Noninvasive Assessment of Sarcopenia May Predict Tolerance to Neo(adjuvant) Chemotherapy in Early-Stage Breast Cancer

Sarcopenia and sarcopenic obesity appear to increase risk of early chemotherapy termination

A new study of patients with early breast cancer suggests that the noninvasive assessment of sarcopenia using bioelectrical impedance analysis (BIA) can help predict toxicity from adjuvant or neoadjuvant chemotherapy.

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Patients in the Cleveland Clinic study who were found to have sarcopenia or sarcopenic obesity on BIA analysis were far more likely to experience grade III-IV toxicity from (neo)adjuvant chemotherapy and had higher rates of early chemotherapy termination than those without the disorders.

Results of the investigation were presented at the 2021 San Antonio Breast Cancer Symposium in December by Gabriel Aleixo, MD, a resident in the Cleveland Clinic Internal Medicine Residency program.

Senior investigator, Halle C.F. Moore, MD, Director of the Breast Cancer Program at the Taussig Cancer Institute, explains that a number of prior studies focused on advanced breast cancer have correlated sarcopenia with poor cancer outcomes and poor tolerance to chemotherapy. “There have not been a lot of studies in early-stage disease in which patients are typically in a good state of health and are treated with curative intent,” she says. In patients with metastatic disease, she explains, computed tomography (CT) is routinely employed to obtain the parameters necessary to calculate sarcopenia and sarcopenic obesity because CT in this setting is used to assess patients’ response to treatment.

“In early-stage breast cancer, we seldom perform routine CT scans, so that information is not readily available from imaging studies,” she says. “However, BIA is a noninvasive way of measuring whole muscle mass and other body composition parameters without exposing patients to radiation. We were interested in evaluating whether sarcopenia would affect outcomes – particularly treatment-related toxicity – in patients with early-stage breast cancer.”

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Study specifics

To accomplish this aim, the researchers examined a database of 713 patients with stage I-III breast cancer who had undergone BIA analysis near the time of their initial cancer diagnosis and treatment, 361 of whom were treated with chemotherapy. The skeletal muscle index (SMI), derived from the skeletal muscle area obtained from BIA analysis and the patient’s height, was calculated to assess for sarcopenia. Patients were divided into normal (SMI >6.75 kg/m2), moderate sarcopenia (SMI of 6.75 to 5.76 kg/m2) and severe sarcopenia (SMI <5.75 kg/m2) groups. In addition, patients were identified as having sarcopenic obesity if their ratio of fat mass (FM) to fat-free mass (FFM) was above the median.

More than one quarter (28%) of study subjects had moderate sarcopenia, and 6% had severe sarcopenia. “Patients with sarcopenia had more grade III-IV toxicity, were more likely to discontinue chemotherapy early, and were more likely to end up in the hospital with their chemotherapy treatment,” reports Dr. Moore.

Seventeen percent of the patients with moderate sarcopenia and 38% with severe sarcopenia terminated their chemotherapy early, compared with 8% of those without sarcopenia (P = 0.0006). Hospitalization rates related to chemotherapy were 17% and 15% for those with moderate and severe sarcopenia, respectively, compared with 8% for those without sarcopenia (P = 0.02). Grade 3-4 neuropathy occurred in 38% of patients with moderate and 12% of those with severe sarcopenia compared with 9% in those without sarcopenia (P = 0.006).

Patients with sarcopenic obesity had significantly higher rates of early chemotherapy termination (16% vs 7%; P = 0.004), hospitalization related to chemotherapy (15% vs 7%; P = 0.008), and grade 3-4 neuropathy (17% vs 6%; P = 0.0004) than those without sarcopenic obesity.

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Sarcopenia was a better predictor of chemotherapy-related side effects than age, body mass index and the number of comorbid medical conditions.

Implications for the future

“More research is needed to determine what to do with this information,” says Dr. Moore. “Right now, dosing of most chemotherapy drugs is based on body surface area, which is calculated according to the patient’s height and weight. That means a 5’6” lean body builder who weighs 160 lbs. is going to get the same chemotherapy dose as an older sedentary individual of the same height and weight. Yet chemotherapy drugs are probably going to be metabolized very differently in those two people. Ultimately, we would like to study whether incorporating sarcopenia measurements into our dosing strategy might mitigate toxicity as well as improve patients’ ability to complete the planned course of therapy.”

Whether individual chemotherapy agents are affected differently by sarcopenia is another area ripe for research, she notes.

“We may need to figure out a strategy to modify dosing based on these differences,” she says. “I would imagine a future clinical trial in a geriatric population in whom we could try to mitigate chemotherapy toxicity by using sarcopenia measures to adjust the dose.”