The DARS study: Targeted therapy for pharyngeal tumours
Most oropharyngeal cancers are treated with chemo-radiotherapy, with often-negative QoL effects. But DO-IMRT may improve swallowing, over standard IMRT.
Pharyngeal cancers are a common pathology
Pharyngeal cancers are a common disease. It affects around 3,000 patients in the UK each year. In Italy, there are approximately 2,800 new cases of laryngeal cancer per year among men and 500 among women. Radiotherapy and chemo-radiotherapy are the main treatment options for most patients. Although often curative, these therapies have significant side effects on quality of life, such as xerostomia, dysphagia and soft tissue fibrosis. The latter are among the most frequent long-term side effects of radiotherapy to the pharynx.
The DARS study
The DARS study, conducted in 22 radiotherapy centres in Ireland and the UK, is the first randomised controlled phase 3 trial to compare standard radiotherapy with a new technique called dysphagia-optimised IMRT (DO-IMRT).
Intensity-modulated radiotherapy (IMRT) is the most widely used radiotherapy technique for head and neck cancer in the UK. Previous studies have confirmed that IMRT can be used to effectively treat head and neck cancer while reducing toxicity by sparing organs at risk, such as the salivary glands. Dysphagia-optimised IMRT (DO-IMRT) is an innovative radiotherapy technique that reduces the radiation dose to the pharyngeal muscles. The researchers' aim was to test the hypothesis that DO-IMRT reduces swallowing problems in the long term compared to standard IMRT.
Between June 2016 and April 2018, the DARS study involved 112 patients with oropharyngeal cancer, randomly assigned to DO-IMRT or standard IMRT. The mean follow-up was 39.5 months. The trial included patients with squamous cell carcinoma of the pharynx, excluding those with metastatic disease and previous malignancies. Randomisation was performed using a minimisation algorithm, and patients and speech therapists were kept in the dark about treatment allocation.
Results collected from the patient's perspective
To obtain a comprehensive view of the effects of DO-IMRT on the swallowing function and quality of life of patients with oropharyngeal carcinoma, the researchers adopted a multidimensional approach, combining demographic data, treatment information, specific questionnaires and adverse event assessments.
Patients completed the MD Anderson Dysphagia Inventory (MDADI) questionnaire at 12 and 24 months after treatment. The MDADI is a widely used scale for assessing swallowing after treatment for head and neck cancer. Other instruments used were the UW-QoL (University of Washington Quality of Life) questionnaire and the PSS-HN (Performance Status Scale for Head and Neck Cancer Patients).
DO-IMRT improves swallowing compared to standard IMRT
Patients undergoing DO-IMRT showed significant improvements in patient-reported swallowing function compared to the control group. Optimised radiotherapy reduced the radiation dose to the pharyngeal constrictor muscles, resulting in a clinically relevant improvement in MDADI questionnaire scores at 12 and 24 months post-treatment.
The choice of the MDADI composite as the main outcome measure reflects the focus of the DARS study on the patient perspective in assessing the effects of radiotherapy on swallowing. Although the difference in MDADI scores at 1 year was below the clinically relevant limit established at study design, the adjusted analysis revealed a significant improvement in swallowing function in patients treated with DO-IMRT.
The comparison of the MDADI subscales, together with the results of the UW-QoL questionnaire, provided further evidence supporting the efficacy of DO-IMRT in improving several swallow-related aspects of quality of life. Patients undergoing DO-IMRT reported normal eating and a greater ability to eat in public compared to the control group, emphasising the positive impact of this therapeutic strategy on eating habits and socialisation.
The encouraging results, however, should not obscure certain limitations of the study, such as the limited follow-up of 2 years and the predominance of patients with HPV-positive oropharyngeal carcinomas. The efficacy of DO-IMRT might vary in other carcinoma subtypes tested in future studies. Furthermore, the variability in the practice of preventive swallowing exercises among patients underlines the need for further research on their efficacy and implementation.
A new standard of care for patients undergoing radiotherapy for pharyngeal tumours
The DARS study results suggest that optimising radiotherapy by reducing the dose to the pharyngeal constrictor muscles may result in a significant benefit for patients with oropharyngeal cancer. These results provide important indications for clinical practice, emphasising the importance of considering not only antitumour efficacy but also the impact on the patient's quality of life during treatment planning.
In conclusion, according to the authors, the DARS study represents a step forward in the optimisation of radiotherapy for oropharyngeal carcinoma, with an emphasis on the patient's quality of life. The positive outcomes pave the way for further therapeutic developments and confirm the importance of a patient-centred perspective in oncology research.
- Nutting C, Finneran L, Roe J, Sydenham MA, Beasley M, Bhide S, Boon C, Cook A, De Winton E, Emson M, Foran B, Frogley R, Petkar I, Pettit L, Rooney K, Roques T, Srinivasan D, Tyler J, Hall E; DARS Trialist Group. Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial. Lancet Oncol. 2023 Aug;24(8):868-880. doi: 10.1016/S1470-2045(23)00265-6. Epub 2023 Jul 6. Erratum in: Lancet Oncol. 2023 Aug;24(8):e328. PMID: 37423227.