Phase 2 Trial of Intensity-Modulated Radiation Therapy +/- Concurrent Doxorubicin for Patients With Locally Advanced or Recurrent Non-anaplastic Thyroid Cancer

Abstract

Given a lack of prospective studies, the use of radiotherapy in the treatment of advanced non-anaplastic thyroid remains controversial. The addition of radiotherapy can potentially limit the associated morbidity with uncontrolled locoregional disease. The purpose of this study was to evaluate the efficacy and tolerability of radiation therapy with or without concurrent chemotherapy in patients with locally advanced non-anaplastic thyroid carcinoma. This was a single-institution non-randomized phase II study for patients with gross residual or unresectable non-anaplastic thyroid carcinoma treated with intensity-modulated radiotherapy (IMRT) with or without concurrent doxorubicin (10mg/m2) (NCT01882816). The primary endpoint was 2-year locoregional progression free survival. Secondary endpoints included overall survival, safety and tolerability. Among 27 evaluable patients enrolled in this study, there were 11 (40.7%) females and 16 (59.3%) males with a median age of 63.9 years (range, 30-83.2 years). Twelve patients (44.4%) had unresectable disease and 15 (55.6%) had gross residual disease. The median number of prior surgeries was 1.0 (range, 0-3). Sixteen (59.3%) patients received prior radioactive iodine therapy. The median IMRT dose was 70Gy. Twenty-six of 27 patients (92.5%) completed the full planned treatment course. One patient was switched to a palliative regimen after 10 fractions (21.2Gy) secondary to rapid tumor progression. A second patient elected to abort therapy against medical advice after 29 fractions (58Gy). Acute treatment related toxicity, regardless of attribution, included dermatitis, mucositis, and dysphagia with limited grade ≥3 toxicity with rates of 22.2%, 7.4%, and 7.4%, respectively. No elective tracheostomy or feeding tubes were placed. Three patients required a tracheostomy, 1 of which was placed for disease progression while the remaining 2 were placed for laryngeal edema, and 2 patients required a feeding tube during or within 90 days of IMRT completion. The incidence of late toxicity was low. With a median follow-up of 23.2 months among surviving patients, the 2-year Kaplan-Meier estimate of locoregional progression free survival and overall survival was 84.1% and 73.1%, respectively. Intensity modulated radiation therapy +/- concurrent doxorubicin was well tolerated and associated with favorable efficacy outcomes in patients with locally advanced non-anaplastic thyroid carcinoma.