650P - Genomic profiling of small bowel adenocarcinoma: A pooled analysis

Background

Several genomic alterations have been described in small bowel adenocarcinoma (SBA) but the prognostic value of these alterations remains unclear. The aim of this multicentre study was to determine the genomic profile of SBA and its impact on the prognosis.

Methods

Three cohorts in France and Italy were pooled. A common dataset of genomic analysis have been performed on 35 genes of interest. MSI (MicroSatellite Instable) and MMR (MisMatch Repair) status were also assessed.

Results

A total of 188 tumour samples had conclusive results for mutation analysis. The patients (pts) were male (55.3%), with duodenum primary (58.5%), stage I-II (39.6%), III (40.6%) and IV (18.8%). with a predisposing disease (21%) mainly Lynch syndrome (LS) (n=19) and Crohn disease (CD) (n=11). The most frequent mutation were KRAS (42.0%) of which 7/79 G12C, TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). TP53 mutations were more frequent in CD (81.8%) but less frequent in LS (15.8%) than in no predisposing disease (39%). ERBB2 mutations were more frequent in LS (26.3%) than in no predisposing disease (7.5%). No APC mutation was observed in CD. KRAS and SMAD4 mutations were more frequent in tumour than in localized tumour (59.4% vs 37.7%, p=0.0164) and (24.3% vs 9.9%, p=0.0187). ERBB2 mutations were less frequent in metastatic than in localized tumour (0% vs 11.9%, p=0.0272). For localized tumour univariate analysis revealed that: age ≥65 (p=0.0327), T4 (p=0.570), high grade (p=0.0028) stage III (p=0.0390) and wild type APC (p=0.395) were associated with a poor overall survival (OS). In multivariate analysis: high grade (p=0.023), age ≥65 (p=0.0123) and wild type APC (p=0.0254) were associated with a poor OS. For metastatic tumour a trend for a better OS was observed in case of a mutated KRAS tumour (HR=0.6 (0.34-1.06), p=0.0797) in univariate analysis. dMMR/MSI status was available in 238 pts. Overall, dMMR/MSI was reported in 29.8%, 31.8% in localized and 11.3% in metastatic tumour. dMMR/MSI was associated with a better OS (HR=0.61 [0.39-0.96], p=0.0333).

Conclusions

There is different genomic profile according to the predisposing disease. MSI/dMMR predict a better prognosis. APC mutation in localized and KRAS mutation in metastatic tumour are associate with a better prognosis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fondation ARCAD, Programme Hospitalier de Recherche Clinique.

Disclosure

All authors have declared no conflicts of interest.