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Researchers have developed a new assessment tool to predict the risk of chemotherapy toxicity in older patients with early-stage breast cancer.

Allison Magnuson, DO, of the University of Rochester Wilmot Cancer Institute in New York, and colleagues created and validated the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score by prospectively analyzing data on 473 patients ages 65 and older with stages I-III breast cancer. The team used logistic regression models to identify independent predictors of toxicity.

As described in the study online in the , the tool combines the following eight clinical and geriatric variables and predicts grade 3-5 chemotherapy toxicity:

• Anthracycline use

• Stage II or III disease

• Planned treatment duration of more than 3 months

• Abnormal liver function

• Low hemoglobin

• Falls

• Limited walking

• Lack of social support

"These findings may be useful to clinicians for predicting individual probability of chemotherapy toxicity and directing therapy, to researchers for designing and interpreting clinical trials, and to policymakers for allocating future resources for new strategies to mitigate the risk of chemotherapy toxicity," the authors wrote.

In the following interview, Magnuson discussed details of the CARG-BC model and how it can be used in clinical practice.

Why was it necessary to develop the CARG-BC risk score? Why aren't other risk assessment tools like Karnofsky or ECOG performance status adequate in older patients?

Magnuson: Performance status measures were developed and validated largely in younger populations, and prior studies have demonstrated that they do not reliably assess the fitness of older adults. Tools such as the geriatric assessment can better describe the overall health status of an older adult.

Prior toxicity models that have included geriatric assessment variables were developed in heterogeneous populations of older adults with various cancer subtypes, stages, and chemotherapy regimens. The goal of the CARG-BC study was to develop and validate a risk prediction tool specifically for older adults with early stage breast cancer who were receiving adjuvant or neoadjuvant chemotherapy.

This study was conceptualized and led by the late , of the City of Hope Medical Center, where she was director of the Center for Cancer and Aging. Dr. Hurria, a former ASCO Board member, tragically passed away at the end of this study. Dr. Hurria's dream was to improve outcomes for older adults with cancer by infusing the principles of geriatrics into oncology, and this study exemplifies her vision, and the results bring us one step closer to realizing her dream.

In your study the CARG-BC score was associated with other factors in addition to toxicity risk. Can you tell us about these?

Magnuson: Yes, the CARG-BC score was also associated with treatment modifications, such as dose reductions, dose delays, early treatment discontinuation, and reduced relative dose intensity.

These are important because prior studies have suggested that patients receiving a relative dose intensity of less than 85% experience poorer relapse-free survival; we observed about one-fourth of the older adults on our study received less than 85% relative dose intensity.

The CARG-BC was also associated with hospitalizations; 38% of patients with a CARG-BC score in the high range experienced hospitalization during their course of therapy.

Two of the measures included in the CARG-BC are related to functional status: fall history and walking ability. How is functional status related to toxicity?

Magnuson: In the general geriatrics literature, several studies have demonstrated that impaired functional status predicts morbidity and mortality in older adults. Reduced functional abilities potentially may suggest that a patient has a lower physiologic reserve to tolerate chemotherapy.

Another predictor in your model is limited social support. Can you tell us how this relates to toxicity risk?

Magnuson: Social support is very important for patients receiving cancer treatment. Often instructions are complex, the number of appointments and extra medications can be intensive, and patients' social supports can help with managing this complexity, assist in recognizing potential symptoms or complications in a timely manner and notifying the care team if there are difficulties with chemotherapy, to facilitate interventions that might minimize toxicity.

In addition to the CARG-BC score, what other factors should go into deciding whether or not to administer chemotherapy or to change the dose in older patients?

Magnuson: Treatment decisions are complex, and many factors are considered. Aside from estimating the risks of treatment, which the CARG-BC can facilitate, the benefits of treatment are obviously a very important aspect. And certainly the patient's preferences are the most important aspect – how they view the potential risks and benefits of treatment and what their overall goals are.

Read the study here and expert commentary about the clinical implications here.