Small Bowel Adenocarcinoma: From Molecular Insights to Clinical Management

Abstract

Small bowel adenocarcinoma (SBA) is a rare malignancy, with a rising incidence in recent decades, and accounts for roughly 40% of all cancers of the small bowel. The majority of SBAs arise in the duodenum and are associated with a dismal prognosis. Surgery remains the mainstay of treatment for localized disease, while systemic treatments parallel those used in colorectal cancer (CRC), both in the adjuvant and palliative setting. In fact, owing to the lack of prospective data supporting its optimal management, SBA has historically been treated in the same way as CRC. However, recent genetic and molecular data suggest a distinct profile from other gastrointestinal malignancies and support a more nuanced approach to its management. Herein, we briefly review the state-of-the-art in the clinical management of early-stage and advanced disease and recent discoveries of potentially actionable genetic alterations or pathways along with the most promising ongoing clinical trials, which will hopefully revolutionize the treatment landscape of this orphan disease in the foreseeable future.

Keywords: genomic profiling; molecular alterations; small bowel.

Figure 1

(A) Most frequently altered genes in MSS SBA. (B) Most frequently altered genes in MSI-H SBA. Abbreviations: MSS, microsatellite-stable. MSI-H, microsatellite instability-high.

Figure 2

Suggested treatment algorithm in patients with a clinical suspicion of SBA. Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; FOLFOX, 5-FU, oxaliplatin; XELOX, capecitabine, oxaliplatin; PD-1, programmed death-1; PD-L1, programmed death-ligand 1; MSI-H, microsatellite instability-high; dMMR, deficient mismatch repair. ^a Chemo-radiotherapy for selected cases of duodenal tumors, after multidisciplinary discussion. ^b Genomic profiling for enrollment in clinical trials with matched target therapies is strongly encouraged. ^c Surgery of metastatic sites can be considered in selected cases with oligometastatic disease, after multidisciplinary discussion.