A long-term retrospective cohort-based risk-benefit analysis of augmenting total cumulative I-131 activity to 37GBq in differentiated thyroid cancer patients with skeletal metastases

OBJECTIVE: Skeletal metastases in differentiated thyroid cancer (DTC) patients are associated with poor prognosis. The objective was to determine the maximum I-131 cumulative activity that could be safely administered without compromising efficacy. The secondary objective was to identify other prognostic factors affecting survival outcomes. MATERIALS AND METHODS: This was a retrospective cohort study done at a tertiary-care institution comprising of data from January 1990-June 2020. 489 DTC patients having skeletal metastases with ≥12 months follow-up were included. Ninety-six percent of patients had thyroidectomy followed by radioiodine therapy for skeletal metastases. All patients were on oral suppressive levothyroxine tablets. External beam radiotherapy (EBRT) and oral tyrosine kinase inhibitors were used whenever indicated. The main outcome measures were overall survival (OS), progression-free survival (PFS), and adverse-events. RESULTS: There were 347 (71%) females and 324 (66%) had follicular carcinoma thyroid. Median follow-up was 78 (interquartile range, IQR: 37–153) months. 333 patients (68%) received ≤37GBq I-131 cumulative activity (group 1) and 156 patients (32%) received >37GBq cumulative RAI activity (group 2). Overall median OS and PFS were 74 (95% confidence interval (CI): 62.2–85.8) and 48 (95%CI: 40.5–55.4) months, respectively. The 5-, 10-, 15- and 20-year estimated overall survival probabilities were 55.7%, 28.4%, 14% and 8.3%, respectively. On multivariate analysis, age(<55years) (p<0.001), female gender(p = 0.01), cumulative I-131 activity >37GBq (p<0.001) and EBRT(p = 0.001) were favourably associated with OS; no factors were significantly associated with PFS. The median OS for groups 1 & 2 were 51 versus 90 months (p<0.001) & median PFS for groups 1 & 2 were 45 versus 53 months respectively (p = 0.9). However, cumulative activity >37GBq resulted in more adverse events (2.4%), particularly bone marrow suppression (3.5%). CONCLUSION: For better survival outcomes, cumulative I-131 activity upto 37GBq could be administered with acceptable toxicity to DTC patients with skeletal metastases.