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Original Investigation |

Treatment Outcomes for T4 Oropharyngeal Squamous Cell Carcinoma

Joseph Zenga, MD1; Michael Wilson, BS2; Douglas R. Adkins, MD3; Hiram A. Gay, MD4; Bruce H. Haughey, MBChB, MS1; Dorina Kallogjeri, MD, MPH1; Loren S. Michel, MD3; Randal C. Paniello, MD, PhD, MBA1; Jason T. Rich, MD1; Wade L. Thorstad, MD4; Brian Nussenbaum, MD1
[+] Author Affiliations
1Department of Otolaryngology–Head and Neck Surgery, Washington University, St Louis, Missouri
2medical student at Washington University, School of Medicine, St Louis, Missouri
3Department of Medical Oncology, Washington University, St Louis, Missouri
4Department of Radiation Oncology, Washington University, St Louis, Missouri
JAMA Otolaryngol Head Neck Surg. 2015;141(12):1118-1127. doi:10.1001/jamaoto.2015.0764.
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Importance  Little is known about treatment outcomes for T4 oropharyngeal squamous cell carcinoma (OPSCC), particularly in the era of human papillomavirus (HPV)-related disease.

Objective  To evaluate oncologic outcomes for T4 OPSCC treated with primary surgical and nonsurgical therapies.

Design, Setting, and Participants  Retrospective cohort study of 131 patients from a single academic hospital, who were treated for T4a or T4b OPSCC (with any N stage and without distant metastatic disease at presentation) between 1998 and 2012 and had a minimum 2-year follow-up (the median follow-up time was 34.6 months). This study was conducted between January 1, 1998, and November 1, 2012.

Interventions  Sixty-nine patients underwent nonsurgical therapy, 47 (68%) of whom had p16-positive tumors. Nonsurgical treatment paradigms included induction chemotherapy followed by chemoradiotherapy (n = 36 [54%]), concurrent chemoradiotherapy (n = 29 [43%]), and induction chemotherapy followed by radiation therapy alone (n = 2 [3%]). Sixty-two patients underwent surgical treatment, 50 (81%) of whom had p16-positive tumors. Fifty-seven surgical patients (92%) received adjuvant therapy.

Main Outcomes and Measures  Overall survival (OS) was the primary outcome measure. Secondary outcome measures included disease-specific survival (DSS), disease-free survival (DFS), 2-year gastrostomy and tracheostomy tube rates, and major complication rates.

Results  Significant baseline differences between the surgical vs nonsurgical groups included age (mean 59.8 vs 55.4 years [P = .005]), sex (male, 95% vs 84% [P = .04]), body mass index (<18.5 [calculated as weight in kilograms divided by height in meters squared], 3% vs 16% [P = .02]), and smoking history of 10 or more pack-years (48% vs 77% [P = .003]). For p16-positive patients, Kaplan-Meier estimates of OS, DSS, and DFS were significantly higher for surgically treated patients than for the nonsurgical group (χ21 = 7.335 for log-rank P = .007, χ21 = 8.607 for log-rank P = .003, and χ21 = 7.763 for log-rank P = .005, respectively). For p16-negative patients, Kaplan-Meier estimates of OS and DSS were higher for the surgical group but did not reach statistical significance (χ21 = 2.649 for log-rank P = .10 and χ21 = 2.077 for log-rank P = .15, respectively), while estimates of DFS were significantly higher for patients treated with primary surgery (χ21 = 3.869 for log-rank P = .049. In a multivariable Cox survival analysis, p16-positive immunohistochemical status had a significant positive association with OS (hazard ratio [HR], 0.55; 95% CI, 0.32-0.95 [P = .03]), DSS (HR, 0.45; 95% CI, 0.22-0.92 [P = .03]), and DFS (HR, 0.55; 95% CI, 0.32-0.95 [P = .03]), and nonsurgical treatment had a significant negative association with OS (HR, 2.79; 95% CI, 1.51-5.16 [P = .001]), DSS (HR, 3.38; 95% CI, 1.59-7.16 [P = .002]), and DFS (HR, 2.59; 95% CI, 1.51-4.45 [P = .001]).

Conclusions and Relevance  Primary surgical treatment may be associated with improved outcomes in patients with T4 OPSCC. p16 Immunohistochemical status remains a strong prognostic indicator even in patients with locally advanced disease.

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Figures

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Figure 1.
Kaplan-Meier Survival Estimates

A, Kaplan-Meier estimates of overall survival stratified by p16 status. B, Kaplan-Meier estimates of disease-specific survival stratified by p16 status. C, Kaplan-Meier estimates of disease-free survival stratified by p16 status. Hash marks represent censored data.

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Figure 2.
Cox Multivariable Survival Analysis

A, Cox multivariable survival analysis for overall survival by treatment modality adjusted for p16 status, alcohol abuse at the time of treatment, smoking history, and year of treatment. B, Cox multivariable survival analysis for disease-specific survival by treatment modality adjusted for p16 status, alcohol abuse at the time of treatment, smoking history, and year of treatment. C, Cox multivariable survival analysis for disease-free survival by treatment modality adjusted for p16 status, alcohol abuse at the time of treatment, smoking history, and year of treatment. HR indicates hazard ratio.

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