Abstract Library

#4545 Analysis of the mutational landscape of pancreatic neuroendocrine tumours before and after temozolomide treatment

Introduction: Temozolomide (TMZ) is an alkylating agent and standard treatment for pancreatic neuroendocrine tumours (pNET). Resistance to TMZ may be acquired through inactivation of the mismatch repair system, leading to high tumour mutation burden (hTMB).

Conference:

Presenting Author: Trevisani E

Authors: Trevisani E, Borghesani M, Reni A, Agnoletto C, Luchini C,

Keywords: neuroendocrine, next generation sequencing, temozolomide, hypermutation, tumour mutational burden,

#4457 Primary mixed hepatocellular carcinoma-neuroendocrine carcinoma: A case report

Introduction: Mixed epithelial neoplasms (MiNENs) are characterised by the coexistence of neuroendocrine and non-neuroendocrine components within a single tumour, each discernible histologically and immunohistochemically, with a minimum tumour proportion of 30%. Primary hepatic MiNENs are exceedingly rare entities.

Conference:

Presenting Author: Tang Y

Authors: Wang Y, Wang R, Yi X, Guo M, Tang Y,

Keywords: pancreatic neuroendocrine tumour, functional, parathyroid hormone related peptide,

#4417 Efficacy of immune checkpoint inhibitors (ICI) in patients with advanced pancreatic NETs displaying high TMB and MMR alterations following treatment with alkylating agents

Introduction: Alkylating chemotherapy (ALK) is frequently used in patients with PanNETs. It may favour grade progression and acquisition of a hypermutator phenotype associated with frequent alterations of the MMR genes, suggesting a potential benefit of ICI.

Conference:

Presenting Author:

Authors: de Mestier L, Apostolidis L, Koumarianou A, Hernando Cubero J, Riechelmann R,

Keywords: immune checkpoint inhibitor, immunotherapy, hypermutagenicity, alkylating agents, tumour mutational burden, mismatch repair,

#4289 Temozolomide-associated hypermutation and response to immunotherapy in advanced pulmonary neuroendocrine tumours

Introduction: Temozolomide (TMZ) cytotoxicity depends on an intact DNA mismatch repair (MMR) pathway and low levels of O6-methylguanine DNA methyltransferase (MGMT). However, absence of MGMT-mediated repair coupled with defective MMR (dMMR) may lead to enrichment of C:G to A:T transitions throughout the genome, a marked increase in tumour mutational burden (TMB), and loss of TMZ-induced cytotoxicity. This resistance mechanism is called TMZ-associated hypermutation (TAH). Theoretically, this effect could lead to sensitivity to checkpoint inhibitor immunotherapy.

Conference:

Presenting Author: Buikhuisen W

Authors: Buikhuisen W, Badrising S, Moonen L, Derks J, Monkhorst K,

Keywords: Pulmonary NET, whole genome sequencing, temozolomide signature, immunotherapy,

#3250 High TMB and MSI-high as independent predictors of survival in NENs

Introduction: To date, there are no validated molecular biomarkers for personalized therapy in NENs. Tumor genome sequencing may help unravel NEN molecular landscape and identify novel targets for an individualized approach.

Conference: 18th Annual ENETS Concerence (2021)

Presenting Author:

Authors: La Salvia A, Barroso G, Espinosa Olarte P, Anton Pascual B, Modrego Sanchez A,

Keywords: molecular profiling, neuroendocrine neoplasm, TMB, microsatellite instability (MSI)/mismatch repair deficiency (MMRd) status, prognosis,