Long-Term Results of External Beam Radiation Therapy with or Without Concurrent Chemotherapy in Differentiated Thyroid Cancer.

Background: A rare group of patients with differentiated thyroid cancers (DTCs) will have gross residual disease or recurrence following the standard primary therapies of surgical resection and radioactive iodine. In these patients with advanced DTC no longer amenable to further surgery, systemic, or radioactive iodine therapies, external beam radiation therapy (RT) is considered. Whether to add concurrent chemotherapy (CRT) to radiation for patients with advanced DTC remains unclear. We review the long-term follow-up of the largest single-institution experience on the use of RT alone versus CRT in advanced DTC. Methods: From 1989 to 2023, 327 patients with recurrent, gross residual, or unresected DTC were treated with RT alone or CRT. Patients with incomplete resection and/or unfavorable histology were preferentially treated with CRT. For this retrospective cohort study, locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Kaplan-Meier method. Results: CRT patients (n = 153) were 46% female and 61.6 ± 11.7 years old versus RT alone (n = 174) were 48% female and 66.8 ± 12.6 years old. Overall median follow-up was 109.7 months [confidence interval 100.3-123.5 months]. There were no differences in 4- and 10-year LRC, DMFS, or OS rates between groups (4-year LRC 89.0% RT alone vs. 86.6% CRT, p = 0.76; 4-year DMFS: 64.2% RT alone vs. 54.5% CRT, p = 0.08; 4-year OS: 58.5% RT alone vs. 56.9% CRT, p = 0.28). Worse grade 3+ acute dermatitis was reported with CRT (29% CRT vs. 10% RT alone, p < 0.0001). Eight patients developed a tracheoesophageal fistula (TEF), six of whom received CRT followed by tyrosine kinase inhibitor (TKI) therapy. TEF developed at a median of 7.3 months (range = 0.5-17.0 months) after TKI initiation. There were no differences in other acute toxicities, any late toxicities, rates of tracheostomy tube, percutaneous endoscopic gastrostomy (PEG) tube within 60 days of RT, or PEG tube persistence past one year. Conclusion: CRT did not demonstrate any benefit over RT alone in this retrospective study, although patients treated with CRT had worse disease. Late toxicities were similar, aside from greater TEF development after TKI therapy in CRT patients. Further research is necessary to elucidate who may benefit from CRT.