title: Value of KRAS, BRAF, and PIK3CA Mutations and Survival Benefit from Systemic Chemotherapy in Colorectal Peritoneal Carcinomatosis.
abstract: 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.
  
  
  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.
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan E-mail : thamaguc@ncc.go.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shoji
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Honma
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwasa
authors.forename: Natsuko
authors.initials: N
authors.lastname: Okita
authors.forename: Atsuo
authors.initials: A
authors.lastname: Takashima
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Yushi
authors.initials: Y
authors.lastname: Nagai
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)