Factors Associated with Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported RTOG trials of concurrent chemoradiotherapy for locally advanced SCCHN (RTOG 91-11; 97-03; and 99-14). Severe late toxicity was defined in this secondary analysis as chronic Grade 3-4 pharyngeal/laryngeal toxicity (RTOG/EORTC late toxicity scoring system) and/or requirement for a feeding tube ≥2 years after registration and/or potential treatment-related death (e.g. pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pre-treatment and treatment potential factors. Results A total of 230 patients were evaluable for this analysis, 99 cases (patients with severe late toxicities) and 131 controls; thus 43% of evaluable patients had a severe late toxicity. On multivariable analysis, significant variables correlated with the development of severe late toxicity were older age (odds ratio 1.05 per year; p = 0.001); advanced T-stage (odds ratio 3.07; p=0.0036); larynx/hypopharynx primary site (odds ratio 4.17; p=0.0041); and neck dissection after chemo-RT (odds ratio 2.39; p=0.018). Conclusions Severe late toxicity following CCRT is common. Older age, advanced T-stage, and larynx/ hypopharynx primary site were strong independent risk American Society of Clinical Oncology. Machtay, M. et al: J. Clin. Oncol. 26 (21), 2008:3582-3589

Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235

PURPOSE: To determine if higher pre-treatment metabolic tumor volume (MTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT). METHODS: This is a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT_Image. Kaplan-Meier curves and Cox proportional hazards regression models were used to associate tMTV with OS. RESULTS: Of the 250 patients enrolled on the study, 230 were evaluable for MTV-pre. Patients with MTV-pre>32 mL (median value) vs. ≤32 mL had worse median OS (14.8 months vs. 29.7 months, p<0.001). As a continuous variable, higher MTV-pre (per 10 mL increase) remained associated with worse OS (HR=1.03, p<0.001) after controlling for other variables. A significant interaction between radiation dose and MTV-pre occurred for OS (p=0.002) demonstrating that as radiotherapy dose increased, the negative prognostic impact of MTV-pre decreased. Among patients with MTV-pre ≤32 mL, there was no difference in survival with radiotherapy dose delivered (p=0.694). However, median OS was inferior in patients with MTV-pre>32 mL who received ≤60 Gy compared with those who received 61-69 Gy or ≥70 Gy (p=0.001). CONCLUSIONS: Higher MTV-pre is associated with significantly worse OS in inoperable stage III NSCLC treated with definitive CRT. Our findings suggest that for patients with large MTV-pre, achieving a therapeutic radiation dose may help maximize OS. Prospective studies are needed to confirm this finding