Brain metastases (BM) from colorectal cancer (CRC) are rare and usually develop late in the disease. However, it has been suggested that more patients will be diagnosed with BM from CRC due to improved diagnostics and increased survival. The aim of this study was to identify biological and clinical characteristics that could predict later BM development in long surviving patient with metastatic (m) CRC.
We retrospectively reviewed a multicenter database and biobank encompassing consecutive patients with mCRC who all received cetuximab in combination with irinotecan as third-line treatment independently of RAS status between 2005 and 2008. We performed RAS (KRAS & NRAS), BRAF, and PIK3CA sequencing of DNA from primary tumor tissue.
Totally, 480 patients were included in the study. BM were diagnosed in 42 patients (8.8 %) at median 29 months after mCRC diagnosis. Patient characteristics are shown in table 1. Patients with BM had a significantly longer survival from mCRC diagnosis than non-BM patients (32 months vs 28 months, p = 0.001). On univariate cox regression analysis the risk of developing BM was increased in patients with rectal cancer (Hazard ratio (HR) = 2.478, p = 0.005), metachronous metastatic disease (HR = 2.296, p = 0.013), and lung metastases at mCRC diagnosis (HR = 4.196, p
The incidence of BM was 8.8 % in our cohort of long surviving patients with mCRC. Having lung metastases at mCRC diagnosis seems to be an independent risk factor for later BM development. Rectal cancer and metachronous metastatic disease were also linked to an increased risk of BM.
|-BM 438 patients||+BM 42 patients|
|Median age at CRC diagnosis||60 years||58 years|
|Rectal cancer||153 (35 %)||26 (62 %)|
|Metachronous metastatic disease||188 (43 %)||28 (67 %)|
|Lung metastases||130 (30 %)||26 (62 %)|
|RAS Mut||184 (42 %)||20 (48 %)|
|BRAF Mut||30 (7 %)||0|
|PIK3CA Mut||58 (13 %)||7 (16 %)|
Clinical trial identification
Legal entity responsible for the study
Troels Dreier Christensen and Dorte Lisbet Nielsen
The Danish Cancer Society
All authors have declared no conflicts of interest.