Abstract 484P
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 MSI. The molecular profile of the BM was compared with the corresponding primary tumor with calculation of concordance rate (%) Table: 484P
Patient baseline characteristics
| ITT (n = 109) | PP (n = 32) | |
| Sex, n (%) | Male: 54 (49.5%) Female: 55 (50.5%) | Male: 16 (50%) Female: 16 (50%) |
| Age, years (median) | 57 (21-79) | 55 (38-76) |
| Site of the primary tumor, n (%) | Left-sided: 89 (81.7%) Right-sided: 20 (18.3%) | Left-sided: 25 (78%) Right-sided: 7 (22%) |
| Extracranial metastases, n (%) | Yes: 88 (80.7%) No: 21 (19.3%) | Yes: 29 (90.6%) No: 3 (9.4%) |
| ECOG, n (%) | 0-1: 55 (50.5%) 2-3: 54 (49.5%) | 0-1: 29 (91%) 2-3: 3 (9%) |
| Number of BM, n (%) | Single: 74 (67.9%) ≥ 2: 35 (32.1%) | Single: 26 (81%) ≥ 2: 6 (19%) |
| Localization of the BM, n (%) | Supratentorial: 65 (59.5%) Subtentorial: 30 (27.5%) Both: 14 (13%) | Supratentorial: 21 (66%) Subtentorial: 9 (28%) Both: 2 (6%) |
Results
According to the results of the second interim analysis (32 of 32 patients), the concordance rate of the primary tumor and BM was 65,6% (21/32). 8 patients (25%) had discordance by the status of the RAS family genes, and 3 patients (9%) – by MSI. All RAS-discordant cases, except one, characterized by the occurrence alteration in the BM when it was initially absent in the CRC. In cases of MSI, two patients initially had MSI in the CRC with conversion to MSS in BM, and the third patient had the opposite. Three patients had discordance in two genes at once: KRAS and BRAF/MSI. RAS family gene mutations were observed in CRC in 50% of patients (16/32) and in BM in 65% of patients (21/32). The BRAF V600E mutation occurred in 13% (4/32) and 9% (3/32), respectively. MSI rate was 6% (2/32) in the CRC and 3% (1/32) in BM. The most common alteration both in the CRC and in BM 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.
Clinical trial identification
NCT06449989.
Editorial acknowledgement
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.