Abstract Library

#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,

#3889 Patterns of recurrence in patients with resected pulmonary carcinoid – A Dutch nationwide study

Introduction: In patients (pts) with resected pulmonary carcinoids (PC), recurrence of disease may occur up to 10 years after surgery, but the exact incidence remains unknown.

Conference:

Presenting Author: Moonen L

Authors: Moonen L, Derks J, Hillen L, den Bakker M, von der Thüsen J,

Keywords: Pulmonary carcinoid, recurrence, surgery, screening, nationwide registry,

#3886 Large cell neuroendocrine carcinoma subtyping based on NEUROD1, ASCL1, POU2F3 and YAP1 expression

Introduction: Large cell neuroendocrine carcinoma (LCNEC) accounts for 1-3% of all types of lung cancer and is, similar to small-cell lung cancer (SCLC), a high-grade tumor with poor prognosis. pRb can also be used to subclassify LCNEC into SCLC-like and NSCLC-like. SCLC can be classified in 4 transcriptomic subtypes (NEUROD1high, ASCL1high, POU2F3high, YAP1high), which may have therapeutic implications. It is unclear whether these subtypes are also found in LCNEC and if they correlate with pRb expression.

Conference:

Presenting Author: Heijboer F

Authors: Rijnsburger N, Heijboer F, Derks J, Hermans B, Hillen L,

Keywords: LCNEC, pulmonary, immunohistochemistry, pathology, pRb, transcription factors,

#3858 OTP, CD44, and Ki-67 – A prognostic marker panel for relapse free survival in patients with surgically resected pulmonary carcinoid

Introduction: Relapse occurs in 10% of patients with resected pulmonary carcinoid (PC). While typical carcinoids (TC) show low relapse rates, safe exclusion from long-term follow-up (FU) is impossible partly due to high interobserver variation in the WHO classification.

Conference:

Presenting Author: Moonen L

Authors: Moonen L, Derks J, den Bakker M, Hillen L, von der Thüsen J,

Keywords: Pulmonary Carcinoid, OTP, CD44, Ki-67, biomarker, prognosis,

#3854 Protein validation of multi-omic classified pulmonary carcinoid – Identification of unique clinical subtypes and potential therapeutic vulnerability

Introduction: Multi-omic studies have identified three pulmonary carcinoid (PC) subtypes (A1, A2, B) with unique expression for OTP, ASCL1 & HNF1a.

Conference:

Presenting Author: Derks J

Authors: Derks J, Moonen L, Leunissen D, von der Thüsen J, den Bakker M,

Keywords: lung carcinoid, biomarker, molecular profile, OTP, ASCL1, HNF1a,