ABSTRACT
BACKGROUND: Randomized trials have found that patients with locoregionally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC) do not benefit from treatment deintensification, even among favorable risk groups. While various methods have been used to identify candidates for treatment deintensification, the optimal approach is unknown. METHODS: We conducted a multi-institutional cohort study of 444 patients with previously untreated p16+ OPSCC undergoing definitive radiotherapy with or without systemic therapy between 2009-2022. We compared two approaches for identifying candidates for deintensification: (1) favorable vs. unfavorable risk, using NRG-HN005 eligibility criteria, and (2) low vs. high relative risk for cancer events, using the HNCIG predictive classifier ("omega score"). We tested differences in outcomes and systemic therapy allocation by risk group using multivariable Cox models, competing event models, and logistic regression, and compared characteristics of hypothetical deintensification trials using the two approaches. PFS events were defined as cancer recurrence (locoregional or distant) or death from any cause. RESULTS: Median follow-up time was 52 months; 120 patients (27.0%) were favorable risk; a different 120 patients had low omega score; 28 patients (6.3%) met both criteria; 184 patients (41.4%) had discordant classification. On ordinal logistic regression, decreasing omega score was associated with a statistically significantly lower odds of receiving intensive therapy (normalized OR 0.37 per standard deviation; 95% CI: 0.24-0.57), with a greater magnitude than favorable risk group (OR 0.66; 95% CI: 0.44-0.99). Among patients receiving cisplatin and/or platinum-based induction (N=374), favorable risk was associated with significantly improved PFS (HR 0.59, 95% CI 0.36-0.99), whereas lower omega score was associated with a significantly decreased relative hazard for cancer events (RHR 0.18, 95% CI 0.070-0.46). In simulations, selecting patients with low omega scores increased the efficiency of hypothetical non-inferiority trials. CONCLUSIONS: Considering patients' relative risk for cancer events can help define optimal populations for treatment deintensification in p16+ OPSCC.
ABSTRACT
BACKGROUND: To test whether nomograms developed by NRG Oncology for oropharyngeal squamous cell carcinoma (OPSCC) patients could be validated in an independent population-based sample. METHODS: The authors tested nomograms for estimating progression-free survival (PFS) and overall survival (OS) in patients from the Veterans Health Administration with previously untreated locoregionally advanced OPSCC, diagnosed between 2008 and 2017, managed with definitive radiotherapy with or without adjuvant systemic therapy. Covariates were age, performance status, p16 status, T/N category, smoking history, education history, weight loss, marital status, and anemia. We used multiple imputation to handle missing data and performed sensitivity analyses on complete cases. Validation was assessed via Cox proportional hazards models, log-rank tests, and c-indexes. RESULTS: A total of 4007 patients met inclusion criteria (658 patients had complete data). Median follow-up time was 3.20 years, with 967 progression events and 471 noncancer deaths. Each risk score was associated with poorer outcomes per unit increase (PFS score, hazard ratio [HR], 1.42 [1.37-1.47]; OS score, HR, 1.40 [1.34-1.45]). By risk score quartile, 2-year PFS estimates were 89.2%, 78.5%, 65.8%, and 48.3%; OS estimates were 92.6%, 83.6%, 73.9%, and 51.3%, respectively (P < .01 for all comparisons). C-indices for models of PFS and OS were 0.65 and 0.67, for all patients, respectively (0.69 and 0.73 for complete cases). The nomograms slightly overestimated PFS and OS in the overall cohort but exhibited high agreement in complete cases. CONCLUSIONS: NRG nomograms were effective for predicting PFS and OS for patients with OPSCC, supporting their broader applicability in the OPSCC population undergoing definitive radiotherapy.