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Role of Surgery in Locally Advanced Pancreatic Cancer

Insights From:Thomas A. Abrams, MD, Harvard Medical School; Johanna Bendell, MD, Sarah Cannon Research Institute; George P. Kim, MD, 21st Century Oncology; Caio Rocha Lima, MD, Gibbs Cancer Center and Research Institute; Philip A. Philip, MD, PhD, FRCP, Wayne State University
Published: Tuesday, Apr 05, 2016


Transcript:

Johanna Bendell, MD:
Totally shifting gears, the patient that could potentially have a resection. When you see a patient, Caio, with an initial diagnosis of pancreas cancer, and it looks like it might be localized to the pancreas, what do you do?

Caio Rocha Lima, MD: The first thing is to review the films with a good radiologist and make sure that the CT scan is up to standard. And the pancreatic protocol CT scan with thin cuts through the pancreatic bed is paramount because the resectability is based on a relationship of the tumor with the surrounding blood vessels. We’re talking about the superior mesenteric artery, the hepatic artery, portal vein, and so forth. So having a good arterial phase and venous phase CAT scan is very important. Having that separation between patients that are borderline resectable is also very important to patients who are clearly unresectable.

The regimens we have today give us the opportunity, because of higher response rates, to have in mind and give the patient the hope that the borderline resectable patients can actually get to a higher resectability rate by being treated with systemic chemotherapy first. The trials are lacking. Unfortunately, we’re using common sense. We are using a leap of faith based on the phase III data, using response rates from phase III trials done in metastatic disease and importing them in the locally advanced disease and borderline resectable patients.

Measuring response is very difficult in patients with borderline and locally advanced disease, but having the good quality scans before and after the treatment can really aid in giving the patient a higher chance for resectability. Based on the response rates with FOLFIRINOX compared to gemcitabine, and with gemcitabine/nab-paclitaxel compared to gemcitabine in two phase III trials in metastatic disease, we feel that this is the way to go in patients with locally advanced disease. But clinical trials are coming, and we’re going to have these answers based on phase III data.

Johanna Bendell, MD: So the patient appears initially resectable. Straight to the operating room or do you give them some treatment beforehand?

Caio Rocha Lima, MD: We had that wonderful discussion this morning. I hope everybody on this panel had an opportunity to attend the view from the medical oncologist and the view from the surgeon. We’ve been through 30 years of history, if you take the initial trial of 5-FU/radiation in the adjuvant setting after resection. The Intergroup took 8 years to complete, showing that 5-FU/radiation was better than radiation therapy alone, keeping in mind that we believe that radiation may have not been the entire story. 5-FU has been established in the adjuvant setting since then. And the CONKO trials came along, and we still found out that the efficacy of gemcitabine is the same as 5-FU in the adjuvant setting.

So progress has not been made for many years. We know that there is a small benefit in the adjuvant setting, but we haven’t had a neoadjuvant trial done to date to tell us if this strategy is advantageous compared to adjuvant treatment. Having said that, it’s so appealing, the high chance of tumor relapse. Only 1 in 5 patients will be alive in five years if you take all-comers with R0 resections, and these patients fail often right away after surgery, so at least a neoadjuvant approach could aid in telling us the biology of the disease, taking away unnecessary surgery in a patient that has rapidly progressing disease that will fail right after Whipple or distal pancreatectomy.

Transcript Edited for Clarity
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Transcript:

Johanna Bendell, MD:
Totally shifting gears, the patient that could potentially have a resection. When you see a patient, Caio, with an initial diagnosis of pancreas cancer, and it looks like it might be localized to the pancreas, what do you do?

Caio Rocha Lima, MD: The first thing is to review the films with a good radiologist and make sure that the CT scan is up to standard. And the pancreatic protocol CT scan with thin cuts through the pancreatic bed is paramount because the resectability is based on a relationship of the tumor with the surrounding blood vessels. We’re talking about the superior mesenteric artery, the hepatic artery, portal vein, and so forth. So having a good arterial phase and venous phase CAT scan is very important. Having that separation between patients that are borderline resectable is also very important to patients who are clearly unresectable.

The regimens we have today give us the opportunity, because of higher response rates, to have in mind and give the patient the hope that the borderline resectable patients can actually get to a higher resectability rate by being treated with systemic chemotherapy first. The trials are lacking. Unfortunately, we’re using common sense. We are using a leap of faith based on the phase III data, using response rates from phase III trials done in metastatic disease and importing them in the locally advanced disease and borderline resectable patients.

Measuring response is very difficult in patients with borderline and locally advanced disease, but having the good quality scans before and after the treatment can really aid in giving the patient a higher chance for resectability. Based on the response rates with FOLFIRINOX compared to gemcitabine, and with gemcitabine/nab-paclitaxel compared to gemcitabine in two phase III trials in metastatic disease, we feel that this is the way to go in patients with locally advanced disease. But clinical trials are coming, and we’re going to have these answers based on phase III data.

Johanna Bendell, MD: So the patient appears initially resectable. Straight to the operating room or do you give them some treatment beforehand?

Caio Rocha Lima, MD: We had that wonderful discussion this morning. I hope everybody on this panel had an opportunity to attend the view from the medical oncologist and the view from the surgeon. We’ve been through 30 years of history, if you take the initial trial of 5-FU/radiation in the adjuvant setting after resection. The Intergroup took 8 years to complete, showing that 5-FU/radiation was better than radiation therapy alone, keeping in mind that we believe that radiation may have not been the entire story. 5-FU has been established in the adjuvant setting since then. And the CONKO trials came along, and we still found out that the efficacy of gemcitabine is the same as 5-FU in the adjuvant setting.

So progress has not been made for many years. We know that there is a small benefit in the adjuvant setting, but we haven’t had a neoadjuvant trial done to date to tell us if this strategy is advantageous compared to adjuvant treatment. Having said that, it’s so appealing, the high chance of tumor relapse. Only 1 in 5 patients will be alive in five years if you take all-comers with R0 resections, and these patients fail often right away after surgery, so at least a neoadjuvant approach could aid in telling us the biology of the disease, taking away unnecessary surgery in a patient that has rapidly progressing disease that will fail right after Whipple or distal pancreatectomy.

Transcript Edited for Clarity
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Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Integrating Novel Targeted Treatment Strategies to Advance Pancreatic Cancer CareNov 30, 20181.0
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