Hypopharyngeal Dose Is Associated With Severe Late Toxicity in Locally Advanced Head-and-Neck Cancer: An RTOG Analysis

Abstract

Background/Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control, but at the expense of increased toxicity. We recently showed that several clinical/pre-treatment factors were associated with the occurrence of severe late toxicity. This study evaluates the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods This was an analysis of long-term survivors from 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 and/or requirement for a feeding tube ≥ 2 years after registration and/or potential treatment-related death (e.g. pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG Headquarters to estimate doses to four 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 pre-treatment and treatment potential factors. Results 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; older age (odds ratio 1.062 per year; p = 0.0021) and radiation dose received by the inferior hypopharynx (odds ratio 1.023 per Gy; p=0.016). The subgroup of patients receiving < 60 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. Conclusions Severe late toxicity following CCRT is common in long term survivors. Age is the most significant factor, but hypopharyngeal dose also was associated.

Definitive Chemoradiation in Locally Advanced Squamous Cell Carcinoma of the Hypopharynx: Long-term Outcomes and Toxicity

“…Due to the close anatomic proximity of the hypopharynx to supraglottic larynx and pharyngeal constrictors, late toxicity, primarily dysphagia, remains a significant concern in patients treated with definitive radiation (20)(21)(22)(23). In our series, 43% of patients experienced grade 3 or more late toxicity, with the majority resolving during long-term follow-up.…”

Head and Neck Cancers, Version 2.2013

“…Although multimodality treatment for head and neck cancers is improving outcomes, it can be associated with severe toxicities. [1][2][3] Many patients with head and neck cancers will receive radiation- …”

“…Memorial Sloan-Kettering Cancer Center; 2 The University of Texas MD Anderson Cancer Center; 3 Duke Cancer Institute; 4 Fox Chase Cancer Center; 5 Massachusetts General Hospital Cancer Center; NCCN Guidelines Insights CE…”

Quality of care and short and long‐term outcomes of oropharyngeal cancer care in the elderly

“…These data suggest that dysphagia is common in laryngeal SCC, but its sequela is responsive to differences in quality of care, with progression to gastrostomy dependence less likely with higher quality care but survival unaffected by quality once gastrostomy dependence was present. [25][26][27] In OPSCC, a dose-response relationship has been demonstrated between the radiation dose to the superior constrictors, the middle constrictors, the base of tongue, and severe dysphagia. Primary site-specific differences in treatment and treatment-related outcomes may explain these differences.…”