학술논문

Alkylating Agent-Induced High Tumor Mutational Burden in Medullary Thyroid Cancer and Response to Immune Checkpoint Inhibitors: Two Case Reports.
Document Type
Article
Source
Thyroid. Nov2023, Vol. 33 Issue 11, p1368-1373. 6p.
Subject
*IMMUNE checkpoint inhibitors
*MEDULLARY thyroid carcinoma
*THYROID cancer
*ALKYLATING agents
*DACARBAZINE
*IMMUNE response
*PROTEIN-tyrosine kinase inhibitors
*IPILIMUMAB
Language
ISSN
1050-7256
Abstract
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. [ABSTRACT FROM AUTHOR]