Small intestinal adenocarcinomas (SIAs) are rare, but they have a poor prognosis and it is unknown which treatment strategy is best for patient outcome. Cancer Center Amsterdam researchers investigate the current evidence to determine the most effective treatment strategies.

Each year, approximately 300 patients in the Netherlands are diagnosed with cancer of the small intestine. “Right now, there is no national treatment guideline for SIAs available,” says Tim de Back, first author of the study and PhD candidate in the group of Louis Vermeulen. “This is because there is a lack of high-quality evidence to base therapy standards on.” Because optimal treatment strategies are largely unknown for this cancer, clinicians usually follow the guidelines for colorectal cancer.

Learning from literature

To gain more insight into effective treatment strategies, Tim de Back and colleagues have reviewed the current evidence regarding the survival benefit of systemic treatment in patients with SIAs. The study was recently published in JAMA Network Open.

The results from the meta-analysis of data from 57 studies covering 35,176 patients showed that adjuvant chemotherapy - systemic therapy in addition to surgery - has significant benefit, regardless of the localization of the cancer, and the benefit increased with each incremental disease stage.

Furthermore, the adjuvant chemotherapy - specifically fluoropyrimidine-based chemotherapy – significantly extended overall survival and progression-free survival, especially in more advanced stage III tumors.

“Palliative chemotherapy also significantly improved overall survival for patients with metastatic SIAs,” says Tim. “Particularly, fluoropyrimidine-oxaliplatin combinations were superior to other regimens.”

Addition of bevacizumab - an antibody against VEGF to inhibit the formation of tumor blood vessels - to first-line chemotherapy significantly improved progression-free survival compared with chemotherapy alone. Finally, immunotherapy seemed to prolong survival for patients with defective mismatch repair (dMMR) tumors, according to the authors, showing a 50% overall response rate in previously treated defective mismatch repair tumors.

“In addition to identifying the most beneficial treatment options for patients with SIAs, these results can be used to guide future clinical trials that seek to improve patient outcome,” concludes Tim de Back.

In addition to identifying the most beneficial treatment options for patients with SIAs, these results can be used to guide future clinical trials that seek to improve patient outcome.
Tim de Back
PhD candidate, Center for Experimental and Molecular Medicine, Amsterdam UMC.

For more information, contact Tim de Back, or read the publication:

de Back T., et al. (2023) Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas: A Systematic Review and Meta-analysis. JAMA Netw Open 6:e230631. doi:10.1001/jamanetworkopen.2023.0631

Researchers involved:

Tim de Back

Isabelle Nijskens (Flevohospital)

Pascale Schafrat

Myriam Chalabi (Netherlands Cancer Institute)

Geert Kazemier

Louis Vermeulen

Dirkje Sommeijer

Funding

This work was supported by the New York Stem Cell Foundation, Oncode Institute, the European Research Council, ZonMw, and the Dutch Cancer Society.

This article was created for Cancer Center Amsterdam.

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