Acute radiation morbidities and dosimetric evaluation of DARS structures: Results from the phase III randomized SWOAR trial.

Abstract

TPS149 Background: The SWOAR is a phase III trial (ClinicalTrials.gov ID NCT05187091) evaluating sparing of dysphagia/aspiration related structures (DARS) & submandibular gland by IMRT. Methods: Patients with T1-4, N0-3, M0 of oropharynx, larynx and hypopharynx treated with radical RT were randomized to arm A (standard IMRT) or arm B (DARS IMRT) in 1:1 manner. Treatment allocation was done based on T stage, concurrent chemotherapy use (weekly 40mg/m2) & subsite. A10-point improvement in MD Anderson Dysphagia Inventory (MDADI) composite score (primary end point of study) at 6 months post RT with SD of 17, power as 90% and two-sided alpha of 5% estimated sample size. SIB IMRT delivered dose of 66Gy (gross disease+0.5cm), 54Gy (gross disease+1cms+regional lymphatics) in 30 fractions. Acute radiation morbidities were scored by RTOG scoring criteria. Aspiration prevention assessment was done by PAS measured by FEES. Results: A total of 166 patients till date have been enrolled, 81 in Arm A & 85 in Arm B. Median age was 58 years, 73.4% had oropharyngeal primary, 89% had stage III-IV & received concurrent chemotherapy. Median composite MDADI scores pre-RT in Arm A was 70.5 (IQR 56.8-75.8) & 69.5 (56.8-75.8) in arm B. Post-RT median score dropped to 54.2 (48.8-60) in arm A & 54.8 (51.6-65.3) in arm B. Reduction in MDADI score pre & post RT in arm A was median 11.1 (0-21) & arm B was 7.9 (0-20) (p=0.28). Pre RT-PAS score was similar in both arms 1 (IOR 1-2), post-RT PAS in arm A was 1 (1-2) & arm B was 1 (1-1). Median of mean dose to SCM was 56.2Gy (46.8Gy-61.2Gy) vs 48.9Gy (36Gy-57.6Gy) p<0.003, MCM 58.5Gy (52.7Gy-63.1Gy) vs 56.2Gy (47.8-63.6) p=0.11, ICM 48.5Gy (46.8Gy-57.7Gy) vs 37.8Gy (26.5-62.4) p<0.001, base of tongue 60.5Gy (53.9Gy-64.3Gy) vs 53.9Gy (40.2Gy-62.4Gy) p=0.001,supraglottic larynx 57.7Gy (49.2Gy-64.4Gy) vs 60.5Gy (46.7-64.6) p=0.63, larynx 46.0Gy(42.4Gy-53.7Gy) vs 28.3Gy (21.5Gy-49Gy) p<0.001, cricopharyngeus 46.0Gy(43.6Gy-49.9Gy) vs 32.6Gy (27.3Gy-47Gy) p<0.001, esophageal inlet 44.6Gy (41.3Gy-47.9Gy) vs 27.2Gy (22.8Gy-39.1Gy) p<0.001, contralateral submandibular gland 52.8Gy (48.5Gy-57.2Gy) vs 40.4Gy (37.3-49.6) p<0.001, all arm A vs arm B respectively. Acute grade 3 occurred in 68.4% in arm A & 54.4% arm B, p=0.07. Acute grade 3 mucositis developed in 34.2% in arm A vs 16.7% arm B, p=0.009. Conclusions: Swallowing-sparing IMRT significantly reduced dose to contralateral submandibular gland & all the DARS structures (except middle constrictor muscle & supra glottic larynx). Dosimetric advantage gained by delivery of Swallowing-sparing IMRT resulted in significant reduction in development of acute grade III mucositis & showed a trend towards reduction in all acute grade III toxicities. Clinical trial information: NCT05187091 .