Phase II randomised controlled trial on postoperative radiotherapy, in high-risk, resected, non-medullary, non-anaplastic thyroid cancers (THYRO-RT).

6082 Background: Locally advanced thyroid cancers have high rates of locoregional recurrence after standard treatment with surgery and radioactive iodine (RAI). Repeated surgery and RAI in recurrent disease contributes to significant morbidity. Retrospective studies have shown that the addition of adjuvant external beam radiotherapy (EBRT) may improve locoregional control in selected high-risk patients. This randomized phase II trial evaluated the role of adjuvant EBRT in reducing locoregional recurrence (LRR) in high-risk resected thyroid cancer. Methods: This was a phase II randomized controlled trial comparing surgery with RAI versus surgery with RAI plus EBRT in high-risk resected thyroid cancers. Patients with resected non-medullary, non-anaplastic thyroid cancer and predefined high-risk features were randomized (1:1) between July 2013 and April 2021. Patients randomized to EBRT received 6-MV IMRT with daily IGRT to a dose of 60 Gy in 30 fractions over six weeks. The primary endpoint was locoregional recurrence. Secondary endpoints included acute and late toxicity (LENT-SOMA scale) and quality of life. Results: Seventy-two patients were randomized, with 36 assigned to each arm; five patients withdrew consent. Overall, 86.6% had pathological T4a disease and 89.6% had pathological N1a/b disease. Further, 71.6% demonstrated extracapsular nodal extension and R1/R2 resection was seen in 49.3% of the patients. With a median follow-up of 102 months, on an intention to treat analysis, LRR occurred in 19.4% of patients in the surgery + RAI arm (OR 1.376, 95% CI 0.852-2.222), and 9.7% in the Surgery+RAI+EBRT arm (OR 0.611, 95% CI 0.299-1.632). This difference was not statistically significant (p = 0.263). Logistic regression analysis did not identify any factor significantly associated with LRR. There was no significant difference in 10 year-locoregional recurrence free survival between the two arms. Grade 3 acute radiation induced toxicity was observed in two patients. At last follow up, there was one death in the entire cohort, which was non-cancer related. Conclusions: In this very high-risk, resected thyroid cancer cohort, the addition of adjuvant EBRT to surgery and RAI did not significantly decrease locoregional recurrence. The overall acute toxicity was low and if adjuvant EBRT is indicated, it can be delivered with acceptable toxicity. Clinical trial information: NCT03669432 .