Dataset Information

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.

SUBMITTER: Gelsomino F

PROVIDER: S-EPMC8870676 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Small Bowel Adenocarcinoma: From Molecular Insights to Clinical Management.

Gelsomino Fabio F Balsano Rita R De Lorenzo Stefania S Garajová Ingrid I

Current oncology (Toronto, Ont.) 20220217 2

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 optim ...[more]

PMID: 35200603

Similar Datasets

Project description:ImportanceSmall-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. To date, comprehensive genomic analysis of SBA is lacking.ObjectiveTo perform in-depth genomic characterization of a large series of SBAs and other gastrointestinal tumors to draw comparisons and identify potentially clinically actionable alterations.Design, setting, and participantsProspective analysis was performed of clinical samples from patients with SBA (n = 317), colorectal cancer (n = 6353), and gastric carcinoma (n = 889) collected between August 24, 2012, and February 3, 2016, using hybrid-capture-based genomic profiling, at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions.ResultsOf the 7559 patients included in analysis, 4138 (54.7%) were male; the median age was 56 (range, 12-101) years. The frequency of genomic alterations seen in SBA demonstrated distinct differences in comparison with either colorectal cancer (APC: 26.8% [85 of 317] vs 75.9% [4823 of 6353], P < .001; and CDKN2A: 14.5% [46 of 317] vs 2.6% [165 of 6353], P < .001) or gastric carcinoma (KRAS: 53.6% [170 of 317] vs 14.2% [126 of 889], P < .001; APC: 26.8% [85 of 317] vs 7.8% [69 of 889], P < .001; and SMAD4: 17.4% [55 of 317] vs 5.2% [46 of 889], P < .001). BRAF was mutated in 7.6% (484 of 6353) of colorectal cancer and 9.1% (29 of 317) of SBA samples, but V600E mutations were much less common in SBA, representing only 10.3% (3 of 29) of BRAF-mutated cases. The ERBB2/HER2 point mutations (8.2% [26 of 317]), microsatellite instability (7.6% [13 of 170]), and high tumor mutational burden (9.5% [30 of 317]) were all enriched in SBA. Significant differences were noted in the molecular profile of unspecified SBA compared with duodenal adenocarcinoma, as well as in inflammatory bowel disease-associated SBAs. Targetable alterations in several additional genes, including PIK3CA and MEK1, and receptor tyrosine kinase fusions, were also identified in all 3 series.Conclusions and relevanceThis study presents to our knowledge the first large-scale genomic comparison of SBA with colorectal cancer and gastric carcinoma. The distinct genomic differences establish SBA as a molecularly unique intestinal cancer. In addition, genomic profiling can identify potentially targetable genomic alterations in the majority of SBA cases (91%), and the higher incidence of microsatellite instability and tumor mutational burden in SBA suggests a potential role for immunotherapy.

Project description:Primary small bowel adenocarcinoma (SBA) is a rare cancer for which effective treatment strategies have not yet been established. The results of previous retrospective studies suggest that chemotherapy contributes to a longer survival time in patients with SBA. However, there are few case reports about the efficacy of molecular targeted agent-containing chemotherapy for SBA. In the present study, the treatment and follow-up data of patients with SBA who received chemotherapy with or without molecular targeted agents were retrospectively analyzed. Each patient was treated in one of ten hospitals participating in the Osaka Gut Forum between April 2006 and March 2014. The following factors were evaluated: Age, sex, Eastern Cooperative Oncology Group performance status (PS), tumor location, tumor differentiation, chemotherapy regimen, resection of primary tumor, tumor biomarker expression, distant metastasis, best response under chemotherapy, time to disease progression, subsequent treatments, survival status and treatment toxicity. A total of 27 patients (17 males and 10 females; mean age, 63.4 years old; range, 36-83 years old) received chemotherapy due to non-curative tumor resection, unresectable tumor or post-operative recurrence. The median overall survival time was 14.8 months (range, 2-58 months). A univariate analysis revealed a PS of 0 (P=0.0228) and treatment with platinum-based chemotherapy (P=0.0048) were significant factors for an improved prognosis. An age-adjusted multivariate analysis also revealed that a platinum-based regimen was a significant positive prognostic factor (P=0.0373). Molecular targeted agents were administered to 8 patients, for whom it was their first- or second-line therapy. Among the 17 patients who received oxaliplatin-based chemotherapy as a first-line chemotherapy, a PS of 0 (P=0.0255) and treatment with bevacizumab (P=0.0121) were significant positive prognostic factors. Toxicities higher than Grade 3 occurred in 8/27 patients with SBA; however, serious side effects due to the molecular targeted agents were not experienced. The results of the present study indicate that chemotherapy containing molecular targeted agents is a well-tolerated and effective treatment option for SBA.

Dataset Information

Small Bowel Adenocarcinoma: From Molecular Insights to Clinical Management.

Publications

Small Bowel Adenocarcinoma: From Molecular Insights to Clinical Management.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets