title: Impact of Primary Tumor Site on Bevacizumab Efficacy in Metastatic Colorectal Cancer.
abstract: BACKGROUND
  With an ever-increasing focus on personalized medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for individual patients. While the prognostic impact of primary tumor site on colorectal cancer (CRC) outcomes is established, emerging data suggest potential differences in response to biologic therapies. We studied the impact of tumor site on bevacizumab efficacy in patients with metastatic CRC.
  
  
  METHODS
  We analyzed data of patients in an Australian prospective multicenter metastatic CRC (mCRC) registry who received first-line chemotherapy. Tumor site was defined as right colon, cecum to transverse; left colon, splenic flexure to rectosigmoid; and rectum. Kaplan-Meier and Cox models were used for survival analyses.
  
  
  RESULTS
  Of 926 patients, 297 had right colon, 354 left colon, and 275 rectum primary disease. Median age was 68.6, 65.9, and 63.3 years, respectively (P = .001). Right colon disease was significantly associated with intraperitoneal spread (P < .0001), while left colon and rectum disease preferentially metastasized to the liver and lungs, respectively (P < .0001 in both settings). A total of 636 patients (68.7%) received bevacizumab. Progression-free survival was superior for bevacizumab-treated patients in all groups but appeared greatest in right colon disease (hazard ratio, 0.46; 95% confidence interval, 0.36-0.60; P ≤ .001). Overall survival was longest in patients with disease of the rectum, followed by left colon and right colon (median, 26.2, 23.6, and 18.2 months, respectively; P = .0004).
  
  
  CONCLUSIONS
  Tumor site appears to be prognostic in mCRC, with rectum and right colon disease associated with the best and worst outcomes, respectively. Patients who received bevacizumab in addition to chemotherapy had superior outcomes, with the effect appearing greatest in patients with right colon disease.
authors.affiliation: Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Wong
authors.affiliation: Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia. Electronic address: Belinda.lee@mh.org.au.
authors.forename: Belinda
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Field
authors.affiliation: Eastern Health, Department of Medical Oncology, Melbourne, Victoria, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Lomax
authors.affiliation: Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Department of Health Education and Research, Melbourne EpiCentre, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Tacey
authors.affiliation: Cabrini Health, Department of Oncology, Malvern, Melbourne, Victoria, Australia; Department of Medicine, Nursing & Health Sciences, Monash University, Parkville, Melbourne, Victoria, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Shapiro
authors.affiliation: Eastern Health, Department of Medical Oncology, Melbourne, Victoria, Australia.
authors.forename: Joe
authors.initials: J
authors.lastname: McKendrick
authors.affiliation: Department of Oncology, Epworth Hospital, Richmond, Victoria, Australia.
authors.forename: Allan
authors.initials: A
authors.lastname: Zimet
authors.affiliation: Department of Medical Oncology, Canberra and Calvary Hospitals, Garran, Australian Capital Territory, Australia.
authors.forename: Desmond
authors.initials: D
authors.lastname: Yip
authors.affiliation: Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Nott
authors.affiliation: Department of Oncology, Epworth Hospital, Richmond, Victoria, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Jennens
authors.affiliation: Cabrini Health, Department of Oncology, Malvern, Melbourne, Victoria, Australia.
authors.forename: Gary
authors.initials: G
authors.lastname: Richardson
authors.affiliation: Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Western Health, Department of Medical Oncology, Footscray, Melbourne, Victoria, Australia.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Tie
authors.affiliation: Western Health, Department of Medical Oncology, Footscray, Melbourne, Victoria, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kosmider
authors.affiliation: Eastern Health, Department of Medical Oncology, Melbourne, Victoria, Australia.
authors.forename: Phillip
authors.initials: P
authors.lastname: Parente
authors.affiliation: Eastern Health, Department of Medical Oncology, Melbourne, Victoria, Australia; Department of Oncology, Ringwood Private Hospital, Ringwood East, Victoria, Australia.
authors.forename: Lionel
authors.initials: L
authors.lastname: Lim
authors.affiliation: Eastern Health, Department of Medical Oncology, Melbourne, Victoria, Australia.
authors.forename: Prasad
authors.initials: P
authors.lastname: Cooray
authors.affiliation: Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Tran
authors.affiliation: Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Desai
authors.affiliation: Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Eastern Health, Department of Medical Oncology, Melbourne, Victoria, Australia; Department of Medicine, Nursing & Health Sciences, Monash University, Parkville, Melbourne, Victoria, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wong
authors.affiliation: Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia; Western Health, Department of Medical Oncology, Footscray, Melbourne, Victoria, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068258:Bevacizumab
keywords: Anti-VEGF therapy; Bowel cancer; Distal colorectal cancer; Personalized medicine; Proximal colorectal cancer