David A Palma1, Eitan Prisman2, Eric Berthelet3, Eric Tran3, Sarah Hamilton3, Jonn Wu3, Antoine Eskander4, Kevin Higgins4, Irene Karam5, Ian Poon5, Zain Husain5, Danny Enepekides4, Michael Hier6, Khalil Sultanem7, Keith Richardson6, Alex Mlynarek6, Stephanie Johnson-Obaseki8, Michael Odell8, Andrew Bayley9, Samuel Dowthwaite10, James E Jackson11, Marcin Dzienis12, John O'Neil11, Shamir Chandarana13, Robyn Banerjee14, Robert Hart13, Jeffson Chung15, Todd Tenenholtz16, Suren Krishnan17, Hien Le18, John Yoo19, Adrian Mendez19, Eric Winquist20, Sara Kuruvilla20, Paul Stewart20, Andrew Warner1, Sylvia Mitchell1, Jeff Chen1, Christina Parker21, Bret Wehrli22, Keith Kwan22, Julie Theurer23, Jinka Sathya1, J Alex Hammond1, Nancy Read1, Varagur Venkatesan1, S Danielle MacNeil19, Kevin Fung19, Anthony C Nichols19. 1. Division of Radiation Oncology, Department of Oncology, Western University, London, Ontario, Canada. 2. Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada. 3. Division of Radiation Oncology, Department of Oncology, University of British Columbia, Vancouver, British Columbia, Canada. 4. Department of Otolaryngology-Head and Neck Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. 5. Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada. 6. Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, Quebec, Canada. 7. Department of Radiation Oncology, McGill University, Montreal, Quebec, Canada. 8. Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Ottawa, Ontario, Canada. 9. Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, Ontario, Canada. 10. Department of Otolaryngology-Head and Neck Surgery, Gold Coast University Hospital, Southport, Queensland, Australia. 11. Icon Cancer Centre, Gold Coast University Hospital, Southport, Queensland, Australia. 12. Department of Medical Oncology, Gold Coast University Hospital, Southport, Queensland, Australia. 13. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Alberta, Canada. 14. Division of Radiation Oncology, University of Calgary, Calgary, Alberta, Canada. 15. Department of Otolaryngology-Head and Neck Surgery, West Virginia University, Morgantown. 16. Department of Radiation Oncology, West Virginia University, Morgantown. 17. Department of Otolaryngology-Head and Neck Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 18. Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 19. Department of Otolaryngology-Head and Neck Surgery, Western University, London, Ontario, Canada. 20. Division of Medical Oncology, Department of Oncology, Western University, London, Ontario, Canada. 21. Department of Audiology, London Health Sciences Centre, London, Ontario, Canada. 22. Department of Pathology, Western University, London, Ontario, Canada. 23. School of Communication Sciences and Disorders, Western University, London, Ontario, Canada.
Abstract
Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.
Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.
Authors: Raymond L Chai; Rocco M Ferrandino; Christine Barron; Kianoush Donboli; Scott A Roof; Mohemmed N Khan; Marita S Teng; Marshall R Posner; Richard L Bakst; Eric M Genden Journal: Front Oncol Date: 2022-08-25 Impact factor: 5.738