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Favorable response to immunotherapy in a pancreatic neuroendocrine tumor with temozolomide-induced high tumor mutational burden.


ABSTRACT: Neuroendocrine neoplasm of the pancreas is a rare tumor with limited treatment options. Among such tumors, treatment for pancreatic neuroendocrine tumor (PanNET) G3 is the most difficult. Temozolomide (TMZ) is commonly used to treat PanNET. However, TMZ may cause tumor gene alkylation, which induces drug resistance and rapid disease progression. Herein, we present a case of a female who was diagnosed with PanNET G3 and achieved a partial response to toripalimab, an anti-programmed cell death-ligand 1 (anti-PD-L1) monoclonal antibody, after multiple cycles of TMZ treatment. Genomic profiling revealed that compared with the patient's samples collected at baseline, the post-TMZ-treatment samples had markedly higher levels of tumor mutational burden (TMB) associated with characteristic alkylating mutational signature representing a positive correlation with favorable response to anti-PD-1 treatment. In addition, we observed a germline truncating mutation of MUTYH (W156*) that was considered to be pathogenic and potentially conferred to genomic instability. This case suggests that anti-PD-1 therapy could be a treatment option for PanNET patients with increased TMB after TMZ-based treatment.

SUBMITTER: Cao Y 

PROVIDER: S-EPMC7743014 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Favorable response to immunotherapy in a pancreatic neuroendocrine tumor with temozolomide-induced high tumor mutational burden.

Cao Yanshuo Y   Ma Yutong Y   Yu Jiangyuan J   Sun Yu Y   Sun Tingting T   Shao Yang Y   Li Jie J   Shen Lin L   Lu Ming M  

Cancer communications (London, England) 20201123 12


Neuroendocrine neoplasm of the pancreas is a rare tumor with limited treatment options. Among such tumors, treatment for pancreatic neuroendocrine tumor (PanNET) G3 is the most difficult. Temozolomide (TMZ) is commonly used to treat PanNET. However, TMZ may cause tumor gene alkylation, which induces drug resistance and rapid disease progression. Herein, we present a case of a female who was diagnosed with PanNET G3 and achieved a partial response to toripalimab, an anti-programmed cell death-lig  ...[more]

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