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New tool helps predict chemotherapy toxicity in older women with early breast cancer

Journal of Clinical Oncology
Reuters Health - 14/01/2021 - Researchers have developed and validated a simple risk-assessment tool that combines eight clinical and geriatric factors to gauge the likelihood of severe side effects from chemotherapy in older women with early-stage breast cancer.

"The decision to pursue chemotherapy as an older patient is complex," Dr. Mina Sedrak, co-first author and deputy director of clinical trials for the Center for Cancer and Aging Research at City of Hope in Duarte, California, told Reuters Health by email.

"We hope that this tool, along with clinical judgment and patient preferences, will improve the care that older adults with early-stage breast cancer receive," Dr. Sedrak said.

The Cancer and Aging Research Group-Breast Cancer (CARG-BC) Score was developed and validated in 473 women (283 in development and 190 in validation cohort) aged 65 and older with stage-I to -III breast cancer treated with neoadjuvant or adjuvant chemotherapy.

Overall, 46% of the women developed grade-3 to -5 chemotherapy toxicities, the researchers report in the Journal of Clinical Oncology.

The researchers identified eight independent predictors of grade 3 to 5 toxicity, each were assigned weighted points: anthracycline use (1 point), stage-II or -III breast cancer (3 points), planned treatment duration more than three 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).

The researchers calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (12 or more points).

In the development cohort, rates of grade-3 to -5 chemotherapy toxicity for these three risk groups were 19%, 54% and 87%, respectively. Compared to women in the low-risk category, the odds of experiencing chemotherapy toxicity were nearly five times greater for women in the intermediate-risk group (odds ratio, 4.91) and 28 times greater for women in high-risk group (OR, 28.13), both significant risk increases.

The risk tool had "good discrimination" with an area under the ROC curve (AUC) of 0.75 (95% confidence interval, 0.70 to 0.81) in the development cohort, the researchers report.

In the validation cohort, the association between CARG-BC score and chemotherapy toxicity was "slightly attenuated but still statistically significant," they note, with rates of grade-3 to -5 toxicity of 27%, 45% and 76%, in the low-, intermediate- and high-risk groups, respectively.

The AUC in the validation cohort was 0.69 (95% CI, 0.62 to 0.77), which was not significantly different from the development cohort.

The CARG-BC score outperformed the general CARG toxicity tool and the Karnofsky performance status (KPS), both of which were developed and validated in younger patients, and was shown to be strongly associated with treatment modifications (dose reductions, delays and early treatment discontinuation) and hospitalizations.

"This tool should not be used as the only factor in deciding whether to administer and/or alter the dose or schedule of chemotherapy. Instead, we envision the CARG-BC score as a facilitator of the conversation between the patient and the doctor," Dr. Sedrak told Reuters Health.

The tool is also included in table 4 of the report. "We purposely included it in the paper as a 'calculator' to allow providers (and patients) to print it, fill it out and obtain a total CARG-BC score that classifies the patient into one of three groups (low, intermediate or high risk of developing grade 3 to 5 chemotherapy toxicity). Eventually, we hope that this tool can be incorporated directly in the electronic health record," Dr. Sedrak said.

The researchers also plan to make it available online via the national Cancer and Aging Research Group website (www.mycarg.org).

The authors have dedicated this research to the late Dr. Arti Hurria, former director of City of Hope's Center for Cancer and Aging Research. Dr. Hurria conceptualized the study, obtained funding and supervised data acquisition and analysis, but died suddenly prior to the drafting of this manuscript, summarizing primary results.

SOURCE: https://bit.ly/3nCIkcE Journal of Clinical Oncology, online January 14, 2021.

By Megan Brooks

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