The tumor mutation burden in gastro-entero-pancreatic-neuroendocrine tumors.

Abstract

654 Background: Neuroendocrine tumors (NET) are rare tumors with limited treatment options. Tumor mutation burden (TMB) has been known as a novel biomarker in various tumor types. However, there has been little study of the role of TMB-high in gastro-entero-pancreatic (GEP)-NETs. Methods: We analyzed 31 metastatic GEP-NET patients who were newly diagnosed between 2013 to 2022. Next-generation sequencing (NGS) including TMB analysis, as a routine clinical practice was performed. The TruSight Oncology 500 assay from Illumina was used as a cancer panel. Results: Among a total of 31 patients, the median TMB was 4.7 mutation/Mb (3.10-6.3). Primary origin was stomach in 4 (12.9%), small bowel in 2 (6.5%), rectum in 7 (22.6%), pancreas in 21 (38.7%), bile duct in 1 (3.2%), gall bladder in 4 (12.9%), liver in 1 (3.2%) patient. 17 (54.8%) patients were diagnosed with well-differentiated NET with grade 1 in 3 (9.7%), and grade 2 in 14 (45.2%) patients. Grade 3 NET (neuroendocrine carcinoma) was confirmed in 14 (45.2%) patients. The median number of metastases was 2.7 (1.0-4.0). The most common metastatic site was the liver (26 patients, 83.9%). All tumors were classified as type of micro-satellite stable (MSS). Only one patient had the tumor with high TMB (266.4 mutation/Mb). This tumor was classified as the grade 3 neuroendocrine carcinoma and the primary tumor site was pancreas. Conclusions: This analysis revealed that the GEP-NETs were generally considered as tumor-type of low TMB. However, uncommonly, GEP-NET with high-TMB could be found. For the precision medicine, the NGS test is needed as a routine clinical practice in this tumor type.