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,

#4459 Sequential alkylating therapy and pembrolizumab induce near-complete response in high tumour mutational burden pancreatic neuroendocrine tumour: A case report

Introduction: Traditional treatment for neuroendocrine tumours (NETs), including surgery, somatostatin therapy, and targeted therapy, often fails in advanced disease. Alkylating therapy can increase tumour mutational burden (TMB), and the recent KEYNOTE-158 study approved pembrolizumab for advanced solid tumours with a high TMB.

Conference:

Presenting Author:

Authors: Paranjpe I, Hornbacker K, Vadde S, Fisher G, Shaheen S,

Keywords: pancreatic neuroendocrine tumour, immunotherapy, pembrolizumab, tumour mutational burden, TMB,

#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,

#2982 Comprehensive Molecular Analysis Identifies Driver Mutations in Metastases of Sporadic Well-Differentiated Neuroendocrine Tumours of the Small Intestine

Introduction: Small intestinal neuroendocrine tumours (SI-NETs) represent a heterogenous group of tumours. The molecular mechanisms which contribute to progression of SI-NETs are poorly elucidated. They are considered to be molecularly distinct from neuroendocrine carcinomas (NECs), which share oncogenic pathways with adenocarcinomas.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Samsom K

Authors: Samsom K, van Veenendaal L, Roepman P, Kodach L, Steeghs N,

Keywords: whole genome sequencing, neuroendocrine tumour, small intestine, genetics,