title: Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials.
abstract: Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy.
  
  
  
  The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed.
  
  
  
  A total of 110 patients were assessable for tumor location; 90 had left-sided tumors. Left-sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P < .0001) and progression-free survival (11.1 vs. 5.6 months, hazard ratio = 0.47, P = .0041) than right-sided tumors; similar results were obtained in multivariate analysis. A subanalysis showed that the association was evident in the FOLFOX group and that tumor location was an independent prognostic factor irrespective of BRAF status in RAS wild-type patients.
  
  
  
  Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first-line cetuximab combined with oxaliplatin-based chemotherapy.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Kanagawa, Japan. Electronic address: y.suna0825@gmail.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sunakawa
authors.affiliation: Division of Medical Oncology, Showa University Fujigaoka Hospital, Kanagawa, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ichikawa
authors.affiliation: Department of Clinical Oncology, Kagawa University Faculty of Medicine Cancer Center, Kagawa University Hospital, Kagawa, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan.
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Denda
authors.affiliation: Department of Medical Oncology, International Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.affiliation: Department of Gastroenterology, Kochi Health Sciences Center, Kochi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Negoro
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Showa University Koto Toyosu Hospital, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Kochi
authors.affiliation: Aizawa Comprehensive Cancer Center, Aizawa Hospital, Nagano, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Gastrointestinal Cancer Center, Sano Hospital, Hyogo, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kotaka
authors.affiliation: Department of Medical Oncology, Japan Labour Health and Welfare Organization Okayama Rosai Hospital, Okayama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanioka
authors.affiliation: Department of Surgery, Hakodate Goryoukaku Hospital, Hokkaido, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Takagane
authors.affiliation: Department of Internal Medicine, Konan Hospital, Hyogo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tani
authors.affiliation: Department of Surgery, Tokyo Metropolitan Cancer and Infections Diseases Center Komagome Hospital, Tokyo, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgery, Himeji Red Cross Hospital, Hyogo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Japan Clinical Cancer Research Organization, Tokyo, Japan.
authors.forename: Toshifusa
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab / Q000008:administration & dosage; 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; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068818:Cetuximab
keywords: BRAF; Cetuximab combination chemotherapy; Colorectal cancer; Prognostic marker; Tumor sidedness