Skeletal Muscle Measures as Predictors of Toxicity, Hospitalization, and Survival in Patients with Metastatic Breast Cancer Receiving Taxane-Based Chemotherapy

Abstract

Purpose Severe skeletal muscle (SM) loss (sarcopenia), is associated with poor cancer outcomes including reduced survival and increased toxicity. This study investigates SM measures in metastatic breast cancer (MBC) patients receiving first line taxane-based chemotherapy and evaluates associations with treatment toxicity and other outcomes. Experimental Design Using computerized tomography (CT) images taken for the evaluation of disease burden, skeletal muscle area (SMA) and density (SMD) were measured at the 3rd lumbar vertebrae. Sarcopenia was defined as Skeletal Muscle Index (SMI=SMA/height2) ≤41. Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD. Fisher’s exact tests, t-tests, the Kaplan-Meier method, and Cox regression modeling were used. Results MBC patients (N=40), median age 55 (rang 34–80), 58% sarcopenic, median SMG 1296 AU (SD 522). Grade 3–4 toxicity was found in 57% of sarcopenic vs 18% of non-sarcopenic patients (p=0.02). Toxicity-related hospitalizations were also higher in sarcopenic patients (39% vs 0%, p=0.005) as were any adverse events -- defined as any grade 3–4 toxicities, hospitalizations, dose reductions, or dose delay -- (74% vs 35%, p=0.02). Low SMG was associated with grade 3–4 toxicity (p=0.04), hospitalization (p=0.01) and time to treatment failure (for progression or toxicity) (p=0.03). Low SMG had a borderline significant association with any adverse event (p=0.06) and overall survival (p=0.07). Conclusions SM measures are associated with toxicity outcomes and survival in MBC patients receiving first line taxane-based chemotherapy. Further studies are needed to explore how routinely obtained CT scans can be used to individualize dosing and improve treatment planning.

Skeletal muscle measures and physical function in older adults with cancer: sarcopenia or myopenia?

“…and showed better correlation with aging than either SMD or SMI alone [31]. SMG has also been associated with toxicity and survival in adults with metastatic breast cancer receiving taxane therapy [32]. …”

Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

“…SMI and SMD are defined independent of the other, and both are demonstrated prognostic indicators for cancer outcomes; integrating the SMI and SMD into a novel measure of skeletal muscle gauge (SMG) could lead to a more unified reporting for body composition and disease outcomes . Recently, SMG was reported as a better predictor of chemotherapy toxicities than either SMI or SMD . Adipose tissue content, including subcutaneous and visceral adipose tissues, has also been associated with cancer outcomes and can be assessed on CT imaging …”

Body Composition as a Predictor of Toxicity in Patients Receiving Anthracycline and Taxane–Based Chemotherapy for Early-Stage Breast Cancer

“…Sarcopenic obesity is another marker for worse outcomes in cancer patients (12). While dosing is usually based on weight and height measures (body surface area (BSA)), there is evidence that pharmacokinetics and drug toxicities are more related to lean body mass (LBM) but to date, muscle measures have not been incorporated into routine chemotherapy dosing(13–16). As both muscle quantity (skeletal muscle index (SMI)) and quality (skeletal muscle density (SMD)) are significantly and independently associated with cancer outcomes, testing a mathematical combination of both has been proposed.…”