Meet The Professors: Pancreatic Cancer Edition, 2016 - Video 22A021101: Preoperative modified FOLFIRINOX followed by capecitabine-based chemoradiation therapy for borderline-resectable pancreatic cancer
5:50 minutes.
TRANSCRIPTION:
DR TEMPERO: I thought this study was important for the simple reason that it was feasible and it was completed. These are complicated studies to do. They involve multiple sites. I wouldn’t have designed this study this way, but the fact that it was done at multiple sites with good quality control, they were able to get everybody through all of the treatment, to get them to surgery and postoperative adjuvant therapy, I thought it, from an experimental point of view, the fact that you can do this just set us up to be able to do these kinds of trials in a larger, more definitive way. DR LOVE: So I’m curious in this study, how do they define, quote, borderline resectable? DR TEMPERO: So borderline resectable is probably — would take me about an hour to actually explain that. But it grew out of the understanding — and this was early on in my tenure as Chair of the National Comprehensive Cancer Network Pancreatic Cancer Panel. Early on, I recognized that the surgeons around the table had different approaches, shall we say, to what they thought was resectable and what wasn’t resectable. And it turns out that what the real concern was, that there were a set of patients that they felt had a high risk of a positive margin. And so I asked them basically to define those patients and tell us what they were, which led to the first definition of borderline resectable disease. That definition has subsequently been evolved a bit with more consensus in the community. But what it really means is that the patient has a high risk of a positive margin. And this is based usually on some degree of vascular involvement, encasement, abutment. DR LOVE: Hmm. So it’s more of a statistical thing? DR TEMPERO: It’s a theoretical. It’s really theoretical. DR LOVE: What are the trials right now that are kind of incorporating this into their design? DR TEMPERO: There’s 2 trials in the cooperative groups that I think are very, very important. One is in borderline resectable disease, in which all patients are getting FOLFIRINOX up front. Then they’re being randomized to chemoradiation versus continued chemotherapy. And this is really going to answer the question about whether chemoradiation is an important part of the management of this disease. It’s not at all clear that it is, but this will answer that question. DR LOVE: And you brought up the potential complications of radiation therapy. Tony, for practical purposes right now, what are you doing in these patients outside a trial? DR BEKAII-SAAB: So it’s a hodgepodge of things. So for borderline resectable patients, patients do receive FOLFIRINOX for about 2 to 3 months, not quite 4 months. I think you reach your maximum response in 2 to 3 months. And then after that, really it’s a multidisciplinary effort. You get with the surgeon and the radiation oncologists and decide. If the surgeon says, “I see a clear-cut response. I’m comfortable taking the patient to surgery,” that’s what the patients are doing, so no radiation. DR LOVE: What about radiation? No radiation. DR BEKAII-SAAB: Radiation only if — so really, the surgeon is dictating whether they think they need the radiation to clear up the margins a little bit more. With clear responses, most of the time — and, in fact, we actually published the results of our own experience with about 40 patients. For the borderline resectable patients, we only needed to give radiation for about 44% of the patients, yet we achieved 86% R0 resection rate. So it’s clear that radiation is limited in its utility in this setting, but I think the study, randomizing patients clearly to radiation versus not, will help with some of the nuances of this. I still think, even if the study says there’s no role for radiation added to FOLFIRINOX, that there’s still a subset of patients where there is a gray zone around the margins that may still benefit from radiation. DR LOVE: So just to drill down a little bit more about what’s really happening when you, quote, convert somebody, say, from borderline resectable to resectable or R1/0 resection or not in liver mets in colon cancer — and Tony and I have done a lot of programs on this — I kind of have an intuitive understanding that maybe there are compressing vessels. You pull them back. You’re not sterilizing anything with chemotherapy. Here, it’s almost kind of hard for me to understand what’s going on. If the tumor’s encasing around it or invading into vessels, is the idea that chemotherapy really makes it go away? Does it pull back? Why are they becoming resectable? DR TEMPERO: First of all, most cases of encasement are never resectable. Short encasement can be resectable with a graft. DR LOVE: Short encasement. DR BEKAII-SAAB: Short segment. DR TEMPERO: Short segment. I’m sorry — with a graft. And you’re quite right. I mean, the goal of therapy is not to, like — it’s not like a balloon that you shrink it down and then you just pluck it out because it’s infiltrative, right? It’s infiltrative everywhere its touching. DR LOVE: I mean, does it really work? DR TEMPERO: So yes, it does work. And we just published our retrospective study, similar to Tony’s, except we had no radiation. And our R0 resection rate was 90%. DR LOVE: But, I mean, was that a randomized study? DR TEMPERO: No, it was not a randomized study. That’s why these studies are so important. |