Acute radiation morbidities and dosimetric evaluation of DARS structures: Results from the phase III randomized SWOAR trial.
Aman Sharma, Abiramasundari Vivekanandan, Adrija Ghosh, Jitendra Kumar Meena, Rajeev Kumar, Abhilash Dagar, Akash Kumar, Abhinav Singhal, Suchita Singh, Kalpa Das, Ashutosh Mishra, Dyuti Shah, Tenzin Choden, Yousra Izzuddeen, Supriya Mallick, Subramani Vellaiyan, Atul Sharma, Alok Thakar, Suman Bhasker, Daya Nand SharmaTPS149
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 .