Anthony C Nichols1, Julie Theurer2, Eitan Prisman3, Nancy Read4, Eric Berthelet5, Eric Tran5, Kevin Fung6, John R de Almeida7, Andrew Bayley8, David P Goldstein7, Michael Hier9, Khalil Sultanem10, Keith Richardson9, Alex Mlynarek9, Suren Krishnan11, Hien Le12, John Yoo6, S Danielle MacNeil6, Eric Winquist13, J Alex Hammond4, Varagur Venkatesan4, Sara Kuruvilla13, Andrew Warner4, Sylvia Mitchell4, Jeff Chen4, Martin Corsten14, Stephanie Johnson-Obaseki14, Libni Eapen15, Michael Odell14, Christina Parker16, Bret Wehrli17, Keith Kwan17, David A Palma4. 1. Department of Otolaryngology-Head and Neck Surgery, Western University, London, ON, Canada. Electronic address: anthony.nichols@lhsc.on.ca. 2. School of Communication Sciences and Disorders, Western University, London, ON, Canada. 3. Department of Otolaryngology, University of British Columbia, Vancouver, BC, Canada. 4. Department of Radiation Oncology, Western University, London, ON, Canada. 5. Department of Radiation Oncology, University of British Columbia, Vancouver, BC, Canada. 6. Department of Otolaryngology-Head and Neck Surgery, Western University, London, ON, Canada. 7. Department of Otolaryngology-Head and Neck Surgery, University Health Network, University of Toronto, Toronto, ON, Canada. 8. Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, ON, Canada. 9. Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, QC, Canada. 10. Department of Radiation Oncology, McGill University, Montreal, QC, Canada. 11. Department of Otolaryngology-Head and Neck Surgery, Royal Adelaide Hospital, Adelaide, Australia. 12. Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia. 13. Department of Medical Oncology, Western University, London, ON, Canada. 14. Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Ottawa, ON, Canada. 15. Department of Radiation Oncology, University of Ottawa, Ottawa, ON, Canada. 16. Department of Audiology, London Health Sciences Centre, London, ON, Canada. 17. Department of Pathology, Western University, London, ON, Canada.
Abstract
BACKGROUND:Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. METHODS: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. FINDINGS:68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. INTERPRETATION: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. FUNDING: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.
RCT Entities:
BACKGROUND: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. METHODS: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. FINDINGS: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. INTERPRETATION:Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. FUNDING: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.
Authors: Anthony T Nguyen; Michael Luu; Jon Mallen-St Clair; Alain C Mita; Kevin S Scher; Diana J Lu; Stephen L Shiao; Allen S Ho; Zachary S Zumsteg Journal: JAMA Oncol Date: 2020-10-01 Impact factor: 31.777
Authors: Catherine T Haring; Collin Brummel; Chandan Bhambhani; Brittany Jewell; Molly Heft Neal; Apurva Bhangale; Keith Casper; Kelly Malloy; Scott McLean; Andrew Shuman; Chaz Stucken; Andrew Rosko; Mark Prince; Carol Bradford; Avraham Eisbruch; Michelle Mierzwa; Muneesh Tewari; Francis P Worden; Paul L Swiecicki; Matthew E Spector; J Chad Brenner Journal: Oral Oncol Date: 2021-06-14 Impact factor: 5.337