Development and Validation of a Risk Tool for Predicting Severe Toxicity in Older Adults Receiving Chemotherapy for Early-Stage Breast Cancer

Abstract

Purpose: Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer.

Methods: Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated.

Results: In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively (P < .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity (P < .01).

Conclusion: The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.

Trial registration: ClinicalTrials.gov NCT01472094.

FIG 1.

Association of CARG-BC score (A) with grade 3-5 chemotherapy toxicity, compared with general CARG toxicity tool (B) and physician-rated KPS (C) in the validation cohort. KPS, Karnofsky performance status. Abbreviations: CARG-BC, Cancer and Aging Research Group-Breast Cancer score; CARG, Cancer and Aging Research Group; and KPS, Karnofsky Performance Status as rated by the physician.

FIG 2.

Association of the CARG-BC score with the proportion of patients observed to have grade 3-5 chemotherapy toxicity (A), hospitalizations (B), dose reductions (C), dose delays (D), early treatment discontinuation (E), and reduced relative dose intensity (F) as observed in the overall cohort.

FIG A1.

CONSORT diagram.

FIG A2.

Calibration plot for the development cohort.