Definitive Radiotherapy for Oligometastatic and Oligoprogressive Thyroid Cancer

Abstract

Local consolidative radiotherapy (LCT) for oligometastatic disease is a promising paradigm improving outcomes for various malignancies but has been underexplored for metastatic thyroid cancer. We hypothesize that LCT to distant sites with definitive RT doses can yield favorable outcomes and defer systemic therapy escalation for these patients. We reviewed 96 thyroid cancer patients who received 175 LCT courses from 2010-2022 to 228 metastatic sites, including: thorax (45%), bone (40%), brain (6%), head/neck (5%), and abdomen (3%). Common prescriptions were 50-55Gy/4-5fxs or 56-70Gy/8-10fxs for lung; 52.5-60Gy/15fxs for mediastinum; and 18-24Gy/1fx or 27-30Gy/3fxs for bone. RECIST v1.1 and CTCAE v5.0 were used to define progression and toxicities, respectively. Outcomes were evaluated via Kaplan-Meier and associations examined via Cox proportional hazards modeling. Median age was 63 years (range: 26-92), with 62 oligometastatic cases (total 1-5 sites) and 34 oligoprogressive (with 1-5 growing sites). Primary disease was controlled in all patients, with 39% receiving post-op RT and 66% prior RAI. Histologies included papillary (40%), anaplastic (25%), follicular (12%), medullary (9%), Hurthle (7%), and poorly-differentiated (7%). Median time from initial diagnosis to LCT was 3 yrs (IQR 1-8), and median follow-up from 1st LCT was 21 mos (IQR 9-51). Patients received an average 2 LCT courses (range 1-8) treating 1-4 sites. Median survival (OS) from 1st LCT was 9 yrs (95% CI = 5-14). On multivariable analysis (MVA), worse OS was associated with anaplastic histology (HR 4.6, p<.01), but longer OS was associated with prior RAI (HR 0.33, p = .02) and oligometastatic disease (HR 0.3, p = .01). For anaplastic histology, median OS was 1.2 years vs. 9.3 years for non-anaplastic; 3-yr OS was 36% vs. 88% (log-rank, p<.01). Five-year OS for oligometastatic cases was 75% vs 53% for oligoprogressive (log-rank, p = .04). Median progression free survival (PFS) from 1st LCT was 15.5 mos (95% C I = 11-20). On MVA for all LCT courses, time to any progression (TTP) was negatively associated with anaplastic histology (HR 1.7, p = .02) and 2nd or higher LCT course (HR 1.45, p = .05), but favorably associated with thoracic site (HR 0.49, p<.01). Following later LCT courses, median TTP was 11 mos vs 17 mos for initial LCT course (log-rank, p = .03). After LCT to lung/chest, TTP was 18.6 mos vs 9.5 mos for non-thoracic sites (log-rank, p<.01). Only 6% of failures occurred at previously treated lesions. Most LCT courses (67%) were without ongoing chemotherapy, while 25% entailed continuing the same regimen and 9% had planned treatment post-RT. There were 2 Grade 3 toxicities (pneumonitis and esophagitis) and no Grade 4-5 events. With high local control rates and minimal toxicity, LCT can be a feasible strategy to defer systemic therapy escalation for oligometastatic and oligoprogressive thyroid cancer.