Functional and survival outcomes in HPV positive oropharyngeal squamous cell cancer treated with response-adaptive de-escalation: A pooled analysis.

Abstract

6068 Background: Human papillomavirus (HPV) positive OPSCC is known to have a favorable prognosis compared to its HPV negative counterparts. It is thus important to limit treatment-related toxicity while preserving functional and survival outcomes. In this pooled study, we report functional and survival outcomes across prospective cohorts treated with chemotherapy-response-adaptive dose and volume de-escalation of radiation. Methods: Patients with non-metastatic HPV positive OPSCC were sequentially treated at an academic center on either an interventional de-escalation trial: OPTIMA 1 (NCT02258659); OPTIMA II (NCT03107182); (NCT04572100 ) or off-protocol in a prospective registry. Eligible patients had N1-3 or T3-4 (AJCC 8 th edition) disease. Very low-risk patients T0-2N0-1 (single lymph node <3cm) were excluded. Patients were stratified as low risk (LR) or high risk (HR) according to T/N stage and smoking history. Following chemotherapy (carboplatin and paclitaxel or nab -paclitaxel) with or without nivolumab, patients received de-escalated treatment with low dose arm (LDA; radiation [RT] alone to 50Gy or transoral robotic surgery), intermediate dose arm (IDA; chemoRT [CRT] to 45-50Gy) or regular dose arm (CRT to 70-75Gy). To analyze functional outcomes, we compared swallowing performance scores (SPS), trismus, percutaneous endoscopic gastrostomy (PEG) tube placement obtained from pre- and post-(C)RT. Comparisons across risk categories and treatment arms using Chi-square, Fisher, and Student t-tests. Survival outcomes were compared using log-rank statistic. Results: Eligible patients (n=242) started treatment between 2014 and 2024: 116 LR and 126 HR patients; 83% received de-escalated treatment (LDA/IDA) and 17% received standard dose (RDA). Post-treatment SPS (p=0.0002) and trismus scores (p=0.0013) was better among de-escalated versus non-de-escalated patients. Lower PEG placement rates were observed among de-escalated patients 33/196 (16.8%) vs 27/39 (69.2%) (p<.0001). With median follow-up of 48 months, no statistically significant differences in overall survival or progression free survival were observed between treatment arms. OS (95.1% (95% CI 90.8%-97.4%) vs 93.7%( 95% CI 77.72%- 98.4%), P=0.185) and PFS (92.2% (95% CI 87.1%-95.2%) vs 90.7% (95% CI 73.9% - 96.9%, p=0.202) were similar in deescalated and non-deescalated patients at 3 years. Low risk individuals also had better OS (97.1% vs 92.1%, p=0.01) and PFS (96.1% vs 88.3%, p=0.004) at three years. Conclusions: Improved functional outcomes including posttreatment swallowing function, trismus, and lower PEG placement rates were observed with chemotherapy-response-adaptive radiation de-escalation with excellent survival in the largest prospective cohort reported to date. Response-adaptive de-escalation warrants further comparative study.