Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

Aged Chemoradiotherapy, Adjuvant Deglutition Deglutition Disorders / etiology Female Hearing Loss / etiology Humans Intention to Treat Analysis Male Middle Aged Neck Dissection / adverse effects Neutropenia / etiology Quality of Life Radiotherapy, Intensity-Modulated / adverse effects Robotic Surgical Procedures / adverse effects Squamous Cell Carcinoma of Head and Neck / complications Stomatitis / etiology Surveys and Questionnaires Tinnitus / etiology Tongue Neoplasms / complications Tonsillar Neoplasms / complications Trismus / etiology

Journal

The Lancet. Oncology
ISSN: 1474-5488
Titre abrégé: Lancet Oncol
Pays: England
ID NLM: 100957246

Informations de publication

Date de publication:
10 2019
Historique:
received: 26 04 2019
revised: 05 06 2019
accepted: 06 06 2019
pubmed: 17 8 2019
medline: 23 6 2020
entrez: 17 8 2019
Statut: ppublish

Résumé

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. 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. 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. 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. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1016/S1470-2045(19)30410-3 PMID: 31416685
pubmed: 31416685
pii: S1470-2045(19)30410-3
doi: 10.1016/S1470-2045(19)30410-3
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT01590355']

Types de publication

Clinical Trial, Phase II Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1349-1359

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : ErratumIn

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Anthony C Nichols (AC)

Department of Otolaryngology-Head and Neck Surgery, Western University, London, ON, Canada. Electronic address: anthony.nichols@lhsc.on.ca.

Julie Theurer (J)

School of Communication Sciences and Disorders, Western University, London, ON, Canada.

Eitan Prisman (E)

Department of Otolaryngology, University of British Columbia, Vancouver, BC, Canada.

Nancy Read (N)

Department of Radiation Oncology, Western University, London, ON, Canada.

Eric Berthelet (E)

Department of Radiation Oncology, University of British Columbia, Vancouver, BC, Canada.

Eric Tran (E)

Department of Radiation Oncology, University of British Columbia, Vancouver, BC, Canada.

Kevin Fung (K)

Department of Otolaryngology-Head and Neck Surgery, Western University, London, ON, Canada.

John R de Almeida (JR)

Department of Otolaryngology-Head and Neck Surgery, University Health Network, University of Toronto, Toronto, ON, Canada.

Andrew Bayley (A)

Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, ON, Canada.

David P Goldstein (DP)

Department of Otolaryngology-Head and Neck Surgery, University Health Network, University of Toronto, Toronto, ON, Canada.

Michael Hier (M)

Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, QC, Canada.

Khalil Sultanem (K)

Department of Radiation Oncology, McGill University, Montreal, QC, Canada.

Keith Richardson (K)

Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, QC, Canada.

Alex Mlynarek (A)

Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, QC, Canada.

Suren Krishnan (S)

Department of Otolaryngology-Head and Neck Surgery, Royal Adelaide Hospital, Adelaide, Australia.

Hien Le (H)

Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia.

John Yoo (J)

Department of Otolaryngology-Head and Neck Surgery, Western University, London, ON, Canada.

S Danielle MacNeil (SD)

Department of Otolaryngology-Head and Neck Surgery, Western University, London, ON, Canada.

Eric Winquist (E)

Department of Medical Oncology, Western University, London, ON, Canada.

J Alex Hammond (JA)

Department of Radiation Oncology, Western University, London, ON, Canada.

Varagur Venkatesan (V)

Department of Radiation Oncology, Western University, London, ON, Canada.

Sara Kuruvilla (S)

Department of Medical Oncology, Western University, London, ON, Canada.

Andrew Warner (A)

Department of Radiation Oncology, Western University, London, ON, Canada.

Sylvia Mitchell (S)

Department of Radiation Oncology, Western University, London, ON, Canada.

Jeff Chen (J)

Department of Radiation Oncology, Western University, London, ON, Canada.

Martin Corsten (M)

Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Ottawa, ON, Canada.

Stephanie Johnson-Obaseki (S)

Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Ottawa, ON, Canada.

Libni Eapen (L)

Department of Radiation Oncology, University of Ottawa, Ottawa, ON, Canada.

Michael Odell (M)

Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Ottawa, ON, Canada.

Christina Parker (C)

Department of Audiology, London Health Sciences Centre, London, ON, Canada.

Bret Wehrli (B)

Department of Pathology, Western University, London, ON, Canada.

Keith Kwan (K)

Department of Pathology, Western University, London, ON, Canada.

David A Palma (DA)

Department of Radiation Oncology, Western University, London, ON, Canada.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Thérapeutique › Radiothérapie › Chimioradiothérapie › Chimioradiothérapie adjuvante › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil buccodentaire et de l'appareil digestif › Phénomènes physiologiques de l'appareil digestif › Déglutition › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Maladies oto-rhino-laryngologiques › Maladies du pharynx › Troubles de la déglutition › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Troubles sensitifs › Troubles de l'audition › Perte d'audition › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques contrôlés comme sujet › Essais contrôlés randomisés comme sujet › Analyse en intention de traitement › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Procédures de chirurgie opératoire › Procédures de chirurgie oto-rhino-laryngologique › Évidement ganglionnaire cervical › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Troubles leucocytaires › Leucopénie › Agranulocytose › Neutropénie › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Mesures épidémiologiques › Démographie › État de santé › Qualité de vie › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Sciences de l'information › Informatique › Informatique médicale › Applications de l'informatique médicale › Prise de décision assistée par ordinateur › Thérapie assistée par ordinateur › Radiothérapie assistée par ordinateur › Radiothérapie conformationnelle › Radiothérapie conformationnelle avec modulation d'intensité › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Technologie, industrie et agriculture › Technologie › Automatisation › Interventions chirurgicales robotisées › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Tumeurs › Tumeurs par siège › Tumeurs de la tête et du cou › Carcinome épidermoïde de la tête et du cou › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Maladies du système stomatognathique › Maladies de la bouche › Stomatite › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Enquêtes et questionnaires › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Troubles sensitifs › Troubles de l'audition › Acouphène › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Maladies du système stomatognathique › Maladies de la bouche › Maladies de la langue › Tumeurs de la langue › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › Maladies oto-rhino-laryngologiques › Maladies du pharynx › Tumeurs du pharynx › Tumeurs de l'oropharynx › Tumeurs de l'amygdale › Radiotherapy versus transoral robotic surgery...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Manifestations neuromusculaires › Spasme › Trismus › Radiotherapy versus transoral robotic surgery...