Ayman Rasmy1,2,3, Alaa Fayed4, Ayman Omar5,6, Nermin Fahmy5,6. 1. Medical Oncology, Zagazig University Hospitals, Zagazig, Egypt. 2. Oncology Department, King Saud Medical City, Riyadh, Saudi Arabia. 3. Oncology Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia. 4. Clinical Oncology Department, Zagazig University, Zagazig, Egypt. 5. Clinical Oncology and Nuclear Medicine Department, Suez Canal University, Ismailia, Egypt. 6. Oncology Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Abstract
BACKGROUND: Nowadays, the outcomes of metastatic colorectal cancer (mCRC) have considerably improved. Genetic studies evaluating KRAS mutational status are important in the personalized therapy era to understand disease heterogeneity, disease behaviors, and treatment outcomes. METHODS: This multicenter retrospective study evaluated 360 patients with mCRC treated at three oncology centers in Saudi Arabia and Egypt between February 2011 and December 2015. Patients were treated with bevacizumab and cetuximab according to guidelines. Therapy outcome, time to progression, and disease-associated death were assessed. KRAS mutational status was evaluated by testing exons 12 and 13. RESULTS: Approximately 220 (61.1%) cases were of wild-type KRAS, whereas KRAS mutation was noted in 38.9%. KRAS mutation was common in the descending colon, whereas a low incidence of the KRAS mutation was observed in the ascending colon (P<0.001). Among patients with KRAS mutation, 64.3% initially presented as emergency cases with obstruction/perforation (P=0.002), and 62.9% had hepatic or pulmonary metastasis. The progression-free survival (PFS) was 10.7 months. Cases without KRAS mutation showed a higher PFS than did those with KRAS mutation (mean PFS: 11.5 vs. 9.6 months, P=0.001). The overall survival was 23.2 months. The survival varied considerably according to KRAS type: patients without mutation survived for 25.0 months and those with mutation survived for 19.6 months (P<0.001). Disease-related death occurred in 132 (36.7%) cases, approximately 57.1% of them (80 cases) had KRAS mutations (P=0.001). CONCLUSIONS: A major association between KRAS mutational status and both disease behavior and treatment outcomes was found in this study. Patients with KRAS mutation show advanced disease presentation, with lower PFS and overall survival. 2019 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Nowadays, the outcomes of metastatic colorectal cancer (mCRC) have considerably improved. Genetic studies evaluating KRAS mutational status are important in the personalized therapy era to understand disease heterogeneity, disease behaviors, and treatment outcomes. METHODS: This multicenter retrospective study evaluated 360 patients with mCRC treated at three oncology centers in Saudi Arabia and Egypt between February 2011 and December 2015. Patients were treated with bevacizumab and cetuximab according to guidelines. Therapy outcome, time to progression, and disease-associated death were assessed. KRAS mutational status was evaluated by testing exons 12 and 13. RESULTS: Approximately 220 (61.1%) cases were of wild-type KRAS, whereas KRAS mutation was noted in 38.9%. KRAS mutation was common in the descending colon, whereas a low incidence of the KRAS mutation was observed in the ascending colon (P<0.001). Among patients with KRAS mutation, 64.3% initially presented as emergency cases with obstruction/perforation (P=0.002), and 62.9% had hepatic or pulmonary metastasis. The progression-free survival (PFS) was 10.7 months. Cases without KRAS mutation showed a higher PFS than did those with KRAS mutation (mean PFS: 11.5 vs. 9.6 months, P=0.001). The overall survival was 23.2 months. The survival varied considerably according to KRAS type: patients without mutation survived for 25.0 months and those with mutation survived for 19.6 months (P<0.001). Disease-related death occurred in 132 (36.7%) cases, approximately 57.1% of them (80 cases) had KRAS mutations (P=0.001). CONCLUSIONS: A major association between KRAS mutational status and both disease behavior and treatment outcomes was found in this study. Patients with KRAS mutation show advanced disease presentation, with lower PFS and overall survival. 2019 Journal of Gastrointestinal Oncology. All rights reserved.
Entities:
Keywords:
Colorectal cancer (CRC); KRAS; molecular study; overall survival (OS); prognostic and predictive factors chemotherapy/target therapy; progression-free survival (PFS)
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