107P - Comprehensive genomic profiling of “The German-registry of incidental gallbladder carcinoma” cases

Background

Gallbladder cancer (GBC) is a biliary tract cancer with an aggressive progression and poor prognosis. Although high throughput sequencing revealed some driver variations in genes like EGFR, TP53, SMAD4, ARID1A, PIK3CA, and CDKN2A/B, there is no specific biomarker for GBC. Due to the low incidence rate, the studies are limited and generally covered under all biliary tract cancer (BTC) types. Here we present the clinical, histopathological, and molecular spectrum of a large series of patients from the German Registry of Incidental GBC.

Methods

A total of 1040 (793 female and 247 male) completely documented cases with a median age of diagnosis 70.79 (min:30-max:98) were enrolled in the study. The majority of tumors were diagnosed at pathological stage pT2 (60.6%), and distant metastasis was detected in 15.2% of cases. The patients presented a tumor grade of G2 or G3 with a ratio of 53% and 36%, respectively. Among the cohort, 116 cases were already analyzed by a targeted panel (FMI Heme Panel) which combines more than 400 DNA and 250 RNA-sequenced genes.

Results

In 91 of the cases, at least one pathogenic gene variation was detected. The median TMB was 4.67 (0–52.95) mutations/Mb, and in 6.5% of the cases, the total TMB was ≥ 10 mutations/Mb (“TMB-intermediate/high”). The tumor with the highest TMB (52.95 mutations/Mb) presented 12 pathogenic variants. TP53 was the most commonly altered gene (59.34%), followed by CDKN2A (20.6%) amplifications. In 11.2% of the cases, likely functional fusions/rearrangements were also detected.

Conclusions

This study presents one of the largest isolated GBC cohorts, analyzed by a comprehensive targeted NGS panel with a precision oncology approach. These findings will provide insights into a rare but severe type of upper GI cancer. The analysis is currently ongoing, and a further 84 patients will be molecularly characterized till the meeting to be able to present complete molecular data of 200 patients.

Clinical trial identification

NCT05222854.

Editorial acknowledgement

Legal entity responsible for the study

Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest.

Funding

AstraZeneca.

Disclosure

All authors have declared no conflicts of interest.