Nichols, Anthony CLang, PencillaPrisman, EitanBerthelet, EricTran, EricHamilton, SarahWu, JonnFung, Kevinde Almeida, John RBayley, AndrewGoldstein, David PEskander, AntoineHusain, ZainBahig, HoudaChristopoulous, ApostolosHier, MichaelSultanem, KhalilRichardson, KeithMlynarek, AlexKrishnan, SurenLe, HienYoo, JohnMacNeil, S. DMendez, AdrianWinquist, EricRead, NancyVenkatesan, VaragurKuruvilla, SaraWarner, AndrewMitchell, SylviaCorsten, MartinRajaraman, MuraliJohnson-Obaseki, StephanieEapen, LibniOdell, MichaelChandarana, ShamirBanerjee, RobynDort, JosephMatthews, T. WHart, RobertKerr, PaulDowthwaite, SamuelGupta, MichaelZhang, HanWright, JimParker, ChristinaWehrli, BretKwan, KeithTheurer, JuliePalma, David A2020-02-162020-02-162020-02-14BMC Cancer. 2020 Feb 14;20(1):125http://hdl.handle.net/1880/11165010.11575/PRISM/45650Abstract Background Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. Methods This is a multicenter phase II study randomizing one hundred and forty patients with T1–2 N0–2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50–60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity. Discussion This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. Trial Registration Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.Journal Article2020-02-16enThe Author(s).https://doi.org/10.1186/s12885-020-6607-z