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Comparative Study
. 2017 Nov 1;3(11):1487-1494.
doi: 10.1001/jamaoncol.2017.0973.

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

Jonathan E Leeman  1 , Jin-Gao Li  2 , Xin Pei  1 , Praveen Venigalla  1 , Zachary S Zumsteg  3 , Evangelia Katsoulakis  1 , Eitan Lupovitch  1 , Sean M McBride  1 , Chiaojung J Tsai  1 , Jay O Boyle  4 , Benjamin R Roman  4 , Luc G T Morris  4 , Lara A Dunn  5 , Eric J Sherman  5 , Nancy Y Lee  1 , Nadeem Riaz  1
Affiliations
Comparative Study

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

Jonathan E Leeman et al. JAMA Oncol. .

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Zumsteg reported serving as a paid consultant for the Scripps Proton Therapy Center and EMD Serono. Dr Morris reported receiving travel expenses for a trial investigator meeting from Bristol-Myers Squibb. Dr Sherman reported serving as a consultant and advisor for Bristol-Myers Squibb, Eisai, and Bayer. Dr Riaz reported serving as a consultant and advisor for Medimmune and receiving research funding from Bristol-Myers Squibb. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Incidence of Treatment Failures Across Subsites
A, Local treatment failure. B, Regional treatment failure. C, Distant failure. D, Overall survival across subsites. Compared with oropharyngeal carcinoma (OPC), oral cavity carcinoma (OCC) demonstrated the highest cumulative incidence of local treatment failure (hazard ratio [HR], 5.2; 95% CI, 3.1-8.6; P < .001), followed by laryngeal carcinoma (LC) (HR, 2.6; 95% CI, 1.4-4.9; P = .004) and hypopharyngeal carcinoma (HPC) (HR, 2.5; 95% CI, 1.0-6.3; P = .06). Compared with OPC, OCC also demonstrated the highest cumulative incidence of regional treatment failure (HR, 2.2; 95% CI, 1.0-45; P = .04), followed by HPC (HR, 1.6; 95% CI, 0.5-5.1; P = .40) and LC (HR, 1.4, 95% CI, 0.6-3.3; P = .40). Hypopharyngeal carcinoma demonstrated the highest incidence of distant treatment failure compared with OPC (HR, 2.6; 95% CI, 1.5-4.6), followed by LC (HR, 1.5; 95% CI, 0.9-2.4; P = .08) and OCC (HR, 1.3; 95% CI, 0.8-2.2; P = .31). Overall survival was significantly longer for patients with OPC positive for human papillomavirus (HPV) or p16 compared with all other subsites combined (HR, 0.45; 95% CI, 0.36-0.57; P < .001).
Figure 2.
Figure 2.. Survival Following Locoregional Recurrence or Metastasis
A, Survival following locoregional recurrence according to head and neck primary tumor subsite. B, Survival following metastasis according to head and neck primary tumor subsite. C, Survival following isolated locoregional failure according to human papillomavirus (HPV) or p16 status. D, Survival following metastasis according to number of metastatic tumors. HPC indicates hypopharyngeal carcinoma; LC, laryngeal carcinoma; OCC, oral cavity carcinoma; and OPC, oropharyngeal carcinoma
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