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Novel Risk Tool for Predicting Severe Toxicity in Older Patients Receiving Chemotherapy for Early-Stage Breast Cancer


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As reported in the Journal of Clinical Oncology, Allison Magnuson, DO, and colleagues have developed a risk tool for predicting severe toxicity in patients aged 65 and older receiving chemotherapy for early-stage breast cancer.

Allison Magnuson, DO

Allison Magnuson, DO

Study Details

The prospective cohort study included 473 patients (from the Hurria Older Patients [HOPE] with Breast Cancer Cohort Study) age ≥ 65 with stage I–II breast cancer from 16 U.S. institutions. Patients were evaluated for geriatric and clinical features predictive of grade 3–5 toxicity from neoadjuvant or adjuvant chemotherapy. The study population consisted of 283 patients in a development cohort and 190 in a validation cohort. A risk model with weighted variable scoring was developed using logistic regression analysis, with model performance assessed by area under the receiver operating characteristic curve (AUC).

Key Findings

Among the 473 patients, 46% developed grade 3–5 chemotherapy toxicities.

The final model, termed the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score, consisted of eight independent predictors of toxicity:

  • Anthracycline use (1 point)
  • Stage II or III disease (3 points)
  • Planned treatment duration of longer than 3 months (4 points)
  • Abnormal liver function (3 points)
  • Low hemoglobin (3 points)
  • Falls (4 points)
  • Limited walking (3 points)
  • Lack of social support (3 points).

Risk scores were calculated for each patient, and three risk groups were defined: low risk (0–5 points), intermediate risk (6–11 points), and high risk (≥ 12 points).

Among 283 patients in the development cohort, the rates of grade 3–5 toxicity were 19% in the low-risk group (n = 93), 54% in the intermediate-risk group (n = 159), and 87% in the high-risk group (n = 30; overall P < .01). Compared with the low-risk group, odds ratios were 4.91 (95% confidence interval [CI] = 2.69–8.96, P < .001) in the intermediate-risk group and 28.13 (95% CI = 9.74–90.56, P <.001) in the high-risk group. The AUC was 0.75 (95% CI = 0.70–0.81).

“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.”
— Allison Magnuson, DO, and colleagues

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Among 190 patients in the validation cohort, rates of grade 3–5 toxicity were 27% in the low-risk group (n = 59), 45% in the intermediate-risk group (n = 98), and 76% in the high-risk group (n = 33; overall P < .0001). The AUC was 0.69 (95% CI = 0.62–0.77), with a P value of .15 vs the development cohort.

For the combined cohorts, the overall AUC for the CARG-BC score was 0.73 (95% CI = 0.68–0.77). Among all patients, 25% received reduced relative dose intensity (< 85% of ideal regimen) and 23% were hospitalized during treatment. Patients in the intermediate- and high-risk groups vs the low-risk group were more likely to receive reduced relative dose intensity (29% and 45% vs 13%, overall P < .001) and to be hospitalized (27% and 38% vs 11%, overall P < .001).  

The investigators concluded, “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.”

Dr. Magnuson, of the Division of Hematology/Oncology, University of Rochester Medical Center & Wilmot Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by the National Institute on Aging, Breast Cancer Research Foundation, Center for Cancer and Aging at City of Hope, National Cancer Institute, American Cancer Society, and Susan G. Komen for the Cure. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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