Results of DARS: a randomised phase III trial of dysphagia-optimised intensity modulated radiotherapy (DO-IMRT) versus standard IMRT (S-IMRT) in oropharyngeal (OPC) and hypopharyngeal (HPC) cancer (2021)

Type of publication:
Conference abstract

Author(s):
Nutting C.; Roe J.; Tyler J.; Bhide S.; Rooney K.; Foran B.; *Pettit L.; Beasley M.; Finneran L.; Sydenham M.; Emson M.; Hall E.; Petkar I.; Frogley R.

Citation:
Oral Oncology; Jul 2021; vol. 118 Supplement ; p. 10-11

Abstract:
Presented by: Chris Nutting (Chris.Nutting@rmh.nhs.uk) Introduction Most newly diagnosed OPC & HPC are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. DARS (ISRCTN:25458988) tested if using DO-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Materials and Methods Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary & nodal tumour; 54 Gy/ 30f to remaining pharyngeal subsite & nodal areas at risk of microscopic disease) or DO-IMRT. The volume of the superior & middle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in DO-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site & AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT with 102 patients needed to detect a 10 point improvement (assuming S-IMRT score of 72, standard deviation (SD) 13.8; 90% power, 2-sided 5% alpha). Patients were blind to treatment allocation. Secondary endpoints assessing swallowing function included University of Washington (UW)-Qol & Performance Status Scale Head & Neck (PSS-HN) scores. Results 112 patients (56 S-IMRT, 56 DO-IMRT) were randomised from 22 UK centres from 06/2016 to 04/2018. Mean age was 57 years; 80% were male; 97% had OPC; 90% had AJCC stage 3&4 disease; 86% had concomitant chemotherapy only, 4% induction & concomitant and 10% no chemotherapy. 111/112 had RT doses as prescribed (1 patient died before RT). Median of the mean inferior PCM dose was SIMRT 49.8 Gy (IQR 47.1-52.4) vs. DO-IMRT 28.4 Gy (21.3-37.4), p < 0.0001; superior & middle PCM dose was
S-IMRT 57.2 Gy (56.3-58.3) vs. DO-IMRT 49.7 Gy (49.4-49.9), p < 0.0001. At 12 months, DO-IMRT had significantly higher MDADI scores: S-IMRT mean: 70.5 (SD 17.3) vs. DO-IMRT 77.7 (16.1), p = 0.037. At 12 months the proportion of patients reporting UW-QoL as being able to swallow “as well as ever” was 40.4% for DO-IMRT & 15.2% for S-IMRT; scores of?>50 were reported for PSS-HN normalcy of diet by 70.6% DO-IMRT & 58.1% S-IMRT patients & for eating in public scores by 84.3% DO-IMRT & 74.4% S-IMRT. Conclusions DOIMRT reduced RT dose to the DARS and improved patient reported swallowing function compared with S-IMRT. This is the first randomised study to demonstrate functional benefit of swallow-sparing IMRT in OPC.