title: 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.
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina. shlomits@email.unc.edu.|Division of Oncology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Shlomit Strulov
authors.initials: SS
authors.lastname: Shachar
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Deal
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Marc
authors.initials: M
authors.lastname: Weinberg
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Williams
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Nyrop
authors.affiliation: Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Karteek
authors.initials: K
authors.lastname: Popuri
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Seul Ki
authors.initials: SK
authors.lastname: Choi
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Muss
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D001823:Body Composition / Q000187:drug effects*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane