BMC Cancer (Feb 2020)
Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial
- Anthony C. Nichols,
- Pencilla Lang,
- Eitan Prisman,
- Eric Berthelet,
- Eric Tran,
- Sarah Hamilton,
- Jonn Wu,
- Kevin Fung,
- John R. de Almeida,
- Andrew Bayley,
- David P. Goldstein,
- Antoine Eskander,
- Zain Husain,
- Houda Bahig,
- Apostolos Christopoulous,
- Michael Hier,
- Khalil Sultanem,
- Keith Richardson,
- Alex Mlynarek,
- Suren Krishnan,
- Hien Le,
- John Yoo,
- S. Danielle MacNeil,
- Adrian Mendez,
- Eric Winquist,
- Nancy Read,
- Varagur Venkatesan,
- Sara Kuruvilla,
- Andrew Warner,
- Sylvia Mitchell,
- Martin Corsten,
- Murali Rajaraman,
- Stephanie Johnson-Obaseki,
- Libni Eapen,
- Michael Odell,
- Shamir Chandarana,
- Robyn Banerjee,
- Joseph Dort,
- T. Wayne Matthews,
- Robert Hart,
- Paul Kerr,
- Samuel Dowthwaite,
- Michael Gupta,
- Han Zhang,
- Jim Wright,
- Christina Parker,
- Bret Wehrli,
- Keith Kwan,
- Julie Theurer,
- David A. Palma
Affiliations
- Anthony C. Nichols
- Department of Otolaryngology – Head and Neck Surgery, Western University
- Pencilla Lang
- Department of Radiation Oncology, London Health Sciences Centre, Western University
- Eitan Prisman
- Division of Otolaryngology – Head and Neck Surgery, University of British Columbia
- Eric Berthelet
- Department of Radiation Oncology, University of British Columbia
- Eric Tran
- Department of Radiation Oncology, University of British Columbia
- Sarah Hamilton
- Department of Radiation Oncology, University of British Columbia
- Jonn Wu
- Department of Radiation Oncology, University of British Columbia
- Kevin Fung
- Department of Otolaryngology – Head and Neck Surgery, Western University
- John R. de Almeida
- Department of Otolaryngology – Head and Neck Surgery, University Health Network, University of Toronto
- Andrew Bayley
- Department of Radiation Oncology, University Health Network, University of Toronto
- David P. Goldstein
- Department of Otolaryngology – Head and Neck Surgery, University Health Network, University of Toronto
- Antoine Eskander
- Department of Otolaryngology – Head and Neck Surgery, Sunnybrook Health Sciences Centre, University of Toronto
- Zain Husain
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto
- Houda Bahig
- Department of Radiation Oncology, CHUM, Université de Montréal
- Apostolos Christopoulous
- Department of Otorhinolaryngology - Head and Neck Surgery, CHUM, Université de Montréal
- Michael Hier
- Department of Otolaryngology – Head and Neck Surgery, McGill University
- Khalil Sultanem
- Department of Radiation Oncology, McGill University
- Keith Richardson
- Department of Otolaryngology – Head and Neck Surgery, McGill University
- Alex Mlynarek
- Department of Otolaryngology – Head and Neck Surgery, McGill University
- Suren Krishnan
- Department of Otolaryngology – Head and Neck Surgery, Royal Adelaide Hospital
- Hien Le
- Department of Radiation Oncology, Royal Adelaide Hospital
- John Yoo
- Department of Otolaryngology – Head and Neck Surgery, Western University
- S. Danielle MacNeil
- Department of Otolaryngology – Head and Neck Surgery, Western University
- Adrian Mendez
- Department of Otolaryngology – Head and Neck Surgery, Western University
- Eric Winquist
- Department of Medical Oncology, Western University
- Nancy Read
- Department of Radiation Oncology, London Health Sciences Centre, Western University
- Varagur Venkatesan
- Department of Radiation Oncology, London Health Sciences Centre, Western University
- Sara Kuruvilla
- Department of Medical Oncology, Western University
- Andrew Warner
- Department of Radiation Oncology, London Health Sciences Centre, Western University
- Sylvia Mitchell
- Department of Radiation Oncology, London Health Sciences Centre, Western University
- Martin Corsten
- Division of Otolaryngology – Head and Neck Surgery, Dalhousie University
- Murali Rajaraman
- Division of Otolaryngology – Head and Neck Surgery, Dalhousie University
- Stephanie Johnson-Obaseki
- Department of Otolaryngology – Head and Neck Surgery, University of Ottawa
- Libni Eapen
- Department of Radiation Oncology, University of Ottawa
- Michael Odell
- Department of Otolaryngology – Head and Neck Surgery, University of Ottawa
- Shamir Chandarana
- Section of Otolaryngology – Head and Neck Surgery, University of Calgary
- Robyn Banerjee
- Department of Radiation Oncology, University of Calgary
- Joseph Dort
- Section of Otolaryngology – Head and Neck Surgery, University of Calgary
- T. Wayne Matthews
- Section of Otolaryngology – Head and Neck Surgery, University of Calgary
- Robert Hart
- Section of Otolaryngology – Head and Neck Surgery, University of Calgary
- Paul Kerr
- Department of Otolaryngology, University of Manitoba
- Samuel Dowthwaite
- Department of Otolaryngology – Head and Neck Surgery, Gold Coast University Hospital
- Michael Gupta
- Division of Otolaryngology – Head and Neck Surgery, McMaster University
- Han Zhang
- Division of Otolaryngology – Head and Neck Surgery, McMaster University
- Jim Wright
- Department of Radiation Oncology, McMaster University
- Christina Parker
- Department of Audiology, London Health Sciences Centre
- Bret Wehrli
- Department of Pathology, Western University
- Keith Kwan
- Department of Pathology, Western University
- Julie Theurer
- School of Communication Sciences and Disorders, Western University
- David A. Palma
- Department of Radiation Oncology, London Health Sciences Centre, Western University
- DOI
- https://doi.org/10.1186/s12885-020-6607-z
- Journal volume & issue
-
Vol. 20,
no. 1
pp. 1 – 13
Abstract
Abstract 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.
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