2018-19 Section 7-Neoplastic and Inflammatory Diseases of the Head and Neck eBook

Reprinted by permission of Cancer. 2018; 124(11):2347-2354.

Original Article

Mature Results of a Prospective Study of Deintensified Chemoradiotherapy for Low-Risk Human Papillomavirus- Associated Oropharyngeal Squamous Cell Carcinoma 1,2 ; Robert J. Amdur, MD 3,4 ; Joel E. Tepper, MD 1,2 ; Xianming Tan, PhD 2 ; Jared Weiss, MD 2,5 ; Juneko E. Grilley-Olson, MD 2,5 ; D. Neil Hayes, MD, MPH 6 ; Adam Zanation, MD 7 ; Trevor G. Hackman, MD 7 ; Samip Patel, MD 7 ; Nathan Sheets, MD 8 ; Mark C. Weissler, MD 7 ; and William M. Mendenhall, MD 3,4 BACKGROUND: The purpose of the current study was to determine quality of life and tumor control from a prospective phase 2 clini- cal trial evaluating deintensified chemoradiotherapy for favorable risk, human papillomavirus (HPV)-associated oropharyngeal squa- mous cell carcinoma. METHODS: Patients with T0-T3, N0-N2c, M0, p16-positive disease and a minimal smoking history were treated with 60 grays of intensity-modulated radiotherapy with concurrent weekly intravenous cisplatin (30 mg/m 2 ). The primary study end- point was the pathologic complete response rate based on biopsy of the primary site and dissection of pretreatment positive lymph node regions. The pathologic complete response rate as previously reported was 86%. Herein, the authors report secondary endpoint measures of local control, regional control, cause-specific survival, distant metastasis-free survival, and overall survival, and patient- reported outcomes (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [EORTC QLQ-C30] and the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events [PRO-CTCAE]). RESULTS: A total of 44 patients enrolled with a median follow-up of 36 months (88% with 2 years). The 3-year local control, regional control, cause-specific survival, distant metastasis-free survival, and overall survival rates were 100%, 100%, 100%, 100%, and 95%, respectively. The mean before and 3-year after EORTC QOL scores were: global: 80 of 78; swallowing: 11 of 11; dry mouth: 16 of 41; and sticky saliva: 6 of 29. The mean before and 3-year after PRO-CTCAE scores were: swallowing: 0.4 of 0.7; and dry mouth: 0.4 of 1.4. Approximately 39% of patients required a feeding tube (median duration, 15 weeks; none were permanent). There were no grade 3 late adverse events reported. CONCLUSIONS: For patients with favorable-risk human papillomavirus-associated oropharyngeal squa- mous cell carcinoma, a substantially decreased intensity of therapy with 60 grays of intensity-modulated radiotherapy and weekly low-dose cisplatin produced better preservation of quality of life compared with standard therapies while maintaining excellent 3-year tumor control and survival. Cancer 2018;124:2347-54 . V C 2018 American Cancer Society . INTRODUCTION Cancer control and survival appears to be excellent in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC), 1 but standard chemoradiotherapy (CRT) regimens produce substantial toxic- ity. 2 The major effort now is to evaluate less intensive (ie, deintensified) treatment regimens with the goals of main- taining excellent cancer control and decreasing toxicity. There are several different approaches that currently are being studied, with varying degrees of actual deintensification. 3-9 The most common approaches have decreased the radiation dose by either: 1) increasing the chemotherapy dose (ie, the addition of neoadjuvant chemotherapy); or 2) adding primary treatment with transoral surgery. 4,8,10 The limitation of these approaches is that there is little change in the overall intensity of the therapy because they increase the intensity of chemotherapy or surgery to decrease the radiation dose. In 2011, we initiated a program of deintensification with a substantial reduction in the radiation and chemotherapy dose without adding neoadjuvant chemotherapy or definitive surgery. Our deintensified CRT regimen consists of 60 gray Corresponding author: Bhishamjit S. Chera, MD, Department of Radiation Oncology, University of North Carolina Hospitals, 101 Manning Dr, CB #7512, Chapel Hill, NC 27599-7512; bchera@med.unc.edu 1 Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina; 2 UNC Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, North Carolina; 3 Department of Radiation Oncology, University of Florida Hospitals, Gainesville, Florida; 4 UF Health Shands Cancer Center, University of Florida Hospitals, Gainesville, Florida; 5 Division of Hematology Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina; 6 Division of Hematology Oncology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; 7 Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Caro- lina; 8 Rex UNC Healthcare, Raleigh, North Carolina We would like to express our sincere gratitude to Becky Green, MSW, Lori Stravers, MPH, Rebecca Beaulieu, MS, and Lois Blausey MSE, RN, OCN for their signifi- cant roles in ensuring the success of this clinical trial. Additional supporting information may be found in the online version of this article. DOI: 10.1002/cncr.31338, Received: December 13, 2017; Revised: January 29, 2018; Accepted: February 3, 2018, Published online March 26, 2018 in Wiley Online Library (wileyonlinelibrary.com) Bhishamjit S. Chera, MD KEYWORDS: deintensification, human papillomavirus (HPV), oropharynx, phase 2, radiation.

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