Beneficial Role of Multi-Disciplinary Treatment for Anaplastic Thyroid Cancer with Initial Distant Metastasis

Abstract

Anaplastic thyroid cancer (ATC) is a rare, highly aggressive tumor, with median survival around 5 months. Approximately half of the ATC patients presents with distant metastases at diagnosis, showing even more devastating prognosis, yet no outcome analysis had been reported. In this study, we aim to evaluate the clinical outcome of M1 ATC patients, and to define the group of patients who would benefit from local treatment based on multi-disciplinary approach. A total of 133 histology-confirmed ATC patients underwent protocol-based multidisciplinary treatment including surgery and chemoradiotherapy (CRT) between May 2016 and January 2022. Patients received intensity-modulated radiotherapy of 30 fractions concurrently with paclitaxel on days 1, 8 and 15 every 4 weeks, and lenvatinib was added upon progression. After 18 fractions of CRT, interim response analysis using modified RECIST was conducted for adaptive treatment planning. We reviewed 58 patients with distant metastasis at diagnosis (stage IVC). Overall survival (OS) and progression-free survival (PFS) were measured from the day of diagnosis. Most common metastatic site was lung (91.4%), followed by bone (31.0%) and brain (5.2%). Lenvatinib was added for 35 patients after any sign of progression. Fourteen patients received upfront surgery (16 debulking and 5 total) followed by adjuvant CRT in 16 patients. Thirty-one patients received upfront CRT with 2 patients receiving total resection after sufficient down-staging. Six (10%) patients could not complete radiotherapy but continued receiving systemic treatment. The median follow-up was 5.9 months. The median and 1-year OS were 6.2 months and 20.5%, and PFS were 3.7 months and 3.5%. Total RT dose over 60 Gy significantly improved median OS (7.5 vs 4.1 months, p = 0.012) and median PFS (4.4 vs 3.0, p = 0.010). Patients with less than 10 initial metastatic tumors showed better median OS (9.1 vs 4.6 months, p = 0.002) but not PFS (5.1 vs 3.6, p = 0.485). At interim analysis, early response (CR, PR and SD) of primary tumor was not associated with survival, while progression of distant metastases showed significantly worse median OS (9.8 vs 4.6 months, p = 0.001). More than 10 metastatic tumors (HR 2.73, 95% CI 1.32-5.66) and stable metastasis at interim analysis (HR 2.39, 95% CI 1.04-5.48) remained as significant factor in the multivariable cox regression analysis. Median OS and PFS of patients with less than 10 metastases showing no progression at interim analysis were 9.1 months, and 5.1 months. Local treatment combined with chemotherapy for M1 ATC patients showed outcome comparable to those of non-metastatic ATC results. Active local treatment should be considered especially for patients with less than 10 metastases, and patients without distant progression in early response evaluation.