%0 Case Reports
%T Alkylating Agent-Induced High Tumor Mutational Burden in Medullary Thyroid Cancer and Response to Immune Checkpoint Inhibitors: Two Case Reports.
%A Moog S
%A Lamartina L
%A Bani MA
%A Al Ghuzlan A
%A Friboulet L
%A Italiano A
%A Lacroix L
%A Postel Vinay S
%A Tselikas L
%A Deschamps F
%A Bonnet B
%A Pani F
%A Baudin E
%A Hadoux J
%J Thyroid
%V 33
%N 11
%D 2023 11 9
%M 37698883
%F 6.506
%R 10.1089/thy.2023.0144
%X Background: Patients with metastatic medullary thyroid cancer (MTC) who progressed under tyrosine kinase inhibitors can benefit from an alkylating agent such as dacarbazine or temozolomide. Patient Findings: We describe two patients with metastatic MTC who developed a hypermutant phenotype after alkylating agent treatment. This phenotype was characterized by a high tumor mutational burden (TMB) and a mutational signature indicative of alkylating agent mutagenesis (single-base substitution 11). Both patients received immune checkpoint inhibitors, with partial morphological responses, clinical benefit, and progression-free survival of 6 and 9 months, respectively. Summary and Conclusions: Based on the described observations, we suggest that a hypermutant phenotype may be induced after alkylating agent treatment for MTC and the sequential use of immunotherapy should be further explored as a treatment option for MTC patients with increased TMB.