Small Bowel Adenocarcinoma
Conditions
Keywords
Small bowel adenocarcinoma, messenger RNA, DNA, T-cell receptor sequencing
Brief summary
Small bowel adenocarcinoma is a rare malignancy, and there is limited knowledge about its optimal clinical management and molecular background. The SBAMOL study is an observational biomarker study that aims to identify prognostic and predictive biomarkers. This effort is intended to lay the groundwork for personalized medicine tailored to this specific patient group.
Detailed description
Small bowel adenocarcinoma (SBA), an orphan cancer, has annual diagnoses of 12,070 in the USA and 100 in Denmark. Despite its rarity, patient management should prioritize evidence-based care, but large trials are not feasible, leading to data scarcity and suboptimal care. As a result, SBA is treated like colorectal cancer, yet its prognosis is worse, indicating this parallel approach is insufficient. The grasp on SBAs molecular landscape is limited compared to prevalent cancers. Scant mutational profiling studies, suggest SBA is a heterogeneous disease where subsets resemble other gastrointestinal cancers. This underscores the potential for personalized treatments, including targeted therapies and immunotherapies. Comprehensive molecular characterization, using DNA, RNA, and T-cell receptor characteristics, can provide much-needed strategic direction for patient care and future trials. Capitalizing on this, the investigators propose a comprehensive molecular characterization aiming to develop consensus molecular subtypes that can direct future trials and SBA therapeutic strategies. The investigators hypothesize that a consensus molecular profiling approach can identify subgroups of SBA with distinct molecular, cellular, and histological characteristics, that will benefit from tailored treatment strategies using chemotherapy, targeted therapy, and immunotherapy. To explore this hypothesis, the investigators will: (WP1) perform molecular and immunological characterization of tumor tissues from SBA patients (n=200) to establish consensus molecular subtypes of SBA and define their biological attributes; (WP2) ascertain therapeutic avenues tailored to each subtype and devise a molecular algorithm to prospectively categorize individual tumors in real-time, laying the groundwork for molecularly-driven management.
Interventions
None listed
Sponsors
Aarhus University Hospital
Rigshospitalet, Denmark
University of Copenhagen
Copenhagen University Hospital at Herlev
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with histologically verified small bowel adenocarcinoma Patients older than 18 years
Exclusion criteria
Insufficient material for molecular testing Patients registered in Vævsanvendelsesregistret& Vævsanvendelsesregistret; refers to a central Danish registry where patients can opt out of allowing their biological material to be used for purposes other than their own disease management.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Molecular characterization of patients with SBA using high-throughput DNA-, mRNA- and T-cell receptor sequencing and targeted protein expression analyses. | 5 years | Due to the scarce knowledge of the biological background of SBA. The primary endpoint of the study is to present a comprehensive descriptive molecular characterisation of patients with SBA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prognostic and predictive DNA biomarkers in patients with SBA | 5 years | DNA aberrations will associated with disease free, progression free and overall survival. Analysis will be performed using the Oncomine comprehensive plus gene panel. Potential aberrations indicative of targeted treatments will be explored and reported. |
| Prognostic and predictive mRNA biomarkers in patients with SBA | 5 years | mRNA aberrations will associated with disease free, progression free and overall survival. Analysis will be performed using high-throughput sequencing. Potential aberrations indicative of targeted treatments will be explored and reported. |
| Prognostic t-cell receptor biomarkers in patients with SBA | 5 years | T-cell receptor clonality and diversity will associated with disease free, progression free and overall survival. Analysis will be performed using a high-throughput t-cell receptor sequencing. |
Countries
Denmark
Contacts
Primary ContactDan Høgdall, MD PhD
Backup ContactJakob HV Schou, MD
Outcome results
None listed