Outcomes after Contemporary Definitive Radiotherapy Alone in Patients with TNM-7 Stage III/IV Head and Neck Squamous Cell Carcinoma

Abstract

This study was undertaken to determine outcomes and prognostic factors of definitive intensity-modulated radiotherapy (IMRT) alone for patients with TNM-7 stage III/IV HNSCC who did not receive concurrent chemotherapy. We evaluated TNM-7 stage III/IV HNSCC patients treated with definitive IMRT alone in our institution from 2004-2019. Patients were reclassified according to TNM-8 staging. Stage II HPV+ oropharyngeal cancers (OPC) were subdivided into T1-2N2 and T3N0-2 for analysis. The rationale for chemotherapy omission was obtained retrospectively from clinical documentation. Recurrence-free survival (RFS) and overall survival (OS) were estimated stratified by HPV status (determined by p16 staining, sometimes supplemented by HPV DNA testing). Multivariable analysis (MVA) identified prognostic factors for RFS and OS, taking into account stage and IMRT regimen. Age, performance status, and smoking were also examined for OS. A total of 1083 patients were included (460 HPV+ and 623 HPV-). Reasons for omission of chemotherapy were: age >70 years or frailty (n = 551, 51%), cisplatin contraindication (n = 241, 22%), patient refusal (n = 106, 10%), and clinician's decision (n = 185, 17%). Median age was 67 years for HPV+ and 70 years for HPV- cohorts. IMRT mostly utilized altered fractionation regimens (n = 1016, 94%): moderately accelerated (Acc) (70 Gy/35 fractions [f]/6 weeks [w], 55%), hypofractionated (Hypo) (60 Gy/25f/5w, 14%), and hyperfractionated-accelerated (Hyper) (64 Gy/40f/4w, 25%). Median follow-up was 5 years. Five-year RFS and OS for HPV+ TNM-8 stage I/T1-2N2/T3N0-N2/III were 89%/86%/76%/52% and 83%/80%/64%/33% respectively (p<0.01). The same outcomes for HPV- TNM-8 stage III/IVA/IVB were 58%/52%/39% and 47%/27%/13%, respectively (p<0.01). MVA confirmed that HPV+ T3N0-2 subset within stage II and stage III (vs stage I) had lower RFS, and HPV- stage IVA and IVB (vs stage III) carried worse RFS and OS (Table). Despite the retrospective nature and inherent selection bias, this large single institutional study shows that altered fractionated IMRT alone is an acceptable alternative for elderly, frail or cisplatin ineligible patients with HPV+ stage I/IIA (T1-2N2) OPC. Patients with HPV+ T3N0-2/stage III OPC and HPV- stage III/IV HNSCC have poor outcomes with IMRT alone and may benefit from alternative strategies.