TY - JOUR
T1 - Clinical calculator for Early mortality in Metastatic colorectal cancer
T2 - An analysis of Patients from 28 clinical trials in the aide et recherche en cancérologie digestive database
AU - Renfro, Lindsay A.
AU - Goldberg, Richard M.
AU - Grothey, Axel
AU - Sobrero, Alberto
AU - Adams, Richard
AU - Seymour, Matthew T.
AU - Heinemann, Volker
AU - Schmoll, Hans Joachim
AU - Douillard, Jean Yves
AU - Hurwitz, Herbert
AU - Fuchs, Charles S.
AU - Diaz-Rubio, Eduardo
AU - Porschen, Rainer
AU - Tournigand, Christophe
AU - Chibaudel, Benoist
AU - Hoff, Paulo M.
AU - Kabbinavar, Fairooz F.
AU - Falcone, Alfredo
AU - Tebbutt, Niall C.
AU - Punt, Cornelis J.A.
AU - Hecht, J. Randolph
AU - Souglakos, John
AU - Bokemeyer, Carsten
AU - Cutsem, Eric Van
AU - Saltz, Leonard
AU - Gramont, Aimery de
AU - Sargent, Daniel J.
N1 - Publisher Copyright:
© 2017 by American Society of Clinical Oncology
PY - 2017/6/10
Y1 - 2017/6/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2016.71.5771
DO - 10.1200/JCO.2016.71.5771
M3 - Article
C2 - 28414610
AN - SCOPUS:85021775812
SN - 0732-183X
VL - 35
SP - 1929
EP - 1937
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 17
ER -