Abstract

BackgroundBrain metastases (BM) due to colorectal cancer (CRC) are an infrequent event. Previous research suggests that patients with pulmonary metastases, rectal primaries and KRAS mutations are at an increased risk of BM. Despite multidisciplinary treatment, survival following BM remains poor. We aimed to analyse the incidence, genomic profiling, treatment administered and survival in patients with BM from CRC within our cancer service. MethodsA retrospective analysis of 1346 CRC patients at two comprehensive cancer centres in Western Sydney identified 52 patients with BM. Data was subsequently collected on patient demographics, tumour and treatment characteristics. KRAS and BRAF mutation status from primary colorectal tumour specimens and surgical resection of BM was assessed. Survival data was analysed by the Kaplan-Meier method. ResultsThe incidence of BM in our cohort was 3.9%. The mean age of patients was 66 (35-82) with 48% female and 52% male in the BM group compared to 36% female and 64% male in the non-BM group. 33% of patients were wildtype (WT), 62% had a RAS mutation and 5% were BRAF mutant. The median time between diagnosis of primary CRC and development of BM did not differ between RAS, RAF and WT (37, 50 and 43 months). 70% of WT patients presented with one BM compared to 45% of KRAS mutated patients although this was not statistically significant (p = 0.13). 38% of patients had surgery while 81% had radiotherapy (56% WBRT, 44% SRS) to treat their BM. The median PFS across all groups was 3.2 months and median OS was 3.9 months. Median PFS was significantly longer in patients who received surgery, chemotherapy and radiotherapy following their diagnosis of BM (12.3 months) versus surgery alone (1 month) or surgery and radiotherapy (4.4 months) (p = 0.022). Mutational status or number of BM did not impact on PFS or OS. Patients with synchronous liver metastases had a significantly shorter median OS of 3 months versus 13 months in those without liver metastases (p = 0.008). ConclusionsBrain metastases remains an infrequent event in patients with metastatic colorectal cancer. KRAS and BRAF mutations do not appear to have any effect on prognosis or response to treatment in CRC patients with BM. Survival of CRC patients following BM is poor and novel approaches are needed. Legal entity responsible for the studyThe authors. FundingWestern Sydney Local Health District. DisclosureK.Y.M. Wong: Advisory / Consultancy: Baxalta; Speaker Bureau / Expert testimony: Sirtex; Travel / ccommodation / Expenses: MSD Oncology. All other authors have declared no conflicts of interest.

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