关键词: alkylating agents hypermutant phenotype immune checkpoint inhibitors medullary mutational signature thyroid cancer

Mesh : Humans Alkylating Agents / adverse effects Carcinoma, Neuroendocrine / drug therapy genetics Immune Checkpoint Inhibitors / therapeutic use Thyroid Neoplasms / drug therapy genetics

来  源:   DOI:10.1089/thy.2023.0144

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.
摘要:
背景:在酪氨酸激酶抑制剂作用下进展的转移性甲状腺髓样癌(MTC)患者可受益于烷化剂如达卡巴嗪或替莫唑胺。
方法:我们描述了两名转移性MTC患者,他们在烷化剂治疗后出现超突变表型。该表型的特征在于高肿瘤突变负荷(TMB)和指示烷化剂诱变的突变特征(单碱基取代11)。两名患者都接受了免疫检查点抑制剂,部分形态反应,临床获益和PFS分别为6个月和9个月。
结论:根据所描述的观察结果,我们建议,在对MTC进行烷化剂治疗后,可能会诱发超突变表型,对于TMB升高的MTC患者,应进一步探索序贯使用免疫治疗作为治疗选择.
公众号