Molecular comparison of primary gastroesophageal cancers and their brain metastases

Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Gastroesophageal Cancers (GENCONCOR-2)

This project will test whether key biomarkers (HER2, MSI, PD-L1, CLDN18.2) match between primary gastroesophageal tumors and their matched brain metastases using archived tissue.

Quick facts

• Study type: Observational
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Blokhin's Russian Cancer Research Center (other)
• Locations: 1 site (Moscow)
• Trial ID: NCT07464470 on ClinicalTrials.gov

What this trial studies

This is a retrospective translational analysis of paired FFPE samples from primary tumors and surgically resected brain metastases drawn from the international GASTROBRAIN cohort. Pathology testing will determine HER2 status (IHC ± FISH), MSI status (IHC ± PCR), PD-L1 combined positive score (CPS), and CLDN18.2 expression by IHC in both sites. The main objective is to compare molecular-genetic concordance between the matched primary and brain metastatic lesions. Findings will be correlated with available clinicopathological and treatment data to contextualize discordance and potential treatment implications.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed gastric, esophageal, or gastroesophageal junction carcinoma who underwent neurosurgical resection of a brain metastasis and have paired archival FFPE tissue and clinical data in the GASTROBRAIN cohort.

Not a fit: Patients without available paired primary and brain metastatic tissue, those with non-epithelial gastrointestinal tumors, multiple other primary malignancies, or missing clinicopathological data are unlikely to be included or benefit from this analysis.

Why it matters

Potential benefit: If successful, the findings could help doctors know whether biomarker results from the primary tumor reliably reflect the brain metastasis and guide testing or targeted treatment decisions.

How similar studies have performed: Paired biomarker concordance in gastroesophageal brain metastases is understudied and this work builds on the GASTROBRAIN cohort, while similar concordance studies in other cancers have shown variable discordance.

Eligibility criteria

Inclusion Criteria:

1. Men and women aged 18 years or older included in the GASTROBRAIN study with available clinicopathological and treatment data.
2. Histologically confirmed gastric adenocarcinoma, esophageal carcinoma (adenocarcinoma or squamous cell carcinoma), or gastroesophageal junction adenocarcinoma.
3. History of neurosurgical resection of brain metastases with available archival tissue material, and histological confirmation of metastatic lesion originating from gastroesophageal cancer.
4. Availability of paired FFPE tissue samples from primary tumor and matched brain metastasis.

Exclusion Criteria:

1. Synchronous or metachronous multiple primary malignancies involving sites other than the stomach, esophagus, or gastroesophageal junction.
2. Primary tumor located outside the gastrointestinal tract.
3. Histologically confirmed non-epithelial gastrointestinal malignancy (e.g., neuroendocrine tumors, sarcoma, gastrointestinal stromal tumor, lymphoma).
4. Intact brain parenchyma (e.g., metastases confined to skull bones or soft tissues of the head without brain parenchymal involvement).
5. Insufficient tumor material or poor sample quality for molecular analysis, defined as:

   * Tumor cell content \< 70% in the area of microdissection, or
   * Significant nucleic acid degradation compromising molecular testing
6. Missing one sample from a paired set (either primary tumor or brain metastasis unavailable).

Where this trial is running

Moscow

• Blokhin's Russian Cancer Research Center — Moscow, Russia (RECRUITING)

Study contacts

• Study coordinator: David Khalafyan, MD

Conditions: Gastric Cancer, Esophageal Cancer, Brain Metastases, Gastroesophageal junction cancer, Brain metastasis, Central nervous system metastases, CNS, Overall survival