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Muscle mass, density may predict risk for treatment-related toxicities
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Muscle mass — particularly loss of muscle and density — appeared associated with poor outcomes and increased chemotherapy-related toxicity among patients with early breast cancer, according to study results published in Clinical Cancer Research.
“The formula currently used in clinical practice for chemotherapy dosing — body surface area — does not really help us predict which patients will develop treatment-related toxicity,” Shlomit Strulov Shachar, MD, a fellow in the geriatric oncology program at UNC Lineberger Comprehensive Cancer Center when the study was conducted and now a medical oncologist in Israel, said in a press release. “This study supports the concept that body composition may be more sensitive than the formula that has been used for decades to dose chemotherapy.”
Prior research showed an association between age-associated muscle loss and poor OS among patients with solid tumors. However, the effect of muscle mass on risks for treatment-associated side effects among patients with early-stage breast cancer have not been established.
Shachar and colleagues evaluated the associations between body composition metrics and treatment-related toxicity in 151 patients (median age, 49 years) with early breast cancer treated with anthracycline- and taxane-based chemotherapy.
One-third (33%) of patients developed grade 3 or 4 toxicities. Researchers observed significantly higher toxicity rates among patients with low skeletal muscle index (RR = 1.29; P = .002), low lean body mass (RR = 1.48; P = .002) and low skeletal muscle gauge (RR = 1.09; P = .01).
Skeletal muscle gauge — a measurement researchers developed that accounted for muscle quality and quantity, including indirect fat content — was the best predictor for grade 3 and grade 4 toxicities.
HemOnc Today spoke with Shachar about the study results, their implications, and whether they may be applicable for individuals with other malignancies.
Question: How did this study come about?
Answer: Along with aging comes low muscle mass, known as sarcopenia. There is a very high prevalence of sarcopenia among patients with cancer, and this has a detrimental effect on survival. Data from many studies have shown body composition can predict chemotherapy toxicity in other cancer types, but we did not find many papers about breast cancer. I was curious to see if patients with breast cancer are affected by sarcopenia, as it is not thought about in this patient population. We set out to determine if patients with early breast cancer experience chemotherapy toxicity and, if so, if it correlates with body composition.
Q: What did you find?
A: Full-body composition metrics — including low muscle mass and low muscle attenuation — were the best predictors for chemotherapy toxicity. This can be a game changer. Every day, people all over the world undergo chemotherapy and experience treatment-associated toxicities. Based upon this formula, that should no longer happen.
Q: Based on these data, what should clinicians do differently?
A : For now, nothing should change in terms of how we dose chemotherapy. The 100-year-old standard formula of how we dose chemotherapy is based upon height and weight. I think there is a better way; however, we have not confirmed this. In the future, I believe we will move toward a more personalized approach in which chemotherapy is dosed based upon each person’s body composition.
Q: Can you describe how the technique works?
A: We use CT scan, which is done through routine staging, just before chemotherapy initiation. We have special software that can calculate the amount and attenuation of muscle.
Q: Could this technique work for patients with other types of cancer?
A: Definitely. This technique can be used for every cancer type treated with chemotherapy. It may work for other types of cancer therapies, as well.
Q: Do you have plans for additional research?
A: This is a very new area of research, so not all medical oncologists know what muscle attenuation is. This is why this research is so important. I am running a prospective trial in lung cancer and breast cancer to gather information about toxicities in elderly patients in Israel. Additional randomized trials should be conducted to see if we could use another formula based on CT scans to measure muscle mass in patients to dose chemotherapy.
Q: Is there anything else that you would like to mention?
A: We are left with two major questions. The first is whether we can change muscle mass. The second is, will it help to reduce toxicity from chemotherapy? We do not have these answers, so we still have much more work to do. – by Jennifer Southall
Reference:
Shachar SS, et al. Clin Cancer Res. 2017;doi:10.1158/1078-0432.CCR-16-2266.
For more information:
Shlomit Strulov Shachar, MD, can be reached at UNC Lineberger Comprehensive Cancer Center, 450 West Drive, Chapel Hill, NC 27599; email: shlomits@email.unc.edu.
Disclosure: Shachar reports no relevant financial disclosures.