Positron Emission Tomography-Computed Tomography Response-Guided Chemoradiotherapy For Anaplastic Thyroid Cancer

Although chemoradiotherapy (CRT) is an important component of multi-modal treatment for anaplastic thyroid cancer (ATC), responses are unpredictable. We report preliminary results of protocol-based, early Positron Emission Tomography-Computed Tomography (PET-CT) response-guided CRT for ATC. Histology-confirmed ATC patients underwent systemic evaluation including PET-CT. Intensity-modulated radiotherapy (IMRT) delivered 30 daily fractions of 2.2 Gy to gross tumor and metastatic lymph nodes, 2.0 Gy to postoperative tumor bed and/or high-risk areas of microscopic disease, and 1.8 Gy to regional nodal areas. Concurrent paclitaxel (70 mg/m2) was delivered on days 1, 8, and 15 every 4 weeks. After 18 fractions of CRT, interim response analysis consisting of second PET-CT and simulation CT was conducted for adaptive treatment plan: lenvatinib 10 mg per day was added when showing progression, whereas CRT was terminated at 25 fractions and followed by surgical resection when gaining resectability. Common Terminology Criteria for Adverse Events version 4.0 was used, and overall survival (OS) was measured from the day of diagnosis. Thirty-three patients were treated between August 2016 and April 2019. Median follow-up was 5.6 months (range, 1.6-28.9). In Group A, 7 patients (1 stage IVA, 5 IVB, and 1 IVC) completed postoperative CRT: all patients are alive with median follow-up of 21.5 months (range, 6.4-28.9), except for 1 who received lenvatinib for lung metastases and survived for 16.1 months. No grade ≥3 toxicities were reported except for grade 3 dermatitis in 1 patient. In Group B, 8 patients (all stage IVB) underwent definitive CRT: 5 received surgical resection after 25 (n = 3) and 30 (n = 2) fractions, and 1 refused treatment at 41.8 Gy. Grade 3 dermatitis (n = 2) and febrile neutropenia (n = 2) were reported, and one died of pneumonia after completing CRT. In Group C, 18 patients with distant metastases received palliative CRT: grade 3 dermatitis (n = 1) and grade 4 (n = 1) and grade 3 (n = 3) febrile neutropenia were reported. Four patients did not complete CRT and died of disease progression (n = 3) and aspiration pneumonia (n = 1), while 4 died of pneumonia and chemoport infection after completing CRT. Median survival (MS) was not reached in Group A and was 8.5 and 4 months for Group B and C, respectively. For 12 patients who received surgery before or after CRT, MS was not reached and 2-year OS was 66%. Among 26 patients who were treated for gross disease, 9 (34.6%) showed partial response within the RT field during CRT. Among the 5 patients who underwent surgery after CRT, no residual or near total tumor necrosis was reported in 3. Response evaluation during CRT may allow effective treatment intensification or de-intensification for ATC. Resection before or after CRT allowed long-term survival. A phase II trial with enhanced toxicity-monitoring is under development.