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

Lindsay A. Renfro, Richard M. Goldberg, Axel F Grothey, Alberto Sobrero, Richard Adams, Matthew T. Seymour, Volker Heinemann, Hans Joachim Schmoll, Jean Yves Douillard, Herbert Hurwitz, Charles S. Fuchs, Eduardo Diaz-Rubio, Rainer Porschen, Christophe Tournigand, Benoist Chibaudel, Paulo M. Hoff, Fairooz F. Kabbinavar, Alfredo Falcone, Niall C. Tebbutt, Cornelis J.A. PuntJ. Randolph Hecht, John Souglakos, Carsten Bokemeyer, Eric Van Cutsem, Leonard Saltz, Aimery de Gramont, Daniel J. Sargent

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1929-1937
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number17
DOIs
StatePublished - Jun 10 2017

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Colorectal Neoplasms
Clinical Trials
Databases
Mortality
Nomograms
Logistic Models
Age Factors
Therapeutics
Proportional Hazards Models
Calibration
Body Mass Index
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Renfro, Lindsay A.; Goldberg, Richard M.; Grothey, Axel F; Sobrero, Alberto; Adams, Richard; Seymour, Matthew T.; Heinemann, Volker; Schmoll, Hans Joachim; Douillard, Jean Yves; Hurwitz, Herbert; Fuchs, Charles S.; Diaz-Rubio, Eduardo; Porschen, Rainer; Tournigand, Christophe; Chibaudel, Benoist; Hoff, Paulo M.; Kabbinavar, Fairooz F.; Falcone, Alfredo; Tebbutt, Niall C.; Punt, Cornelis J.A.; Hecht, J. Randolph; Souglakos, John; Bokemeyer, Carsten; Cutsem, Eric Van; Saltz, Leonard; Gramont, Aimery de; Sargent, Daniel J.

In: Journal of Clinical Oncology, Vol. 35, No. 17, 10.06.2017, p. 1929-1937.

Research output: Contribution to journalArticle

Renfro, LA, Goldberg, RM, Grothey, AF, Sobrero, A, Adams, R, Seymour, MT, Heinemann, V, Schmoll, HJ, Douillard, JY, 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, Cutsem, EV, Saltz, L, Gramont, AD & Sargent, DJ 2017, '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 of Clinical Oncology, vol. 35, no. 17, pp. 1929-1937. https://doi.org/10.1200/JCO.2016.71.5771
Renfro, Lindsay A. ; Goldberg, Richard M. ; Grothey, Axel F ; Sobrero, Alberto ; Adams, Richard ; Seymour, Matthew T. ; Heinemann, Volker ; Schmoll, Hans Joachim ; Douillard, Jean Yves ; Hurwitz, Herbert ; Fuchs, Charles S. ; Diaz-Rubio, Eduardo ; Porschen, Rainer ; Tournigand, Christophe ; Chibaudel, Benoist ; Hoff, Paulo M. ; Kabbinavar, Fairooz F. ; Falcone, Alfredo ; Tebbutt, Niall C. ; Punt, Cornelis J.A. ; Hecht, J. Randolph ; Souglakos, John ; Bokemeyer, Carsten ; Cutsem, Eric Van ; Saltz, Leonard ; Gramont, Aimery de ; Sargent, Daniel J. / 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. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 17. pp. 1929-1937.
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abstract = "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 Canc{\'e}rologie 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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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 F

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.

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.

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