Predicting Early Discontinuation of Adjuvant Chemotherapy and its Impact on Survival among Individuals with Stage III Colon Cancer
Date
2020-08-05
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Abstract
Background: Approximately one in three patients with stage III colon cancer fail to complete the entirety of their adjuvant chemotherapy prescription. Two questions arise from this observation: 1) Can we predict which patients will discontinue adjuvant chemotherapy? and 2) Does a shortened duration of adjuvant chemotherapy impact overall survival? Evidence pertaining to the first question is limited. While question two was recently addressed within a large randomized trial, results from this trial have been controversial. Methods: To address question one, we conducted a systematic review and survey of medical oncologists to identify factors that predict non-completion of adjuvant chemotherapy. Building upon the results of this investigation, we developed an online calculator to predict the risk of discontinuation at the individual-level. For question two, a systematic review and meta-analysis was performed. In addition, we emulated a target trial that examined the effect of a shortened duration of adjuvant chemotherapy on overall survival using real-world data.Results: According to a systematic review of 18 studies and survey of 14 medical oncologists, there was evidence that increased comorbidity, worse performance status, higher T stage, and adjuvant CAPOX chemotherapy or poor oxaliplatin candidacy were associated with an increased risk of discontinuation. Using information from 1,378 patients, an online risk calculator was developed. Internal validation suggested that this calculator accurately predicted and classified patients with respect to their risk of discontinuation (optimism-adjusted C-statistic=0.80; 95% CI:0.79-0.82; calibration plots were within acceptable limits). A meta-analysis of 22 studies suggested that a shortened duration of adjuvant chemotherapy was harmful among patients prescribed a monotherapy (HR: 0.59; 95% CI: 0.52-0.68) but not among among those prescribed FOLFOX or CAPOX (HR: 0.80; 95% CI: 0.58-1.09). In a target trial analysis of 485 colon cancer patients, both the overall and subgroup-specific hazard ratios were consistent with those from a randomized trial. Conclusions: Results from this investigation can help assess and communicate the risk of early discontinuation within this study population. Results from our meta-analysis and target trial emulation suggest that a shortened duration of adjuvant chemotherapy may be appropriate for some patients which supports findings from a recent randomized trial.
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Clinical Epidemiology, Oncology, Health Services Research, Risk Prediction, Causal Inference
Citation
Boyne, D. J. (2020). Predicting Early Discontinuation of Adjuvant Chemotherapy and its Impact on Survival among Individuals with Stage III Colon Cancer (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.