Personalizing Cancer Treatment Based on Muscle Mass to Reduce Toxicity

Using body composition metrics to guide the dose in patients receiving anthracyclines-taxane—based chemotherapy for breast cancer can reduce treatment-related toxicity. These were the findings of a study conducted at the University of North Carolina Lineberger Comprehensive Cancer Center.

Patients often have to compromise when it comes to side effects of anticancer agents. However, similar to the variation observed in treatment response, not all patients react in the same way or to the same extent. The premise of this study was to identify factors that are responsible for this variance, and the authors have published results that are focused on the quality and quantity of the patient’s muscle mass.

Participants (n = 151) in the study ranged from 23 to 75 years in age, and had been diagnosed with early stage breast cancer. Prior to treatment initiation, researchers documented computerized tomography (CT) images for skeletal muscle area (SMA), density (SMD), and fat tissue at the 3rd lumbar vertebrae. They also calculated the skeletal muscle gauge (SMG) and skeletal muscle index (SMI).

“More and more studies are showing that muscle mass, especially loss of muscle and function, or so-called sarcopenia, is associated with poor outcomes, poor survival and more toxicity with cancer treatment,” Hyman B. Muss, MD, director of the UNC Lineberger Geriatric Oncology Program, explained in a statement. Muss, the senior author on the study, added that muscle mass might regulate chemotherapy metabolism, such that individuals with a low muscle mass who, therefore, are less fit, may have a lower tolerance for chemotherapy. This would make them more vulnerable to adverse effects.

The authors found that of the 33% (n = 50) patients who developed grade 3 or 4 toxicity, those with a low SMI (relative risk (RR), 1.29; P = .002) and low SMG (RR, 1.09; P = .01) had a greater relative risk of developing those toxicities. SMG, the authors found, was an ideal predictor of developing grade 3 and 4 toxicities following chemotherapy. Further, after adjusting for age and body surface area, the authors found that low SMG (less than 1475 units) was significantly associated with hematological (RR, 2.12; P = .02) and gastrointestinal (RR, 6.49; P = .02) grade 3-4 toxicities, and hospitalizations (RR, 1.91; P = .05).

According to the study’s first author, Shlomit Strulov Shachar, MD, using body surface area as a measure to calculate drug dose “doesn’t really help us predict which patients will develop treatment-related toxicity. This study supports the concept that body composition may be more sensitive than the formula that has been used for decades to dose chemotherapy.”

The study has been published in Clinical Cancer Research.