ONCAlert | Upfront Therapy for mRCC

Case 2: Newly Diagnosed Ovarian Cancer, gBRCA-Mutated

Targeted Oncology
Published Online:12:30 PM, Wed May 29, 2019


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Robert L. Coleman, MD: Let’s move on to another case, similar in nature, but I think it’ll take us a little bit further into that treatment paradigm. I’m going to have Shannon go ahead and just give us the context of this case, and then we’ll move on.

Shannon N. Westin, MD: Absolutely, no problem. So this is a 55-year-old African American woman who presented to her gynecologist complaining of abdominal pain, bloating, and weight gain—the usual suspects. Her past medical history is significant for mild hypertension, which is managed with hydrochlorothiazide, and type 2 diabetes, managed with metformin. She does have a family history of a mother who died of breast cancer at age 54, a maternal aunt who died of breast cancer at age 65, and a father who is alive with prostate cancer. Her physical exam is significant. Her abdomen has a bilateral lower-quadrant tenderness. She does have a positive fluid wave for ascites. Her pelvic exam demonstrates a large nodular mass on the left side.

Imaging is obtained. A CT [computed tomography scan] of the abdomen and pelvis demonstrates bilateral adnexal masses. The left side is 8 cm, and the right side is 3.5 cm. She has ascites and diffuse peritoneal carcinomatosis. She does undergo a paracentesis of 4.5 L, and her cytology is significant for high-grade adenocarcinoma. A core biopsy of the omentum is then obtained with a high-grade serous carcinoma. Her CA 125 [cancer antigen 125 level] was elevated, at 305 [U/mL].

She gets treatment. She undergoes an exploratory laparotomy followed with an omentectomy, BSO [bilateral salpingo-oophorectomy], appendectomy, and resection of all gross pelvic nodes. She does have microscopic residual disease of R1, and germline molecular testing demonstrates a BRCA1 alteration. Her final pathology is high-grade epithelial ovarian cancer involving the omentum, ovaries, and 5 lymph nodes.

Robert L. Coleman, MD: OK, great case. So let me ask you a couple of things. Obviously, her past medical history is screaming for a BRCA mutation.

Shannon N. Westin, MD: You think?

Robert L. Coleman, MD: She is young, with a huge family history. It’s almost overboard. But we looked at this, and I understand it has been looked at in many places as well. How reliable is the family history? In the first case, we had a 44-year-old with a negative family history. How reliable is family history?

Shannon N. Westin, MD: It’s fairly reliable, but you’re going to miss a big proportion. About 45% of patients who have a BRCA mutation don’t really have any significant family history and are not what we would consider of young age. So I think over age 50. It’s really interesting, so that’s why we really push for universal testing of all patients with any high-grade ovarian, fallopian, or peritoneal cancer.

Robert L. Coleman, MD: I was impressed by that. You know, back in the day we used to use these computer algorithms. We would bring in bits of family history, and then it would spit out a likelihood for a BRCA mutation. The ASCO [American Society of Clinical Oncology] policy at the time was that it had to be 10% or higher. And so we did a study and saw that in that group of patients that were predicted to be 10% or lower, we end up missing, like, 25% of our mutations.

Shannon N. Westin, MD: A huge proportion.

Robert L. Coleman, MD: And I think it just drills home the point regarding, as you mentioned, should we just be testing everybody? What’s your policy?

David O’Malley, MD: We are trying to test everybody with paired testing up front. So germline and somatic. You know, currently the commercially available entities will leave some holes and opportunities. So we’re trying to figure out the best way to do it. We’re actually in the process of changing our algorithm right now. If we have someone on neoadjuvant chemotherapy, we’ll often wait to test them until their surgery so that we’ll have more tissue rather than just a core biopsy. Because often the core biopsy is not adequate to perform somatic testing on. So we’re trying to test everybody with germline and somatic at the time of a surgical diagnosis.

Robert L. Coleman, MD: Surgical diagnosis, OK. Shannon, I was going to ask you this before, but let me get to it now. This patient had a paracentesis done, and then she had to have a core biopsy. First of all, why did she have to have both? And how confident are you on the cytology from the fluid?

Gregory Riedlinger, MD, PhD: This is probably another case where you’re going to stump me, but it sounds as if it’s something that you guys all know about. Maybe the paracentesis is unreliable. But obviously, as a pathologist, you always hear that the tissue is the issue. You always want more tissue. And so, ideally for the patient, you don’t want to have to go back in if you can do it off, you know, whatever is a paracentesis. And do the immunohistochemical work-up that way. For this patient, it seems that they have to go back in there for some reason and obtain another biopsy, and maybe they just didn’t have enough tissue up front. I’m not sure.

Shannon N. Westin, MD: It seems that a fair amount of times with the paracentesis alone, you just get an adenocarcinoma diagnosis, which is fine, because generally for the up-front treatment we’re going to treat these patients the same. But you know, personally, you want to know if they have clear cell or endometrioid, because there’s going to be such a different molecular milieu in those patients.
 
Susana M. Campos, MD, MPH: It’s become standard in our institution that we rely on the core biopsy.

David O’Malley, MD: The problem is the timeliness of the core biopsies from our interventional radiology colleagues. Now, I would want it on this patient because her CA 125 is only 350 [U/mL]. We don’t know what her CEA [carcinoembryonic antigen level] is, but it does bring up the question of a nonserous histology, which may or may not make any difference in your management, but it would be nice to know.

Robert L. Coleman, MD: Yeah, and I think that given they had such a large volume of ascites, I wonder if that was done just for that purpose. It was symptomatic. At the time of surgery, when we have a patient with a large amount of ascites, we’ll end up draining at the time that we do the incision, and then we go from there. But you know, however the sequence is done, they end up getting both the tissues and then ultimately make that diagnosis. But yeah, I was also thinking, with the 44-year-old, that clear cell or endometrioid are tumors I’d be thinking about as an alternative histology.

Transcript edited for clarity.
 


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Robert L. Coleman, MD: Let’s move on to another case, similar in nature, but I think it’ll take us a little bit further into that treatment paradigm. I’m going to have Shannon go ahead and just give us the context of this case, and then we’ll move on.

Shannon N. Westin, MD: Absolutely, no problem. So this is a 55-year-old African American woman who presented to her gynecologist complaining of abdominal pain, bloating, and weight gain—the usual suspects. Her past medical history is significant for mild hypertension, which is managed with hydrochlorothiazide, and type 2 diabetes, managed with metformin. She does have a family history of a mother who died of breast cancer at age 54, a maternal aunt who died of breast cancer at age 65, and a father who is alive with prostate cancer. Her physical exam is significant. Her abdomen has a bilateral lower-quadrant tenderness. She does have a positive fluid wave for ascites. Her pelvic exam demonstrates a large nodular mass on the left side.

Imaging is obtained. A CT [computed tomography scan] of the abdomen and pelvis demonstrates bilateral adnexal masses. The left side is 8 cm, and the right side is 3.5 cm. She has ascites and diffuse peritoneal carcinomatosis. She does undergo a paracentesis of 4.5 L, and her cytology is significant for high-grade adenocarcinoma. A core biopsy of the omentum is then obtained with a high-grade serous carcinoma. Her CA 125 [cancer antigen 125 level] was elevated, at 305 [U/mL].

She gets treatment. She undergoes an exploratory laparotomy followed with an omentectomy, BSO [bilateral salpingo-oophorectomy], appendectomy, and resection of all gross pelvic nodes. She does have microscopic residual disease of R1, and germline molecular testing demonstrates a BRCA1 alteration. Her final pathology is high-grade epithelial ovarian cancer involving the omentum, ovaries, and 5 lymph nodes.

Robert L. Coleman, MD: OK, great case. So let me ask you a couple of things. Obviously, her past medical history is screaming for a BRCA mutation.

Shannon N. Westin, MD: You think?

Robert L. Coleman, MD: She is young, with a huge family history. It’s almost overboard. But we looked at this, and I understand it has been looked at in many places as well. How reliable is the family history? In the first case, we had a 44-year-old with a negative family history. How reliable is family history?

Shannon N. Westin, MD: It’s fairly reliable, but you’re going to miss a big proportion. About 45% of patients who have a BRCA mutation don’t really have any significant family history and are not what we would consider of young age. So I think over age 50. It’s really interesting, so that’s why we really push for universal testing of all patients with any high-grade ovarian, fallopian, or peritoneal cancer.

Robert L. Coleman, MD: I was impressed by that. You know, back in the day we used to use these computer algorithms. We would bring in bits of family history, and then it would spit out a likelihood for a BRCA mutation. The ASCO [American Society of Clinical Oncology] policy at the time was that it had to be 10% or higher. And so we did a study and saw that in that group of patients that were predicted to be 10% or lower, we end up missing, like, 25% of our mutations.

Shannon N. Westin, MD: A huge proportion.

Robert L. Coleman, MD: And I think it just drills home the point regarding, as you mentioned, should we just be testing everybody? What’s your policy?

David O’Malley, MD: We are trying to test everybody with paired testing up front. So germline and somatic. You know, currently the commercially available entities will leave some holes and opportunities. So we’re trying to figure out the best way to do it. We’re actually in the process of changing our algorithm right now. If we have someone on neoadjuvant chemotherapy, we’ll often wait to test them until their surgery so that we’ll have more tissue rather than just a core biopsy. Because often the core biopsy is not adequate to perform somatic testing on. So we’re trying to test everybody with germline and somatic at the time of a surgical diagnosis.

Robert L. Coleman, MD: Surgical diagnosis, OK. Shannon, I was going to ask you this before, but let me get to it now. This patient had a paracentesis done, and then she had to have a core biopsy. First of all, why did she have to have both? And how confident are you on the cytology from the fluid?

Gregory Riedlinger, MD, PhD: This is probably another case where you’re going to stump me, but it sounds as if it’s something that you guys all know about. Maybe the paracentesis is unreliable. But obviously, as a pathologist, you always hear that the tissue is the issue. You always want more tissue. And so, ideally for the patient, you don’t want to have to go back in if you can do it off, you know, whatever is a paracentesis. And do the immunohistochemical work-up that way. For this patient, it seems that they have to go back in there for some reason and obtain another biopsy, and maybe they just didn’t have enough tissue up front. I’m not sure.

Shannon N. Westin, MD: It seems that a fair amount of times with the paracentesis alone, you just get an adenocarcinoma diagnosis, which is fine, because generally for the up-front treatment we’re going to treat these patients the same. But you know, personally, you want to know if they have clear cell or endometrioid, because there’s going to be such a different molecular milieu in those patients.
 
Susana M. Campos, MD, MPH: It’s become standard in our institution that we rely on the core biopsy.

David O’Malley, MD: The problem is the timeliness of the core biopsies from our interventional radiology colleagues. Now, I would want it on this patient because her CA 125 is only 350 [U/mL]. We don’t know what her CEA [carcinoembryonic antigen level] is, but it does bring up the question of a nonserous histology, which may or may not make any difference in your management, but it would be nice to know.

Robert L. Coleman, MD: Yeah, and I think that given they had such a large volume of ascites, I wonder if that was done just for that purpose. It was symptomatic. At the time of surgery, when we have a patient with a large amount of ascites, we’ll end up draining at the time that we do the incision, and then we go from there. But you know, however the sequence is done, they end up getting both the tissues and then ultimately make that diagnosis. But yeah, I was also thinking, with the 44-year-old, that clear cell or endometrioid are tumors I’d be thinking about as an alternative histology.

Transcript edited for clarity.
 
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