Newly diagnosed oropharyngeal and hypopharyngeal cancers are typically treated with chemoradiotherapy with curative intent. However, this approach can result in severe dysphagia requiring a permanent gastrostomy tube and long-term care. The phase 3 DARS trial compared dysphagia-optimised intensity-modulated radiotherapy (DO-IMRT) with standard IMRT in pharyngeal cancer patients. Results of this trial, recently published in The Lancet, showed a better swallowing function after 12 months with DO-IMRT compared to classical IMRT, supporting DO-IMRT as a new standard of care for pharyngeal cancer patients receiving radiotherapy.
Newly diagnosed oropharyngeal and hypopharyngeal cancers are commonly treated with chemoradiotherapy or radiotherapy. While these treatments are effective and often curative, they can negatively impact the quality of life of these patients. The most common long-term side effects of radiotherapy are dry mouth, dysphagia, and soft tissue fibrosis. Swallowing issues after radiotherapy can be severe, especially if they cause food aspiration into the lungs, requiring a permanent gastrostomy tube and long-term care. Dysphagia-optimised intensity-modulated radiotherapy IMRT (DO-IMRT) is a novel radiotherapy technique which reduces the radiation dose to the pharyngeal muscles (i.e., dysphagia and aspiration risk structures). The phase 3 DARS trial investigated whether DO-IMRT reduces the risk for long-term swallowing issues compared to standard IMRT.
The phase 3 DARS trial was conducted across 22 radiotherapy centres in Ireland and the UK. Participants had T1-4, N0-3, M0 oropharyngeal or hypopharyngeal cancer, a WHO performance status of 0 or 1, and no pre-existing swallowing dysfunction. In total, 112 patients were randomly assigned (1:1) to receive DO-IMRT or standard IMRT. Radiotherapy was given in 30 fractions over six weeks, with doses of 65 Gy to the primary and nodal tumours and 54 Gy to the remaining pharyngeal and nodal areas at risk of microscopic disease. Patient-reported outcomes were measured 12 months after radiotherapy using the MD Anderson Dysphagia Inventory (MDADI, primary endpoint). This composite total score ranges from 20, indicating deficient functioning, to 100, indicating extremely high functioning and is the sum of the emotional, functional, and physical problems subscales.
Patients belonging to the DO-IMRT group exhibited notably higher MDADI composite scores at the 12-month mark compared to those in the standard IMRT group (mean score 77.7 vs. 70.6, respectively; mean difference 7.2 [95%CI: 0.4-13.9]; p=0.037). After adjusting for baseline score and clinical balancing factors, the mean difference increased to 9.8 (95%CI: 3.5-16.0; p=0.0030). Importantly, the difference in the MDADI composite score persisted at 24 months. The most common grade 3-4 late adverse events (AEs) were hearing impairment (16% vs. 13% in the DO-IMRT and IMRT groups, respectively), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15 %). During radiotherapy, 75% vs. 87% of patients reported grade ≥3 AEs in the DO-IMRT and IMRT groups, respectively. The most common AEs (reported by >25% of all participants) were dysphagia (48% vs. 58%), oral mucositis (38% vs. 56%), anorexia (29% vs. 47%), pharyngeal mucositis (25% vs. 38%) and dry mouth (20% vs. 33%). There were no treatment-related deaths.
These findings show that DO-IMRT improves patient-reported swallowing function compared to standard IMRT and support DO-IMRT as the new radiotherapy standard of care for patients with pharyngeal cancer.
Nutting C, Finneran L, Roe J, et al. 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;24(8):868-80.