This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube ¡Ý2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors.
A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46 % of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving ¡Ü60 Gy to the inferior hypopharynx had a 40 % rate of severe late toxicity compared with 56 % for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome.
Severe late toxicity following CCRT is common in long-term survivors. Age is the most significant factor, but hypopharyngeal dose also was associated.