Radiation vs. trans-oral surgery for treatment de-escalation in HPV-related oropharyngeal cancers: Primary analysis of the ORATOR2 randomized trial.
David A Palma, Eitan Prisman, Eric Berthelet, Eric Tran, Sarah Hamilton, Jonn Wu, Antoine Eskander, Kevin Higgins, Irene Karam, Ian Poon, Zain Husain, Danny Enepekides, Michael Hier, Keith Richardson, Alex Mlynarek, Stephanie Johnson-Obaseki, Marc Gaudet, Andrew Bayley, Samuel Dowthwaite, James E Jackson, Marcin Dzienis, John O'Neil, Shamir Chandarana, Robyn Banerjee, Robert Hart, Jeffson Chung, Todd Tenenholtz, Hien Le, John Yoo, Adrian Mendez, Eric Winquist, Sara Kuruvilla, Paul Stewart, Andrew Warner, Sylvia Mitchell, Jeff Chen, Christina Parker, Keith Kwan, Julie Theurer, Houda Bahig, Apostolos Christopoulos, Lucas C Mendez, Jinka Sathya, J Alex Hammond, Nancy Read, Varagur Venkatesan, Kevin Fung, Anthony C Nichols
Author Information
David A Palma: Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada. Electronic address: david.palma@lhsc.on.ca.
Eitan Prisman: Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
Eric Berthelet: Department of Radiation Oncology, Centre Hospitalier de l'Universit�� de Montr��al, Montr��al, Quebec, Canada.
Eric Tran: Division of Radiation Oncology, Department of Oncology, University of British Columbia, Vancouver, British Columbia, Canada.
Sarah Hamilton: Division of Radiation Oncology, Department of Oncology, University of British Columbia, Vancouver, British Columbia, Canada.
Jonn Wu: Division of Radiation Oncology, Department of Oncology, University of British Columbia, Vancouver, British Columbia, Canada.
Antoine Eskander: Department of Otolaryngology - Head and Neck Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Kevin Higgins: Department of Otolaryngology - Head and Neck Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Irene Karam: Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
Ian Poon: Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
Zain Husain: Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
Danny Enepekides: Department of Otolaryngology - Head and Neck Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Michael Hier: Department of Otolaryngology - Head and Neck Surgery, McGill University, Montreal, Quebec, Canada.
Keith Richardson: Department of Otolaryngology - Head and Neck Surgery, McGill University, Montreal, Quebec, Canada.
Alex Mlynarek: Department of Otolaryngology - Head and Neck Surgery, McGill University, Montreal, Quebec, Canada.
Stephanie Johnson-Obaseki: Department of Otolaryngology - Head and Neck Surgery, University of Ottawa, Ottawa, Ontario, Canada.
Marc Gaudet: Division of Radiation Oncology, University of Ottawa, Ottawa, Ontario, Canada.
Andrew Bayley: Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Samuel Dowthwaite: Department of Otolaryngology - Head and Neck Surgery, Gold Coast University Hospital, Southport, Queensland, Australia.
James E Jackson: Icon Cancer Centre, Gold Coast University Hospital, Southport, Queensland, Australia.
Marcin Dzienis: Department of Medical Oncology, Gold Coast University Hospital, Southport, Queensland, Australia.
John O'Neil: Department of Otolaryngology - Head and Neck Surgery, Gold Coast University Hospital, Southport, Queensland, Australia.
Shamir Chandarana: Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Alberta, Canada.
Robyn Banerjee: Division of Radiation Oncology, University of Calgary, Calgary, Alberta, Canada.
Robert Hart: Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Alberta, Canada.
Jeffson Chung: Department of Otolaryngology - Head and Neck Surgery, West Virginia University, Morgantown, WV, United States.
Todd Tenenholtz: Department of Radiation Oncology, West Virginia University, Morgantown, WV, United States.
Hien Le: Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia.
John Yoo: Department of Otolaryngology - Head and Neck Surgery, Western University, London, Ontario, Canada.
Adrian Mendez: Department of Otolaryngology - Head and Neck Surgery, Western University, London, Ontario, Canada.
Eric Winquist: Division of Medical Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Sara Kuruvilla: Division of Medical Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Paul Stewart: Division of Medical Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Andrew Warner: Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Sylvia Mitchell: Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Jeff Chen: Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Christina Parker: Department of Audiology, London Health Sciences Centre, London, Ontario, Canada.
Keith Kwan: Department of Pathology, Western University, London, Ontario, Canada.
Julie Theurer: School of Communication Sciences and Disorders, Western University, London, Ontario, Canada.
Houda Bahig: Department of Radiology, Radio-Oncology and Nuclear Medicine, Division of Radio-Oncology, Centre Hospitalier de l'Universit�� de Montr��al (CHUM), Universit�� de Montr��al, Montr��al, Quebec, Canada.
Apostolos Christopoulos: Division of Otorhinolaryngology-Head and Neck Surgery, Centre Hospitalier de l'Universit�� de Montr��al (CHUM), Universit�� de Montr��al, Montr��al, Quebec, Canada.
Lucas C Mendez: Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Jinka Sathya: Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada.
J Alex Hammond: Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Nancy Read: Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Varagur Venkatesan: Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada.
Kevin Fung: Department of Otolaryngology - Head and Neck Surgery, Western University, London, Ontario, Canada.
Anthony C Nichols: Department of Otolaryngology - Head and Neck Surgery, Western University, London, Ontario, Canada.
BACKGROUND: The optimal treatment de-escalation approach for HPV-related oropharyngeal squamous cell carcinomas (OPSCC) is unknown. The objective was to assess two de-escalation approaches: primary radiotherapy (RT) vs. transoral surgical (TOS). PATIENTS AND METHODS: Patients with T1-T2 N0-2 HPV-related OPSCC were randomly assigned to primary RT (60���Gy with concurrent weekly cisplatin in node-positive) vs. TOS +���neck dissection (ND) (and adjuvant reduced-dose RT depending on pathology). The primary endpoint was 2-year OS (hypothesized to be 94���% in each arm, compared to 84���%). Secondary endpoints included comparisons of survival and quality of life between arms. The trial was stopped early due to two treatment related deaths in the surgical arm. RESULTS: Sixty-one patients were randomized (n���=���30 in RT arm and n���=���31 in TOS+ND arm), with a median age of 62 years (IQR: 57-68). The majority were male (n���=���51) and never-smokers (n���=���31). Median follow-up was 3.7 years (IQR: 3.1-4.5 years). In the RT arm, the primary endpoint for acceptability was met (p���=���0.008), and two-year OS was 100���% (95���% confidence interval [CI]: 100-100���%). In the TOS+ND arm, the primary endpoint was not met (p���=���0.296) and two-year OS was 90���% (95���% CI: 71-97���%), significantly worse than the RT arm (p���=���0.041). Two-year progression-free survival (PFS) were 100���% (95���% CI: 100-100���%) vs. 86���% (95���% CI: 67-95���%) respectively (p���=���0.012). Mean (�����SD) 2-year MDADI total scores were 89��������13 vs. 83��������11, respectively (p���=���0.11), and grade 2-5 toxicity rates were similar (n���=���21 vs. n���=���24 respectively, p���=���0.51), with no additional grade 5 events. CONCLUSION: For treatment de-escalation, a primary RT approach achieved excellent oncologic and functional outcomes and should be tested in phase III de-escalation trials. TRIAL REGISTRATION: Clinicaltrials.gov NCT03210103.
