Chemoradiation in head and neck cancer and the need for big cancer centres
Prof June Corry - Peter MacCallum Cancer Centre, Melbourne, Australia
My brief was to talk about chemoradiation in oral cavity cancer and when I saw the brief there were about four speakers all pretty much speaking the same thing so I said, “No, this is too boring. I’m going to change my topic to the devil in the detail of chemoradiation in oral cavity cancer.” Because I think people talk about chemotherapy and radiotherapy as if it’s the same everywhere in a completely universal treatment delivery. We know from our Head Start study and also from the recent publication from the RTOG study on centre and volume that there’s a 20% difference in outcomes in head and neck cancer patients treated in a big centre compared to little centres, 20% difference in overall survival. So I think that’s huge and then I was trying to really delve into some of the detail of why this might be the case.
Usually we’re aiming for a 10% difference with all different treatment regimen comparisons in randomised controlled trials. But that’s actually not the focus of my talk, I guess, today. Tomorrow my talk is really trying to look at details of radiotherapy and details of chemotherapy. So, for example, postoperative radiotherapy is indicated in certain conditions like close margins and yet there is no consensus in surgery for what constitutes a close margin. If you look at the RTOG trials that were published in The New England Journal in 2010 now, they used a close margin as right up to the edge of the specimen whereas the EORTC use less than 5mm. So such an important topic in head and neck cancer, you’ve got no consensus.
Similarly in chemotherapy people talk about that as if it’s a uniform treatment but there is a lot of variation in the delivery of chemotherapy and intensive chemotherapy. Again, even though the patient may be planned to have three cycles of chemotherapy with their radiotherapy, in 60% of cases they only get two, for example. So I think there’s a lot of variation in these sorts of details that may be important.
Also in radiotherapy there are a lot of differences in technique. For example, in the oral cavity you can treat unilaterally or bilaterally and the doses vary and techniques vary. All those factors can be important and often they’re too subtle to test in a controlled trial. Of course in many important aspects of medicine there’s no funding. Trials have become so expensive if you just want to look at a very useful basic clinical question, for example comparing high dose cisplatin in weeks 1, 4 and 7 with weekly cisplatin, the latter is used commonly because it’s less toxic, the total dose of cisplatin given over the period of time is the same and yet there won’t be a trial done on that because cisplatin is an old drug and there is no pharma money for it. So that’s another concern in clinical trials is that the trials get done to some extent dictated by the pharmaceutical companies and I think that’s something we’ve really got to be very strong about having investigator driven trials.
Do you think we need state-funded trials?
That’s clearly a cleaner product, in a sense, but the funding is tight everywhere and getting tighter. Trials are way too complex. If you look at the difference in a protocol now compared to fifteen years ago, just the volume of them is about six times as great. So I think the pendulum has to swing back a little bit to being not as complicated and not as expensive. We have to just work better with the pharmaceutical companies. They’re a great resource but we can find common goals to a common end without compromising our scientific integrity.
How do you think doctors should work with pharmaceutical companies?
A lot of the time you need collaboration. Often an important question is too difficult to answer in one centre, in any one centre. So by linking up with other centres you can get the answer much faster. So the collaboration between centres is important and that should be easier now in the technological world we live in, that someone has a good idea and other centres can join in to answer the question more quickly and more efficiently.
Sometimes that may just be a prospective study rather than a randomised controlled study but just looking at a prospective study, particularly in institutions who have a very different practice. For example, at ASCO there was a presentation on the UK trial of planned neck dissection versus observation after PET-CT. We wouldn’t have been able to participate in that study because we’ve been doing that for the last decade and so we haven’t been doing planned neck dissections. So that was great that that study was done but it just highlights the different practices that evolve. Whilst that was wonderful to have a randomised controlled trial confirming what we do, for example, there are many other areas where you may not get a randomised controlled trial up and running but you can still get useful scientific information from prospective databases, really.
What’s the take-home message?
Head and neck cancer is complex, it’s not common and it should be centralised in big head and neck cancer centres. The smaller centres should have a link to them so that there can be appropriate triaging of cases that can be treated locally versus those that should be treated at bigger centres.
