title: Modified two-dimensional response as surrogate marker of overall survival in patients with metastatic colorectal cancer.
abstract: The identification of surrogate markers for long-term outcomes in patients with metastatic colorectal cancer (mCRC) may help in designing treatment regimens. The aim of this study was to assess whether two-dimensional response (2-DR) can serve as a new surrogate marker for overall survival (OS) in patients with mCRC. The study group consisted of 99 patients with mCRC from two independent cohorts who were treated with oxaliplatin-based chemotherapy plus bevacizumab. Two-dimensional response was defined as an area enclosed by coordinate points, including early tumor shrinkage at 8 weeks, depth of response at nadir, and 20% increase over nadir at progression. Each variable was weighted by its contribution rate to OS. The model was developed and internally validated in the learning cohort, and the performance of this model was externally verified in the validation cohort. Spearman correlation coefficients for 2-DR and OS in the learning and validation cohorts were 0.593 and 0.661, respectively. The C-indexes in predicting OS were 0.724 (95% confidence interval, 0.623-0.815) in the learning cohort and 0.762 (95% confidence interval, 0.651-0.873) in the validation cohort. Overall survival was significantly longer in patients with high 2-DR values than in patients with low 2-DR values in both the learning (37.0 vs. 24.1 months, P < 0.001) and validation (41.2 vs. 20.4 months, P < 0.001) cohorts. In contrast, differences in early tumor shrinkage and depth of response were not statistically significant. Multivariate analyses showed that 2-DR was an independent prognostic factor for OS.
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. goro@med.nagoya-u.ac.jp.
authors.forename: Goro
authors.initials: G
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Division of Biostatistics, Clinical Research Center, Aichi Medical University Hospital, Nagakute, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Murotani
authors.affiliation: Department of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Uehara
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D015203:Reproducibility of Results; D019233:Retreatment; D012189:Retrospective Studies; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D015415:Biomarkers
keywords: Bevacizumab; colorectal cancer; overall survival; quantitative measurement; surrogate marker