Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1

Lone E Forner; François J Dieleman; Richard J Shaw; Anastasios Kanatas; Chris J Butterworth; Göran Kjeller; Jan Alsner; Jens Overgaard; Søren Hillerup; Ole Hyldegaard; Per Arnell; Christian von Buchwald; Johannes H A M Kaanders; Ludi E Smeele; Lena Specht; Jørgen Johansen; Max J H Witjes; Matthias A W Merkx; Erik C Jansen

doi:10.1016/j.radonc.2021.11.021

Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1

Radiother Oncol. 2022 Jan:166:137-144. doi: 10.1016/j.radonc.2021.11.021. Epub 2021 Nov 26.

Authors

Lone E Forner¹, François J Dieleman², Richard J Shaw³, Anastasios Kanatas⁴, Chris J Butterworth⁵, Göran Kjeller⁶, Jan Alsner⁷, Jens Overgaard⁷, Søren Hillerup⁸, Ole Hyldegaard⁹, Per Arnell¹⁰, Christian von Buchwald¹¹, Johannes H A M Kaanders¹², Ludi E Smeele¹³, Lena Specht¹⁴, Jørgen Johansen¹⁵, Max J H Witjes¹⁶, Matthias A W Merkx¹⁷, Erik C Jansen⁹

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Center of Head and Orthopedics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Anaesthesia, Center of Head and Orthopedics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
² Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center, Utrecht, The Netherlands; Department of Oral and Maxillofacial Surgery, Radboud University Medical Center Nijmegen, The Netherlands. Electronic address: f.j.dieleman-3@umcutrecht.nl.
³ Department of Head and Neck Surgery, Aintree University Hospital, Liverpool, UK.
⁴ Oral & Maxillofacial Surgery Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
⁵ Maxillofacial Prosthodontics, Department of Maxillofacial Surgery, Aintree University Hospital, Liverpool, UK.
⁶ Department of Oral and Maxillofacial Surgery, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Sweden.
⁷ Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
⁸ Department of Oral and Maxillofacial Surgery, Center of Head and Orthopedics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁹ Department of Anaesthesia, Center of Head and Orthopedics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁰ Department of Anaesthesiology and Intensive Care Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹¹ Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹² Department of Radiation Oncology, Radboud University Medical Center Nijmegen, The Netherlands.
¹³ Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
¹⁴ Department of Oncology, Rigshospitalet, University of Copenhagen, Denmark.
¹⁵ Department of Oncology, Odense University Hospital, Odense, Denmark.
¹⁶ Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁷ Department of Oral and Maxillofacial Surgery, Radboud University Medical Center Nijmegen, The Netherlands; Netherlands Comprehensive Cancer Organization Utrecht, The Netherlands.

PMID: 34843843
DOI: 10.1016/j.radonc.2021.11.021

Abstract

Purpose: Osteoradionecrosis (ORN) of the mandible is a serious complication of head and neck radiotherapy. This study aims to investigate the effect of hyperbaric oxygen (HBO) treatment on ORN in two randomized, controlled multicentre trials.

Methods and materials: Patients with ORN with indication for surgical treatment were randomised to either group 1: surgical removal of necrotic mandibular bone supplemented by 30 pre- and 10 postoperative HBO exposures at 243 kPa for 90 min each, or group 2: surgical removal of necrotic bone only. Primary outcome was healing of ORN one year after surgery evaluated by a clinically adjusted version of the Common Toxicity Criteria of Adverse Events (CTCAE) v 3.0. Secondary outcomes included xerostomia, unstimulated and stimulated whole salivation rates, trismus, dysphagia, pain, Activities of Daily Living (ADL) and quality of life according to EORTC. Data were combined from two separate trials. Ninety-seven were enrolled and 65 were eligible for the intent-to-treat analysis. The 33% drop-out was equally distributed between groups.

Results: In group 1, 70% (21/30) healed compared to 51% (18/35) in group 2. HBO was associated with an increased chance of healing independent of baseline ORN grade or smoking status as well as improved xerostomia, unstimulated whole salivary flow rate, and dysphagia. Due to insufficient recruitment, none of the endpoints reached a statistically significant difference between groups. ADL data could only be obtained from 50 patients.

Conclusion: Hyperbaric oxygen did not significantly improve the healing outcome of osteoradionecrosis after surgical removal of necrotic bone as compared to standard care (70% vs. 51%). This effect is not statistically significant due to the fact that the study was underpowered and is therefore prone to type II error.

Keywords: Head and neck cancer; Hyperbaric oxygen treatment; Mandible; Osteoradionecrosis; Radiation therapy; Randomised clinical trial.

Publication types

Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Activities of Daily Living
Deglutition Disorders* / therapy
Head and Neck Neoplasms* / therapy
Humans
Hyperbaric Oxygenation* / adverse effects
Mandible
Osteoradionecrosis* / etiology
Osteoradionecrosis* / therapy
Oxygen
Quality of Life
Randomized Controlled Trials as Topic
Xerostomia* / therapy

Substances

Oxygen