As far as standard of care, GFunk pretty much spoke for me on the issue. I'll add a few thoughts:
"First of all, the standard of care for locally advanced H&N is (IMO) dose-painted IMRT with concurrent cisplatin x3"--Solid answer. The one respect in which this differs from the preponderance of clinical practice is the chemo schedule. Many have adopted a standard of 30 mg/m^2 weekly, rather than the 100 mg/m^2 days 1, 22, and 43. To my knowledge, this schedule hasn't been rigorously tested in prospective trials, although there is certainly a robust cohort of retrospective outcomes reported. One kind of obscure trial tested 20mg/m^2 weekly and was actually negative (Haselow et al., 1990). To be clear, I'm fine with the once weekly approach despite the lack of randomized data. Certainly, there are those who would say "If you're going to use the RCT data to support your treatment approach, you have to treat the way the trials did". Fair enough, but how many of those pivotal trials used IMRT planning? That would be none.
Let's do what we did in the prostate thread and apply a little context and thought to the process. The major benefit of concurrent chemo is to potentiate the effect of radiation, as evidenced in the 2009 MACH-NC meta-analysis. If this is the case, doesn't lower but more frequent dosing of chemo make sense from a pharmacokinetics standpoint? I'm hunting for the reference, but I believe that one positive chemoRT trial used 5mg/m^2 daily, but I think this isn't likely to be widely adopted. I fully agree with the comments regarding both the Bonner trial and 0522. The unfortunate reality in modern trial design is that there is a big incentive to come up with trials that are more likely to generate a positive result. A comparison of RT-cis vs RT-cetux would have a greater impact on clinical practice, but it is also less likely to generate a definitive result. I doubt a non-inferiority trial of this sort would have cemented FDA approval of cetuximab the way the Bonner trial did. As an aside, I find that nearly everyone in my community uses concurrent cetuximab for SCCHN unless the patient's insurance doesn't pay for it.
As far as induction chemo goes, I've previously been open to using it as TarHeel implied, primarily on big T4 or N3 tumors, but I've certainly struggled with the concept of field reduction. I've never reduced a field for a T4 lesion even with a good response to chemo, but I have done so in N3 necks simply because the compartment at risk is physically smaller. When comparing before and after CTs, and observing that your pre-chemo GTV would now extend outside the patients neck, I think even the docs in the consensus panel would give you the green light to pare the field down. My main concern with
widespread adoption of induction chemo for SCCHN is three-fold:
1) There is no evidence that it is superior to concurrent chemo, and actually data from the MACH-NC (albeit via indirect comparison) that concurrent chemo is superior in terms of overall survival. As alluded to earlier, the Vermorken and Posner trials are touting one induction regimen as superior to other without addressing the question of why one should do induction in the first place.
2) If one buys in to the concept of accelerated repopulation in SCCHN (I do), then delaying definitive local therapy seems like a bad idea.
3) The attrition rate for induction chemo has been commented upon. In the Posner trial, nearly 1/3 of patients discontinued treatment dring the induction phase, half for adverse events and half due to progressive disease. While the therapeutic nihilist in me sees some value in allowing biologically aggressive disease to "declare itself" during induction, I can't help but wonder if we might have altered outcomes in some of those patients by early initiation of local therapy.
Once again, great exchange!
