This afternoon I gave a talk at the IGILUC Conference on pre-operative chemoradiation therapy for pancreatic cancer. I was trying to impress upon the audience that there is a role for chemoradiation in pancreatic cancer and the magnitude of benefit is more as one goes from clearly resectable patients to potentially resectable to borderline resectable patients. As one goes along that continuum the magnitude of benefit from chemoradiation is higher and it stems from a number of factors. First, the intent is to see if we can convert some of these borderline resectable patients into clearly better resectable patients by getting a cleaner resection margin by giving them chemoradiation. The second is that we use this chemoradiation time as a way of enriching for patients who truly have localised disease and don’t have metastatic disease. So if they had some metastatic disease to begin with that wasn’t evident on the best imaging that we had, during the chemoradiation if that disease declares itself then you’ve precluded or you’ve spared them the need for a big surgery where there’s no benefit from the surgery.
We also talked about how, in the pre-operative setting, you’re treating a tumour that’s well oxygenated and more sensitive to radiation. The likelihood that you can downstage these tumours the greater chance that you get a resection margin that’s negative by giving pre-operative treatment. Using this stress tester chemoradiation to see if patients are going to respond and not wither away because their performance status deteriorates and then backload instead of frontloading the most complicated part of treatment, the surgery. Backload it after the chemoradiation in the subset of patients who can tolerate the chemoradiation and are likely to declare themselves as truly localised and not have metastatic disease pop up.
We went through the ways of doing this and I also talked about trying to give a slightly higher dose to the tumour, possibly to the vascular margin, to increase the likelihood of getting a clean resection margin. We chatted a little bit about trying to not ding the spleen, if you will, and reduce the lymphocyte count because that has been shown to correlate with poor outcomes in pancreatic cancer. Just by aiming beams away from the spleen or using IMRT or stereotactic radiation one can reduce the likelihood of hitting the spleen and thereby reduce the likelihood of lymphopenia. That was the gist of what I spoke about.
What does the future look like in this area?
There is increasing awareness about the benefit of pre-operative chemoradiation. There’s increasing acceptance in the community that this is a logical treatment approach. There has always been some anxiety about leaving the tumour in the body while doing chemoradiation but more and more people recognise that this is a way to get the highest likelihood of not leaving behind tumour at the time of surgery because if you left behind tumour at the time of surgery it’s as good as not having done the surgery. So it’s a huge disservice that you do to the patient by going to the OR and leaving behind a positive margin. So by doing this hopefully we will reduce that likelihood.
We also mentioned that that doesn’t lead to increased risk of anastomotic leaks or fistulas or cysts developing because the complication rate is lower when you give chemoradiation before surgery than if you went straight to surgery.
So there will be greater and greater adoption of this as more of a standard of care approach for clearly borderline resectable patients and maybe some potentially resectable patients as well. There’s an ongoing study that’s looking at SBRT in this setting where patients get chemotherapy followed by surgery or chemotherapy followed by SBRT and then surgery. This is an ALLIANCE trial which has accrued most of the patients that they need to accrue so we should be hearing soon as to what that showed in terms of benefit of radiation.
This is an ideal cohort or an ideal setting in which we can test new strategies because you have a biopsy before treatment, you have the surgical sample and you have this intervening time when you can do chemo, chemoradiation and look for some changes that you’d like to achieve either with a new biologic or some additional therapy. You have pre and post tissue accessible which is not easy in pancreatic cancer to attain. So this is probably the way we will be going in the future. In our experience, if we take about a hundred patients with borderline resectable pancreatic cancer, subject them to chemoradiation, in the old days 40% of them would go to surgery, in the more recent updates it’s more than 60% of patients who can go to surgery. Whenever they go to surgery the likelihood of negative margin is 94% so it’s a very high chance that we’re selecting the right subset of patients to go to surgery and we don’t leave them with a positive margin.
If one were to push the envelope a little further one could take more of these patients, a slightly higher risk of leaving behind a positive margin, but the impact of that potential positive margin may not be as bad as having a positive margin right at the time of surgery because these are cells that are still there in the surgical specimen but maybe they are on their way to dying and responding to treatment, you just went in and took the tumour out a week too early or two weeks too early. So there’s still the chance that we can move the needle further by taking more patients to surgery with this approach. So there’s lots of room for excitement.