What Is the Benefit of Adjuvant Radiation Doses Above 60 Gy in Head and Neck Cancer Patients?

Abstract

Radiation dose response data in the postoperative management of Head and Neck Squamous Cell Carcinoma (HNSCC) are limited. We compared radiation dose trends and outcomes of HNSCC treated with adjuvant radiation, with or without concurrent chemotherapy. Patients with non-metastatic HNSCC who were treated between 2004 and 2014 with primary site surgery, lymph node dissection, and adjuvant radiation with an equivalent dose in 2 Gy (EQD2) of ≥ 56.64 Gy (equivalent to 57.6 Gy in 32 fractions) and ≤ 72 Gy were identified in the National Cancer Database. Radiation doses of EQD2 < 56.64 Gy and > 72 Gy were respectively interpreted to reflect incomplete radiation courses or attempted salvage of gross recurrences prior to the initiation of radiation and were excluded. Standard dose radiation was defined as an EQD2 of ≥ 56.64 Gy and ≤ 60 Gy and high dose radiation as an EQD2 of > 60 Gy and ≤ 72 Gy. Radiation regimens employed in < 10 patients were excluded. We used multivariate logistic regression to model receipt of high dose radiation, and multivariate cox proportional hazards regression to assess the association between dose and survival within the cohorts of interest. We identified 19,492 patients managed with adjuvant radiation. Oral cavity, oropharynx, larynx, hypopharynx, and nasal cavity comprised 43%, 38%, 14%, 3%, and 2% of the primary sites, respectively. HPV status was available for 3496 (47%) oropharynx patients. High dose radiation was prescribed to 52% of patients. Factors that predicted for increased use of high dose radiation included extra-nodal extension (ENE), positive or unknown surgical margins, fewer examined lymph nodes, increased number of positive lymph nodes, increased N staging, concurrent chemotherapy, and non-tonsil primary site. When adjusted for known poor prognostic factors to control for high dose being prescribed to a worse prognosis cohort, there was a decrease in overall survival (OS) in the high dose group (HR = 1.10; 95% CI 1.03-1.17). High dose radiation was independently associated with worse OS in HPV positive oropharynx patients when controlling for poor prognostic factors (HR = 2.03; 95% CI 1.22-3.37). In non-oropharynx primary or HPV negative oropharynx primary that had positive margins, ≥ 5 positive lymph nodes, and/or ENE, high dose radiation was not associated with improvement in OS (HR 1.03; 95% CI 0.94-1.13). Factors known to predict for poor outcomes are associated with higher rates of high dose adjuvant radiation in this large national cohort. However, when controlling for poor prognostic factors, there was no survival benefit from postoperative dose escalation above EQD2 of 60 Gy.