title: DARS: a phase III randomised multicentre study of dysphagia- optimised intensity- modulated radiotherapy (Do-IMRT) versus standard intensity- modulated radiotherapy (S-IMRT) in head and neck cancer.
abstract: Persistent dysphagia following primary chemoradiation (CRT) for head and neck cancers can have a devastating impact on patients' quality of life. Single arm studies have shown that the dosimetric sparing of critical swallowing structures such as the pharyngeal constrictor muscle and supraglottic larynx can translate to better functional outcomes. However, there are no current randomised studies to confirm the benefits of such swallow sparing strategies. The aim of Dysphagia/Aspiration at risk structures (DARS) trial is to determine whether reducing the dose to the pharyngeal constrictors with dysphagia-optimised intensity- modulated radiotherapy (Do-IMRT) will lead to an improvement in long- term swallowing function without having any detrimental impact on disease-specific survival outcomes.
  
  
  
  The DARS trial (CRUK/14/014) is a phase III multicentre randomised controlled trial (RCT) for patients undergoing primary (chemo) radiotherapy for T1-4, N0-3, M0 pharyngeal cancers. Patients will be randomised (1:1 ratio) to either standard IMRT (S-IMRT) or Do-IMRT. Radiotherapy doses will be the same in both groups; however in patients allocated to Do-IMRT, irradiation of the pharyngeal musculature will be reduced by delivering IMRT identifying the pharyngeal muscles as organs at risk. The primary endpoint of the trial is the difference in the mean MD Anderson Dysphagia Inventory (MDADI) composite score, a patient-reported outcome, measured at 12 months post radiotherapy. Secondary endpoints include prospective and longitudinal evaluation of swallow outcomes incorporating a range of subjective and objective assessments, quality of life measures, loco-regional control and overall survival. Patients and speech and language therapists (SLTs) will both be blinded to treatment allocation arm to minimise outcome-reporting bias.
  
  
  
  DARS is the first RCT investigating the effect of swallow sparing strategies on improving long-term swallowing outcomes in pharyngeal cancers. An integral part of the study is the multidimensional approach to swallowing assessment, providing robust data for the standardisation of future swallow outcome measures. A translational sub- study, which may lead to the development of future predictive and prognostic biomarkers, is also planned.
  
  
  
  This study is registered with the International Standard Randomised Controlled Trial register, ISRCTN25458988 (04/01/2016).
authors.affiliation: The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.|The Institute of Cancer Research (ICR), 123 Old Brompton Road, London, SW7 3RP, UK.
authors.forename: Imran
authors.initials: I
authors.lastname: Petkar
authors.affiliation: Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Rooney
authors.affiliation: The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
authors.forename: Justin W G
authors.initials: JW
authors.lastname: Roe
authors.affiliation: Speech and Language Therapy Department, Sunderland City Hospitals NHS Foundation Trust, Kayll Road, Sunderland, SR4 7TP, UK.|Institute of Health and Society, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Patterson
authors.affiliation: The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Bernstein
authors.affiliation: The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
authors.forename: Justine M
authors.initials: JM
authors.lastname: Tyler
authors.affiliation: The Institute of Cancer Research (ICR), 123 Old Brompton Road, London, SW7 3RP, UK.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Emson
authors.affiliation: The Institute of Cancer Research (ICR), 123 Old Brompton Road, London, SW7 3RP, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Morden
authors.affiliation: The Institute of Cancer Research (ICR), 123 Old Brompton Road, London, SW7 3RP, UK.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Mertens
authors.affiliation: Mount Vernon Hospital, Rickmansworth Road, Northwood, HA6 2RN, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miles
authors.affiliation: University Hospitals Bristol, Horfield Road, Bristol, BS2 8ED, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Beasley
authors.affiliation: Norfolk and Norwich University Hospital NHS Trust, Colney Lane, Norwich, NR4 7UY, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Roques
authors.affiliation: The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.|The Institute of Cancer Research (ICR), 123 Old Brompton Road, London, SW7 3RP, UK.
authors.forename: Shreerang A
authors.initials: SA
authors.lastname: Bhide
authors.affiliation: The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Newbold
authors.affiliation: The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.|The Institute of Cancer Research (ICR), 123 Old Brompton Road, London, SW7 3RP, UK.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Harrington
authors.affiliation: The Institute of Cancer Research (ICR), 123 Old Brompton Road, London, SW7 3RP, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Hall
authors.affiliation: The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK. Chris.Nutting@rmh.nhs.uk.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Nutting
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D017326:Clinical Trials, Phase III as Topic; D003680:Deglutition Disorders / Q000209:etiology / Q000517:prevention & control*; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D015337:Multicenter Studies as Topic; D011788:Quality of Life; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: Dysphagia; Dysphagia-optimised intensity-modulated radiotherapy; Pharyngeal cancer; Pharyngeal constrictor muscle