Richard Shaw1, Binyam Tesfaye2, Matt Bickerstaff2, Paul Silcocks2, Christopher Butterworth3. 1. Department of Molecular and Clinical Cancer Medicine, University of Liverpool & Head & Neck Division, Aintree University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool Cancer Research Centre, University of Liverpool, Block C Waterhouse Building, 1-3 Brownlow Street, L69 3GL, UK. Electronic address: richard.shaw@liverpool.ac.uk. 2. Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool Cancer Research Centre, University of Liverpool, Block C Waterhouse Building, 1-3 Brownlow Street, L69 3GL, UK. 3. Department of Molecular and Clinical Cancer Medicine, University of Liverpool & Head & Neck Division, Aintree University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; Department of Restorative Dentistry, Liverpool University Dental Hospital, Pembroke Place, Liverpool L3 5PS, UK.
Abstract
INTRODUCTION: Mandibular osteoradionecrosis (ORN) is a common and serious complication of head and neck radiotherapy for which there is little reliable evidence for prevention or treatment. The diagnosis and classification of ORN have been inconsistently and imprecisely defined, even in clinical trials. METHODS: A systematic review of diagnosis and classifications of ORN with specific focus on clinical trials is presented. The most suitable classification was evaluated for consistency using blinded independent review of outcome data (clinical photographs and radiographs) in the HOPON trial. RESULTS: Of 16 ORN classifications found, only one (Notani) appeared suitable as an endpoint in clinical trials. Clinical records of 217 timepoints were analysed amongst 94 randomised patients in the HOPON trial. The only inconsistency in classification arose where minor bone spicules (MBS) were apparent, which occurred in 19% of patients. Some trial investigators judged MBS as clinically unimportant and not reflecting ORN, others classified as ORN based on rigid definitions in common clinical use. When MBS was added as a distinct category to the Notani classification this ambiguity was resolved and agreement between observers was achieved. DISCUSSION: Most definitions and clinical classifications are based on retrospective case series and may be unsuitable for prospective interventional trials of ORN prevention or treatment. When ORN is used as a primary or secondary outcome in prospective clinical trials, the use of Notani classification with the additional category of MBS is recommended as it avoids subjectivity and enhances reliability and consistency of reporting.
INTRODUCTION: Mandibular osteoradionecrosis (ORN) is a common and serious complication of head and neck radiotherapy for which there is little reliable evidence for prevention or treatment. The diagnosis and classification of ORN have been inconsistently and imprecisely defined, even in clinical trials. METHODS: A systematic review of diagnosis and classifications of ORN with specific focus on clinical trials is presented. The most suitable classification was evaluated for consistency using blinded independent review of outcome data (clinical photographs and radiographs) in the HOPON trial. RESULTS: Of 16 ORN classifications found, only one (Notani) appeared suitable as an endpoint in clinical trials. Clinical records of 217 timepoints were analysed amongst 94 randomised patients in the HOPON trial. The only inconsistency in classification arose where minor bone spicules (MBS) were apparent, which occurred in 19% of patients. Some trial investigators judged MBS as clinically unimportant and not reflecting ORN, others classified as ORN based on rigid definitions in common clinical use. When MBS was added as a distinct category to the Notani classification this ambiguity was resolved and agreement between observers was achieved. DISCUSSION: Most definitions and clinical classifications are based on retrospective case series and may be unsuitable for prospective interventional trials of ORN prevention or treatment. When ORN is used as a primary or secondary outcome in prospective clinical trials, the use of Notani classification with the additional category of MBS is recommended as it avoids subjectivity and enhances reliability and consistency of reporting.
Authors: Richard Shaw; Christopher Butterworth; Binyam Tesfaye; Matthew Bickerstaff; Susanna Dodd; Gary Smerdon; Seema Chauhan; Peter Brennan; Keith Webster; James McCaul; Peter Nixon; Anastasios Kanatas; Paul Silcocks Journal: Trials Date: 2018-01-10 Impact factor: 2.279
Authors: Gustaaf J C van Baar; Lars Leeuwrik; Johannes N Lodders; Niels P T J Liberton; K Hakki Karagozoglu; Tymour Forouzanfar; Frank K J Leusink Journal: Front Oncol Date: 2021-02-22 Impact factor: 6.244