Radiation Therapy Demonstrates Persistent Overall Survival Benefit in Locally Advanced or Metastatic Anaplastic Thyroid Cancer

Abstract

Anaplastic thyroid cancer (ATC) is an aggressive form of undifferentiated thyroid cancer associated with poor prognosis. Rapid tumor enlargement results in compression or invasion of nearby critical structures and mortality is often secondary to complications of tumor volume rather than metastatic disease. Therefore, the role of radiotherapy (RT) in local tumor control is critical. Given the rarity of disease, there is limited guidance on radiotherapy modality, fractionation, and dose. Here we report a large, single institutional experience of RT in locally advanced or metastatic ATC. We identified 104 patients (pts) with histologically confirmed ATC presenting to our center between 1984 and 2017 who received definitive or post-operative RT. Clinical and treatment characteristics were recorded. Overall survival (OS), locoregional control (LRC), and distant metastasis (DM) were analyzed with the Kaplan-Meier method. Prognostic factors were analyzed by Cox proportional hazards modeling. Adverse events (AE) were graded according to CTCAE v.5.0 and categorized by acute (≤3 months from RT), subacute (3-6 months) and late (>6 months) effects. Median age at diagnosis was 63 years (28-87) with a median follow-up of 5.5 months. Twenty-seven (26%) patients had metastatic disease at diagnosis or prior to radiotherapy and 14 (13%) were alive at last follow-up. Concurrent chemotherapy with RT was administered in 99 (98%) pts and trimodality therapy in 52 (50%) pts. Of the 52 surgical pts, 37 (67%) had close surgical margins and 33 (59%) had positive lymph nodes. Systemic therapy included doxorubicin (70%), paclitaxel and pazopanib (25%), and other systemic agents (5%). Eighty-five pts (82%) were treated with IMRT; 77 (74%) were treated daily with a standard fractionation and 27 (26%) twice daily with a quad shot regimen. Of the pts receiving standard fractionation, median dose was 59.4Gy (0.6-70Gy) and median fractionation was 33 (3-36). One-year OS and LRC were 31% and 81% respectively. Patients receiving >50Gy had longer 1-year OS compared to those receiving <50Gy (38% vs 11%, p<0.001). Persistent OS benefit was observed in locally advanced ATC for RT >50Gy (HR 0.3, 95%CI 0.2-0.7) and surgical resection (HR 0.5, 95%CI 0.3-0.9) in the multivariate analysis. No difference in LRC or DM was observed in patients based on radiation dose. Most commonly observed acute Grade 3 AE’s include dermatitis (20%), mucositis (13%), dysphagia 8%), fatigue (7%), and voice changes (2%). There were 3 cases of subacute Grade 3 fatigue, and 4 cases of late Grade 3 fatigue and 1 case of Grade 3 mucositis. There were no Grade 4 subacute or late AEs. Radiotherapy demonstrates a dose-dependent persistent OS benefit in locally advanced ATC with an acceptable toxicity profile. Aggressive radiotherapy plays an important role in the treatment of ATC and further prospective investigation is warranted to better characterize standard doses and regimens.