J. Purchla1, W. H. Ward1, F. Lambreton1, N. Nweze1, T. Li2, N. Goel1, S. Reddy1, E. Sigurdson1, J. M. Farma1 1Fox Chase Cancer Center,Department Of Surgical Oncology,Philadelphia, PA, USA 2Fox Chase Cancer Center,Philadelphia, PA, USA
Introduction: Colorectal adenocarcinoma is a disease with varying causative molecular mechanisms, where chromosomal instability leads to gene specific mutations in proto-oncogenes and tumor suppressors. Among the most well-known mutations, the BRAF gene is associated with decreased disease-free and overall survival. This investigation strives to characterize patient and disease-related outcome measures among patients with BRAF-mutated colorectal adenocarcinoma.
Methods: A retrospective study was performed using molecular profiling (MP) data of 35 colorectal patients of any stage who were treated at our tertiary cancer center between 2006 and 2017. Those who did not undergo molecular profiling or those with incomplete data were excluded. If completed, additional genetic analyses performed within or external to our institution were also included. Demographic, clinical, and pathological data were collected and analyzed. Recurrence free survival was assessed using Kaplan-Meier estimation method.
Results: Out of 481 colorectal patients, 35 (7.3%) were identified as having a BRAF mutation. The median age at diagnosis was 73 years old (range 36-90), 25 (71%) were female, and 29 (82.9%) were white. There were 29 (82.9%) colon primary sites, 16 (55.2%) of those right-sided, and 6 (17.1%) rectal. 9 (25.7%) were stage IV, 15 (42.9%) were stage III, 7 (20.0%) were stage II, and 4 (11.4%) were stage I. A majority of patients (77.1%) exhibited more than just a BRAF mutation, with 15 (42.9%) positive for defective mismatch repair/microsatellite instability (dMMR/MSI), 10 (28.6%) with a P53 mutation, 4 (11.4%) SMAD4, 3 (8.6%) APC, and 3 (8.6%) PIK3CA. A total of 5 (14.3%) patients had a prior history of other cancer types. From this cohort, 29 (82.9%) had surgery, and 23 (79.3%) achieved an R0 resection. A total of 19 (54.3%) patients underwent adjuvant therapy. Targeted therapy with EGFR inhibitor was administered in 10 (28.6%) patients. Recurrence occurred in 10 (28.6%) patients, with the median time to recurrence 22.2 months. The recurrence free survival rate to 1 year was 74.5% and to 2 years was 37.1%. The overall survival rate to 1 year was 89.6%, and to 2 years was 56.8%.
Conclusions: In this cohort, patients with BRAF mutated colorectal cancer were generally older, white and female, and more likely to present with advanced disease. Of those who relapsed, more than 60% of patients did so within 2 years of diagnosis. Overall survival decreased substantially after 1 year. Tumors were primarily in the colon, specifically right-sided colon, with a MP likely to show more than 1 mutation. Our investigation shows that this cohort of BRAF-mutated tumors exhibits a poorer prognosis. To better characterize these patients and their disease-related outcomes, further investigation with a larger cohort is warranted.