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

Abstract

Purpose: Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC), there is a paucity of evidence regarding the impact of BCM on toxicities. This study investigates associations between BCM and treatment-related toxicity in patients with EBC receiving anthracyclines and taxane-based chemotherapy.Experimental Design: Pretreatment computerized tomographic (CT) images were evaluated for skeletal muscle area (SMA), skeletal muscle density (SMD), and fat tissue at the third lumbar vertebrae. Skeletal muscle index (SMI = SMA/height²) and skeletal muscle gauge (SMG = SMI × SMD) were also calculated. Relative risks (RR) are reported for associations between body composition measures and toxicity outcomes, after adjustment for age and body surface area (BSA).Results: BCM were calculated for 151 patients with EBC (median age, 49 years; range, 23-75 years). Fifty patients (33%) developed grade 3/4 toxicity, which was significantly higher in those with low SMI (RR, 1.29; P = 0.002), low SMG (RR, 1.09; P = 0.01), and low lean body mass (RR, 1.48; P = 0.002). Receiver operating characteristic analysis showed the SMG measure to be the best predictor of grade 3/4 toxicity. Dividing SMG into tertiles showed toxicity rates of 46% and 22% for lowest versus highest tertile, respectively (P = 0.005). After adjusting for age and BSA, low SMG (<1,475 units) was significantly associated with hematologic (RR, 2.12; P = 0.02), gastrointestinal grade 3/4 toxicities (RR, 6.49; P = 0.02), and hospitalizations (RR, 1.91; P = 0.05).Conclusions: Poor BCMs are significantly associated with increased treatment-related toxicities. Further studies are needed to investigate how these metrics can be used to more precisely dose chemotherapy to reduce treatment-related toxicity while maintaining efficacy. Clin Cancer Res; 23(14); 3537-43. ©2017 AACR.

Figure 1

Skeletal muscle gauge and toxicity-Both female-BSA 1.70 Left–normal SMG (2535 AU), no toxicity; Right-low SMG (844 AU), had grade 3–4 toxicity. Abbreviations: BSA:Body Surface area; HU:Hounsfield units; AU: arbitrary units

Figure 2

Risk of toxicity based on tertiles of body composition measures Abbreviations: SMG: skeletal muscle gauge, SMI: skeletal Muscle index, SMD: skeletal muscle density, LBM: lean body mass, HU: Hounsfield units, AU: arbitrary units ; *p-values from unadjusted Jonckheere-Terpstra tests

Figure 3

Risk of toxicity based on skeletal muscle gauge^{a a}p values from Poisson regression models adjusting for age at diagnosis and BSA *Grade 3–4 toxicity Abbreviations: SMG: skeletal muscle gauge; BSA: body surface area