Next-Generation Sequencing in Sporadic Medullary Thyroid Cancer Patients: Mutation Profile and Disease Aggressiveness.

CONTEXT

Next-generation sequencing (NGS) analysis of sporadic medullary thyroid carcinoma (sMTC) has led to increased detection of somatic mutations, including M918T, which has been considered a negative prognostic indicator.

OBJECTIVE

This study aimed to determine the association between clinicopathologic behavior and somatic mutation identified on clinically motivated NGS.

METHODS

In this retrospective cohort study, patients with sMTC who underwent NGS to identify somatic mutations for treatment planning were identified. Clinicopathologic factors, time to distant metastatic disease (DMD), disease-specific survival (DSS), and overall survival (OS) were compared between somatic mutations.

RESULTS

Somatic mutations were identified in 191 sMTC tumors, including M918T (53.4%), other codons (10.5%), (18.3%), somatic indels (8.9%), and wild-type (WT) status (8.9%). The median age at diagnosis was 50 years (range, 11-83); 46.1% were female. When comparing patients with M918T, Other, and WT (which included and WT), there were no differences in sex, TNM category, systemic therapy use, time to DMD, DSS, or OS. On multivariate analysis, older age at diagnosis (HR 1.05, < .001; HR 1.06, .001) and M1 stage at diagnosis (HR 3.17, = .001; HR 2.98, = .001) were associated with decreased DSS and OS, respectively, but mutation cohort was not. When comparing M918T to indels there was no significant difference in time to DMD, DSS, or OS between the groups.

CONCLUSION

Somatic mutations do not portend compromised DSS or OS in a cohort of sMTC patients who underwent clinically motivated NGS.