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Biomarkers and Molecular Testing in Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACS, FACOG, University of Arizona, Creighton University, & Arizona Oncology Practice of US Oncology; Ursula Matulonis, MD, Dana-Farber Cancer Institute; David OMalley, MD, The Ohio State University; Matthew Powell, MD, Washington University; Shannon N. Westin, MD, MPH, MD Anderson Cancer Center
Published: Thursday, Apr 26, 2018



Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Dave, you mentioned biomarkers ready for prime time. When do you test for BRCA? How do you test for BRCA in your newly diagnosed ovarian, fallopian tube, and peritoneal cancer patients?

David O’Malley, MD: I think there are multiple ways to do it. When we do it at Ohio State—we’ve actually now published a paper on how we do this—we have embedded our genetic counselors right into our gynecologic oncology clinics. MD Anderson is doing an amazing job of having it hardwired, of getting the genetic testing. But it’s not just about genetic testing. It’s not just about germline BRCA, right? It’s germline, probably, multigene testing. There is consideration for somatic, tissue, or molecular testing. We are currently testing both germline and somatic in all of our newly diagnosed ovarian cancers.

Bradley J. Monk, MD, FACS, FACOG: And peritoneal and fallopian tube cancers.

David O’Malley, MD: That’s a very important point. So, with that, we’re also using somatic testing. The NCCN guidelines changed with recurrent disease. The guidelines are now recommending molecular testing, at the very least, to include BRCA, HRD genes, mismatch repair proteins, and MSI.

Bradley J. Monk, MD, FACS, FACOG: I love it. Ursula, you’ve been a leader, at your center, with molecular testing and profiling. What are you doing?

Ursula Matulonis, MD: Very similar to what Dave said, we have genetic counselors in our clinic. We have folks who typically see patients by cycle 2 or cycle 3. They’re embedded in our clinics. We are still doing germline testing first. We also have a research platform that tests about 400 different genes. So, we’re doing somatic testing as well. I really do see the field moving toward initial tumor testing and then reflexive germline testing. I think it’s great to see the genomic panel, beyond these panel tests. It would really broaden our view of the molecular underpinnings of the cancer, up front.

Bradley J. Monk, MD, FACS, FACOG: You’re testing those in house, right? Do you do in-house molecular testing or do you send it out?

Shannon N. Westin, MD, MPH: Our somatic testing is done in-house. But we do a send-out panel. We generally do our germline testing up front, and that includes a panel test for all of the things that Dr O’Malley mentioned. Then we lean on the somatic testing in the recurrent setting.

Bradley J. Monk, MD, FACS, FACOG: Do you send that out? Or do you do it in-house?

Shannon N. Westin, MD, MPH: We do it in-house.

Bradley J. Monk, MD, FACS, FACOG: Interesting.

Shannon N. Westin, MD, MPH: Yes. We have about a 400-gene panel as well.

Bradley J. Monk, MD, FACS, FACOG: Do you guys do in-house molecular testing?

Matthew Powell, MD: We do. One of the challenges we have is that we can’t all afford embedded genetic counselors in our clinics. We’ve really had a big transition. Now, I’m providing the counseling and I’m testing. Posttest counseling is handled by a genetic counselor. So, we know that everybody needs to be tested. That’s a no-brainer now.

Bradley J. Monk, MD, FACS, FACOG: I’m progressive like you. My nurse practitioners love to talk about this. They’re so passionate. My nurse practitioners are actually trained in genetic counseling.

Matthew Powell, MD: I think that’s an efficient model.

David O’Malley, MD: A paper was just published in the Journal of Clinical Oncology on direct counseling in both North America and Europe. Now, that’s only for BRCA. It becomes much more complicated when you’ve extended gene testing, particularly in the VUS (variant of uncertain significance).

Bradley J. Monk, MD, FACS, FACOG: I now send patients to the genetic counselor and he or she contacts every family member. My nurse practitioner’s not going to be able to contact the entire kindred, which is really important.

Matthew Powell, MD: If we talk about insurance implications, we do the right process. Then we get them tested. Our testing rate certainly goes way up when we do that. And they trust us.

Bradley J. Monk, MD, FACS, FACOG: I work in US Oncology. As I said, Arizona Oncology, particularly. We don’t have in-house testing. We send all of our germline testing and molecular profiling out. There are a number of very well-respected vendors. I think there are some subtle differences. We probably don’t have time to go into that. But whenever you do a next-generation sequencing protein, or RNA evaluation, the first question is, what do you report? In next-generation sequencing, you have the whole genome. You say 400, or 700, or 600 genes. Why not 200? Why not 800? So, what do you report? And once you make that decision, you have to correctly interpret it. I know that all of you are available for some of these interpretations. That’s really the fun part. There are some actionable mutations that are agnostic. You mentioned HRD and MSI, but there are some EGF–activating mutations and HER2.

Those appear to be tumor agnostic. So, it’s exciting. Everything that we’ve talked about has a foundation in clinical trials. We sat here and had a 45-minute discussion about a clinical trial in HIPEC, intraperitoneal chemotherapy, or neoadjuvant chemotherapy, bevacizumab, or immuno-oncology. I really appreciate your commitment. It’s a personal sacrifice. But it’s a sacrifice for the right reason because it helps patients.

Transcript Edited for Clarity 

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Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Dave, you mentioned biomarkers ready for prime time. When do you test for BRCA? How do you test for BRCA in your newly diagnosed ovarian, fallopian tube, and peritoneal cancer patients?

David O’Malley, MD: I think there are multiple ways to do it. When we do it at Ohio State—we’ve actually now published a paper on how we do this—we have embedded our genetic counselors right into our gynecologic oncology clinics. MD Anderson is doing an amazing job of having it hardwired, of getting the genetic testing. But it’s not just about genetic testing. It’s not just about germline BRCA, right? It’s germline, probably, multigene testing. There is consideration for somatic, tissue, or molecular testing. We are currently testing both germline and somatic in all of our newly diagnosed ovarian cancers.

Bradley J. Monk, MD, FACS, FACOG: And peritoneal and fallopian tube cancers.

David O’Malley, MD: That’s a very important point. So, with that, we’re also using somatic testing. The NCCN guidelines changed with recurrent disease. The guidelines are now recommending molecular testing, at the very least, to include BRCA, HRD genes, mismatch repair proteins, and MSI.

Bradley J. Monk, MD, FACS, FACOG: I love it. Ursula, you’ve been a leader, at your center, with molecular testing and profiling. What are you doing?

Ursula Matulonis, MD: Very similar to what Dave said, we have genetic counselors in our clinic. We have folks who typically see patients by cycle 2 or cycle 3. They’re embedded in our clinics. We are still doing germline testing first. We also have a research platform that tests about 400 different genes. So, we’re doing somatic testing as well. I really do see the field moving toward initial tumor testing and then reflexive germline testing. I think it’s great to see the genomic panel, beyond these panel tests. It would really broaden our view of the molecular underpinnings of the cancer, up front.

Bradley J. Monk, MD, FACS, FACOG: You’re testing those in house, right? Do you do in-house molecular testing or do you send it out?

Shannon N. Westin, MD, MPH: Our somatic testing is done in-house. But we do a send-out panel. We generally do our germline testing up front, and that includes a panel test for all of the things that Dr O’Malley mentioned. Then we lean on the somatic testing in the recurrent setting.

Bradley J. Monk, MD, FACS, FACOG: Do you send that out? Or do you do it in-house?

Shannon N. Westin, MD, MPH: We do it in-house.

Bradley J. Monk, MD, FACS, FACOG: Interesting.

Shannon N. Westin, MD, MPH: Yes. We have about a 400-gene panel as well.

Bradley J. Monk, MD, FACS, FACOG: Do you guys do in-house molecular testing?

Matthew Powell, MD: We do. One of the challenges we have is that we can’t all afford embedded genetic counselors in our clinics. We’ve really had a big transition. Now, I’m providing the counseling and I’m testing. Posttest counseling is handled by a genetic counselor. So, we know that everybody needs to be tested. That’s a no-brainer now.

Bradley J. Monk, MD, FACS, FACOG: I’m progressive like you. My nurse practitioners love to talk about this. They’re so passionate. My nurse practitioners are actually trained in genetic counseling.

Matthew Powell, MD: I think that’s an efficient model.

David O’Malley, MD: A paper was just published in the Journal of Clinical Oncology on direct counseling in both North America and Europe. Now, that’s only for BRCA. It becomes much more complicated when you’ve extended gene testing, particularly in the VUS (variant of uncertain significance).

Bradley J. Monk, MD, FACS, FACOG: I now send patients to the genetic counselor and he or she contacts every family member. My nurse practitioner’s not going to be able to contact the entire kindred, which is really important.

Matthew Powell, MD: If we talk about insurance implications, we do the right process. Then we get them tested. Our testing rate certainly goes way up when we do that. And they trust us.

Bradley J. Monk, MD, FACS, FACOG: I work in US Oncology. As I said, Arizona Oncology, particularly. We don’t have in-house testing. We send all of our germline testing and molecular profiling out. There are a number of very well-respected vendors. I think there are some subtle differences. We probably don’t have time to go into that. But whenever you do a next-generation sequencing protein, or RNA evaluation, the first question is, what do you report? In next-generation sequencing, you have the whole genome. You say 400, or 700, or 600 genes. Why not 200? Why not 800? So, what do you report? And once you make that decision, you have to correctly interpret it. I know that all of you are available for some of these interpretations. That’s really the fun part. There are some actionable mutations that are agnostic. You mentioned HRD and MSI, but there are some EGF–activating mutations and HER2.

Those appear to be tumor agnostic. So, it’s exciting. Everything that we’ve talked about has a foundation in clinical trials. We sat here and had a 45-minute discussion about a clinical trial in HIPEC, intraperitoneal chemotherapy, or neoadjuvant chemotherapy, bevacizumab, or immuno-oncology. I really appreciate your commitment. It’s a personal sacrifice. But it’s a sacrifice for the right reason because it helps patients.

Transcript Edited for Clarity 
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