Role of Adjuvant Radiation Therapy in Pancreas Cancer
Panelists: Johanna C. Bendell, MD, Sarah Cannon Research Institute; Winson Y. Cheung, MD, MPH, University of Calgary and CancerControl Alberta; Manuel Hidalgo, MD, PhD, Harvard Medical School and Beth Israel Deaconess Medical Center; Ramesh K. Ramanathan, MD, Mayo Clinic; Tanios Bekaii-Saab, MD, FACP, Mayo Clinic; Thomas Seufferlein, MD, University of Ulm
Johanna C. Bendell, MD: We’ve heard everybody naysaying radiation. My radiation oncologist is so kind, and I wince every time I tell him in the tumor board, “No, I wouldn’t use radiation.” Tony, you have some very strong feelings about radiation. Can you tell us a little bit about them? I think they’re actually all of our same feelings as well.
Tanios Bekaii-Saab, MD, FACP: Yes. My feelings are, you do what’s best for the patient and take the best evidence into account. And radiation is not, as a lot of our radiation colleagues would like to think, innocuous. And it’s very expensive. There’s absolutely zero evidence right now that it has value.
In fact, the other argument that I keep on hearing is, “Well, how about R1 resections?” These are the patients who have little cells floating around. These are the patients who are actually more likely to be metastatic than the R0 resections. And so, I think if we look at the cumulative data, clearly there’s a study that says radiation may worsen the outcome. There are a lot of issues with that study. What the study does show is that chemotherapy improves outcome and radiation does not add value.
Then, we look at the cumulative evidence beyond that point. If you look at the risk of locoregional recurrence across all studies that included radiation and those that did not, they all fall within the same line. There may be a little bit of an advantage for local recurrence with radiation, but locoregionally, it’s about the same. It’s a wash. Survival, no improvement. Cost, more. Toxicity, more. At this point in time, there’s no indication for radiation (whether it’s for R0 or R1 resection). Hopefully, we’ll never see an R2 resection. There’s no role for radiation. There is only a role for chemotherapy.
There’s a study, RTOG 0848, that is struggling a little bit in terms of accrual. But it raises an interesting question. Can we, after we maximize adjuvant chemotherapy—meaning 5, 6 months of gemcitabine or gemcitabine/capecitabine, now—randomize patients to receive consolidative radiation or finish the chemotherapy? That study may give us a hint, at least, as to whether there is a role for radiation if you maximize systemic control. And again, not to downgrade the role of radiation, I think pancreas cancer remains a systemic disease. Until we have much more effective systemic regimens that control the systemic disease, there’s very little role for consolidative local procedures beyond surgery.
Johanna C. Bendell, MD: Ramesh, what about locally advanced pancreas cancer? That’s another place where we’ve seen radiation and some controversy between studies.
Ramesh K. Ramanathan, MD: In locally advanced disease, the LAP 07 study, which gave chemotherapy, first, and randomized patients to chemoradiation or continued chemotherapy, did not show a benefit in terms of impact on survival. Having said that, that study was with gemcitabine, not with FOLFIRINOX or gemcitabine/Abraxane. In my practice—again, this varies across the whole Mayo Clinic system that is spread across 3 different states—we obviously want to put them on a clinical trial, first. We do have some clinical trials with SBRT, with or without radiation. But I typically give chemotherapy. The LAPACT study, which I think we might talk about, showed that gemcitabine/Abraxane was a good reference regimen for locally advanced disease. After 4 to 6 months, I do consider radiation in some patients, especially if they have neuropathy. Then, they need to take a break from systemic chemotherapy.
Johanna C. Bendell, MD: And pain control, maybe?
Ramesh K. Ramanathan, MD: And for pain control. Exactly. There has to be a reason to do radiation. Not every single patient gets it.
Johanna C. Bendell, MD: Can you tell us about the LAPACT study?
Ramesh K. Ramanathan, MD: The LAPACT study was an industry-sponsored study for locally advanced pancreatic cancer. It enrolled about 100 patients. These patients were treated with gemcitabine and nab-paclitaxel for an induction period of 16 weeks, or 4 months, after which, at investigator discretion, they could get chemoradiation. Some were downstaging and could get surgery or continue with chemotherapy. I don’t remember the exact median survival. I don’t think it was reported. But the response rate was about 35%, which is impressive. I think about 30% of patients underwent surgical exploration and half of them were R0. So, that was encouraging. These were well-staged unresectable patients, to start with, and some of them were downstaged. So, I think gemcitabine/nab-paclitaxel certainly could be effective. Certainly, it’s a standard regimen for locally advanced disease. There are other studies with FOLFIRINOX, as well.