What dose are you routinely using for adjuvant RT for intermediate risk p16+ SCC of the OPX s/p TORS?

It's still just a phase II trial. Even the authors state in the introduction that their primary objectives were to demonstrate the feasibility of a prospective multi-institutional study of TOS for HPV+ OPC followed by risk-adjusted adjuvant therapy and that a planned phase III trial is in development using the arm (50 Gy) regimen as the experimental arm, because of a combination of favorable oncologic and toxicity results from PROs presented here, to be compared with standard-of-care CRT (Ferris et al., PMID 34699271).

So, until there's a larger phase III study powered to directly compare Arm C of the trial and SOC, I think it's scientifically premature to change practice just yet. That being said, it does change the nature of my discussion when patients are looking to stop treatment early due to toxicities.

I think this question exemplifies the problem with dose de-escalation, as the question asks what dose, but doesn't specify to what. ECOG 3311 gave 50 Gy to a larger volume and then randomized a 10 gy yes/no boost. So both 50 and 60 Gy are the correct standards of care.

Most 'intermediate risk' TOR patients fall into this category based on neck findings, such as multiple ipsilateral nodes, a node larger than 3 cm, or 'minimal ENE'. In the era of IMRT, boosting a relatively small neck volume from 50 to 60 Gy isn't surprising. The lack of differences in QOL found in 3311 isn't unexpected, given this small volume. However, what are the detriments of this extra 10 Gy? It involves a small amount of throw-off into the mucosa and the possibility of this small volume going to a higher dose causing late RAD due to neuropathy or an uncertain risk of carotid stenosis, and having the patient come one more week.

Regarding 'intermediate risk' to the primary, it usually involves negative margins of less than 3 cm. Although uncommon, especially when working with surgeons who exercise good judgment for patient selection, this still entails a 10 Gy difference to a small mucosal volume, reaching at most 60 Gy. It's worth noting that the paper lacked details on radiation therapy (XRT), with only one XRT doctor among the numerous authors. The protocol mandated small volumes to the primary site since the surgery defined the target and margins. Essentially the dose to the primary was to the divot with a few minimal margins.

Finally, while 3311 was a phase II study, the old MDA dose-seeking PORT trial was phase III, and 57.6 Gy in 32 fractions, which is close to 50-54 at 2 Gy to the at-risk areas, was very efficacious for patients who were not "high" risk, i.e., no ENE or +ve margins. I remain uncomfortable with de-escalating minimal ENE patients since the data is very weak and many pathologists still don't use this.

Unfortunately, without supportive data, the 'control' of 60 Gy remains deeply ingrained in our practices.

If we are going to make gains, we need bigger reductions. Consideration could involve eliminating bilateral necks for N0-N1 patients, even in the base of the tongue (I know this is HN RT heresy), and significantly lower doses to elective sites. A good study that randomizes treatment or avoidance of the primary site, particularly when the risk pertains solely to the neck, might be beneficial, especially given the practice variation observed (even within the trial, noted in one of the appendix tables). Also, consideration of observing patients with larger or multiple nodes, especially if they have just 2 or 3, could be considered. Most HPV nodes are larger only due to a large non-malignant cystic component. A minority will have recurrences, and the vast majority can be salvaged. Granted, the MAYO DART 36 GY in 2 weeks approach may be a fair compromise.

60 Gy/30 fractions.

60 Gy high-risk post-op site/54 Gy low-risk neck in 30 Fx with SIB technique, until we have quality phase III data as mentioned above. For some appropriately selected patients, we can get away with unilateral neck treatment. I would love to have phase III justification for reducing my doses for this population.