys, with a prominent intersitial expression of CCL5/RANTES. The mayor CCR1-expressing cell subset were F4/80-positive macrophages. Compared to vehicle-treated controls BX471 sig-nificantly reduced the amount of macrophages and T lymphocytes in interstitial lesions by 51 % and 22 %, respectively. Markers of renal fibrosis such as interstitial fibroblasts (48 %) and interstitial volume (23 %) were significantly reduced by BX471 treatment. In contrast, the extent of proteinuria and glomerular sclerosis was not affected by BX471 treatment. Conclusion. Blockade of CCR1 substantially reduced interstitial leukocyte accumulation and the subsequent renal fibrosis in a murine model of nephrotic syndrome and FSGS. These find-ings support a role for CCR1 in interstitial leukocyte recruitment and suggest that CCR1 blockade might be a new therapeutic strategy in progressive nephropathies such as FSGS.