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.

Imran Petkar,Shreerang A Bhide,Tom Roques,Emma Hall,Kevin J Harrington,Elizabeth Miles,Marie A Emson,Kathrin Mertens,Christopher M Nutting,James P Morden,David Bernstein,Keith Rooney,Justin W G Roe,Justine M Tyler,Joanne M Patterson,Kate L Newbold,Matthew Beasley

doi:10.1186/s12885-016-2813-0

Abstract

BackgroundPersistent 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.Methods/designThe 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.DiscussionDARS 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.Trial registrationThis study is registered with the International Standard Randomised Controlled Trial register, ISRCTN25458988 (04/01/2016)

Highlights

Persistent dysphagia following primary chemoradiation (CRT) for head and neck cancers can have a devastating impact on patients’ quality of life
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 significant proportion of survivors, subsequently suffer from long-term treatment- related toxicities such as xerostomia and dysphagia. Improving such functional outcomes is pivotal in an era where younger and healthier patients are increasingly cured of their human papillomavirus (HPV)- driven tumours with CRT [3], only to be exposed to decades of debilitating radiation- induced morbidity resulting in an adverse impact on health- related quality of life (HRQoL)

Summary

Discussion

The DARS trial is, to the best of our knowledge, the first RCT aiming to demonstrate that reducing the radiation dose to critical swallowing structures can safely improve long- term swallowing function and quality of life. The DARS trial recognises the importance of a comprehensive assessment for evaluating swallowing by including a multidimensional, longitudinal panel of functional outcome measures integrating instrumental, clinician- rated and patient- reported scales. The MDADI composite score, the primary endpoint of DARS, is generated from a feasible and validated patientreported swallow- specific questionnaire incorporating information from a patient’s physical, functional and emotional level at various recovery time points. It is being adopted as functional outcome tool for a number of head and neck cancer trials [44, 45].

Background

Methods/design

Findings