Pre-treatment and treatment related risk factors for severe late toxicity after chemo-RT for head and neck cancer: An RTOG analysis

Abstract

5500 Background: Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) improves tumor control, but its toxicity is formidable. This study evaluates factors that might predict for severe late toxicity following CCRT. Methods: Patients treated with CCRT were analyzed from three RTOG trials of locally advanced SCCHN: 91–11 arm #2 (XRT + high dose cisplatin for larynx cancer); 97–03 (phase II study of various doublets of chemotherapy with XRT); and 99–14 (phase II study of accelerated XRT + high dose cisplatin). Severe late toxicity was defined in this secondary analysis as late (>180 days from the start of XRT) Grade 3–4 pharyngeal/laryngeal toxicity (RTOG/EORTC late toxicity scoring system); requirement for a feeding tube ≥2 years after registration; or potential treatment-related death (e.g. pneumonia) within 3 years. Case-control analysis was performed to determine factors predictive of severe late toxicity, with a multivariate logistic regression model that included pre-treatment and treatment potential factors. Results: The total sample size of patients treated with CCRT from these three studies was 479; 226 were evaluable (119 patients had severe pre-treatment laryngopharynx dysfunction and 134 had persistent/recurrent cancer). There were 98 cases (patients with severe late toxicity) and 128 controls. In the multivariate model, significant predictors of severe late toxicity were older age (odds ratio 1.05 per year, p = 0.002); advanced T-stage (odds ratio 2.21; p = 0.014); larynx/hypopharynx tumor site (odds ratio 3.20; p = 0.011); and neck dissection (ND) after XRT (odds ratio 2.22; p = 0.029). Radiotherapy dose intensity and chemotherapy dose intensity were not predictive. Among 47 patients who underwent post-XRT ND, the crude rate of severe late toxicity was 55%, compared with 40% for the subgroup of 179 patients who did not undergo post-XRT ND (p = 0.05). Conclusions: Severe late toxicity following CCRT is common. Older age, advanced T-stage, and larynx/hypopharynx primary site were independent risk factors. Neck dissection after CCRT may be associated with an increased risk of these complications. This work was supported in part by the Commonwealth of Pennsylvania (Tobacco Settlement Grant). No significant financial relationships to disclose.