Body Composition Variables as Radiographic Biomarkers of Clinical Outcomes in Metastatic Renal Cell Carcinoma Patients Receiving Immune Checkpoint Inhibitors

• Type of Material: Article
• Authors: Dylan J. Martini, Emory University; T. Anders Olsen, Emory University; Subir Goyal, Emory University; Yuan Liu, Emory University; Sean T Evans, Emory University; Benjamin Magod, Emory University; Jacqueline T. Brown, Emory University; Lauren Yantorni, Emory University; Greta Anne Russler, Emory University; Sarah Caulfield, Emory University; Jamie M. Goldman, Emory University; Bassel Nazha, Emory University; Haydn Kissick, Emory University; Wayne Harris, Emory University; Omer Kucuk, Emory University; Bradley Carthon, Emory University; Viraj Master, Emory University; Mehmet Bilen, Emory University
• Language: English
• Date: 2021-07-09
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Martini, Olsen, Goyal, Liu, Evans, Magod, Brown, Yantorni, Russler, Caulfield, Goldman, Nazha, Kissick, Harris, Kucuk, Carthon, Master and Bilen
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fonc.2021.707050
• Title of Journal or Parent Work: FRONTIERS IN ONCOLOGY
• Volume: 11
• Start Page: 707050
• End Page: 707050
• Grant/Funding Information: Research reported in this publication was supported in part by the Breen Family Foundation and The Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: Science & Technology; TARGETED THERAPY; COMPUTED-TOMOGRAPHY; adiposity; immune checkpoint inhibitors; body composition; sarcopenia; ADIPOSE-TISSUE; mRCC; Life Sciences & Biomedicine; RISK; Oncology; prognostic model; MASS INDEX; biomarkers; MORTALITY
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology; Biology, Cell

Abstract

Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). Biomarkers for mRCC patients treated with ICI are limited, and body composition is underutilized in mRCC. We investigated the association between body composition and clinical outcomes in ICI-treated mRCC patients. Methods: We performed a retrospective analysis of 79 ICI-treated mRCC patients at Winship Cancer Institute from 2015-2020. Baseline CT images were collected at mid-L3 and segmented using SliceOMatic v5.0 (TomoVision). Density of skeletal muscle (SM), subcutaneous fat, inter-muscular fat, and visceral fat were measured and converted to indices by dividing by height(m)2 (SMI, SFI, IFI, and VFI, respectively). Total fat index (TFI) was defined as the sum of SFI, IFI, and VFI. Patients were characterized as high versus low for each variable at gender-specific optimal cuts using overall survival (OS) as the primary outcome. A prognostic risk score was created based on the beta coefficient from the multivariable Cox model after best subset variable selection. Body composition risk score was calculated as IFI + 2*SM mean + SFI and patients were classified as poor (0-1), intermediate (2), or favorable risk (3-4). Kaplan-Meier method and Log-rank test were used to estimate OS and PFS and compare the risk groups. Concordance statistics (C-statistics) were used to measure the discriminatory magnitude of the model. Results: Most patients were male (73%) and most received ICI as first (35%) or second-line (51%) therapy. The body composition poor-risk patients had significantly shorter OS (HR: 6.37, p<0.001), PFS (HR: 4.19, p<0.001), and lower chance of CB (OR: 0.23, p=0.044) compared to favorable risk patients in multivariable analysis. Patients with low TFI had significantly shorter OS (HR: 2.72, p=0.002), PFS (HR: 1.91, p=0.025), and lower chance of CB (OR: 0.25, p=0.008) compared to high TFI patients in multivariable analysis. The C-statistics were higher for body composition risk groups and TFI (all C-statistics ≥ 0.598) compared to IMDC and BMI. Conclusions: Risk stratification using the body composition variables IFI, SM mean, SFI, and TFI may be prognostic and predictive of clinical outcomes in mRCC patients treated with ICI. Larger, prospective studies are warranted to validate this hypothesis-generating data.