Comparison of Standard vs. Relative Risk Models to Define Candidates for Deintensification in Locoregionally Advanced P16+ Oropharyngeal Cancer

Various methods to identify candidates for treatment deintensification with p16+ oropharyngeal squamous cell carcinoma (OPSCC) have been used, but the optimal approach is unknown.Multi-institutional cohort study of 385 patients with previously untreated p16+ OPSCC undergoing definitive radiotherapy (RT) with or without systemic therapy between 2009-2020. Chemotherapy intensity was categorized as high (bolus cisplatin and/or induction chemotherapy), medium (weekly cisplatin), or low (non-cisplatin or RT alone). Standard favorable vs. unfavorable risk was defined using NRG HN005 eligibility criteria. High vs. low relative risk (RR) group was defined using the HNCIG omega score (≥ 0.80 vs. < 0.80), which quantifies the proportion of a patient's overall event risk due to cancer. We used multivariable ordinal logistic regression to estimate effects of age (yrs), sex, performance status (PS), Charlson comorbidity index (CCI), T/N (AJCC 8th), current smoking, and pack-years (> 10 vs. ≤ 10) on treatment allocation. Effects on relative event hazards were estimated using generalized competing event regression.Median follow-up time was 44.2 months. Chemotherapy intensity was high in 206 (54%), medium in 108 (28%), and low in 71 (18%). 280 patients (73%) were unfavorable risk and 197 (51%) were high RR. 178 patients (46%) had discordant risk classification. On univariable analysis, significant predictors of higher intensity chemotherapy (normalized odds ratio (OR)) were CCI 0-1 (OR 1.49, 95% CI: 1.23-1.79), high omega score (OR 1.46; 1.20-1.77), decreased age (OR 1.43; 1.18-1.74), and PS 0 (OR 1.22; 1.01-1.48). Controlling for CCI, higher omega score was associated with significantly higher odds of intensive chemotherapy (OR 1.35; 1.10-1.65, but unfavorable risk (HN005 ineligibility) was not (OR 1.19; 0.98-1.44). Higher omega score was also associated with significantly higher RR for cancer recurrence (Rec) vs. competing mortality (CM) events (relative HR (rHR) 1.76; 1.12-2.75), but unfavorable risk was not (rHR 1.05; 0.63-1.75). Among patients receiving cisplatin, 50 favorable risk patients (58%) had high RR; all of their event risk was due to cancer recurrence (Table). The 110 unfavorable risk patients (48%) with low omega score had significantly lower RR for cancer events compared to the high omega score group (rHR 0.49; 0.29-0.84).Many patients with favorable risk p16+ OPSCC have high relative risk for cancer events, which correlates with a benefit of intensive treatment. The HNCIG omega score is a strong predictor of allocation to intensive chemotherapy and may help identify candidates for deintensification.