Clinical Calculator for Early Mortality in Metastatic Colorectal Cancer: An Analysis of Patients From 28 Clinical Trials in the Aide et Recherche en Cancérologie Digestive Database.


Journal Article

Purpose Factors contributing to early mortality after initiation of treatment of metastatic colorectal cancer are poorly understood. Materials and Methods Data from 22,654 patients enrolled in 28 randomized phase III trials contained in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were pooled. Multivariable logistic regression models for 30-, 60-, and 90-day mortality were constructed, including clinically and statistically significant patient and disease factors and interaction terms. A calculator (nomogram) for 90-day mortality was developed and validated internally using bootstrapping methods and externally using a 10% random holdout sample from each trial. The impact of early progression on the likelihood of survival to 90 days was examined with time-dependent Cox proportional hazards models. Results Mortality rates were 1.4% at 30 days, 3.4% at 60 days, and 5.5% at 90 days. Among baseline factors, advanced age, lower body mass index, poorer performance status, increased number of metastatic sites, BRAF mutant status, and several laboratory parameters were associated with increased likelihood of early mortality. A multivariable model for 90-day mortality showed strong internal discrimination (C-index, 0.77) and good calibration across risk groups as well as accurate predictions in the external validation set, both overall and within patient subgroups. Conclusion A validated clinical nomogram has been developed to quantify the risk of early death for individual patients during initial treatment of metastatic colorectal cancer. This tool may be used for patient eligibility assessment or risk stratification in future clinical trials and to identify patients requiring more or less aggressive therapy and additional supportive measures during and after treatment.

Full Text

Duke Authors

Cited Authors

  • Renfro, LA; Goldberg, RM; Grothey, A; Sobrero, A; Adams, R; Seymour, MT; Heinemann, V; Schmoll, H-J; Douillard, J-Y; Hurwitz, H; Fuchs, CS; Diaz-Rubio, E; Porschen, R; Tournigand, C; Chibaudel, B; Hoff, PM; Kabbinavar, FF; Falcone, A; Tebbutt, NC; Punt, CJA; Hecht, JR; Souglakos, J; Bokemeyer, C; Van Cutsem, E; Saltz, L; de Gramont, A; Sargent, DJ; ARCAD Clinical Trials Program,

Published Date

  • June 10, 2017

Published In

Volume / Issue

  • 35 / 17

Start / End Page

  • 1929 - 1937

PubMed ID

  • 28414610

Pubmed Central ID

  • 28414610

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.2016.71.5771


  • eng

Conference Location

  • United States