Chapters Transcript Video Case #3: Neo-adjuvant Therapy in Triple Negative Breast Cancer Back to Symposium Alright, I've had a decaf coffee. We're ready for round 2. Uh, so first, um, thinking about neoadjuvant therapy in triple negative or HER2 positive breast cancer, how do we actually stage these patients? How do we understand the extent of their disease? So, presented at San Antonio was the Alliance, a 11104 or Akron 6694 trial. There's no real name for this, so the surgeons are worse than the medical oncologists at coming up with creative names. I'm just calling it effective preoperative MRI. And so, obviously, we know there's a lack of consensus about the use of preoperative MRI in early breast cancer, and its routine use is certainly controversial. We know that MRI is more sensitive at finding additional disease, but whether or not that matters is the point of contention. Uh, we know that it also increases the rate of mastectomy, uh, converting patients who were BCS eligible to potentially BCS ineligible. However, much of the data that we have guiding the use of preoperative MRI are retrospective. There have been some International randomized trials and those data are mixed, but one prospective single institution study that was fairly high quality and recent, uh, reported no difference in the use uh in oncologic outcomes, whether or not preoperative MRI was utilized. But this study was enriched with hormone receptor positive patients. And so this trial really looked at these higher risk cancers and hypothesized that preoperative breast MRI was going to. Improve the staging of HER2 positive and triple negative breast cancer, uh, thereby lowering the rates of local recurrence. There were 319 patients enrolled in this study, clinical stage 1 to 2, either HER2 positive or triple negative. They must have been BCS eligible based on mammogram or ultrasound. Uh, multifocal was, uh, multifocality was, uh, OK, as long as that could be excised with one single resection. Uh, and no BRCA germline pathogenic variants were permitted. They were randomized to either MRI or no MRI. They were stratified by important factors. And in the MRI group, a new biopsy was required. If the new, if a new focus of MRI enhancement was identified 2 centimeters from the index lesion, or if the new focus would. Make the patient BCS ineligible. Here are the characteristics of the, uh, of the cohort, and you can see one of the imbalances here is that those who underwent no MRI were slightly older than those who underwent MRI. Interestingly, even after MRI, the number of lesions that were needed to be excised in these patients was the same. Uh, looking at PCR because neoadjuvant chemotherapy was permitted, there was no statistical difference. However, there's certainly a numerical difference in the rates of PCR between the groups, which was a criticism of the study. Half of patients had a PCR in the no MRI group and only 1/3 in the MRI in the MRI group. When they looked at local regional recurrence free survival, there is no difference between uh between the groups. Uh, however, there was a lower than expected event rate, meaning fewer local regional recurrences than they had estimated based on calculate when they were calculating their sample size, and the, the study also did not meet its initial accrual goal. When they did some initial subset analyses, there was no difference when looking at the BCS group alone, meaning getting rid of the patients who ultimately underwent mastectomy, in those who were younger than 50, the HER2 subtype, and when they analyzed the data for distant disease-free survival or overall survival. So, they concluded that MRI did not improve local regional control even in these higher risk disease subtypes, and there was no difference according to age or tumor subtype. They, they hypothesize that advances in breast imaging, that being tomosynthesis, improved use, uh, and interpretation of ultrasound, may have explained the lack of benefit, and all of these patients were enrolled prior to initiation or standard of care of keynote regimen. And so they think even the, uh, the event rate would be lower if they tried to redo this study, means uh we're doing pretty well from a neoadjuvant therapy perspective. Uh, many questions from the audience when this was presented regarding the number of additional biopsies that were required. What the pathology was on those additional biopsies, contralateral breast cancer, they're still in the process of analyzing that, so we'll get more data from this, from this study. Next was the Axona or the U breast 3 study, which I think is a really interesting, uh, study. We know that one key indication, especially in triple negative breast cancer, is to downstage the axilla. We take clinically node positive patients, hopefully making them YCN0, meaning they don't have clinically evident disease at the end of neoadjuvant chemotherapy, and hopefully have a nodal PCR such that we're able to perform less axillary surgery. Uh, oncologic data comparing surgical techniques in this situation are scarce, however, uh, and we know it's hard to study because axillary recurrence rates, no matter what we do, are rare, less than 2% at 3 years. But what the Axa study is, it's an ongoing international non-interventional prospective registry study. It ran, it, uh, it was following patients who were clinically N1 to 3A who, uh, downstaged to clinically node negative after neoadjuvant chemotherapy, who then underwent the surgeon's choice of axillary surgery. And they described this as technique-free, meaning that the surgeon could use dual tracer, single tracer, localization of the node, no localization, etc. So, really a wide heterogeneity here. 26 countries, 288 sites, and so, there's a lot of Heterogeneity, yes, heterogeneity, as I said, but in a short presentation, not all of the baseline and technique characteristics were presented. I'll be looking forward to the manuscript for those. Uh, this was the first presentation of three-year data, again, acknowledging that this is an ongoing study. There were about 6500 clinically node positive patients, 2700 of whom downstaged to clinically node negative, and they analyzed those who both had a nodal PCR and those who did not. A third underwent axillary dissection with 16% conventional sentinel node biopsy and over half undergoing targeted axillary dissection, which is sentinel node biopsy and localization. Of the previously biopsied lymph node. Targeted lymph node biopsy, meaning removal of only that lymph node that had previously been biopsied, was rare, but was performed in a small group of patients. Half of patients experienced a nodal PCR and the median follow-up was 2 years. Again, ongoing study, first presentation of the data, only 17% had 3 years of follow-up. The patients who underwent axillary lymph node dissection, as one might expect, were at higher risk than those who did not. So higher initial T stage, number of suspicious nodes, higher rates of mastectomy, lack of nodal PCR, and radiation. But there was no difference in several other key demographics as listed here. What they found is the 3-year axillary recurrence-free survival was excellent, 99.2% among those who underwent axillary lymph node dissection and 98.8% among those who had either a sentinel node biopsy or TAAD. Uh, so no matter what we did, again, a really excellent. Uh, when they did their multivariable analysis, there was also no difference in key other key oncologic outcomes, invasive disease-free survival, local and axillary recurrence, distant disease-free survival, and overall survival, though those that are bolded with an asterisk did have worse outcomes, uh, in the ALND group, uh, in on univariate analysis, but that's explained by the fact that those, that group is enriched with a higher, uh, disease burden. Interestingly, uh, there's not yet a subgroup analysis of a group we really care about, and those, those are the patients who failed to achieve a nodal PCR and did not undergo an axillary lymph node dissection. As we talked about, we'll get more information, uh, in a randomized fashion from the Alliance trial as well as Taxis. Uh, when they compared sentinel, uh, lymph node biopsy techniques, uh, so sentinel node biopsy conventionally or TAAD using targeted axillary lymph node dissection, the sentinel node biopsy group had a higher T stage, a higher rate of nodal PCR, and axillary, uh, radiotherapy, but this was likely because of different guidelines, national guidelines, institutional guidelines, etc. But there were no, no other differences. Interestingly, the rate of the retrieval of the clipped node was not presented in the presentation. As expected, excellent axillary recurrence-free survival with no difference between the groups and no difference on both univariate and multivariable analysis in key oncologic outcomes. And so, we know that axillary recurrence-free survival and many of the other oncologic outcomes really are excellent in patients who downstage from clinically node positive to clinically node negative after neoadjuvant chemotherapy. TAD and sentinel lymph node biopsy is non-inferior to axillary lymph node dissection in the overall group, but we do need more data to understand what the value of targeting that clipped node is and localize. that because they can conclude here that sentinel node biopsy and TA are both safe, but they can't declare one superior. The data certainly need to mature. Again, it's an ongoing study, and we need more granular outcomes in further reports from this study of those who failed to achieve a PCR and didn't undergo axillary lymph node dissection, as well as more understanding of who underwent axillary radiotherapy. And lastly, there were several rapid-fire presentations at San Antonio this year that really were trying to understand what other predictors outside of pathologic complete response that we have in terms of outcomes for patients undergoing new adjuvant chemotherapy. We know that those who do achieve a PCR have improved outcomes, but many of those who fail to achieve a PCR still do very well. So other factors may help us further subdivide these individuals outside of this binary KI-67, tumor infiltrating lymphocytes or TILs, and circulating tumor DNA or CT DNA. And I'll review four very quickly abstracts that ask this question. So, an analysis of the NSABPB59 study, which was a study of neoadjuvant chemotherapy plus Uh zalidazumab, and triple negative breast cancer. Uh, what they found is that in patients who had tills greater than 30%, there was an improved PCR and event-free survival, and they further studied these tumors with various techniques, uh, calling some immune-activated. And as we would expect, those tumors also had improved PCR and event-free survival. Uh, an analysis of the ECOG-ACR EA 1131 study, which is a study of the use of platinum agents for residual triple negative breast cancer after neoadjuvant chemotherapy, uh, also looked at, um, tumor infiltrating lymphocytes. And interestingly, and also not surprisingly, they first found that When they compared the proportion of patients that had high tills after chemotherapy to the proportion of patients who had high tills before, it's very different. So, about 25% of the triple negative breast cancer patients have high tills before, only 6% after. Meaning that those who achieve a PCR are those that had high tills, right? Um, low tills and a basal subtype in this study had worse invasive disease-free survival, um, and a trend toward worse overall survival, though that was not significant. And then an analysis, a combined analysis of nine neoadjuvant trials from the German breast group, which totaled about 3000 patients, looked at both KI-67 and TILS in features of residual tumors. So KI-67, greater than 15%. Uh, was associated with worse outcomes. And then when they actually grouped that based on deciles, as one increased in decile in the proportion of KI 67 or the measurement of KI 67, there was also worse oncologic outcomes. Patients who had tills greater than 50% associated with better outcomes. And if we sort of look up at the top of the screen, we use 30% as a threshold, we look at the bottom of the screen, we're using 50%. This, we really probably need to start standardizing some of these things so we can actually employ these data to understand how our patients are going to do. But, I, I think what was an interesting thing that they did is they had a combined signature of both the KI-67 being low. And the tills being high, and the combination signature was really predictive of better outcomes, and there was a difference of 40%, uh, of in survival at 5 years. So, I, I think that we can start really sort of looking at some of these things, but we probably need to standardize a bit more. And lastly, CTRC TN, which is the first prospective triple negative breast cancer CTDNA trial of about 150 patients, uh, looked at CTDNA in two different ways. One matched to the tumor, so really looking at the, uh, mutations within a tumor and looking for that specific signature in the, in, uh, circulating DNA, uh, and those assays that really just look at abnormal methylation patterns. Uh, they obviously concluded that CTDNA detected at any time was associated with worse recurrence-free survival. But interestingly, they found a longer clinical lead time with the abnormal methylation, meaning that patients, there was no patient in the study who had their tumor matched CTDNA appear on their blood draws before this abnormal methylation. So, maybe that's actually a better signal than looking at their specific uh uh mutation burden. Uh, so binary PCR may not be the only factor that influences treatment decisions in the future, so more to come on all of this. Thanks. Thank you to the organizers, especially Doctor Jane, for inviting me to speak to you about early-stage triple negative breast cancer tonight. Our case, uh, that was associated with, with this session is a very young patient with a 3 centimeter triple negative breast cancer and clinically palpable lymph nodes on presentation. And so, the first question for our patient is, what is the current standard of care for high-risk early-stage triple negative breast cancer? We know that the keynote 522 regimen that incorporates pembrolizumab in combination with chemotherapy for patients with high-risk early stage triple negative breast cancer has yielded impressive improvements in both event-free survival and overall survival that have matured over time. When this study was designed, the addition of carboplatin to the chemotherapy, the taxane anthracycline chemotherapy backbone seemed a little bit Potentially premature to some of us because at that time, we did not yet have consistent improvement in EFS or long-term outcome with carboplatinum and triple negative breast cancer. So the next question for our patient is, what have we learned about the role of carboplatin in treating early stage triple negative disease? And we have seen these trials mature over time, and we now have seen some new trials as well. So the early trials in the neoadjuvant setting that added carboplatin to chemotherapy listed on this slide all showed pretty significant improvements in pathologic complete response rates that were impressive, but Consistent benefit in long-term outcome was not appreciated in all trials. We now have seen the Tata Memorial trial. Remember hearing about this one at San Antonio a few years ago. This is now finally published in manuscript form, and this trial, uh, looked at the addition of carboplatin to, uh, it was Paclitaxel with or without carboplatin and Adriamycin and Cytoxan. Event-free survival was the primary endpoint for this study, and age and menopausal status were stratification factors. So what was interesting in this analysis is the benefit of the carboplatin on this trial was confined to pre-menopausal patients where you saw a really significant improvement in event-free survival with adding carboplatin. Next, the Pearly trial has now looked at adding carboplatin to preoperative chemotherapy in, uh, both the adjuvant and the neoadjuvant phase. So 71% of patients on Pearli were treated neoadjuvantly, 29% were treated in the adjuvant setting. And again, impressive improvement in event-free survival with the addition of carboplatin with a hazard ratio of 0.67. Next, NRGBR 003. We heard about this one at ASCO this year. So this, uh, looked at carboplatin added to AC Paclitaxol, and there was a numeric improvement in disease-free survival, but it did not reach statistical significance. So this is the outlier. Uh, why, why did this trial not cooperate? Well, interestingly, when you look at, at the data, the carboplatin delivery on this trial was quite low, um, only 75%, uh, carboplatin delivery. This was in stark contrast to the delivery rate in the Tata Memorial trial and the Pearly trial where we had over 95% carboplatin delivery. So that could potentially be explanatory. The pattern trial compared Paclitaxel and carboplatin for six cycles, a non-anthracycline chemotherapy approach to anthracycline taxane chemotherapy in the adjuvant setting, and improved 5-year disease-free survival there with a hazard ratio of 0.65. So if you're getting tired, the carbo trials are positive for triple negative. OK, so now we have two more, just two more from San Antonio this year, Citrine and RJBC 1501. So these are two more trials in the adjuvant setting, um. And they came in at San Antonio this year. So the citrine study I've summarized, um, on this slide, this was EC with, uh, Pali dose tense EC with Paclitaxel with or without carboplatin. And this, uh, was associated with an improvement in disease-free survival with a hazard ratio of 0.64 and an absolute benefit of 6.5%. This benefit was most pronounced in the early follow-up, uh, in the 1st 12 months on the trial, and the treatment effect, as you can see in the forest plot was really consistent across all subgroups, menopausal status, lymph node status, stage, etc. although there were no stratification factors. Uh, on Satrine, the addition of carboplatin was also associated with improvements in recurrence-free survival, distance, distant disease-free survival, and overall survival. And next, RJBC 1501 was another trial in the adjuvant setting presented at San Antonio this year, and this trial also showed that it was a really similar chemotherapy backbone with EC, uh, followed by Paclitaxel or docetaxel with or without carboplatin. And again you can see improvements in. Um, disease-free survival, distance disease-free survival, and overall survival, and the hazard ratios are remarkably similar to what was seen in Satrine. What's interesting about this trial is they did include some pretty low risk patients for this adjuvant chemotherapy study, so 46% of them had T1 tumors and only 28% were node positive. I'm looking at Igor when I say that because we argue about carbo a lot, so. Um, so now this is, uh, the exploratory analysis from that trial, and this was a little odd that the benefit on RJBC was confined mostly to patients older than 50 years of age. So this was completely opposite what. was seen on the Tata Memorial study, where the benefit was only seen in the younger patients. And it was also in contrast to Citrine and Pearly, where there was consistent bene benefit across all subgroups. So we really don't know why this occurred on this study. Um, there was some postulation that perhaps it could be due to, uh, the amounts of mutation carriers that were included, but that, that data was not available. So we're not really sure. And then finally, there was a pooled analysis also shown with 3, the 3 big neoadjuvant trials that I started with. So this pooled analysis of the 3 randomized clinical trials was data from over 1000 patients. And the addition of carboplatin to neoadjuvant chemotherapy was associated with higher PCR rates in all patients, except, interestingly, it was not associated with higher PCR rates in patients with germline BRCA1 and 2 mutations. Um, so, I don't know why it keeps skipping ahead. Sorry. Uh, the, however, the addition of carboplatin to chemotherapy was associated with better event-free survival in all patients, including patients with, uh, wild type and mutant BRCA status. The, the addition of carboplatin was also not significantly associated with overall survival, but, um, the, the curves did appear to be trending in that direction, but it wasn't statistically significant. This, uh, again, now we're, they, they did look at gene expression signatures as potential predictive markers of. Of benefit on this trial, so they looked at 8, gene expression signatures and only 4 of them, all of, all of these 4 GEPs were immune associated gene expression profiles, so only 4 of them were associated with, um, prognostic. Predictive value for EFS, um, and overall survival and PCR, but none of the tested gene expression signatures were predictive of PCR EFSOS benefit due to the addition of carboplatin. So they, they seem, uh, prognostic, but not predictive for carboplatin. So this summarizes in one big table. It's not my table. I got permission to borrow it from the discussant, uh, the phase 3 carboplatin trials without immunotherapy, and the take-home message is that 4 out of the 5 trials show improvement in long-term outcomes, with 3 of them showing overall survival improvement. So, I would tell our patient that there's actually ample evidence that the addition of carboplatin, both in the neoadjuvant and the adjuvant setting now improves long-term outcome in early-stage triple negative breast cancer. But what toxicities do our patients face as they go through these difficult treatments? We know that adding carboplatin increases hematologic toxicity. Including neutropenia, thrombocytopenia, and anemia, and reported rates vary across trials. This is likely due to differences in growth factor use, dosing, taxing partner, and chemotherapy schedule. But reassuringly, it does not appear to increase febrile neutropenia or neuropathy. Neuropathy, I was, was something I was worried about. And interestingly, the trials are not reporting increased neuropathy rates. And a quality of life analysis from the Pearly trial actually reported no significant difference between the carboplatin and non-carboplatin containing arms. We also heard from the IS SpyY investigators at San Antonio this year, and this was an interesting analysis looking at PROs. We know ISpyY is a novel preoperative trial for patients with high-risk breast cancer where they collect serial MRI and biomarker data, but they actually also collect PROs, and these PROs are collected at regular intervals for 33 symptoms, evaluated weekly, ranked on a Leichhardt scale. And this was, I thought was really interesting because patients have actually asked me this, this question in clinic and, and said, well, I feel really good and does the fact that I'm not having side effects mean that the treatment's not working? And I've always said, no, it's fine, you know, and this, this was actually fascinating that moderate to severe symptoms within weeks 1 through 3 were associated with a higher likelihood of a pathologic complete response. So, and this was enriched for headaches, joint pain, mouth and throat sores had the highest odds ratio, no idea why, and muscle pain. Um, so this was only seen in the early phase. The effect was not seen at later time points. This association was not seen. They also saw that higher severe severity of swelling early on during treatment was correlated with greater decrease in functional tumor volume on, on the MRIs. And then the same group reported that immune related adverse events, the presence or absence of the immune-related adverse events did not differ between responders and non-responders, which is like completely opposite what I would have thought for that, but there's a poster about that, um, that I've listed on the slide. So, you know, we do need to monitor carefully for these, these toxicities as our patients go through this difficult treatment. And the next question is, how can we tailor future treatment for early stage triple negative breast cancer and what emergent biomarkers which, uh, uh, Austin has already presented, uh, could help us tailor treatment and guide therapeutic decision making. So in the future, can we omit anthracyclines? We saw excellent pathologic complete response rates and 86% 3-year event-free survival on the NOA study that was carboplatin, docetaxel, and pembrolizumab for 6 cycles prior to surgery. So, could we just get rid of the anthracycline? There's a number of trials looking at anthracycline de-escalation and early-stage triple negative breast cancer, including the large Scarlett trial that I think is open in some of your centers locally. And the Scarlett trial is comparing docetaxel, carboplatin, and pembrolizumab, uh, to the Keynote 522 regimen in the preoperative setting. So we, we really look forward to data from that trial. We've already talked about the ISpy trial. That, uh, looks at escalation and de-escalation and adaptive response. We also have, uh, trials like the Tropion Breastto 4 trial that is looking at ADC plus immunotherapy with Dato DXD on that study. And then, uh, de-escalation and adaptive strategies based on the presence of tills, which we started to, to hear about tonight too, could be, um, uh, uh, an area to watch. We saw one abstract where they actually aimed to omit chemotherapy altogether. So, TBCRC 056 was germline BRCA1 and 2 mutation carriers or PAL-B2 mutation carriers, and they were, um, treated with, uh, on this phase two study with a combination of a PAARP inhibitor and anti-PD1 antibody. So it was nerapirib and dos. Dostarumab, sorry. But, um, this, the results from the two triple negative arms on this trial were presented at San Antonio this year and, uh, the rationale for this study was that we know that PARP inhibitors as monotherapy yield PCR rates of about 50% for germline BRCA. Uh, mutation carriers with triple negative breast cancer. And there was pre-clinical data that suggested combining PAARP inhibitors and immunotherapy could be synergistic. So for the two, for AM A and AM B, which again, were both nerapirib plus dearliab, but ARMB did a run-in with Nerapirib alone for 3 weeks. They had the same pathologic complete response rate in both arms of about 50%. So it wasn't really clear whether the immunotherapy added too much, because that's what we would have expected with the PARP inhibitor in this patient population. But what was more interesting is they looked at baseline tills, uh, and associations with pathologic complete response. So baseline tills were significantly higher in the patients with the pathologic complete response. So I think we're continuing to hear that theme that high tills are, are good prognostically and associated with good response. Although change in tills from baseline to cycle two. Uh, and baseline PDL1 and baseline ER status, whether it was low or completely negative, were not associated with pathologic complete response. So, the conclusions for our patient, we know the standard of care. We know, I think we can all feel pretty comfortable saying that carboplatin is improving outcome. Um, we need to monitor for adverse events in our patients. We, we're getting a bit of a glimpse into how we may tailor therapy, escalate, de-escalate, and what biomarkers might guide decision making. What's been frustrating to me is that Uh, a lot of these biomarkers seem prognostic, but not necessarily predictive for who doesn't need these therapies is what, what, what we really need. Um, and there's, there were a few abstracts about, uh, molecular subtypes. Again, kind of looking prognostic, but not necessarily predictive. So I think we just need to continue to collect samples on these trials and learn how to treat patients in a more safe and efficacious, efficacious way. And finally, I was asked to, um, end with a slide for our advanced practice practitioners, nurses, and pharmacists. And what I wanted to emphasize was, uh, the fact that the immune-related AEs can be quite serious and dangerous. And we know that based on the keynote 522 study, that the majority of them happen in the combined phase when you're giving chemotherapy and immunotherapy prior to surgery. Uh, but they can still happen in the ad, the adjuvant phase after surgery. And what I've noticed is there's now what I'm starting to notice is a danger zone. And it's right after the patient finishes their last neoadjuvant therapy and they're waiting for surgery. And, um, they're not necessarily being monitored by anybody in that setting because, you know, they can't go to surgery right away. They're finished with their neoadjuvant treatment. Um, and so I'm leaving you with Uh, a hypothetical case that came from my own clinic. So, your patient completes her keynote 522 treatment and has a robust response on her post-treatment MRI. Unfortunately she's scheduled for surgery, but it's 7 weeks, uh, to allow time for coordination with plastics, you know, the classic story. So, uh, several weeks after her last neoadjuvant treatment, she gets short of breath, lightheaded, and fatigued, and she goes to her local ER, uh, and they presume she's dehydrated as she's a little bit tachycardic and slightly hypotensive. The troponin and EKG are normal, so they send her home. She calls your nurse a week later and says, she says she still feels weak, has palpitations and extreme fatigue. Your nurse thankfully advises her to come in for evaluation. Uh, and on physical exam, she's alert, not in acute distress, but she's tachycardic, and her blood pressure is normal. You start reviewing the painful to navigate care everywhere section of her chart and look at her outside hospital ER visit from a week ago and you feel a drop in your stomach when you see that her labs drawn that day show a cortisol of 0.3 and an ACTH of less than 1.5. It is now 4:25 p.m. and you're starting to sweat, uh, huh, on a Friday, right? Yeah, you, you call an endocrinology colleague who thank God answers the phone and tells you to give the patient 50 mg of IV hydrocortisone immediately. And given that the patient is alert and not in distress, you make plans for her to start oral hydrocortisone twice daily and follow up with endocrinology soon for what is, uh, immune checkpoint inhibitor induced isolated ACTH deficiency and central adrenal insufficiency. So the patient feels much better when she goes on steroids. However, she will now need lifelong hydrocortisone as a life sustaining medication. At times of physical stress, she will need higher doses until her physical illness improves. If she ever becomes unable to take pills by mouth, she will have to go to the nearest ER immediately for IV Solu Cortef, and she now is advised to wear a medical alert bracelet. Denoting her adrenal insufficiency for the rest of her life. So, please monitor your patients, and I, I personally am now making them all come back after the last neoadjuvant treatment for a checkup before surgery. It's the way I changed my practice after this case, um, but it's, we need better biomarkers to de-escalate in some of these people. Thank you. That was amazing. Um, we're going to move on to case number 4, and then maybe after case number 4, for those of you that want to stick around and ask a couple of questions, we can do that. Created by Related Presenters Rachel Jankowitz, MD Austin Williams, MD Assistant Professor, Department of Surgery, Fox Chase Cancer Center Assistant Professor, Department of Surgery, Fox Chase Cancer Center View full profile
