3629 - Long-Term Results of External Beam Radiation Therapy (RT) with or without Concurrent Chemotherapy in Loco-Regionally Advanced or Recurrent Differentiated Thyroid Cancer (DTC)

J. Choi¹, E. Sherman², I. Youssef³, J. J. Kang⁴, K. Zakeri³, Y. Yu³, L. Chen³, A. Shamseddine³, S. McBride³, N. Riaz³, T. Hung⁵, W. Wong², L. Michel², L. Dunn⁵, A. Ho⁵, R. M. Tuttle⁵, L. G. Morris⁶, A. Shaha⁷, R. J. Wong⁶, and N. Y. Lee³; ¹SUNY Downstate College of Medicine, Brooklyn, NY, ²Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ³Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁴Yale University Department of Radiation Oncology, New Haven, CT, ⁵Memorial Sloan Kettering Cancer Center, New York, NY, ⁶Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, ⁷Memorial Sloan Kettering Cancer Center, Department of Head and Neck Surgery, New York, NY

Purpose/Objective(s): To review the largest single-institution experience on the use of RT without or with chemotherapy (CRT) in patients with gross residual or unresectable non-anaplastic, non-medullary differentiated thyroid cancers (DTC). All patients who were not surgical candidates and who failed systemic, targeted, and radioactive iodine therapies were included. Given that obtaining locoregional control in this group of patients is paramount and given the radiosensitizing effects of chemotherapy, we changed our practice from RT alone (1989-2009) to CRT (2010 to present), with the latter administered for more advanced disease. Materials/

Methods: From 1989 to 2023, 327 patients with multiply recurrent, gross residual, or unresectable DTC were treated with RT or CRT. Locoregional control (LRC), distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. Multivariate analyses (MVA) of the effects of covariates on LRC, DMFS, and OS were conducted using backwards stepwise Cox regression with p = 0.1.
Results: Of 327 patients, 172 (53%) received RT alone and 155 (47%) received CRT. All patients received intensity-modulated RT except 10 who received proton beam RT (n = 6 proton CRT). All but 8 patients in the CRT group received doxorubicin. Median follow-up of all living patients was 67.5 months (2.8-224.7 months). There were no differences in the 4-year LRC, DMFS, or OS rates between RT and CRT (LRC: 89% RT vs. 86% CRT, p = .67; DMFS: 64% RT vs. 54% CRT, p = .09; OS: 59% RT vs. 56% CRT, p = .10). On MVA, only unresectable disease had worse LRC (HR 2.43, p = .03). Worse OS was seen in M1 status before RT (HR 2.50, p < .0001), poorly differentiated (HR 1.77, p < .001), and Hurthle cell histologies (HR 1.72, p = .03). 34% of patients had grade 3+ acute toxicity: dermatitis (RT 10% vs. CRT 29%, p < .0001), mucositis (12% in both, p = .68), and dysphagia (RT 12% vs. CRT 11%, p = .46). There were no late toxicity differences between the groups or in percutaneous endoscopic gastrostomy rates before (12% RT vs. 10% CRT, p = .46), during/within 60 days of RT (6% RT vs. 10% CRT, p = .46), or >1 year after (4% in both, p = .96). Prior to 2010, 28/116 patients (24%) received CRT; after 2010, 127/211 (60%) received CRT. There was no difference in 4-year LRC by treatment era (85% before 2010 vs. 89% after 2010, p = .84), but the 4-year OS was higher in those treated after 2010 (47% before 2010 vs. 64% after 2010, p = .02).
Conclusion: RT is a safe and effective means to achieve local control in patients with gross residual or unresectable DTC who have failed systemic, targeted, and radioactive iodine therapies, with a 4-year LRC of 88%. CRT was not associated with worse late toxicities and should be considered in patients with more advanced disease.