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Borderline Resectable Pancreatic Cancer

Panelists: Edward Kim, MD, University of California Davis; John Marshall, MD, Georgetown University Lombardi Comprehensive Cancer Center; Paul Oberstein, MD, NYU Langone Perlmutter Cancer Center; Allyson Ocean, MD, Weill Cornell Medical College; Shubham Pant, MD, The University of Texas MD Anderson Cancer Center
Published: Friday, Aug 09, 2019



Transcript:

John Marshall, MD: Let’s just remind everybody off-script: You have a patient with pancreatic cancer. They get diagnosed by a scan done for some reason. What’s the proper staging for this disease? What testing are you doing at baseline?

Shubham Pant, MD: At baseline we do a pancreatic protocol CT [computed tomography] scan in which we look at the vessels. Pancreatic cancer patients always ask about staging. I think the big thing in pancreatic cancer is the association with the blood vessels.

John Marshall, MD: A good CT. Is that where everybody is? MRIs [magnetic resonance imaging] or no?

Shubham Pant, MD: A good CT.

Allyson Ocean, MD: Along with an endoscopic ultrasound [EUS].

John Marshall, MD: EUS, particularly for head masses, right?

Shubham Pant, MD: They usually get it for a biopsy and for diagnosis.

John Marshall, MD: Often that’s not enough for molecular profiling, but sometimes it is.

Shubham Pant, MD: The data that we have for molecular profiling is mostly in the metastatic setting. In the resectable setting, we really still don’t have the data to say that we should be doing molecular profiling, because it’s mostly in the metastatic setting.

John Marshall, MD: If it was your cancer, would you want to know?

Shubham Pant, MD: Frankly, no. If it’s resectable, I wouldn’t do molecular profiling on the tumor.

Paul Oberstein, MD: Just to throw it in there, we do CT, and I do chest as well, to look for metastasis. There’s a growing value to doing PET [positron emission tomography] scans. We don’t do them routinely, and I don’t think insurance pays for them routinely, but there’s more and more evidence showing that it’s actually a good predictor for response to therapy.

John Marshall, MD: Yes, you just got me an 800-call into Aetna to get that approved, right?

Paul Oberstein, MD: We don’t do it outside clinical trials. When we’re doing some trials, we’re actually using that as 1 of the markers.

John Marshall, MD: But as a standard, you’re saying, “Not necessarily.”

Paul Oberstein, MD: I don’t think it’s the standard of care.

John Marshall, MD: Let’s say you have that little ditzel. There’s always something on the liver that you can’t really tell what it is—that lung nodule. Is that a deal breaker? Do you go further? Is that when you get your PET?

Paul Oberstein, MD: MRIs are really what we use for the liver, and that’s where most of the questions come up.

John Marshall, MD: CT, EUS, blood testing, and get a baseline CA19-9 [carbohydrate antigen 19-9]. Is everybody doing some sort of tumor marker routinely?

Shubham Pant, MD: Yes.

Allyson Ocean, MD: CEA [carcinoembryonic antigen].

John Marshall, MD: CEA?

Edward Kim, MD: I don’t know what others’ experiences are, but our surgeons see some inherent value in the CA19-9 cutoff over 1000.

John Marshall, MD: Yes.

Edward Kim, MD: I’m not sure where that comes from, but that seems to be an additional piece.

John Marshall, MD: They want to give chemotherapy then.

Edward Kim, MD: Yes, and then they’re more inclined.

Shubham Pant, MD: Even lower than that—if you look at even a 300 cutoff or something. Again, everybody is different. I do think if you have a CA19-9 of anything north of 180—most of these adjuvant trials that are there did not allow patients to go on with a higher CA19-9. Hence, maybe they had better survival than a regular pancreatic cancer patient. I think it’s really important, but if you have a really high CA19-9, you’re looking at systemic disease. In the thousands there is some evidence of systemic disease. You just cannot see that at this time.

John Marshall, MD: Back pain, high CA19-9—these are bad markers. Allyson, I think this whole discussion is easiest with some sort of borderline tumor, because it’s easy to make the choice to get to chemotherapy first. Give me a little sense about what you guys are doing outside a clinical trial in somebody with a borderline resectable tumor.

Allyson Ocean, MD: We determine borderline or not based on the intersection between the tumor and the fat planes around the major arteries. If it’s clear in the celiac, SMA [superior mesenteric artery], or hepatic artery, they go right to surgery. If it’s not that and it’s not metastatic—it’s borderline—we are treating first with chemotherapy, mostly using FOLFIRINOX [folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin], followed by radiation. We had the ALLIANCE study opened, so we enrolled to that, but that just closed.

John Marshall, MD: Chemo for a few months? How long were you giving it?

Allyson Ocean, MD: Three months.

John Marshall, MD: Three months. Then what kind of radiation are you doing? Is this SBRT [stereotactic body radiation therapy]? Is it short-course?

Allyson Ocean, MD: Most patients go for SBRT if we can get it approved. If not, then we do a short course. But for most of our patients, we can get SBRT approved.

John Marshall, MD: You’ve got to get a proton; that’s the only way to go. We just proton everything. I proton my lunch when it’s cold to warm it up nowadays.

Edward Kim, MD: You mentioned the ALLIANCE. The SBRT arm closed because of lack of evidence of benefit.

Paul Oberstein, MD: It triggered a futility, but it didn’t…

Shubham Pant, MD: Yes, but there are nuances to that, obviously, about different sites and everything. Is everybody getting the same-quality SBRT and everything? Again, I think the radiation question is a debatable question.

John Marshall, MD: Is it automatic? Let me interrupt. Often, you do your 3 months, 6 cycles of chemotherapy, and you do another scan.

Allyson Ocean, MD: Sometimes our responses are so good with FOLFIRINOX, so it’s not automatic.

John Marshall, MD: If they look at that point, you go to the OR [operating room]?

Allyson Ocean, MD: Right.

John Marshall, MD: If they’re still borderline, that’s a patient in whom you might do some radiation. Is that fair?

Allyson Ocean, MD: Correct.

John Marshall, MD: It’s sort of a stepwise—does that patient then go to the OR for exploration, even in the absence of regression?

Shubham Pant, MD: It depends on a lot of factors, so that’s where the multidisciplinary tumor board comes out. Really, that’s a very specific patient-related question. It depends what you’ve done with the CA19-9.

John Marshall, MD: The important thing is that we think about it, right? You might say in the end, no, but even in the absence of a response, I think we’ve all seen these scenarios in which the surgeon goes in there, it actually is much freer from the vessels than the imaging told us. My only point there is that it’s not unreasonable to explore that patient.

Paul Oberstein, MD: There is a lot of potential risk in that surgery. For all the good cases where you go in and it’s clear, you have to remember, there are patients who are doing well with chemotherapy and may have months if not years of survival, who go in and have a surgery and lose that.

John Marshall, MD: Ed?

Edward Kim, MD: There is also the timing issue of radiation and surgery. There is a window of time after radiation, so I think it is important to strategize when you pull the trigger for doing radiation. If you’re going to do radiation, understand that if you’re ever going to explore the patient, that’s going to have to come within a window. You want to be close to a potential resection, and then, I would say we would want to explore the patient even if you don’t see a clear change, because there’s clear evidence that what you see on a scan is not necessarily what you get.

Shubham Pant, MD: I completely agree with that. You’re right. The scans can be fairly deceptive when you’re looking at the biology of these patients with pancreatic cancer. You look at clinical science—how those patients are doing, how they’ve done on the chemotherapy, if you had a CA19-9 to follow and that’s dipped—and you have much more confidence going in and looking at those patients surgically. You use all these other parameters when you’re trying to judge who can go or not.

Transcript Edited for Clarity

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Transcript:

John Marshall, MD: Let’s just remind everybody off-script: You have a patient with pancreatic cancer. They get diagnosed by a scan done for some reason. What’s the proper staging for this disease? What testing are you doing at baseline?

Shubham Pant, MD: At baseline we do a pancreatic protocol CT [computed tomography] scan in which we look at the vessels. Pancreatic cancer patients always ask about staging. I think the big thing in pancreatic cancer is the association with the blood vessels.

John Marshall, MD: A good CT. Is that where everybody is? MRIs [magnetic resonance imaging] or no?

Shubham Pant, MD: A good CT.

Allyson Ocean, MD: Along with an endoscopic ultrasound [EUS].

John Marshall, MD: EUS, particularly for head masses, right?

Shubham Pant, MD: They usually get it for a biopsy and for diagnosis.

John Marshall, MD: Often that’s not enough for molecular profiling, but sometimes it is.

Shubham Pant, MD: The data that we have for molecular profiling is mostly in the metastatic setting. In the resectable setting, we really still don’t have the data to say that we should be doing molecular profiling, because it’s mostly in the metastatic setting.

John Marshall, MD: If it was your cancer, would you want to know?

Shubham Pant, MD: Frankly, no. If it’s resectable, I wouldn’t do molecular profiling on the tumor.

Paul Oberstein, MD: Just to throw it in there, we do CT, and I do chest as well, to look for metastasis. There’s a growing value to doing PET [positron emission tomography] scans. We don’t do them routinely, and I don’t think insurance pays for them routinely, but there’s more and more evidence showing that it’s actually a good predictor for response to therapy.

John Marshall, MD: Yes, you just got me an 800-call into Aetna to get that approved, right?

Paul Oberstein, MD: We don’t do it outside clinical trials. When we’re doing some trials, we’re actually using that as 1 of the markers.

John Marshall, MD: But as a standard, you’re saying, “Not necessarily.”

Paul Oberstein, MD: I don’t think it’s the standard of care.

John Marshall, MD: Let’s say you have that little ditzel. There’s always something on the liver that you can’t really tell what it is—that lung nodule. Is that a deal breaker? Do you go further? Is that when you get your PET?

Paul Oberstein, MD: MRIs are really what we use for the liver, and that’s where most of the questions come up.

John Marshall, MD: CT, EUS, blood testing, and get a baseline CA19-9 [carbohydrate antigen 19-9]. Is everybody doing some sort of tumor marker routinely?

Shubham Pant, MD: Yes.

Allyson Ocean, MD: CEA [carcinoembryonic antigen].

John Marshall, MD: CEA?

Edward Kim, MD: I don’t know what others’ experiences are, but our surgeons see some inherent value in the CA19-9 cutoff over 1000.

John Marshall, MD: Yes.

Edward Kim, MD: I’m not sure where that comes from, but that seems to be an additional piece.

John Marshall, MD: They want to give chemotherapy then.

Edward Kim, MD: Yes, and then they’re more inclined.

Shubham Pant, MD: Even lower than that—if you look at even a 300 cutoff or something. Again, everybody is different. I do think if you have a CA19-9 of anything north of 180—most of these adjuvant trials that are there did not allow patients to go on with a higher CA19-9. Hence, maybe they had better survival than a regular pancreatic cancer patient. I think it’s really important, but if you have a really high CA19-9, you’re looking at systemic disease. In the thousands there is some evidence of systemic disease. You just cannot see that at this time.

John Marshall, MD: Back pain, high CA19-9—these are bad markers. Allyson, I think this whole discussion is easiest with some sort of borderline tumor, because it’s easy to make the choice to get to chemotherapy first. Give me a little sense about what you guys are doing outside a clinical trial in somebody with a borderline resectable tumor.

Allyson Ocean, MD: We determine borderline or not based on the intersection between the tumor and the fat planes around the major arteries. If it’s clear in the celiac, SMA [superior mesenteric artery], or hepatic artery, they go right to surgery. If it’s not that and it’s not metastatic—it’s borderline—we are treating first with chemotherapy, mostly using FOLFIRINOX [folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin], followed by radiation. We had the ALLIANCE study opened, so we enrolled to that, but that just closed.

John Marshall, MD: Chemo for a few months? How long were you giving it?

Allyson Ocean, MD: Three months.

John Marshall, MD: Three months. Then what kind of radiation are you doing? Is this SBRT [stereotactic body radiation therapy]? Is it short-course?

Allyson Ocean, MD: Most patients go for SBRT if we can get it approved. If not, then we do a short course. But for most of our patients, we can get SBRT approved.

John Marshall, MD: You’ve got to get a proton; that’s the only way to go. We just proton everything. I proton my lunch when it’s cold to warm it up nowadays.

Edward Kim, MD: You mentioned the ALLIANCE. The SBRT arm closed because of lack of evidence of benefit.

Paul Oberstein, MD: It triggered a futility, but it didn’t…

Shubham Pant, MD: Yes, but there are nuances to that, obviously, about different sites and everything. Is everybody getting the same-quality SBRT and everything? Again, I think the radiation question is a debatable question.

John Marshall, MD: Is it automatic? Let me interrupt. Often, you do your 3 months, 6 cycles of chemotherapy, and you do another scan.

Allyson Ocean, MD: Sometimes our responses are so good with FOLFIRINOX, so it’s not automatic.

John Marshall, MD: If they look at that point, you go to the OR [operating room]?

Allyson Ocean, MD: Right.

John Marshall, MD: If they’re still borderline, that’s a patient in whom you might do some radiation. Is that fair?

Allyson Ocean, MD: Correct.

John Marshall, MD: It’s sort of a stepwise—does that patient then go to the OR for exploration, even in the absence of regression?

Shubham Pant, MD: It depends on a lot of factors, so that’s where the multidisciplinary tumor board comes out. Really, that’s a very specific patient-related question. It depends what you’ve done with the CA19-9.

John Marshall, MD: The important thing is that we think about it, right? You might say in the end, no, but even in the absence of a response, I think we’ve all seen these scenarios in which the surgeon goes in there, it actually is much freer from the vessels than the imaging told us. My only point there is that it’s not unreasonable to explore that patient.

Paul Oberstein, MD: There is a lot of potential risk in that surgery. For all the good cases where you go in and it’s clear, you have to remember, there are patients who are doing well with chemotherapy and may have months if not years of survival, who go in and have a surgery and lose that.

John Marshall, MD: Ed?

Edward Kim, MD: There is also the timing issue of radiation and surgery. There is a window of time after radiation, so I think it is important to strategize when you pull the trigger for doing radiation. If you’re going to do radiation, understand that if you’re ever going to explore the patient, that’s going to have to come within a window. You want to be close to a potential resection, and then, I would say we would want to explore the patient even if you don’t see a clear change, because there’s clear evidence that what you see on a scan is not necessarily what you get.

Shubham Pant, MD: I completely agree with that. You’re right. The scans can be fairly deceptive when you’re looking at the biology of these patients with pancreatic cancer. You look at clinical science—how those patients are doing, how they’ve done on the chemotherapy, if you had a CA19-9 to follow and that’s dipped—and you have much more confidence going in and looking at those patients surgically. You use all these other parameters when you’re trying to judge who can go or not.

Transcript Edited for Clarity
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