Predicting Severe Toxicities and Mortality in Older Patients with Colorectal Cancer: An Analysis of 3 Clinical Trials and 3 Prospective Cohorts
Abstract
INTRODUCTION: Patients over 75 years old account for 40% of incident colorectal cancer (CRC) cases. Predicting chemotherapy (CT)-related toxicities is crucial for guiding treatment decisions. This study aimed to identify predictors of severe toxicities (ST) after 3 months of CT in older CRC patients; the secondary endpoint was 36-month mortality. MATERIALS AND METHODS: We analyzed three prospective cohorts and three trials involving patients aged ≥\,75 years. ST was defined as grade ≥\,3 toxicity. Multivariable logistic regression was used to assess factors associated with ST. For mortality, a multivariable Cox proportional hazards model was used. RESULTS: 777 patients were included, with a median age of 80·3 years. 20·6% had ECOG-PS >\,2, 20·8% had impaired independence for essential activities of daily living (ADL<6), and 46% had impaired IADL (<8). 48·4% had metastatic disease and 45·0% received doublet CT. ST occurred in 25·0% and 43·7% of patients in cohorts and trials, respectively. The independent risk factors for ST were: female sex, cognitive impairment in men, doublet CT, low albumin level in patients receiving single-agent CT, and low glomerular filtration rate. A model combining these parameters had an AUC of 0·700. The independent factors associated with 12-month mortality among metastatic patients were: impaired IADL, higher neutrophil count, and lower albumin. A model combining these variables with targeted therapy use and a history of primary tumor surgery achieved an AUC of 0.691. DISCUSSION: By pooling six trials and cohorts dedicated to older CRC patients, we identified clinical and biological factors associated with ST and mortality. If confirmed through external validation, these findings may inform personalized treatment decisions.
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BibTeX
@article{remond2026predicting,
title = {{Predicting Severe Toxicities and Mortality in Older Patients with Colorectal Cancer: An Analysis of 3 Clinical Trials and 3 Prospective Cohorts}},
author = {Maxime Rémond and Thomas Aparicio and Claudia Martinez-Tapia and Karine Le Malicot and Elena Paillaud and Rabia Boulahssass and Pierre Soubeyran and Selim Turk and Michael Bringuier and Carine Bellera and Sandrine Lavau-Denes and Jacques Cretin and Christophe Locher and Jérôme Martin-Babau and Sylvie Kirscher and Ludovic Evesque and Soraya Mebarki and Daniel Gonzalez and Olayidé Boussari and Florence Canoui-Poitrine},
journal = {European journal of cancer},
year = {2026},
month = sep,
doi = {10.1016/j.ejca.2026.116935},
url = {https://hal.science/hal-05736260v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Predicting Severe Toxicities and Mortality in Older Patients with Colorectal Cancer: An Analysis of 3 Clinical Trials and 3 Prospective Cohorts
AU - Maxime Rémond
AU - Thomas Aparicio
AU - Claudia Martinez-Tapia
AU - Karine Le Malicot
AU - Elena Paillaud
AU - Rabia Boulahssass
AU - Pierre Soubeyran
AU - Selim Turk
AU - Michael Bringuier
AU - Carine Bellera
AU - Sandrine Lavau-Denes
AU - Jacques Cretin
AU - Christophe Locher
AU - Jérôme Martin-Babau
AU - Sylvie Kirscher
AU - Ludovic Evesque
AU - Soraya Mebarki
AU - Daniel Gonzalez
AU - Olayidé Boussari
AU - Florence Canoui-Poitrine
PY - 2026
DA - 2026/09/03
JO - European journal of cancer
DO - 10.1016/j.ejca.2026.116935
UR - https://hal.science/hal-05736260v1
AB - INTRODUCTION: Patients over 75 years old account for 40% of incident colorectal cancer (CRC) cases. Predicting chemotherapy (CT)-related toxicities is crucial for guiding treatment decisions. This study aimed to identify predictors of severe toxicities (ST) after 3 months of CT in older CRC patients; the secondary endpoint was 36-month mortality. MATERIALS AND METHODS: We analyzed three prospective cohorts and three trials involving patients aged ≥\,75 years. ST was defined as grade ≥\,3 toxicity. Multivariable logistic regression was used to assess factors associated with ST. For mortality, a multivariable Cox proportional hazards model was used. RESULTS: 777 patients were included, with a median age of 80·3 years. 20·6% had ECOG-PS >\,2, 20·8% had impaired independence for essential activities of daily living (ADL<6), and 46% had impaired IADL (<8). 48·4% had metastatic disease and 45·0% received doublet CT. ST occurred in 25·0% and 43·7% of patients in cohorts and trials, respectively. The independent risk factors for ST were: female sex, cognitive impairment in men, doublet CT, low albumin level in patients receiving single-agent CT, and low glomerular filtration rate. A model combining these parameters had an AUC of 0·700. The independent factors associated with 12-month mortality among metastatic patients were: impaired IADL, higher neutrophil count, and lower albumin. A model combining these variables with targeted therapy use and a history of primary tumor surgery achieved an AUC of 0.691. DISCUSSION: By pooling six trials and cohorts dedicated to older CRC patients, we identified clinical and biological factors associated with ST and mortality. If confirmed through external validation, these findings may inform personalized treatment decisions.
SN - 0014-2964
ER -