Very thoughtful commentary from the stellar Red Journal H&N editors! redjournal.org/article/S0360…

Updated results from JCOG 1008 (bolus versus weekly cis for postoperative CRT in high-risk patients) are out. Weekly cisplatin was clearly non-inferior and in fact numerically superior from both a disease- and safety- perspective. The clear winner. It will be very interesting to see the final results from HN009 (definitive CRT), especially in an HPV-negative population that may be at higher risk for treatment-related toxicity. ascopubs.org/doi/full/10.120…

It is a well-written editorial, and I agree with some parts and disagree with others. However, I am very disappointed that @TheLancet would choose a member of the scientific advisory board of IBA (a proton manufacturer) to write an editorial about protons. The author of an important commentary should not have such an intrinsic conflict of interest with the subject matter.

Come for the critically important data on protons for oropharyngeal cancer, stay for the beautifully written paper. TORPEdO is out, and it is fascinating and instructive. I will warn you upfront that this is a long thread, but there is a lot here to discuss! thelancet.com/journals/lance…

@Jdcramer has made a critical point below about KEYNOTE-689. The EFS rules in KN-689 require careful review to interpret these results.  A protocol-specific event was determined by blind independent central review (BICR), but if growth in the pre-surgical CT was perceived to be a “flare” (i.e. potential progression), surgery was supposed to proceed unless unresectable (protocol quote below). In order to be considered an event, repeat imaging was required 4-8 weeks later, and obviously if the tumor was still resectable the patient would go to surgery before then. This definition means it was extremely difficult to have an event before surgery, even if the tumor grew and the surgery was more extensive than initially anticipated. Thus some patients may have been harmed by neoadjuvant treatment, but we would not see that in the event data. Thus there is this important disconnect: 82 patients in the pembro arm stopped the drug due to progression (by the investigator, as shown in the CONSORT diagram), even though there were only 69 progression events (by BICR, used for endpoint analyses). Is perioperative immunotherapy doing something favorable and important in a subset of these patients? Yes, and hopefully we can refine its use to the right population and with the right regimen (adding neoadjuvant chemo or RT?). Is it distinctly possible/probable that some patients are progressing on neoadjuvant pembro, leading to a worse outcome in some domain, but we cannot see that in these data? Yes, unfortunately, also true.