Blood-borne Assessments of Stromal Activation to Guide Therapy in Esophageal Adenocarcinoma – BASALT

Oncode’s Affordable Healthcare program is set up with the aim to make cancer treatment available to patients at an affordable price. Together with ZonMw, Oncode focuses on Proof of concept studies that aim to contribute to sustainable healthcare: studies that contribute to lowering health costs and research that will lead to the development of effective, safe and affordable medicines and personalized precision diagnostics.

Oncode Investigator Jan Paul Medema and researcher Maarten Bijlsma (both of Amsterdam UMC), together with clinician Hanneke van Laarhoven (Amsterdam UMC) submitted a proposal on guided therapy in a specific type of esophageal cancer: esophageal adenocarcinoma.

Approximately 2,500 patients are diagnosed with esophageal adenocarcinoma in the Netherlands each year. Esophageal adenocarcinoma is a disease entity with a distinct etiology, molecular makeup, and poorer prognosis compared to squamous carcinomas of the esophagus. In patients eligible for resection, the standard care currently includes neoadjuvant chemotherapy and radiation followed by surgery (CROSS regimen). Despite this intense regimen, median overall survival is just over 3.5 years. Thus, there is a dire need of improvement.

In gastrointestinal cancers, including esophageal adenocarcinoma, non-tumor cells such as fibroblasts and extracellular matrix material often comprise the bulk of tumor tissue (‘stroma’). This stroma is now well recognized to harbor significant tumor-promoting properties, and suspected to hamper treatment response, for instance to neoadjuvant chemoradiation, as recently shown by the investigators. The research group has discovered a substance that is produced in the stroma and which prevents the effective treatment of esophageal adenocarcinoma patients. In addition, they have developed a so-called biomarker (a substance to be measured in the blood) that can indicate the amount of the treatment-inhibiting stroma in patients.

This clinical study aims to find out how safe and effective the addition of stroma-targeting agent Tocilizumab is to the standard care of esophageal cancer. Tocilizumab is already used in the treatment of other diseases, however the combination of Tocilizumab with chemotherapy and radiation in the treatment of esophageal cancer has not been studied before.

A positive outcome from this study will provide a much-needed stratification tool to improve outcome of currently available stroma-targeting compounds that have failed to demonstrate encouraging efficacy. These findings are not restricted to esophageal adenocarcinoma and can include other stroma-rich tumors with poor outcome, such as pancreatic and colorectal cancer. Gastrointestinal cancers belong to the deadliest cancers worldwide, with a five-year survival rate below 50%, underscoring the clinical need for improvement of treatment outcome and the potential impact of this stratification approach.

Marlinde Smit
Program Manager

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