Patient factors associated with chemotherapy modifications: Results from the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study.
Authors: Kantor Elizabeth , Bhimani Jenna , Gallagher Grace B , Blinder Victoria Susana , Burganowski Rachael P , Griggs Jennifer J. , Kolevska Tatjana , Kroenke Candyce , Laurent Cecile , Liu Raymond , Nakata Kanichi G , O'Connell Kelli , Persaud Sonia , Rivera Donna , Roh Janise M. , Valice Emily , Wang Peng , Bandera Elisa Victoria , Bowles Erin Aiello , Kushi Lawrence H. 
Published: May 2024

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Background: Understanding patient factors associated with an increased likelihood of receiving chemotherapy modifications is important for treatment planning and anticipating which patient groups might require extra support through the course of treatment. Methods: We have evaluated patient and tumor factors associated with chemotherapy modifications in a cohort of 9700 women receiving adjuvant chemotherapy for breast cancer at Kaiser Permanente Northern California (KPNC) and Kaiser Permanente Washington (KPWA) in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study diagnosed between 2005-2019. The outcome variable, receipt of a ‘chemotherapy modification’ is defined as a composite representing any of the following deviations from the intended regimen: dose reduction >10% (first cycle or overall), extensive delay (any single delay >14 days), regimen change, or receipt of fewer cycles of any given drug than intended in the original chemotherapy plan. Multivariable-adjusted prevalence ratios (PR) and corresponding 95% confidence intervals (95% CI) were calculated using generalized linear models of the Poisson family with a log link-function and robust standard errors. Results: Several factors were associated with chemotherapy modifications. Notably, older age was associated with an increased likelihood of modifications (p-trend<0.001), with adults aged 80+ years at diagnosis 1.93-fold more likely to experience modification than adults 18-39 years (95% CI: 1.50-2.50). Increased comorbidity and BMI were also associated with increased likelihood of modification (p-trend for both:<0.001), with patients with a Charlson Comorbidity Index of 3+ (vs 0) having an PR of 1.33 (95% CI: 1.19-1.48) and those with a BMI of 35+ kg/m2 (vs <25 kg/m2) having an PR of 1.53 (95% CI: 1.41-1.65). HER2+ status (PR HER2+ vs HER2-: 1.99 95% CI: 1.89-2.10) and higher stage of disease (PR IIIA vs I:1.24; 95% CI: 1.13-1.35; p-trend<0.001) were associated with increased likelihood of chemotherapy modification, while hormone receptor positivity was associated with lower likelihood of modification (PR ER+ and/or PR+ vs ER-/PR-: 0.93; 95% CI: 0.88-0.99). Diagnosis in more recent years was also associated with decreased likelihood of modification (PR 2015-2019 vs 2004-2009: 0.70; 95% CI: 0.66-0.75), as was higher neighborhood income (PR Q4 vs Q1: 0.78; 95% CI: 0.72-0.84). Conclusions: Several patient-level and clinical factors were associated with chemotherapy modifications, including age, comorbidity, BMI, and ER/PR/HER2 status. Future research might focus on the groups noted to have increased risk of treatment modification to better understand the factors underlying these changes, as well as the impact on patient outcomes.