Locally Advanced Pancreatic Cancer: Considering Resection

John Marshall, MD:When I first started, resectable pancreas cancer had a very strict definition. You had to have a tumor that wasn’t really involving anything and that you could easily get out. Surgeons are amazing with what they are doing now. The bar or the margin of what can be resected has expanded and expanded. Vascular reconstructions are routine nowadays. Our frontline chemotherapies cause these tumors to pull back so that when we go in to explore them, even though it looks like the tumor is around the blood vessel, it’s all scar tissue. It’s now technically feasible. I don’t think we have a strict set of rules. We have guidelines. We have parameters. Ultimately, we often end up going in and looking around to try to figure out whether, in fact, our imaging correlates with what we see. Is it technically possible, regardless of what the imaging shows? There is no strict rule about who’s going to the OR and who’s not, particularly with the advent of new chemotherapy.

Locally advanced pancreas cancer has been thought of as incurable or unresectable. But our new chemotherapy regimens have changed some of that. We have newer studies that suggest we do convert some of those folks to being resectable. That leaves us with the question of, what do we do about radiation? When I was young, a long time ago, the standard of care with a locally advanced patient was in fact to give radiation as the initial treatment. As our chemotherapies improved, it took a side priority to chemotherapy. But that really raises the question of should we bring it back, particularly in a preoperative setting? We have new technologies, too. We have the traditional radiation of a 5-week course, maybe with some capecitabine in conjunction, but we also have these new stereotactic radiation methods, CyberKnife, which can deliver a very effective dose of radiation over the course of just a few days. My bias is that there is a role for some preoperative radiation in locally advanced pancreas cancers that respond to chemotherapy, just as in the patient in our case. After an initial response to chemotherapy, I think preoperatively giving some radiation to further improve our chances of resectability is an appropriate step.

You’re faced with a patient with locally advanced pancreas cancer hoping you might be able to get the patient to surgery. You’ve got 2 basic recipes for chemotherapy today. You have FOLFIRINOX, and you have gemcitabine/Abraxane, or gemcitabine/nab-paclitaxel. We have somewhat of a bias that FOLFIRINOX is the better, more appropriate regimen, but we all know that some patients respond to FOLFIRINOX and some people respond to gemcitabine/nab-paclitaxel. And so, when we’re sitting there looking at the patient, we’re guessing, pure and simple. We know that the 3-drug cocktail is pretty spicy and the 2-drug cocktail is pretty easy, or relatively easy. We don’t want to lose our window to cure patients, and so our bias has generally been to use the FOLFIRINOX regimen in this kind of patient for whom we have such noble aspirations. But I think more and more, we are seeing that the 2-drug cocktail can likewise convert patients to being resectable.

Transcript edited for clarity.

May 2017

• A 64-year-old female was diagnosed with locally advanced pancreatic adenocarcinoma and referred for consultation at a high-volume center
• CT with contrast showed a 2.8-cm mass in the pancreatic body, invading the common hepatic, celiac, and splenic arteries, with abutment more than 180° to the superior mesenteric artery (SMA) but no encasement
• Staging laparoscopy showed no distant metastasis; peritoneal washing cytology showed no malignant cells
• She received FOLFIRINOX followed by capecitabine and concurrent RT

December 2017

• Six months after the initial treatment, the tumor size had decreased to 1.2 cm, and abutment to the main artery was diminished but still detectable
• She underwent distal pancreatectomy with celiac artery resection
• Histopathology showed fibrous changes around the celiac artery; Evans grade IIb
• No evidence of residual tumor at the periphery; R0