Winson Y Cheung1, Lindsay A Renfro2, David Kerr2, Aimery de Gramont2, Leonard B Saltz2, Axel Grothey2, Steven R Alberts2, Thierry Andre2, Katherine A Guthrie2, Roberto Labianca2, Guido Francini2, Jean-Francois Seitz2, Chris O'Callaghan2, Chris Twelves2, Eric Van Cutsem2, Daniel G Haller2, Greg Yothers2, Daniel J Sargent2. 1. Winson Y. Cheung, British Columbia Cancer Agency, Vancouver, British Columbia; Chris O'Callaghan, Queen's University, Kingston, Ontario, Canada; Lindsay A. Renfro, Axel Grothey, Steven R. Alberts, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; David Kerr, University of Oxford, Oxford; Chris Twelves, University of Leeds and St James Institute of Oncology, Leeds, United Kingdom; Aimery de Gramont, Franco-British Institute, Levallois-Perret; Thierry Andre, Hospital Saint-Antoine and Pierre and Marie Curie University, Paris; Jean-Francois Seitz, La Timone Hospital, Aix-Marseille University, Marseille, France; Leonard B. Saltz, Memorial Sloan Kettering Cancer Center, New York, NY; Katherine A. Guthrie, Fred Hutchinson Cancer Center, Seattle, WA; Roberto Labianca, Ospedale Giovanni XXIII, Bergamo; Guido Francini, University of Siena, Siena, Italy; Eric Van Cutsem, University Hospital Leuven, Leuven, Belgium; Daniel G. Haller, University of Pennsylvania, Philadelphia; and Greg Yothers, University of Pittsburgh, Pittsburgh, PA. wcheung@bccancer.bc.ca. 2. Winson Y. Cheung, British Columbia Cancer Agency, Vancouver, British Columbia; Chris O'Callaghan, Queen's University, Kingston, Ontario, Canada; Lindsay A. Renfro, Axel Grothey, Steven R. Alberts, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; David Kerr, University of Oxford, Oxford; Chris Twelves, University of Leeds and St James Institute of Oncology, Leeds, United Kingdom; Aimery de Gramont, Franco-British Institute, Levallois-Perret; Thierry Andre, Hospital Saint-Antoine and Pierre and Marie Curie University, Paris; Jean-Francois Seitz, La Timone Hospital, Aix-Marseille University, Marseille, France; Leonard B. Saltz, Memorial Sloan Kettering Cancer Center, New York, NY; Katherine A. Guthrie, Fred Hutchinson Cancer Center, Seattle, WA; Roberto Labianca, Ospedale Giovanni XXIII, Bergamo; Guido Francini, University of Siena, Siena, Italy; Eric Van Cutsem, University Hospital Leuven, Leuven, Belgium; Daniel G. Haller, University of Pennsylvania, Philadelphia; and Greg Yothers, University of Pittsburgh, Pittsburgh, PA.
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%, and 1% 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 6 months. Of those patients who died by 6 months post-random assignment, 40% had documented disease recurrence prior to death. Early disease recurrence was associated with a markedly 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 early mortality, 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.
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%, and 1% 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 6 months. Of those patients who died by 6 months post-random assignment, 40% had documented disease recurrence prior to death. Early disease recurrence was associated with a markedly 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 early mortality, 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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