33P - Molecular-genetic concordance of the primary tumor and brain metastases of colorectal cancer (GENCONCOR-1)

Background

Brain metastases (BM) from colorectal cancer (CRC) are a rare event reported in less than 4% of patients with metastatic CRC. This course is associated with a poor prognosis, and treatment of these patients remains challenging. Nevertheless, given the rarity of the event, at this time not enough is known about molecular biology of BM from CRC.

Methods

In N.N. Blokhin NMRCO over 26 years (1998-2024) identified 109 patients with BM from CRC. Of this number, 72 patients had a history of neurosurgical resection of BM. In turn, for 32 patients access to a pair of tumor samples: from the primary tumor and from intracranial metastases. GENCONCOR-1 study is translational research aimed to investigate the biological concordance between the CRC and BM. The study was conducted by post hoc analysis of pairs of FFPE tissue blocks. Tumor samples was tested for status of genes KRAS, NRAS, BRAF and microsatellite instability (MSI). The molecular profile of the BM was compared with the corresponding primary tumor with calculation of concordance rate (%). Table: 33P

Baseline patient characteristics

Results

According to the results of the first interim analysis (15 of 32 patients), the concordance rate of the primary tumor and BM was 67% (5/15). Three patients (20%) had discordance by the status of the RAS family genes, and 2 patients (13%) by MSI. All RAS-discordant cases characterized by the occurrence alteration in the BM when it was initially absent in the CRC. In cases of MSI, one patient initially had MSI in the CRC with conversion to microsatellite stability in BM, and the second patient had the opposite. One patient had discordance in two genes at once: KRAS and BRAF. RAS family gene mutations were observed in CRC in 54% of patients (8/15) and in BM in 73% of patients (11/15). The BRAF V600E mutation occurred in 13% (2/15) and 6% (1/15), respectively. In both the primary tumor and BM, the MSI rate was 6% (1/15). The most common alteration in primary CRC was the KRAS G12V mutation, which occurred in half of the RASmut cases.

Conclusions

Every third patient with BM of CRC demonstrates a change in the mutational status of the tumor.

Editorial acknowledgement

Clinical trial identification

NCT06449989.

Legal entity responsible for the study

The Blokhin National Medical Research Center of Oncology.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.