Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer
| Autor: | Jonathan S. Silver, M Silver, S Marwah, Maria Tzardi, John Souglakos, Shuji Ogino, Dianne M. Finkelstein, V. Georgoulias, Rui Wang, Susanne M. Hooshmand, Z. Saridaki, Charles S. Fuchs, Matthew H. Kulke, Ramesh A. Shivdasani, Juliet Philips, Jeffrey A. Meyerhardt, Ellen Freed, Eunice L. Kwak |
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| Rok vydání: | 2009 |
| Předmět: |
Oncology
Male Cancer Research Pathology endocrine system diseases Colorectal cancer Salvage therapy Cetuximab medicine.disease_cause Metastasis Phosphatidylinositol 3-Kinases 0302 clinical medicine Neoplasm Metastasis Aged 80 and over 0303 health sciences Hazard ratio Antibodies Monoclonal Middle Aged Prognosis 3. Good health 030220 oncology & carcinogenesis Predictive value of tests Female KRAS Colorectal Neoplasms medicine.drug Adult Proto-Oncogene Proteins B-raf medicine.medical_specialty Class I Phosphatidylinositol 3-Kinases Antibodies Monoclonal Humanized BRAF Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Predictive Value of Tests Internal medicine Proto-Oncogene Proteins medicine Humans neoplasms Molecular Diagnostics 030304 developmental biology Aged Salvage Therapy business.industry Cancer PIK3CA prediction medicine.disease digestive system diseases Mutation ras Proteins business metastatic CRC |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 |
| Popis: | Background: We address the prognostic and predictive value of KRAS, PIK3CA and BRAF mutations for clinical outcomes in response to active agents in the treatment of metastatic colorectal cancer (mCRC). Methods: We determined KRAS, BRAF and PIK3CA mutations in tumours from 168 patients treated for mCRC at two institutions. All patients received 5-FU-based first-line chemotherapy and treatment outcome was analysed retrospectively. Results: KRAS, BRAF and PIK3CA mutations were present in 62 (37%), 13 (8%) and 26 (15%) cases, respectively. Multivariate analysis uncovered BRAF mutation as an independent prognostic factor for decreased survival (hazard ratio (HR) 4.0, 95% confidence interval (CI) 2.1–7.6). In addition, patients with BRAF-mutant tumours had significantly lower progression-free survival (PFS: HR 4.0, 95% CI 2.2–7.4) than those whose tumors that carried wild-type BRAF. Among 92 patients treated using chemotherapy and cetuximab as salvage therapy, KRAS mutation was associated with lack of response (P=0.002) and shorter PFS (P=0.09). BRAF (P=0.0005) and PIK3CA (P=0.01) mutations also predicted reduced PFS in response to cetuximab salvage therapy. Conclusions: These results underscore the potential of mutational profiling to identify CRCs with different natural histories or treatment responses. The adverse significance of BRAF mutation should inform patient selection and stratification in clinical trials. |
| Databáze: | OpenAIRE |
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