Prognostic impact of KRAS and BRAF mutations in patients who underwent simultaneous resection for initially resectable colorectal liver metastases

被引:1
作者
Lin, Qi [1 ]
Jian, Mi [1 ]
Niu, Zheng-Chuan [1 ]
Xu, Ping-Ping [1 ]
Zheng, Peng [1 ]
Xu, Jian-Min [1 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Gen Surg, 180 Fenglin Rd, Shanghai 200032, Peoples R China
关键词
Synchronous colorectal liver metastases; simultaneous resection; KRAS; BRAF; prognosis; HEPATIC RESECTION; RAS MUTATIONS; CANCER PATIENTS; SURVIVAL; RECURRENCE; CETUXIMAB; HETEROGENEITY; CHEMOTHERAPY; HEPATECTOMY; PATTERNS;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This study aimed to explore the prognostic impact of KRAS and BRAF mutations in patients who underwent simultaneous resection for synchronous colorectal liver metastases (SCRLMs) that were initially resectable. Clinicopathological and outcome data of 139 consecutive patients with SCRLMs who underwent resection between July 2003 and July 2013 was collected from our prospectively established SCRLM database. The KRAS and BRAF genotypes were evaluated in the primary cancer tissues by pyrosequencing. The prognostic value of KRAS and BRAF status was assessed by Kaplan-Meier and Cox regression analyses. KRAS and BRAF mutated in 28.8% and 7.2% of the patients with SCRLMs, respectively, but the genotypes did not significantly associate with any clinicopathologic characteristics. By Kaplan-Meier survival analysis, we found KRAS mutation was not significantly associated with short overall survival (OS) (P = 0.213), but was significantly correlated with short disease-free survival (DFS) (P = 0.041); BRAF mutation was significantly associated with both short OS and DFS (P = 0.001, P < 0.001, respectively). Multivariate survival analysis showed KRAS mutation was an independent negative prognostic factor for DFS (P = 0.005) and BRAF mutation was an independent negative prognostic factor for OS and DFS (P = 0.001, P < 0.001, respectively). KRAS and BRAF mutation similarly contributed to an adverse prognostic effect in patients who underwent simultaneous resection for SCRLMs that were initially resectable. These findings should suggest the use of KRAS and BRAF status in current practice as an important determinant for precision surgery for initially resectable SCRLMs.
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收藏
页码:5981 / 5991
页数:11
相关论文
共 49 条
[1]   A Validated Prognostic Multigene Expression Assay for Overall Survival in Resected Colorectal Cancer Liver Metastases [J].
Balachandran, Vinod P. ;
Arora, Arshi ;
Gonen, Mithat ;
Ito, Hiromichi ;
Turcotte, Simon ;
Shia, Jinru ;
Viale, Agnes ;
Snoeren, Nikol ;
van Hooff, Sander R. ;
Rinkes, Inne H. M. Borel ;
Adam, Rene ;
Kingham, T. Peter ;
Allen, Peter J. ;
DeMatteo, Ronald P. ;
Jarnagin, William R. ;
D'Angelica, Michael I. .
CLINICAL CANCER RESEARCH, 2016, 22 (10) :2575-2582
[2]   Prevalence and Heterogeneity of KRAS, BRAF, and PIK3CA Mutations in Primary Colorectal Adenocarcinomas and Their Corresponding Metastases [J].
Baldus, Stephan E. ;
Schaefer, Karl-L. ;
Engers, Rainer ;
Hartleb, Dinah ;
Stoecklein, Nikolas H. ;
Gabbert, Helmut E. .
CLINICAL CANCER RESEARCH, 2010, 16 (03) :790-799
[3]   Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study [J].
Bokemeyer, C. ;
Bondarenko, I. ;
Hartmann, J. T. ;
de Braud, F. ;
Schuch, G. ;
Zubel, A. ;
Celik, I. ;
Schlichting, M. ;
Koralewski, P. .
ANNALS OF ONCOLOGY, 2011, 22 (07) :1535-1546
[4]   How to find the Ariadne's thread in the labyrinth of salvage treatment options for metastatic colorectal cancer? [J].
Bronte, Giuseppe ;
Rolfo, Christian ;
Peeters, Marc ;
Russo, Antonio .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2014, 14 (06) :743-748
[5]   High Survival Rate After Two-Stage Resection of Advanced Colorectal Liver Metastases: Response-Based Selection and Complete Resection Define Outcome [J].
Brouquet, Antoine ;
Abdalla, Eddie K. ;
Kopetz, Scott ;
Garrett, Christopher R. ;
Overman, Michael J. ;
Eng, Cathy ;
Andreou, Andreas ;
Loyer, Evelyne M. ;
Madoff, David C. ;
Curley, Steven A. ;
Vauthey, Jean-Nicolas .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (08) :1083-1090
[6]   Meta-analysis of KRAS mutations and survival after resection of colorectal liver metastases [J].
Brudvik, K. W. ;
Kopetz, S. E. ;
Li, L. ;
Conrad, C. ;
Aloia, T. A. ;
Vauthey, J. -N. .
BRITISH JOURNAL OF SURGERY, 2015, 102 (10) :1175-1183
[7]   RAS Mutation Predicts Positive Resection Margins and Narrower Resection Margins in Patients Undergoing Resection of Colorectal Liver Metastases [J].
Brudvik, Kristoffer Watten ;
Mise, Yoshihiro ;
Chung, Michael Hsiang ;
Chun, Yun Shin ;
Kopetz, Scott E. ;
Passot, Guillaume ;
Conrad, Claudius ;
Maru, Dipen M. ;
Aloia, Thomas A. ;
Vauthey, Jean-Nicolas .
ANNALS OF SURGICAL ONCOLOGY, 2016, 23 (08) :2635-2643
[8]   Trends in long-term survival following liver resection for hepatic colorectal metastases [J].
Choti, MA ;
Sitzmann, JV ;
Tiburi, MF ;
Sumetchotimetha, W ;
Rangsin, R ;
Schulick, RD ;
Lillemoe, KD ;
Yeo, CJ ;
Cameron, JL .
ANNALS OF SURGERY, 2002, 235 (06) :759-765
[9]   Adjuvant Radioimmunotherapy Improves Survival of Rats After Resection of Colorectal Liver Metastases [J].
de Jong, Gabie M. ;
Hendriks, Thijs ;
Eek, Annemarie ;
Oyen, Wim J. G. ;
Nagtegaal, Iris D. ;
Bleichrodt, Robert P. ;
Boerman, Otto C. .
ANNALS OF SURGERY, 2011, 253 (02) :336-341
[10]   Rates and Patterns of Recurrence Following Curative Intent Surgery for Colorectal Liver Metastasis An International Multi-Institutional Analysis of 1669 Patients [J].
de Jong, Mechteld C. ;
Pulitano, Carlo ;
Ribero, Dario ;
Strub, Jennifer ;
Mentha, Gilles ;
Schulick, Richard D. ;
Choti, Michael A. ;
Aldrighetti, Luca ;
Capussotti, Lorenzo ;
Pawlik, Timothy M. .
ANNALS OF SURGERY, 2009, 250 (03) :440-448