TY - JOUR
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
AU - Alberts, Steven R.
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.
N1 - Publisher Copyright:
©2016 by American Society of Clinical Oncology.
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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U2 - 10.1200/JCO.2015.65.1158
DO - 10.1200/JCO.2015.65.1158
M3 - Article
C2 - 26858337
AN - SCOPUS:84963721687
SN - 0732-183X
VL - 34
SP - 1182
EP - 1189
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -