Real-World Outcomes of Next-Generation Sequencing of Progressive Radioactive Iodine Refractory Metastatic Thyroid Cancer and Treatment of These Patients With Redifferentiation Protocol

Radioactive iodine (RAI) refractory papillary and follicular thyroid can­cer have poor prognoses. These tumors often harbor BRAF V600E and NRAS Q61R mutations, which can be targeted with BRAF and MEK inhibitors to pro­mote redifferentiation. In this study, patients underwent next-generation se­quencing (NGS) testing and a 6-week protocol of trametinib and dabrafenib (pa­tients with BRAF V600E mutation) or trametinib alone (patients with NRAS Q61R mutation), followed by dosimetry and therapeutic RAI. Imaging and biochemi­cal analysis were performed at regular intervals. Of 26 patients, 24 showed RAI uptake post-redifferentiation. The correlation between RAI dose and time to re­sponse was negligible (0.033), while higher RAI doses showed a moderate neg­ative correlation with progression-free survival (PFS) (−.438), though not statis­tically significant (P = .278). Telomerase reverse transcriptase (TERT) positivity significantly reduced PFS by 4.5 months (P = .016). Larger studies are needed to refine patient selection for redifferentiation therapy.