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

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)

Late Feeding Tube Dependency in Head and Neck Cancer Patients Treated with Definitive Radiation Therapy and Concurrent Systemic Therapy

“…Using these contouring guidelines to mark the delineation of FSUs may reduce toxicity, leading to better outcomes [20,21]. A new randomized control trial is planned to more definitively explore the role of IMRT in reducing dysphagia [22]. Regarding our study, more than half of our cohort received IMRT-based therapy.…”

Long-Term Aspects of Quality of Life in Head and Neck Cancer Patients Treated With Intensity Modulated Radiation Therapy: A 5-Year Longitudinal Follow-up and Comparison with a Normal Population Cohort

“…A randomized phase III trial focusing on this issue is currently ongoing. 23 A stratified analysis was added, addressing the heterogeneity of the included patients. No significant differences in mean score changes were found in patients with added surgery, with different tumor sites or stages, possibly owing to few patients in some of the groups.…”

Dysphagia optimized radiotherapy to reduce swallowing dysfunction severity in patients undergoing treatment for head and neck cancer: A systematized scoping review

“…As highlighted by this scoping review, the current evidence base is highly heterogeneous and limited to single prospective cohorts with a lack of comparison groups. Recognizing such literature shortfalls, a research group based in the United Kingdom recently released a protocol for a phase III randomized control trial, with the study aim being to explore whether reducing dose to the PCM via dysphagia‐optimized IMRT (Do‐IMRT) will result in improved long‐term swallowing function and overall health‐related QoL . This study may assist in further quantifying the benefit of active DARS sparing radiotherapy for swallow function.…”