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HCP Roundtable: Exploring CLL Mutations and Best Practices for Side Effect Management

HCP Roundtable: Exploring CLL Mutations and Best Practices for Side Effect Management from Patient Empowerment Network on Vimeo.

As the chronic lymphocytic leukemia (CLL) treatment landscape evolves, how can healthcare professionals deepen their understanding of mutation profiles, including the emergence of novel CLL mutations over time? What innovative approaches are transforming the management of CLL side effects? Additionally, how can barriers in CLL practice be removed to enhance physician-patient communication and promote shared decision-making? 

Dr. Jennifer Brown from the Dana-Farber Cancer Institute and Dr. Callie Coombs from the University of California, Irvine, share their expertise and best practices for CLL healthcare providers.

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Transcript:

Dr. Nicole Rochester:

Welcome to this Empowering Providers to Empower Patients or EPEP Program. I’m Dr. Nicole Rochester, founder and CEO of Your GPS Doc. EPEP is a patient empowerment network program that serves as a secure space for healthcare providers to learn techniques for improving physician-patient communication and overcome practice barriers.

In this CLL roundtable, we are tackling exploring CLL mutations and best practices for side effect management. As the chronic lymphocytic leukemia treatment landscape evolves, how do CLL healthcare providers better understand mutation profiles, including the emergence of novel CLL mutations over time? What groundbreaking CLL therapeutic targets are emerging, tailored specifically to molecularly defined patient subgroups? And what innovative approaches are transforming CLL side effect management? These are just some of the things that we’re going to discuss today. We’re going to talk about the complexities of CLL mutations and the clonal evolution and resistance mechanisms in CLL.

We’ll discuss clinical trials and novel targets focused on molecularly defined patient subgroups. And lastly, we’ll talk about strategies for healthcare provider to healthcare provider communication regarding the management of side effects.It’s my privilege to be joined by Dr. Jennifer Brown, Director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute, and the Worthington and Margaret Collette Professor of Medicine in the field of Hematologic Oncology at Harvard Medical School. Thank you so much for joining us, Dr. Brown.

Dr. Jennifer Brown:

My pleasure. Thank you for having me.

Dr. Nicole Rochester: 

It’s also my privilege to be joined by Dr. Callie Coombs, an Associate Clinical Professor at the University of California, Irvine. Dr. Coombs primary clinical focus is in the care of patients with chronic lymphocytic leukemia and small lymphocytic lymphoma. She has participated in multicenter studies examining the real world implications of novel therapeutic agents on the lives of patients, and has served as an investigator on a number of clinical trials. Thank you so much for joining us, Dr. Coombs.

Dr. Callie Coombs:

Thank you for having me as well.

Dr. Nicole Rochester:

So let’s jump in as we have a lot to discuss as it relates to understanding CLL mutations and best practices for side effect management in CLL. So we’re going to start with the complexities of CLL mutations. And the first question, I’ll start with you, Dr. Brown, how do CLL healthcare providers better understand mutation profiles including the emergence of novel CLL mutations over time?

Dr. Jennifer Brown:

Well, the first thing that’s important to recognize is that CLL is not defined by any particular mutation. The landscape is quite varied and we see a large number of different mutations at low percentages. Well, the second key point to remember is that there are different mutations at baseline and then there can be acquired mutations that include some of what we see at baseline, but also novel resistance mutations that we don’t ever see at base.

So at baseline, the most common mutations, which are somewhere in the 10 to 20 percent range of patients, although less than that if you have very early stage patients, affect the p53 gene, NOTCH1, SF3B1, and ATM. P53 is the most important because that one does influence our thinking about the patients and our choice of therapy in some cases. P53 can be altered in CLL in two different ways. Actually, the most common way is as a deletion, deletion of the short arm of chromosome 17 or 17P deletion. About 75 to 80 percent of patients that have that deletion will have a point mutation usually in the other p53 allele. So they have double knockout of p53.

A small percentage of people with the deletion will not have the mutation. And then a certain number of patients will have just the mutation without the deletion. And one of the things that I’ve been very interested in for a while that we’re still trying to understand better is the implications of these different combinations of the way p53 can be affected in people with CLL, and that it may, in fact, be more adverse to have both alleles knocked out than single, although we don’t have great data for that as yet because most of the data that we have has combined all of it together.

But it’s very important to test for the p53 mutation alone because even if patients have only that one, at present, we consider the treatment implications of it all similarly regardless of how the p53 gene is affected. And then NOTCH1 is a fairly common mutation that always worries us a lot, because it’s associated with Richter’s transformation, which is a very high-risk event, but we don’t know anything to do about that to try and prevent it or to alter our therapy based on it.

So at the moment it’s mostly something that we are aware of that we keep an eye on but not that changes therapy. And SF3B1, ATM, and this long list of other genes that can be mutated in just a few percent of CLL, and mostly what we know about them is some biology that’s been studied, and then the fact that the more of these mutations are mutated in a patient that is associated with a worse prognosis, just a total number.

But that’s not something also that really alters our therapy. And then when patients go through lines of therapy, they can sometimes acquire mutations in these genes. So a patient can acquire a mutation in p53 or in NOTCH after their second or third line of therapy. But the mutations that are hottest right now, or that people are most interested in are some of the mutations that occur as resistance to therapy. So in particular, that means BTK mutations.

Covalent BTK inhibitors have transformed the therapy of CLL, and they bind to the cysteine 481 residue of BTK. So that means, as you might imagine, that if you mutate that cysteine so that the inhibitor can’t bind, that will be associated with resistance. And that, in fact, is what has been found that the cysteine to serine mutation at 481 is the most common resistance mutation in patients on covalent BTK inhibitors.

And in the case of ibrutinib (Imbruvica), it makes the inhibitor into a much weaker and non-covalent inhibitor. In the case of acalabrutinib (Calquence) and zanubrutinib (Brukinsa), it probably abrogates all activity. And so that’s a mutation that we will sometimes look for in patients with clinical progression on those drugs. There’s also a mutation in BCL2 that can occur in patients in venetoclax (Venclexta).

So another example of an on target resistance mutation. The role of that one is a little bit less clear, and testing for it is not as widely available, but we’re still working on that. Resistance to venetoclax is probably more complicated than resistance to BTK inhibitors, although there’s also a subset of patients who will get BTK inhibitors who have novel mechanisms of resistance not related to BTK that we don’t really know anything about as yet.

And then finally, the non-covalent BTK inhibitors are becoming available, pirtobrutinib (Jaypirca) was approved for CLL in the United States in December for patients who’ve had covalent BTK inhibitors and venetoclax. And we’re starting to see different mutations in BTK at different sites, even though pirtobrutinib has activity against the 481 mutation. So there’s going to be a lot of activity in this area in the next few years probably.

Dr. Nicole Rochester:

Thank you so much, Dr. Brown, that was a very comprehensive overview of the mutations. Dr. Coombs, do you have anything that you want to add to what Dr. Brown said perhaps specifically around mutations associated with the progression of CLL?

Dr. Callie Coombs:

Sure. So, that’s a hard act to follow. She really took us through a whirlwind of everything mutation-related. I think what I would like to focus on in my answer is, well, what should we be testing for on a day-to-day basis in our CLL practices and what are some common misconceptions? So specific to TP53, I would say this is the most important test as far as all of the genetic tests that influences what we do day to day in the care of patients with CLL.

I test for this for my newly diagnosed patients who I think may be interested in enrolling in a clinical trial, first of all, so the standard of care in CLL is watch and wait, however, patients with higher risk disease may be eligible for trials looking at early intervention specifically the SWOG EVOLVE trial looking at early treatment. And so that’s one of the risk markers that can get a patient into the higher risk category of CLL where they could be eligible for a trial.

A common misconception I see is that 17p is the same thing as a TP53 mutation, it’s definitely not. So these are two different tests that have to be sent. 17p can be picked up on karyotype testing and on FISH testing where it looks for 17p deletion. However, mutations are a different test. And so I usually send a next gen sequencing assay that includes other genes.

However, you can test purely just for mutations in the TP53 gene, but again, that’s a sequencing test, so I’d like to convey that, somewhat a misunderstanding, but it’s such an important gene in CLL because when patients have TP53 aberrations, whether that’s 17p or a TP53 mutation or both, given that they can occur in isolation or together, these patients should never get chemotherapy, because they have extremely terrible responses to chemo, and that should not be part of the therapies offered to these patients.

The other interesting, I’d say controversy at least in 2024, is what is the role for mutation testing in the clinic in the setting of acquired resistance to inhibitors? So I think it’s very clearly important in the research setting where I think learning about the C481 mutation among others in the setting of covalent BTK inhibitors has shown us a lot about mechanism of resistance. But in the clinic, I don’t necessarily think that’s something that needs to be universally applied, given that it most of the time doesn’t affect what we would do clinically.

And so one example is a patient comes in progressing on ibrutinib, maybe about two-thirds of them may have a mutation in the C481S. However, if they’re clinically progressing, they need to switch therapy. And so I think an argument could be made in practice whether or not sending these mutation tests is beneficial, but research, clearly important, and I think it’s going to give us key insights into our therapeutic sequencing strategies going forward. So I’m certainly a proponent of doing the testing in a well-monitored setting, but I don’t think it’s ready for prime time to be applied completely broadly to our patients.

Dr. Nicole Rochester:

Thank you, Dr. Coombs, and I appreciate you adding that additional practical tips and information specifically for our healthcare providers. And you kind of moved into the next topic, which was really around new diagnostic tools and technologies that are available to detect and monitor mutations. So I’m going to go back to you, Dr. Brown, to see if you have any additional information that you’d like to share about new diagnostic tools, technologies with regard to these mutations and any other tips perhaps for our healthcare provider audience.

Dr. Jennifer Brown:

Well,  really the only issue is what Dr. Coombs mentioned that it’s very important to get a next generation sequencing test to evaluate the p53 mutation, that it really is not well-evaluated by any other test, and is often missed because it’s thought that checking for the deletion is sufficient. So I would just reemphasize that point that she made very clearly. Other than that, we don’t really need any additional tools to monitor for mutations.

In the research setting we’re trying to do more and more sensitive assays to try and see when the earliest time that these mutations may emerge is and is there a way we could prevent that or, and just to better understand some of the biology, but it’s not really anything that’s needed in clinical practice. And we’re also not using the mutations to monitor residual disease. It turns out that the best way to do that is probably looking at the B-cell receptor itself, which is again, something that we’re studying in the research setting, but is not really something that needs to be done in clinical practices yet.

Dr. Nicole Rochester:

Wonderful. Thank you, Dr. Brown. We definitely want to leverage you all’s expertise in this area. And so my next question has to do with practices. And you’ve really kind of addressed this to some extent already. Are there any unforeseen or perhaps outdated practice-related barriers that may either hinder your work or that of your colleagues specifically related to better understanding CLL mutations?

Dr. Callie Coombs:

Yeah, I mean, I think in addition to what I mentioned about 17p and TP53, one type of mutation we haven’t talked about is assessing for the mutation status of IGHV.  So that’s actually something else that I’ve seen frequently missed as far as the routine testing of a CLL patient. But I do think it’s very important to send. Is it as important as when we were in the chemoimmunotherapy era where it would be hugely predictive for who had a long remission and who wouldn’t? Maybe not as important, but I do think if someone’s unmutated that still can really help inform certain aspects of their journey. One is the time that between diagnosis and when he or she’ll need their first treatment.

But two, also the expected length of remission should this patient embark upon a time-limited regimen such as venetoclax and obinutuzumab (Gazyva). But the separate question is, again, coming down to the practical aspect of how IGVH is tested. So another misunderstanding that I’ve seen is FISH tests look for the IGH locus. And so I’ve seen on recurrent occasions if that’s deleted, they say, “Oh, that’s a mutation.” Well that’s definitely not the same thing, and so it’s just to realize the IGHV test is a very specific test.

Some large facilities do it as an in-house test, I myself have been sending mine out to the Mayo Clinic, there’s other vendors where you can do it, but what they do is they specifically sequence IGHV and then compare the patient sequence to a consensus germline sequence to determine the percent of mutation, and it’s actually a good thing to be mutated with this gene, these are the patients that often have a longer time until they need their first treatment, if they need treatment at all, and then they generally have better responses to therapy. Though with BTK inhibitors, that difference is often becoming quite slim given that they work in both groups of patients.

Dr. Nicole Rochester:

Wonderful. Thank you so much, Dr. Coombs. So now we’re going to shift to talking about clinical trials and novel targets focused on molecularly defined patient subgroups. So, Dr. Brown, can you talk about any emerging CLL trials targeting specific molecular subgroups, and also how can CLL experts stay updated on these advancements in clinical trials?

Dr. Jennifer Brown:

So, as you heard from Dr. Coombs, there’s increasing interest in looking at high-risk patients in particular, and I think looking specifically at patients with p53 aberration in dedicated clinical trials, it’s become increasingly clear that the behavior of the disease when it’s higher risk based on p53 mutation, NOTCH mutation, IGHV status is quite different, particularly with time limited therapy compared to lower risk disease.

And so having dedicated trials that evaluate outcomes specifically in certain of these subgroups is increasingly important. We do have more trials than we used to focusing specifically on p53 aberration. My personal belief is that we would be well served to have trials separately in the IGHV groups that Dr. Coombs mentioned, although that has not gained as much traction.

And then what we are seeing is now that there are resistance mutations, it actually has turned out that some of the drugs that we use in that setting, venetoclax and pirtobrutinib, seem to have pretty similar activity in patients with and without the mutations. But as drugs are being studied in this context, there’s been an increasing tendency to study them in specific subgroups.

So patients who have the mutation and had clinical progression on a covalent inhibitor, patients who don’t have the mutation and had clinical progression, patients who may have come off their covalent inhibitor for adverse events who may not actually be resistant, what is their response to the next line of therapy? And so all of that is just helping us understand in a more nuanced way what the best benefit for patients will be as we look at these different subgroups of patients.

Dr. Nicole Rochester:

Thank you, Dr. Brown. Appreciate that. Dr. Coombs, do you have anything to add?

Dr. Callie Coombs:

Yeah, so I echo all of Dr. Brown’s comments, and I think I’m the person that is bringing all the practical aspects of CLL care because it’s, she’s so thorough. I just always like to contribute a few little pearls. So, pirtobrutinib has been an exciting drug, to see it become available for our double refractory patients. So the current FDA indication is for patients failed by not only a covalent BTKi but also venetoclax. But it’s the first BTK inhibitor that we can effectively use in the setting of a prior BTK inhibitor.

And that’s because of this unique aspect where instead of forming a covalent bond at the C481 residue, it binds reversibly, and we can still see activity. But the practical aspect is that that’s not an effective strategy when you have a patient progressing on, say, ibrutinib, you can’t switch them to acalabrutinib (Calquence) or zanubrutinib (Brukinsa) because of their shared mechanism of resistance. They’re all covalent inhibitors. They all share the same mechanism of resistance.

And so that’s one thing I’d like to bring up. However, there’s a very different and very common clinical situation that I encounter really a lot in my clinic, which is intolerance. And so that’s where it would be a very effective strategy to switch a patient from one covalent drug to another. And so literally in the past couple weeks of clinic, I’ve had patients with chronic long-standing toxicities to ibrutinib that perhaps went underrecognized where I say, “Hey, you’ve had…noticed your blood pressure has gone up a lot. Let’s switch you over to acalabrutinib,” or other patients, “Oh, you’ve had issues with atrial fibrillation…let’s try switching you to zanubrutinib.” Because the rates are a lot lower and a lot of patients can have improvement or just complete resolution of the prior side effect.

And so I hope that that emphasizes this is something that we think about every day, and switching is appropriate in the setting of intolerance. It’s not appropriate when you’re staying in the covalent class to switch in the setting of progression. But pirtobrutinib being a non-covalent inhibitor is certainly very effective after a covalent. And I think once we see readout of some of the ongoing Phase III trials, we may be able to use it in that setting under an approved FDA label, though that is to be seen in the future.

Dr. Nicole Rochester:

Awesome. Thank you. Thank you to both of you. And that leads us very nicely into our next topic. And so we’ve been talking about improving CLL treatment efficacy, we’ve talked about mutations, we’ve talked about really providing better outcomes for our patients by using therapies that are very specifically designed for the molecular characteristics of their disease. But along with all those therapies, of course, come potential side effects. And so, Dr. Coombs, I’m going to start with you and then we’ll go to Dr. Brown. Are there any strategies that you can share with our healthcare provider audience around innovative approaches or protocols that have been implemented to mitigate and manage the CLL side effects from the treatment?

Dr. Callie Coombs:

Well, I think it comes down to your internal resources, but I would say taking care of CLL patients is clearly a team effort. And so it’s not just me, but also a team of additional practitioners that I work with. So I’d like to emphasize how important pharmacists are because I’ve definitely seen some side effects that come about because a patient is now on a medication that interacts with whatever their CLL therapy is, which drives up the levels of the drug and then brings out certain toxicities so they can help us identify these.

If, perhaps I missed it or didn’t ask the patient about a supplement, et cetera. Next is nurse practitioners and oncology nurses. And so number one is it’s a team-based approach, and I think it’s certainly very important to have protocols internally. But also to just realize what the common toxicities are and how can we mitigate these.

One of the most common reasons that I’ve seen for patients stopping a drug prematurely actually is venetoclax. It very commonly causes neutropenia. And I’ve seen the drug given up on very early without any growth factor support, and so I think if you become educated and experienced with using drugs, you can realize there’s very clear strategies in improving patients with neutropenia, by supporting them with growth factor and getting them through whatever their defined plan course of venetoclax may be.

And then BTK inhibitors have a whole smattering of side effects as well where perhaps working with cardio oncologists can help in addition to other strategies depending on exactly what side effect the patient may encounter. So in summary, definitely a team-based effort and growing experience with the common side effects helps I think all comers with strategies to help prevent or mitigate such side effects.

Dr. Nicole Rochester:

Thank you so much, Dr. Coombs. Dr. Brown, do you have some additional best practices you’d like to share with regard to the management of treatment side effects?

Dr. Jennifer Brown:

Well, I agree completely with Dr. Coombs. I would just add that I think it helps a lot when you warn the patients ahead of time about things that may happen but that often go away or that you can manage. So, for example, headaches often happen early on when you initiate acalabrutinib but they go away typically very quickly. And so if patients know that, then they’re much less worried, and then you can talk to them about the strategies, because caffeine or acetaminophen (Tylenol) will often help with that. If you warn them that they may have some joint aches or pains, that can also help, since those are often transient.

With venetoclax, warning them about some nausea or diarrhea, and then we often manage that by subsequently moving the drug to the evening after they’re done with their ramp up, or initiating an antiemetic, things like this. And then oftentimes many patients who have that in the beginning, it doesn’t persist throughout the whole time that they’re on the drug. Sometimes the diarrhea may, but many times it doesn’t. So getting the patients through that early phase with the close management. Which again, it helps, have your team help with that, the nurse practitioners, et cetera, and then hopefully things settle out and everyone’s happy.

Dr. Nicole Rochester:

Wonderful. I just want to emphasize two things. One that each of you said. One is this idea of a team-based approach, which is important in the treatment of all diseases, but of course very important in the treatment of the cancer. And also this idea of educating our patients so that they know ahead of time what to expect and really involving them as part of the team. So I really appreciate those, both of those points.

Well, it’s time to wrap up our roundtable. I have really enjoyed this conversation and I’d like to get closing thoughts from each of you. So I’ll start with you, Dr. Coombs. What is the most important takeaway message you’d like to leave with healthcare professionals who may be listening as they watch this program and understand better about CLL mutations, clinical trials, and managing side effects?

Dr. Callie Coombs:

So what is the most important thing, there’s so many, I would just say CLL is a chronic disease that affects our primarily elderly patients, and so it’s a marathon, not a sprint. However, with all of the advances that we’ve had in excellent drug therapies, despite these resistance mutations, patients can attain many, many, many years of high quality of life. But it’s incumbent upon us as their providers to help ensure that quality of life through effective management of side effects that may be encountered over the course of their time on therapy for the patients that do need therapy.


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HCP Roundtable: Breaking Barriers and Cultivating Clinical Excellence in Endometrial Cancer Care

HCP Roundtable: Breaking Barriers and Cultivating Clinical Excellence in Endometrial Cancer Care from Patient Empowerment Network on Vimeo.

What are obstacles faced by healthcare providers (HCPs) treating endometrial cancer patients and families? How can HCPs foster a culture of innovation and continuous improvement in clinical practice? Dr. Radhika Gogoi of Karmanos Cancer Institute and Dr. Charlotte Gamble of MedStar Health unravel the complexities of endometrial cancer care, providing HCPs with the insights and tools needed to navigate challenges effectively and to deliver optimal care to their patients and families.

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Transcript:

Dr. Nicole Rochester:

Welcome to this Empowering Providers to Empower Patients or EPEP Program. I’m Dr. Nicole Rochester, founder and CEO of Your GPS Doc. EPEP is a Patient Empowerment Network program that serves as a secure space for healthcare providers to learn techniques for improving physician patient communication and to overcome practice barriers. In this endometrial cancer healthcare provider roundtable, we are discussing breaking barriers and cultivating clinical excellence in endometrial cancer care. 

This program aims to improve healthcare provider awareness of screening and access disparities to specialized care in endometrial cancer, while also addressing solutions to overcome practice barriers such as lack of awareness, outdated practices, and inertia. Today, we’ll talk about some of the complexities of endometrial cancer care and we’ll provide healthcare providers with the insights and tools needed to navigate challenges effectively.

Our discussion will cover enhancing healthcare provider awareness of diagnostic and access disparities to specialized care in endometrial cancer, actionable strategies to overcome practice barriers in endometrial cancer care and empowering providers through fostering a culture of innovation and continuous improvement in clinical practice. 

It is my privilege to be joined by Dr. Radhika Gogoi from Karmanos Cancer Institute. Dr. Gogoi is a dedicated clinician and cancer researcher focused on exploring the Hippo pathway in gynecologic cancers, aiming to uncover novel therapeutic approaches. Thank you so much for joining us today, Dr. Gogoi.

Dr. Radhika Gogoi:

Thank you, Dr. Rochester, and thank you for having me. It’s great to be here.

Dr. Nicole Rochester:

It’s also my honor to be joined by Dr. Charlotte Gamble, gynecologic oncologist at MedStar Washington Hospital Center and MedStar Southern Maryland Hospital. Dr. Gamble is dedicated to taking care of patients who have historically been marginalized and are vulnerable to poor health outcomes. Her research examines the role of safety net hospital systems in gynecologic cancer care. Thank you so much for joining us today, Dr. Gamble.

Dr. Charlotte Gamble:

Thank you so much for having me. It’s a pleasure to be here.

Dr. Nicole Rochester:

So we’re going to start today’s discussion by diving into enhancing healthcare provider awareness of diagnostic and access disparities in endometrial cancer care. And I want to start by just framing the current situation. Black women are twice as likely to die from endometrial cancer when compared to their white women counterparts.

There is no current screening test for endometrial cancer, and diagnosis is usually made after patients present with symptoms. Sadly, the list doesn’t end there. So I’m going to start with you, Dr. Gogoi. What are the primary barriers to accessing specialized care for endometrial cancer that you’ve observed in your practice and perhaps in others?

Dr. Radhika Gogoi:

So thank you for that question. I guess I just want to start by just level setting a little bit and talking about specifically endometrial cancer disparities. So unlike other gynecologic cancers, which actually have been shown to be decreasing in incidence, endometrial cancer is actually one of the cancers that is increasing. We know that low grade endometrial cancers really have an excellent prognosis, but higher grade endometrial cancers really have a much poorer prognosis.

And that’s the specific subgroup that seems to be increasing in all women. Black women, again, as you mentioned, have the lowest survival rate, and that is even when corrected for the specific type of endometrial cancer and the stage of endometrial cancer. So with that sort of background and problem, the question really becomes how do we allow and educate our patients about the barriers that they face when accessing specialized care?

And so some of the barriers, at least that I’ve noticed, and certainly in the hospital that I practice in is really as you pointed out, that there is no good current screening test. Black women tend to have a delayed onset from the time of their symptoms, which in this case is really postmenopausal bleeding to actually obtaining a diagnosis.

And there are studies that have shown that some of that is education or there is an understanding that perhaps postmenopausal bleeding is not as significant an issue, doesn’t lead necessarily, to obtaining healthcare which as you can appreciate then delays the onset of the diagnosis. There is also that Black women present with more advanced disease. This is, again, likely due to the delay in diagnosis and the delay from diagnosis to getting treated.

Dr. Nicole Rochester:

Thank you. Thank you, Dr. Gogoi for level setting and for getting us started with a better understanding of those disparities. And I’d love to go to you, Dr. Gamble. In your experience, what are the primary barriers to addressing specialized care for endometrial cancer?

Dr. Charlotte Gamble:

Yeah, thank you so much.  I’ll just add some additional context. I think there are so many places in which these barriers can happen. So as Dr. Gogoi alluded to, sometimes that can happen at the patient level due to just not recognizing that having irregular, unpredictable bleeding, bleeding after menopause, bleeding even before menopause has happened, but really heavy bleeding or heavy periods that any sort of abnormal, heavy irregular bleeding is not normal and has to be evaluated in a timely fashion. But that’s at the patient level.

And sometimes, people have competing priorities where they might recognize that it’s a problem but not be able to make it to their doctor’s office. Have other kinds of things that are happening in their day-to-day lives where they just are not able to prioritize their own health. We also see then how the system can affect that.

If someone hasn’t had a gynecologist in years, or their gynecologist said, bye, you don’t need to see me anymore because you’re over the age of 65, you no longer need pap smears and they’ve fallen out of care, or patients who don’t have health insurance or patients who live really far away from their doctors. Accessing the healthcare system in the year of our Lord 2024 is actually really, really hard. If you lack the resources or lack the wherewithal to navigate that.

Additionally, what we see on the healthcare standpoint is that maybe patients do actually access the healthcare system. They call the gynecologist’s office. They call their primary care doctor, and they’re told by an admin staff or someone else that hears them, but that says, okay, fine, we’ll get you in, but it’s going to be in about three-and-a-half months.

And so sometimes those barriers and those delays come from the health system in general, which is also a challenge. And then even after they present to their doctor, sometimes they’re told, “Okay, let’s go ahead and let’s get an ultrasound first, and based on what your ultrasound looks like, then we’ll decide if we need to do a uterine biopsy to diagnose you.” But we also know that for certain types of these uterine cancers, specifically the really aggressive ones, that sometimes their ultrasound might look totally fine, but there still can be cancer underlying there.

And so I think that there are multiple barriers to getting even. That’s before the diagnosis even happens much less what comes after the diagnosis is had, how one gets from their gynecologist to a surgical subspecialist called the gynecological oncologist that Dr. Gogoi and I, this is our field. And there are multiple barriers and referral pathways there. But that’s to give a little bit more context that these things might start at the patient level, but the healthcare system, unfortunately, can contribute in rarely challenging ways to the barriers that patients face.

Dr. Nicole Rochester:

Thank you both for that. I think we have a really good idea of the breadth of this issue, and I appreciate both of you pointing out that there are patient level factors, but there are also system level factors that come into play. And, Dr. Gamble, you just kind of ended by talking about referrals.

So I’m going to pick up there. And let’s talk about referral patterns. And I’ll start with you for this question. How do those referral patterns impact access to specialized care gynecologic oncologists like yourself and Dr. Gogoi for women who are diagnosed with endometrial cancer and specifically for those underserved populations?

Dr. Charlotte Gamble:

Yeah, this is a complicated question and multi-layered. Again, I think big picture referral patterns. We know that there are barriers for patients who live rurally. We know there are barriers for patients who don’t have insurance or their insurance might be, they might be underinsured. And so there’s kind of system level barriers that we see on the macro level in some of our referral pathways.

And occasionally, sometimes patients with gynecologic cancers will actually be referred to not gynecologic oncologists, which are surgical subspecialists that work specifically with gynecologic malignancies, but might be referred to a general surgeon first, or a general gynecologist who may or may not know kind of what they’re getting into in terms of the care. I think what I’ve noticed in real life is that when I’m getting referrals, sometimes I’m getting a text message, sometimes I’m getting an email, sometimes getting a message in the medical record system, and the referrals are coming in many different ways.

Occasionally, patients are calling themselves. And so the ways that referrals actually then happen in real life and how those spread to kind of the macro levels is really interesting to me. It can be very complicated, very complex, and I think this is where the role of having healthcare navigators comes into play where folks can really assist patients in getting to the right surgical subspecialists.

Dr. Nicole Rochester:

Absolutely. And we know there’s a lot of evidence for the role of healthcare navigators in other disease spaces and specifically in cancer. So I appreciate you mentioning that. We’ve talked a little bit about patient level factors, and we’ve talked about system level factors. We haven’t talked a lot about maybe some provider level factors.

And I want to talk about cultural competency and the role that that plays in addressing disparities in endometrial cancer, specifically with regard to diagnosis. And I’m going to start with you, Dr. Gogoi on this one. And if you can share the role that you believe cultural competency plays in addressing some of these disparities that we’ve been talking about.

Dr. Radhika Gogoi:

Yeah, so I think you heard from us a little bit that oftentimes some of the symptoms that our patients have had are either ignored, or patients haven’t had a chance to fully address them, or the providers haven’t fully evaluated kind of the importance of their symptoms. And I think, so again, I think nurse navigators community educators are essential in sort of educating our communities about the importance of seeking care when you have sort of the symptoms that Dr. Gamble talked about and in a really timely fashion. I think that that’s really important as well.

So I think it obviously, cultural competency is important in sort of all facets of a patient’s journey as they kind of have the diagnosis through their treatment. But I think that the other place is really once they enter the healthcare system being aware and mindful of sort of healthcare mistrust both from the provider, from the institution, from a much larger governmental level and being aware of that distrust and really trying to take time to address their concerns.

That specifically at least comes up a lot in terms of clinical trials where we know that minority populations, Black patients are met vastly underrepresented. And so I think specifically in that area, there is really the opportunity to do a much better job in providing transparency about the trial design, about recruiting specifically minority patients. Interestingly, a lot of these landmark trials actually didn’t include race as a measure. And so we know that they’re underrepresented, but we actually don’t know how much minority populations are underrepresented. So important to really understand where patients are coming from when they enter a healthcare institution.

Dr. Nicole Rochester: 

Absolutely. Thank you. Thank you so much for that. Dr. Gamble, can you speak to awareness? You spoke about the fact that sometimes patients are referred to perhaps the wrong provider. You know, there was that sent, you mentioned to a general surgeon instead of to a gynecologic oncologist. And so we can imagine that there may be some challenges both in the primary care setting and perhaps even among general obstetrician gynecologists. So can you speak to how we can elevate the level of awareness to enhance healthcare provider awareness of diagnosis and access disparities and really appropriate referral patterns?

Dr. Charlotte Gamble:

Yeah, absolutely. I think it’s a tough question. I think it’s, again, like all things, it’s a little bit nuanced. Sometimes, again different levels of providers, different parts of the country, everybody practices a little bit differently. So everyone knows once you get a cancer diagnosis, you should probably go to a cancer specialist. And so generally, that’s coming to a gynecologic oncologist generally, or that’s sometimes that’s going to a medical oncologist. But occasionally, sometimes patients will have symptoms where it’s just abnormal bleeding, and they’re seeing a general gynecologist who then does a hysterectomy, and there’s a surprise diagnosis of an endometrial cancer.

Usually they’re, hopefully, they’re not making it too much to kind of the general surgery pathway our general surgery colleagues are awesome, but it’s kind of a different kettle of fish and the type of hysterectomy that’s needed and the type of specific surgery that’s needed to include lymph node assessment is different for somebody who’s getting a cancer surgery for uterine cancer compared to, let’s say, for fibroids or for adenomyosis or a non-gynecologic cancer situation.

I think, again, I’m on the receiving end of all of this, so I see patients who have made it to my doorstep and gotten kind of through the hoops and the barriers, but there’s definitely those out there that we know from the data somehow ended up with their surgery, not exactly in the appropriate hands.

And it’s hard to say, I don’t know if I actually even have advice for like how this is supposed to happen. I think we need to understand kind of the as Dr. Gogoi alluded to earlier, just kind of how prevalent endometrial cancer is right now and how the rates are rising and that abnormal bleeding has to be taken very seriously. And the thing that I harp on the most is a normal ultrasound does not mean there’s nothing else to explore there. There has to be a tissue biopsy.

And really impressing that on both patients as well as the first kind of people that they see, either their primary care doctor or even a nurse practitioner, a physician assistant. Just because there’s a normal ultrasound does not mean that your work is done. And we have studies to really demonstrate how that can delay patient’s care and missed diagnoses can happen. So it’s hard to answer your question, to like, how do we fix the referral pathway system? I don’t know the answer to that, and maybe Dr. Gogoi can speak to that, but I will say from like a screening standpoint, since there’s no great screening test, an ultrasound is not, might be the first step, but it’s definitely not the only step and it cannot be the last.

Dr. Nicole Rochester:

I appreciate that. As you were talking, I was thinking like this needs to be a major awareness campaign, not just for healthcare providers, but for patients as well. You know, this idea that abnormal or or postmenopausal bleeding is never normal and make sure your doctor gets a tissue biopsy and not just an ultrasound. Dr. Gogoi, we’ve talked already about some of the obstacles and barriers faced by patients. Can you talk about some of the obstacles or barriers that are faced by healthcare providers when treating endometrial cancer?

Dr. Radhika Gogoi:

Yeah, I think that the one other barrier that sort of comes up a lot specifically in terms of maybe even in terms of getting a patient to their referring providers or a G1 oncologist is transportation. I find that transportation is a huge issue for our patients. And it’s mostly associated with cost. So I think that one of the things that really, that we can do as a community is to somehow provide means or ways for our patients to get to us once they’re diagnosed. It’s hard enough to get them to us but when they’re facing challenges of cost and transportation, that becomes even more challenging.

So I think that that’s from a patient standpoint. And then, and then I think what Dr. Gamble mentioned about really the barriers for providers is really education around ultrasound and how those how specifically perhaps even in Black women, that it’s not as predictive of endometrial cancer risk and that an ultrasound alone is not enough of a workup for a number of these patients to rule out some underlying pathology. So that’s huge, and again mistrust of the medical profession is something that all healthcare providers deal with. And allowing time for patients to ask their questions, to be transparent about what it is that you’re doing and why I think goes a long way towards overcoming those challenges.

Dr. Nicole Rochester:

Thank you both for that. I think we’ve gotten a lot of information around the causes of the disparities and some actions that we can begin taking. Are there any unforeseen or outdated practice-related barriers that may hinder your work and that of your colleagues? And on that same note, are there any solutions or actions related to those? And I’ll start with you on this one, Dr. Gamble.

Dr. Charlotte Gamble:

Well, starting all the way back, I think an outdated practice is not listening to patients, and not recognizing your own privilege as a provider. I think that to Dr. Gogoi’s point that she’s mentioned a couple of times now, I have innumerable patients that just felt that they were not listened to felt that they couldn’t…that their stories were not being heard, that they faced no’s, no’s, no’s at multiple levels in trying to seek care for abnormal bleeding, and come to me very frustrated and kind of weary. And I think just really understanding how vulnerable patients are when they’re seeking care, and being cognizant of the privilege that we have as healthcare providers is something that is more contemporary compared to an outdated practice of being very paternalistic.

I guess sometimes I have had patients who are like, yeah, I was told that I needed a biopsy and I just…the way that they told me and the way that they said that it had to be done tomorrow, it freaked me out, and I couldn’t do it. And it’s just kind of unfortunate when the recommendations might be correct, but the way in which it’s being delivered is not being received by the patients in a way that they’re able to be receptive to.

I think another outdated practice again that I harp on that I’m such a strong believer in is like just the role of the ultrasound. I really, I don’t like it. I hate it. I think it’s useful for knowing uterine size and maybe if there’s some kind of stuff inside the uterus, but abnormal bleeding either before menopause or after menopause has to have a tissued biopsy. So I think that’s outdated to just get an ultrasound and have the patient come back, because it continues to perpetuate delays in care, and I think disparities to an extent. Another outdated…no, I don’t know. Is there anything else, Dr. Gogoi, that you’d add to this?

Dr. Radhika Gogoi:

I feel like this is a lot lot older now. It used to be at one point that we used to do all our endometrial cancer patients with open surgery. I think that now, I guess it’s even more outdated than outdated. Most of the surgeries are now pretty much done either minimally, invasively laparoscopically or robotically. There are obviously extenuating circumstances to both of those things, but I think approach to surgery is also sort of evolved.

The treatment paradigm for patients with advanced endometrial cancers has evolved even more so in the last maybe two years or so with the role of immunotherapy. So encouraging our patients to be educated about their options, both for route of surgery, for treatment and to make sure to ask those questions at the time of their office visit I think is something that we should all encourage.

Dr. Charlotte Gamble:

I would dovetail from that and also say, to kind of harken back to some of the other things we discussed in terms of referral pathways and things like that, and just how gynecologic oncology care is delivered in different parts of the country, there are various models for this, and so classically, patients who have gynecologic cancers, including endometrial cancer are managed solely by the gynecologic oncologist, meaning a surgical subspecialist like myself or Dr. Gogoi, who not only do the surgery, but also deliver if patients need it chemotherapy or specialized systemic therapies afterwards, sometimes with a component in partnership with a radiation oncologist.

But there are parts of the country by institution or by geography where the care that comes after the initial surgery done by the gynecologic oncologist might be shared with a medical oncologist who may or may not actually have super sub-specialized training when it comes to gynecologic cancers, because again, historically, this has been an area that’s been managed really by our subspecialty.

And so I encourage patients as well as referring doctors, et cetera, et cetera, to make sure that whoever, if there’s additional therapies that are needed after the hysterectomy is done, such as chemotherapy or immunotherapy, as Dr. Gogoi alluded to, that that is done in partnership with a gynecologic oncologist, because our field is kind of driving where so much of the contemporary understanding of how to manage these conditions long-term is coming from. And to make sure that if a medical oncologist is doing this, they feel very competent. They do this all the time, and they’re working in close partnership with their gynecologic oncology colleagues.

Dr. Nicole Rochester:

Wonderful. Thank you for that. So as we talk about outdated practices, I guess the other side of the coin is innovation and continuous improvement. And so I’ll turn this question to you, Dr. Gogoi. How can healthcare providers and hospital leaders foster a culture of innovation and continuous improvement? So that’s some of these outdated practices that you all, that you and Dr. Gamble, discussed are really no longer a thing?

Dr. Radhika Gogoi:

Yeah. So I couldn’t agree more.I think that some of those innovative approaches really come from enrolling in clinical trials. And so I think that the importance of having minority populations, equally represented in clinical trials is essential. Otherwise we’re not going to make the progress that we need to make to really equal the playing field here, so to speak. So I think that that really is a huge player trying to educate patients about clinical trial options, being transparent about what those look like, who benefits, what the data suggests, why it’s important to me is again, really key.

Dr. Nicole Rochester:

Wonderful. And Dr. Gamble, if we were to be specific, are there any healthcare provider to healthcare provider strategies, anything that you’ve seen work, maybe things that you’ve done yourself, innovative approaches or protocols with regard to this idea of innovation and continuous improvement?

Dr. Charlotte Gamble:

Yeah, I think different institutions have different cultures, and I think having institutional culture that embraces change that is, desires to be on the vanguard of advancing science, and the science could be in terms of bench research. It could be in terms of clinical trials, it could be in terms of healthcare delivery, really trying to advance and push forward. The science and how we get the best care to our patients in the most timely fashion I think is really important. Culture is hard to change, and we all work in institutions that have various different cultures. I think that healthcare provider to healthcare provider, I think open lines of communication are great. I tell folks, text, call, email, whatever you need to do to get patients in a timely fashion is necessary.

I think the understanding of we are one person working within a team is really necessary. So patients might say, oh, Dr. Gamble this, Dr. Gamble that, but I always, always, always tell them that I cannot do this work without my nurse navigator, without my fellow, without my residents, without my inpatient floor nurses, the oncology nurses, and really understanding that oncology care specifically is a really big team sport.

And healthcare leaders, when we’re thinking about things from a system level, I think sometimes have different like just help making sure that everybody understands how much of a team sport that this is. How much the radiation oncologists, the medical oncologists interface with us on a regular basis, I think is really important. And to understand that we’re all in this together to deliver the best care to our patients. I really think the role of health, like nurse navigators and lay navigators needs to be further pushed forward within our field, including not only gynecologic oncology, but just gynecology in general, and that’s some of the work that I’m doing from a research standpoint now. And so I’d love to see the role of navigators be fully embraced and somehow reimbursed by healthcare systems in general.

Dr. Nicole Rochester:

Absolutely. Well, it is time to wrap up this roundtable. I have really enjoyed talking with both of you as always. I have learned a lot. I’m sure that our audience will learn a lot from this conversation. And before we go, I’d love to get closing thoughts. So I’m going to start with you, Dr. Gogoi. What is one takeaway message that you would like to leave with the healthcare professionals who will watch this program?

Dr. Radhika Gogoi:

So I guess the one takeaway would be that, as I think about my role in sort of disparities prevention, if you say it is really as an educator, and so the importance of community education on symptoms, on diagnosis, on treatment approaches, I think it’s essential that we don’t think of ourselves as a silo. I’m not just, but I’m part of the larger community as Dr. Gamble spoke about. And to be part of that larger community means that I need to be within that community and function within the community. So whether it’s me, community navigators, health educators to really play a role in educating our patients about how to approach their symptoms.

Dr. Nicole Rochester: 

Wonderful. Thank you, Dr. Gogoi. And what about you, Dr. Gamble, what’s your closing thought that you would like to leave with the audience?

Dr. Charlotte Gamble: 

Yeah, I think for healthcare providers in general, I think the thing that I think is most important is, again, being able to listen to patients, working and encouraging the systems that we are housed into, be able to be responsive to them, so that if patients are educated, do know that there’s something wrong. They’re able to not only get a hold of someone, but also be listened to and heard and taken seriously. And we have a lot to do in that regard. So I think just understanding again, our role and how privileged we are to be in our jobs, in this line of work, and being able to leverage that to listen to patients and get them the timely care that they need.

Dr. Nicole Rochester:

Wonderful. Well, thank you both again, Dr. Gogoi, Dr. Gamble, thank you for this enlightening conversation. We’ve learned so much about endometrial cancer. I think for me, the main takeaway is postmenopausal bleeding, abnormal irregular bleeding is never normal. It needs to be evaluated. You both spoke about the importance of biopsy and not just an ultrasound, and in fact that ultrasound can be normal.

And with regard to disparities, I really appreciate both of your thoughts around community education, and this being a team sport and listening to our patients. So again, thank you so much for being here today, and thank you all for watching the program and tuning into this Empowering Providers to Empower Patients, Patient Empowerment Network program. I’m Dr. Nicole Rochester. Thanks again for watching.


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