Value of KRAS, BRAF, and PIK3CA Mutations and Survival Benefit from Systemic Chemotherapy in Colorectal Peritoneal Carcinomatosis

  • Sasaki, Yusuke (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Hamaguchi, Tetsuya (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Yamada, Yasuhide (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Takahashi, Naoki (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Shoji, Hirokazu (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Honma, Yoshitaka (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Iwasa, Satoru (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Okita, Natsuko (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Takashima, Atsuo (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Kato, Ken (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Nagai, Yushi (Exploratory Oncology Research & Clinical Trial Center, National Cancer Center) ;
  • Taniguchi, Hirokazu (Pathology and Clinical Laboratory Division, National Cancer Center Hospital) ;
  • Boku, Narikazu (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital) ;
  • Ushijima, Toshikazu (Division of Epigenomics, National Cancer Center Research Institute) ;
  • Shimada, Yasuhiro (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital)
  • Published : 2016.03.07


Background: It is well known that peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is associated with a poor prognosis. However, data on the prognostic significance of modern chemotherapy containing bevacizumab, cetuximab or panitumumab are not available. Materials and Methods: This retrospective review concerned 526 patients with metastatic CRC who were classified into two groups according to the presence or absence of PC, and were treated with systemic chemotherapy, with or without bevacizumab or anti-EGFR antibodies. The genetic background, in particular KRAS, BRAF, and PIK3CA gene mutations, and overall survival (OS) were compared between the two groups. Results: The median OS values were 23.3 and 29.1 months for PC and non-PC patients, respectively (hazard ratio [HR]=1.20; p=0.17). Among all patients, tumor location, number of metastatic sites and BRAF mutation status were significant prognostic factors, whereas the presence of PC was not. In the PC group, chemotherapy with bevacizumab resulted in a significantly longer OS than forchemotherapy without bevacizumab (HR=0.38, p<0.01), but this was not the case in the non-PC group (HR=0.80, p=0.10). Furthermore, the incidence of the BRAF V600E mutation was significantly higher in PC than in non-PC patients (27.7% versus 7.3%, p<0.01). BRAF mutations displayed a strong correlation with shorter OS in non-PC (HR=2.26), but not PC patients (HR=1.04). Conclusions: Systemic chemotherapy, especially when combined with bevacizumab, improved survival in patients with PC from CRC as well as non-PC patients. While BRAF mutation demonstrated a high frequency in PC patients, but it was not associated with prognosis.


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