Determinants of earlymortality among 37,568 patientswith colon cancerwho participated in 25 clinical trials from the adjuvant colon cancer endpoints database

Winson Y. Cheung, Lindsay A. Renfro, David Kerr, Aimery De Gramont, Leonard B. Saltz, Axel F Grothey, Steven Robert Alberts, Thierry Andre, Katherine A. Guthrie, Roberto Labianca, Guido Francini, Jean Francois Seitz, Chris O'Callaghan, Chris Twelves, Eric Van Cutsem, Daniel G. Haller, Greg Yothers, Daniel J. Sargent

Research output: Contribution to journalArticle

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Abstract

Purpose Factors associated with early mortality after surgery and treatment with adjuvant chemotherapy in colon cancer are poorly understood. We aimed to characterize the determinants of early mortality in a large cohort of colon cancer trial participants. Methods A pooled analysis of 37,568 patients in 25 randomized trials of adjuvant systemic therapy was conducted. Multivariable logistic regression models with several definitions of early mortality (30, 60, and 90 days, and 6 months) were constructed, adjusting for clinically and statistically significant variables. A nomogram for 6-month mortality was developed and validated. Results Median age among patients was 61 years, patient demographics included 54% men and 90% White, 29%and 71%had stage II and III disease, respectively, and 79%, 20%, and1%had an Eastern Cooperative Oncology Group performance status (PS) of 0, 1, and $ 2, respectively. Early mortality was low: 0.3%at 30 days, 0.6%at 60 days, 0.8%at 90 days, and 1.4%at 6months. Of those patients who died by 6 months post-random assignment, 40% had documented disease recurrence prior to death. Early disease recurrencewas associated with amarkedly increased risk of death during the first 6 months post-treatment (hazard ratio, 82.6; 95%CI, 66.9 to 102.1). In prognostic analyses, advanced age, male sex, poorer PS, increasing ratio of positive to examined lymph nodes, earlier decade of enrollment, and higher tumor stage and grade predicted a greater likelihood of earlymortality,whereas treatment received was not strongly predictive. A multivariable model for 6-month mortality showed strong optimism-adjusted discrimination (concordance index, 0.73) and calibration. Conclusion Early mortality was infrequent but more prevalent in patients with advanced age and a PS of $ 2, underscoring the need to carefully consider the risk-to-benefit ratio when making treatment decisions in these subgroups.

Original languageEnglish (US)
Pages (from-to)1182-1189
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number11
DOIs
StatePublished - Apr 10 2016

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Colonic Neoplasms
Colon
Clinical Trials
Databases
Mortality
Logistic Models
Therapeutics
Nomograms
Adjuvant Chemotherapy
Calibration
Decision Making
Lymph Nodes
Demography
Recurrence
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Determinants of earlymortality among 37,568 patientswith colon cancerwho participated in 25 clinical trials from the adjuvant colon cancer endpoints database. / Cheung, Winson Y.; Renfro, Lindsay A.; Kerr, David; De Gramont, Aimery; Saltz, Leonard B.; Grothey, Axel F; Alberts, Steven Robert; Andre, Thierry; Guthrie, Katherine A.; Labianca, Roberto; Francini, Guido; Seitz, Jean Francois; O'Callaghan, Chris; Twelves, Chris; Van Cutsem, Eric; Haller, Daniel G.; Yothers, Greg; Sargent, Daniel J.

In: Journal of Clinical Oncology, Vol. 34, No. 11, 10.04.2016, p. 1182-1189.

Research output: Contribution to journalArticle

Cheung, WY, Renfro, LA, Kerr, D, De Gramont, A, Saltz, LB, Grothey, AF, Alberts, SR, Andre, T, Guthrie, KA, Labianca, R, Francini, G, Seitz, JF, O'Callaghan, C, Twelves, C, Van Cutsem, E, Haller, DG, Yothers, G & Sargent, DJ 2016, 'Determinants of earlymortality among 37,568 patientswith colon cancerwho participated in 25 clinical trials from the adjuvant colon cancer endpoints database', Journal of Clinical Oncology, vol. 34, no. 11, pp. 1182-1189. https://doi.org/10.1200/JCO.2015.65.1158
Cheung, Winson Y. ; Renfro, Lindsay A. ; Kerr, David ; De Gramont, Aimery ; Saltz, Leonard B. ; Grothey, Axel F ; Alberts, Steven Robert ; Andre, Thierry ; Guthrie, Katherine A. ; Labianca, Roberto ; Francini, Guido ; Seitz, Jean Francois ; O'Callaghan, Chris ; Twelves, Chris ; Van Cutsem, Eric ; Haller, Daniel G. ; Yothers, Greg ; Sargent, Daniel J. / Determinants of earlymortality among 37,568 patientswith colon cancerwho participated in 25 clinical trials from the adjuvant colon cancer endpoints database. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 11. pp. 1182-1189.
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abstract = "Purpose Factors associated with early mortality after surgery and treatment with adjuvant chemotherapy in colon cancer are poorly understood. We aimed to characterize the determinants of early mortality in a large cohort of colon cancer trial participants. Methods A pooled analysis of 37,568 patients in 25 randomized trials of adjuvant systemic therapy was conducted. Multivariable logistic regression models with several definitions of early mortality (30, 60, and 90 days, and 6 months) were constructed, adjusting for clinically and statistically significant variables. A nomogram for 6-month mortality was developed and validated. Results Median age among patients was 61 years, patient demographics included 54{\%} men and 90{\%} White, 29{\%}and 71{\%}had stage II and III disease, respectively, and 79{\%}, 20{\%}, and1{\%}had an Eastern Cooperative Oncology Group performance status (PS) of 0, 1, and $ 2, respectively. Early mortality was low: 0.3{\%}at 30 days, 0.6{\%}at 60 days, 0.8{\%}at 90 days, and 1.4{\%}at 6months. Of those patients who died by 6 months post-random assignment, 40{\%} had documented disease recurrence prior to death. Early disease recurrencewas associated with amarkedly increased risk of death during the first 6 months post-treatment (hazard ratio, 82.6; 95{\%}CI, 66.9 to 102.1). In prognostic analyses, advanced age, male sex, poorer PS, increasing ratio of positive to examined lymph nodes, earlier decade of enrollment, and higher tumor stage and grade predicted a greater likelihood of earlymortality,whereas treatment received was not strongly predictive. A multivariable model for 6-month mortality showed strong optimism-adjusted discrimination (concordance index, 0.73) and calibration. Conclusion Early mortality was infrequent but more prevalent in patients with advanced age and a PS of $ 2, underscoring the need to carefully consider the risk-to-benefit ratio when making treatment decisions in these subgroups.",
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T1 - Determinants of earlymortality among 37,568 patientswith colon cancerwho participated in 25 clinical trials from the adjuvant colon cancer endpoints database

AU - Cheung, Winson Y.

AU - Renfro, Lindsay A.

AU - Kerr, David

AU - De Gramont, Aimery

AU - Saltz, Leonard B.

AU - Grothey, Axel F

AU - Alberts, Steven Robert

AU - Andre, Thierry

AU - Guthrie, Katherine A.

AU - Labianca, Roberto

AU - Francini, Guido

AU - Seitz, Jean Francois

AU - O'Callaghan, Chris

AU - Twelves, Chris

AU - Van Cutsem, Eric

AU - Haller, Daniel G.

AU - Yothers, Greg

AU - Sargent, Daniel J.

PY - 2016/4/10

Y1 - 2016/4/10

N2 - Purpose Factors associated with early mortality after surgery and treatment with adjuvant chemotherapy in colon cancer are poorly understood. We aimed to characterize the determinants of early mortality in a large cohort of colon cancer trial participants. Methods A pooled analysis of 37,568 patients in 25 randomized trials of adjuvant systemic therapy was conducted. Multivariable logistic regression models with several definitions of early mortality (30, 60, and 90 days, and 6 months) were constructed, adjusting for clinically and statistically significant variables. A nomogram for 6-month mortality was developed and validated. Results Median age among patients was 61 years, patient demographics included 54% men and 90% White, 29%and 71%had stage II and III disease, respectively, and 79%, 20%, and1%had an Eastern Cooperative Oncology Group performance status (PS) of 0, 1, and $ 2, respectively. Early mortality was low: 0.3%at 30 days, 0.6%at 60 days, 0.8%at 90 days, and 1.4%at 6months. Of those patients who died by 6 months post-random assignment, 40% had documented disease recurrence prior to death. Early disease recurrencewas associated with amarkedly increased risk of death during the first 6 months post-treatment (hazard ratio, 82.6; 95%CI, 66.9 to 102.1). In prognostic analyses, advanced age, male sex, poorer PS, increasing ratio of positive to examined lymph nodes, earlier decade of enrollment, and higher tumor stage and grade predicted a greater likelihood of earlymortality,whereas treatment received was not strongly predictive. A multivariable model for 6-month mortality showed strong optimism-adjusted discrimination (concordance index, 0.73) and calibration. Conclusion Early mortality was infrequent but more prevalent in patients with advanced age and a PS of $ 2, underscoring the need to carefully consider the risk-to-benefit ratio when making treatment decisions in these subgroups.

AB - Purpose Factors associated with early mortality after surgery and treatment with adjuvant chemotherapy in colon cancer are poorly understood. We aimed to characterize the determinants of early mortality in a large cohort of colon cancer trial participants. Methods A pooled analysis of 37,568 patients in 25 randomized trials of adjuvant systemic therapy was conducted. Multivariable logistic regression models with several definitions of early mortality (30, 60, and 90 days, and 6 months) were constructed, adjusting for clinically and statistically significant variables. A nomogram for 6-month mortality was developed and validated. Results Median age among patients was 61 years, patient demographics included 54% men and 90% White, 29%and 71%had stage II and III disease, respectively, and 79%, 20%, and1%had an Eastern Cooperative Oncology Group performance status (PS) of 0, 1, and $ 2, respectively. Early mortality was low: 0.3%at 30 days, 0.6%at 60 days, 0.8%at 90 days, and 1.4%at 6months. Of those patients who died by 6 months post-random assignment, 40% had documented disease recurrence prior to death. Early disease recurrencewas associated with amarkedly increased risk of death during the first 6 months post-treatment (hazard ratio, 82.6; 95%CI, 66.9 to 102.1). In prognostic analyses, advanced age, male sex, poorer PS, increasing ratio of positive to examined lymph nodes, earlier decade of enrollment, and higher tumor stage and grade predicted a greater likelihood of earlymortality,whereas treatment received was not strongly predictive. A multivariable model for 6-month mortality showed strong optimism-adjusted discrimination (concordance index, 0.73) and calibration. Conclusion Early mortality was infrequent but more prevalent in patients with advanced age and a PS of $ 2, underscoring the need to carefully consider the risk-to-benefit ratio when making treatment decisions in these subgroups.

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