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Original Investigation
May 25, 2017

Patterns of Treatment Failure and Postrecurrence Outcomes Among Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma After Chemoradiotherapy Using Modern Radiation Techniques

Author Affiliations
  • 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, China
  • 3Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California
  • 4Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
  • 5Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
JAMA Oncol. Published online May 25, 2017. doi:10.1001/jamaoncol.2017.0973
Key Points

Question  What are the patterns of treatment failure and postrecurrence outcomes among patients with head and neck squamous cell carcinoma (HNSCC) treated with modern definitive therapy?

Findings  This cohort study of 1000 patients with HNSCC found that locoregionally recurrent disease among patients positive for human papillomavirus is associated with an improved prognosis and that, compared with other HNSCCs, patients with oral cavity carcinoma displayed unique patterns of treatment failure and particularly poor outcomes after metastasis. The study also found a subset of patients with oligometastasis who experienced prolonged survival.

Meaning  Survival after recurrence of HNSCC is influenced by the HNSCC subsite and human papillomavirus status. An oligometastatic phenotype is associated with improved survival.

Abstract

Importance  Even though 15% to 50% of patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence, relatively little is known regarding patterns of treatment failure and postrecurrence outcomes after chemoradiotherapy using modern radiation techniques (intensity-modulated radiotherapy [IMRT]). Recurrence patterns are significantly affected by variations in the quality of radiotherapy, which may confound findings from multicenter trials.

Objective  To assess patterns of treatment failure and postrecurrence outcomes for patients with HNSCC treated with contemporary radiotherapy techniques.

Design, Setting, and Participants  This large single-institution cohort study reviewed the outcomes of 1000 consecutive patients with stage III to IVB oropharyngeal carcinoma (n = 703), laryngeal carcinoma (n = 126), or hypopharyngeal carcinoma (n = 46) treated with definitive IMRT with or without concurrent chemotherapy, as well as patients with oral cavity carcinoma (n = 125) treated with postoperative IMRT with or without concurrent systemic therapy, from December 1, 2001, to December 31, 2013, with a median follow-up of 65.1 months among surviving patients. Data analysis was performed from January 31, 2016, to February 17, 2017.

Main Outcomes and Measures  Patterns of treatment failure and overall survival following locoregional failure or distant metastasis.

Results  Among the 1000 patients (186 women and 814 men; mean [SD] age, 59.3 [10.8] years), there were no marginal or isolated out-of-radiation-field failures. Among subsites, the cumulative incidence of local failure was highest among patients with oral cavity carcinoma vs those with oropharyngeal carcinoma (hazard ratio, 5.2; 95% CI, 3.1-8.6; P < .001). Furthermore, patients with oral cavity carcinoma experienced significantly shorter survival following distant metastasis (hazard ratio, 3.66; 95% CI, 1.98-6.80; P < .001). Patients with oropharyngeal carcinoma positive for human papillomavirus or p16 lived longer after locoregional failure compared with patents with oropharyngeal carcinoma negative for human papillomavirus or p16 (median survival, 36.5 vs 13.6 months; P = .007) but not after distant metastasis. Salvage surgery was associated with improved overall survival following locoregional failure (hazard ratio, 0.51; 95% CI, 0.34-0.77; P = .001); oligometastatic disease (1 vs ≥2 lesions: hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001) was associated with improved overall survival following distant metastasis.

Conclusions and Relevance  Overall survival after recurrence of HNSCC is influenced by the HNSCC subsite and human papillomavirus or p16 status, as well surgical and systemic interventions. An oligometastatic phenotype characterizes patients with solitary metastasis after chemoradiotherapy. These findings have important implications for clinical trial designs for HNSCC in the recurrent and oligometastatic setting.

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