BRAFV600E Mutation Analysis in Patients with Metastatic Colorectal Cancer (mCRC) in Daily Clinical Practice: Correlations with Clinical Characteristics, and Its Impact on Patients’ Outcome
作者： Zacharenia Saridaki , Maria Tzardi , Maria Sfakianaki , Chara Papadaki , Alexandra Voutsina
DOI: 10.1371/JOURNAL.PONE.0084604
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摘要: Background To prospectively evaluate the usefulness of BRAFV600E mutation detection in daily clinical practice patients with metastatic Colorectal Cancer (mCRC). Patients and Methods 504 mCRC treated systemic chemotherapy ± biologics were analyzed. Results A statistically significant higher incidence BRAF was observed ECOG-PS 2 (p=0.001), multiple sites (p=0.002),> 65 years old (p=0.004), primary tumors located colon (p<0.001), high-grade (p=0.001) those mucinous features (p=0.037). Patients mutated had a significantly reduced progression-free survival (PFS) compared to wild-type (wt) ones (4.1 11.6 months, respectively; p<0.001) overall (OS) (14.0 vs. 34.6 p<0.001). In multivariate analysis emerged as an independent factor associated PFS (HR: 4.1, 95% CI 2.7–6.2; OS 5.9, 3.7–9.5; Among 273 salvage cetuximab or panitumumab, correlated (2.2 6.0 months; p<0.0001) (4.3 17.4 p<0.0001). Conclusions The presence BRAFV600E-mutation characterizes subgroup distinct biologic, pathological is very poor patients’ prognosis.
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paperity.org参考文章(23)
Susana Benlloch, Artemio Payá, Cristina Alenda, Xavier Bessa, Montserrat Andreu, Rodrigo Jover, Antoni Castells, Xavier Llor, F. Ignacio Aranda, Bartomeu Massutí, Detection of BRAF V600E Mutation in Colorectal Cancer : Comparison of Automatic Sequencing and Real-Time Chemistry Methodology The Journal of Molecular Diagnostics. ,vol. 8, pp. 540- 543 ,(2006) , 10.2353/JMOLDX.2006.060070
C.H. Köhne, R. Labianca, T. Price, W. Scheithauer, A. Sobrero, J. Tabernero, D. Aderka, S. Barroso, G. Bodoky, J.Y. Douillard, H. El Ghazaly, J. Gallardo, A. Garin, R. Glynne-Jones, K. Jordan, A. Meshcheryakov, D. Papamichail, P. Pfeiffer, I. Souglakos, S. Turhal, A. Cervantes, H.J. Schmoll, E. Van Cutsem, A. Stein, V. Valentini, B. Glimelius, K. Haustermans, B. Nordlinger, C.J. van de Velde, J. Balmana, J. Regula, I.D. Nagtegaal, R.G. Beets-Tan, D. Arnold, F. Ciardiello, P. Hoff, D. Kerr, ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making Annals of Oncology. ,vol. 23, pp. 2479- 2516 ,(2012) , 10.1093/ANNONC/MDS236
J Souglakos, J Philips, R Wang, S Marwah, M Silver, M Tzardi, J Silver, S Ogino, S Hooshmand, E Kwak, E Freed, J A Meyerhardt, Z Saridaki, V Georgoulias, D Finkelstein, C S Fuchs, M H Kulke, R A Shivdasani, Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. British Journal of Cancer. ,vol. 101, pp. 465- 472 ,(2009) , 10.1038/SJ.BJC.6605164
Harith Rajagopalan, Alberto Bardelli, Christoph Lengauer, Kenneth W. Kinzler, Bert Vogelstein, Victor E. Velculescu, Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature. ,vol. 418, pp. 934- 934 ,(2002) , 10.1038/418934A
Carla Oliveira, Mafalda Pinto, Alex Duval, Caroline Brennetot, Enric Domingo, Eloi Espín, Manel Armengol, Hiroyuki Yamamoto, Richard Hamelin, Raquel Seruca, Simó Schwartz, BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency. Oncogene. ,vol. 22, pp. 9192- 9196 ,(2003) , 10.1038/SJ.ONC.1207061
Wade S. Samowitz, Carol Sweeney, Jennifer Herrick, Hans Albertsen, Theodore R. Levin, Maureen A. Murtaugh, Roger K. Wolff, Martha L. Slattery, Poor Survival Associated with the BRAF V600E Mutation in Microsatellite-Stable Colon Cancers Cancer Research. ,vol. 65, pp. 6063- 6069 ,(2005) , 10.1158/0008-5472.CAN-05-0404
Z Saridaki, D Papadatos-Pastos, M Tzardi, D Mavroudis, E Bairaktari, H Arvanity, E Stathopoulos, V Georgoulias, J Souglakos, BRAF mutations, microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients' outcome. British Journal of Cancer. ,vol. 102, pp. 1762- 1768 ,(2010) , 10.1038/SJ.BJC.6605694
Jolien Tol, Iris D. Nagtegaal, Cornelis J.A. Punt, BRAF mutation in metastatic colorectal cancer. The New England Journal of Medicine. ,vol. 361, pp. 98- 99 ,(2009) , 10.1056/NEJMC0904160
S. Ogino, K. Nosho, G. J Kirkner, T. Kawasaki, J. A Meyerhardt, M. Loda, E. L Giovannucci, C. S Fuchs, CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer Gut. ,vol. 58, pp. 90- 96 ,(2009) , 10.1136/GUT.2008.155473
Zacharenia Saridaki, Maria Tzardi, Chara Papadaki, Maria Sfakianaki, Fraga Pega, Aristea Kalikaki, Eleftheria Tsakalaki, Maria Trypaki, Ippokratis Messaritakis, Efstathios Stathopoulos, Dimitris Mavroudis, Vassilis Georgoulias, John Souglakos, None, Impact of KRAS, BRAF, PIK3CA Mutations, PTEN, AREG, EREG Expression and Skin Rash in ≥2nd Line Cetuximab-Based Therapy of Colorectal Cancer Patients PLoS ONE. ,vol. 6, pp. e15980- ,(2011) , 10.1371/JOURNAL.PONE.0015980