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Genomic profiling to provide new treatment opportunities in ampullary carcinoma

Authors :
Carles Fabregat Franco
Florian Castet
Nadia Saoudi Gonzalez
Gloria Castillo
Daniel Acosta Eyzaguirre
Maria Teresa Salcedo
Helena Verdaguer
Teresa Macarulla
Source :
Journal of Clinical Oncology. 41:582-582
Publication Year :
2023
Publisher :
American Society of Clinical Oncology (ASCO), 2023.

Abstract

582 Background: Ampullary carcinoma (AC) is a rare heterogeneous group of diseases with an abysmal prognosis. Treatment options are limited, and the molecular landscape of this disease and its therapeutic implications have been incompletely explored. Here, we aim to provide a clinical and genomic characterization of AC and explore opportunities for precision oncology. Methods: Patients diagnosed with AC and treated at a single tertiary institution between 2010 and 2022 were reviewed. Molecular profiles were analyzed by applying an in-house exome-targeted panel or the FoundationOne CDx panel. Gene mutations were categorized into molecular pathways and potentially targetable alterations were classified according to the ESCAT scale. Overall survival (OS) and disease-free survival (DFS) were estimated by using the Kaplan-Meier method. Results: We included 64 patients with a median age of 66 years, 51.6% were women, most were classified as pancreatobiliary tumours (PB, 58.3%), followed by intestinal (INT, 33.3%) and mixed histologies (8.3%). 18.8%, 23.4%, 32.8% and 25.0% of the patients were diagnosed at stage I, II, III and IV, respectively. 81.2% of the patients were treated with surgery. The INT subtype was enriched in WNT pathway alterations (28.6 vs 6.2%, p=0.02) and showed a non-significant enrichment in the apoptotic pathway (57.1 vs 34.4%, p=0.08). Conversely, BP showed a non-significant enrichment in HRR pathway alterations (16.7 vs 54.5%, p=0.3). The frequency of KRAS mutations were similar in both subtypes (38.1 vs 37.5%). Potentially actionable molecular alterations were found in 46.7% of the patients (9 ERBB2, 8 HRD, 8 PI3KCA, 2 MSI, 2 BRAF, 2 PTEN and 1 KRAS G12C). Importantly, KRASwt tumours were enriched in potentially targetable alterations (ESCAT I-IIIA), including 20% ERBB2 amplification/mutations, 6% MSI and 3% BRCA1. 6 patients received matched targeted therapies during their disease course, 66% of which responded and 100% stable disease, with a median TTD of 7 months. Conclusions: More than 45% of AC harbor potentially targetable genomic alterations that may provide novel therapeutic opportunities and enhance personalized medicine in this rare disease entity.

Subjects

Subjects :
Cancer Research
Oncology

Details

ISSN :
15277755 and 0732183X
Volume :
41
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi...........4b3cd48063b1432e4abafb2b1af9d3fe
Full Text :
https://doi.org/10.1200/jco.2023.41.4_suppl.582