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Original Investigation
From the American Head and Neck Society
August 13, 2020

Evaluating Adjuvant Therapy With Chemoradiation vs Radiation Alone for Patients With HPV-Negative N2a Head and Neck Cancer

Author Affiliations
  • 1Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston
  • 2Department of Public Health Sciences, Medical University of South Carolina, Charleston
  • 3Division of Medical Oncology, Department of Medicine, Medical University of South Carolina, Charleston
  • 4Department of Radiation Oncology, Medical University of South Carolina, Charleston
  • 5Department of Cell & Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston
  • 6Department of Otolaryngology–Head and Neck Surgery, Washington University, St Louis, Missouri
  • 7Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee
JAMA Otolaryngol Head Neck Surg. 2020;146(12):1109-1119. doi:10.1001/jamaoto.2020.2107
Key Points

Question  Is the addition of chemotherapy to adjuvant radiation therapy associated with improved survival among patients with human papillomavirus–negative head and neck squamous cell carcinoma with extranodal extension in a single lymph node smaller than 3 cm (American Joint Committee on Cancer Staging Manual, 8th Edition, category pN2a)?

Findings  In this cohort study of 504 patients from the National Cancer Database with pN2a human papillomavirus–negative head and neck squamous cell carcinoma who underwent margin-negative resection, adjuvant chemoradiation therapy was not associated with improved overall survival relative to adjuvant radiation therapy alone.

Meaning  Adding chemotherapy to adjuvant radiation therapy was not associated with improved survival in this study, suggesting the need for additional research to identify optimal treatment paradigms for these patients.

Abstract

Importance  The American Joint Committee on Cancer staging system (Cancer Staging Manual, 8th Edition) for head and neck squamous cell carcinoma (HNSCC) now categorizes human papillomavirus (HPV)–negative HNSCC in a single positive lymph node smaller than 3 cm with pathologic extranodal extension (ENE) as N2a. The standard of care for pathologic ENE is adjuvant chemoradiation therapy (CRT). Whether adding chemotherapy concurrent with adjuvant radiation therapy improves survival in this clinical scenario is unknown.

Objective  To assess whether adjuvant CRT relative to radiation therapy alone is associated with improved survival among patients with pN2a HPV-negative HNSCC with ENE.

Design, Setting, and Participants  This retrospective cohort study included 504 patients with pN2a HPV-negative HNSCC with ENE who had undergone margin-negative surgery and adjuvant therapy. The patients were identified from the National Cancer Database from January 1, 2004, to December 31, 2015. Statistical analyses were conducted from September 1, 2019, to April 16, 2020.

Main Outcomes and Measures  The primary end point was overall survival. The association of adjuvant CRT with overall survival was analyzed using univariate and multivariate Cox proportional hazards regression analyses. Planned subset analyses were conducted in patients younger than 70 years with no comorbidities (the subset most likely to be eligible for a clinical trial of cisplatin-based chemoradiation) and in patients with pT3/T4 disease classification.

Results  Of 504 patients (mean [SD] age, 60.5 [12.7] years; 319 [63.3%] men; 434 [86.1%] White) with pN2a HPV-negative HNSCC with ENE who had undergone margin-negative surgery and adjuvant therapy, 298 patients (59.1%) received adjuvant CRT. For the overall cohort of patients with pN2a ENE, adjuvant CRT was not associated with improved overall survival relative to adjuvant radiation therapy alone in a multivariate analysis (adjusted hazard ratio, 0.98; 95% CI, 0.74-1.30). Adjuvant CRT was still not associated with improved overall survival in a subset analysis of 304 patients younger than 70 years with no comorbidities (adjusted hazard ratio, 0.98; 95% CI, 0.66-1.45) nor in a subset of 220 patients with pT3/T4 disease classification (adjusted hazard ratio, 1.03; 95% CI, 0.70-1.54).

Conclusions and Relevance  This study found that for patients with pN2a HPV-negative HNSCC with ENE who underwent margin-negative surgery and adjuvant therapy, adding chemotherapy concurrent with adjuvant radiation therapy was not associated with improved overall survival. Additional research is necessary to identify the optimal treatment paradigm for this clinical scenario.

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