Originally published as JCO Early Release 10.1200/JCO.2007.14.8841 on June 16 2008

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

Mitchell Machtay, Jennifer Moughan, Andrew Trotti, Adam S. Garden, Randal S. Weber, Jay S. Cooper, Arlene Forastiere, K. Kian Ang

From the Jefferson Medical College and Kimmel Cancer Center of Thomas Jefferson University; Radiation Therapy Oncology Group Headquarters and Statistical Center and the American College of Radiology, Philadelphia, PA; Moffitt Cancer Center of University of South Florida, Tampa, FL; Departments of Radiation Oncology and Head and Neck Surgery, M.D. Anderson Cancer Center, Houston, TX; Maimonides Medical Center, NY; and Johns Hopkins University Medical Center, Baltimore, MD

Corresponding author: Mitchell Machtay, MD, Department of Radiation Oncology, Thomas Jefferson University Hospital, 111 S 11th St, Philadelphia, PA 19107; e-mail: mitchell.machtay{at}jeffersonhospital.org

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 Radiation Therapy Oncology Group (RTOG) trials of CCRT 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 to 4 pharyngeal/laryngeal toxicity (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity scoring system) and/or requirement for a feeding tube 2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pretreatment and treatment potential factors.

Results A total of 230 patients were assessable for this analysis: 99 patients with severe late toxicities and 131 controls; thus, 43% of assessable 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 = .001); advanced T stage (odds ratio, 3.07; P = .0036); larynx/hypopharynx primary site (odds ratio, 4.17; P = .0041); and neck dissection after CRT (odds ratio, 2.39; P = .018).

Conclusion Severe late toxicity after CCRT is common. Older age, advanced T-stage, and larynx/hypopharynx primary site were strong independent risk factors. Neck dissection after CCRT was associated with an increased risk of these complications.

published online ahead of print at www.jco.org on June 16, 2008.

Supported by Grants No. CA21661 and CA32115 from the National Cancer Institute and by a grant from the Commonwealth of Pennsylvania C.U.R.E. Program (Tobacco Settlement Act 77-2001).

Presented in part at the 42nd Annual Meeting American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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