Top Line: Upfront reduced-dose radiation is a way to potentially reduce treatment intensity for HPV-mediated oropharyngeal cancer, so what about dose-reduced post-TORS radiation?
The Study: The randomized, phase 2 ECOG/ACRIN E3311 trial sought to determine the feasibility, efficacy, and safety of treatment deintensification with transoral surgery (TORS) and risk-adapted postoperative radiation (PORT). Important to note is that it was not technically powered to provide a true comparison among arms–particularly between reduced and standard dose PORT. The 495 enrolled patients had AJCC 7 stage III-IVA (remember this is way different from AJCC 8 stage), p16+ T1 or T2 squamous cell carcinoma of the oropharynx that was amenable to transoral surgery. After surgery, they were categorized as low risk (11%; negative margins (< 3 mm), AJCC-7 N0-N1, no ENE), intermediate risk (58%; close margin < 3 mm, N1-N2 with ≤ 1 mm ENE, 2-4 positive nodes), and high risk (31%; positive margins, > 4 LN, > 1 mm ENE). The most frequent reason for high risk categorization was >1 mm ENE, while the positive margin rate was only 3.3%. Low risk patients were observed, and high risk patients received standard post-op chemoradiation. The intermediate risk group was randomized to dose-reduced (50 Gy) or standard dose (60 Gy) post-op RT. The rate of 3-year PFS was 96.9% for low risk, 94.9% for reduced RT dose intermediate risk, 93.4% for standard RT dose intermediate risk, and 90.7% for high risk. Overall survival at 2 years was > 95% in all arms. During the surgery component, the rate of grade 3+ toxicity was 17%. During the adjuvant component, the grade 3+ toxicity rate was significantly different: 15% for reduced RT dose intermediate risk, 24% for standard dose intermediate risk, and 61% for high risk. Swallowing function transiently declined in the low and intermediate risk groups but returned to baseline while there was a permanent slight decrease in the high risk arm. Check out the protocol for further planning details.
TBL: E3311 found that, in patients with p16+ oropharyngeal cancer with intermediate risk features, TORS followed dose-reduced RT resulted in favorable disease control, survival, and toxicity and could be a good candidate for comparison with standard of care treatment in a phase 3 trial. | Ferris, J Clin Oncol 2021