Kunal K. Dalal, MD1, John Gaughan, MS, PhD, MBA1, Vikram Patel, MD1, Jamin Morrison, MD2; 1Cooper University Hospital, Camden, NJ; 2MD Anderson Cancer Center At Cooper, Camden, NJ
Introduction: Colorectal cancer (CRC) is the second overall leading cause of cancer death in the general US population. KRAS mutation is prevalent in 30–50%, and MSI-H (high microsatellite instability) is in 15% of all colorectal cancers of which 12% are sporadic and 3% are lynch syndrome. EGFR-targeted therapy is effective in CRC lacking KRAS mutations¸ and checkpoint inhibitor therapy is effective in CRC with MSI-H. Generally, MSI-H tumors are right sided and found in younger patients with Lynch syndrome epidemiology. Concurrent with understanding of tumor biology, there is increasing disease incidence within the younger patient population. We aim to retrospectively evaluate the KRAS mutation status and MSI status in colon adenocarcinoma with respect to tumor anatomy, and assess correlation with age of diagnosis. Methods: Patients aged 18–90 years with colorectal cancer diagnosed between 2010 and 2013 were identified from the National Cancer Database. Data from 1469 US hospitals. Chi squared and logistic regression were used to analyze demographic and clinical characteristics by molecular subtype. SAS v9.4 was used for statistical analysis. Results: The dataset had 459,810 total patients of which reported KRAS status in 55,927 patients and MSI status in 91,961 patients. KRAS mutations in 9,602 were age < 50 and 46,325 were age >50 of which 11,020 were >age 75. KRAS mutations were present in 39.6% of patients age >50 vs 38.5% in patients age< 50. KRAS mutations located in proximal colon vs rectosigmoid vs rectum, was 75.4%, 7.6%, and 17.0% respectively. MSI positive in 14,823 were age < 50 and 77,138 were age >50 of which 23,508 were > age 75. MSI presence in 24.5% of patients age >50 vs 21.5% in patients age < 50. MSI located in proximal colon vs rectosigmoid vs rectum, was 85.9%, 4.9%, and 9.3% respectively. After adjustment for areas and extents, the 51-75 group had a 26% lower chance of being MSI positive than the >75 group (OR=0.741, p=0.037). For MSI, colon area 1.85x higher than the rectum (OR=1.851, p=0.0075). Discussion: KRAS mutation status was not different based on age, and was more prevalent in proximal colon. Despite our hypothesis, MSI was more prevalent in older patients, likely the sporadic variation, and most age > 75. MSI was prevalent in proximal colon and may be associated with other clinicopathological features. Guidelines for when to test for MSI on pathology specimens should take elder age into account. Personalized cancer care can be further delineated with more studies.
Disclosures: Kunal Dalal indicated no relevant financial relationships. John Gaughan indicated no relevant financial relationships. Vikram Patel indicated no relevant financial relationships. Jamin Morrison indicated no relevant financial relationships.