Outcomes Following Radiation Therapy for Anaplastic Thyroid Cancer

Abstract

Anaplastic thyroid cancer is a highly aggressive malignancy with dismal survival rates. The role of radiation therapy for this disease has not been clearly defined. Herein, we report on a large cohort of locally advanced or metastatic anaplastic thyroid cancer treated with radiation therapy in the pre-operative or adjuvant settings. We identified 104 patients who received definitive or postoperative radiation therapy for anaplastic thyroid cancer between 1984-2017. We assessed overall survival (OS), locoregional control (LRC), and distant metastasis (DM) using the Kaplan-Meier method and performed survival analysis using Cox proportional hazard models. The median age at diagnosis was 63 (range 28-87). The median follow-up was 5.5 months in the entire cohort and 72 months in surviving patients. Twenty-seven patients (26%) had evidence of metastatic disease at diagnosis or developed metastasis prior to radiation therapy start. Ninety-nine patients (98%) received concurrent chemotherapy with radiation, and 52 (50%) received trimodality therapy with surgical resection followed by concurrent chemoradiation. Of those patients receiving surgical intervention, 37 (67%) had close surgical margins and 33 (59%) had positive lymph nodes. Of the patients who received systemic therapy, 70 (70%) received doxorubicin, 25 (25%) received paclitaxel and pazopanib, and 5 (5%) received other systemic agents. Median radiation dose was 5940cGy (range 600-7025cGy). Ninety (87%) patients died at the time of last follow-up. For those patients who were M1 at time of diagnosis (n=27), 10 underwent trimodality treatment and 17 proceeded with chemoradiation only. The median OS for the entire cohort was 5.6 months after initiation of radiation. The 1-year rates of OS and LRC were 31±5% and 81%±5%, respectively. DM was assessed among patients with non-metastatic disease at radiation therapy start (n=76). The 1-year rate of DM in patients with locally advanced disease at diagnosis was 33%±6%. Patients who received a radiation dose >5000 cGy had longer 1-year OS (38% vs. 11%, log-rank P<.001) compared to those receiving dose <5000 cGy. Multivariate Cox regression restricting to those patients without DM at diagnosis and controlling for age, sex, surgical status, and concurrent chemotherapy, radiation demonstrated persistent OS benefit of receiving radiation >5000 cGy (Hazard Ratio=0.3; 95% CI=0.2-0.7) and surgical resection (Hazard Ratio=0.5; 95% CI=0.3-0.9). There was no difference in LRC and DM between patients receiving different doses of radiation. Results from the current study suggest a beneficial role of aggressive radiation therapy in addition to surgical resection in the management of anaplastic thyroid cancer.