Grant Number:	5R01CA233885-04 Interpret this number
Primary Investigator:	Furberg-Barnes, Anna Helena
Organization:	Sloan-Kettering Inst Can Research
Project Title:	Body Composition and the Obesity Paradox in Clear Cell Renal Cell Carcinoma
Fiscal Year:	2022

ABSTRACT Clear cell renal cell carcinoma (ccRCC) is the most lethal urologic malignancy and its incidence is increasing. The proposed molecular epidemiology study moves beyond body mass index (BMI) to identify ccRCC patients at risk of poor prognosis while considering molecular tumor subtype based on gene expression, and is in direct response to an ASCO position statement that calls for more obesity-related research to ultimately inform weight recommendations and refine prognostic factors for cancer patients. The inverse association between BMI and mortality that is consistently observed among ccRCC patients presents a significant clinical challenge for patients, clinicians, and researchers because it is not clear how to interpret it. Mechanisms underlying the obesity paradox remain largely unexplored. In the proposed study, we will derive new body composition variables from existing, pre-surgical computed tomography (CT) scans, and transcriptomically-characterize the archived tumor specimens from 1200 non-metastatic ccRCC patients who were treated by nephrectomy at Memorial Sloan Kettering Cancer Center between 1995-2017 and followed for clinical outcomes. Based on strong preliminary data we hypothesize that the obesity paradox is influenced by disease heterogeneity and specific body composition features including low skeletal muscle and visceral adipose tissue radiodensity. In Aim 1 we will examine how body composition variables (i.e., area and density of skeletal muscle and adipose tissues) are associated with BMI and with validated ccRCC molecular tumor subtypes that are strongly associated with prognosis. In Aim 2 we will identify which aspects of body composition are independently associated with survival after accounting for molecular tumor subtype. By exploring how tumor RNA expression of immunologic, inflammatory, angiogenic and other cancer-related genes differ by body composition and survival in Aim 3, we will not only further our understanding of the link between body size and biological processes, but may also identify novel targets for tertiary prevention studies. The proposed research has the potential to make a lasting impact on the fields of cancer epidemiology and survivorship by clarifying the clinical interpretation of the obesity paradox, identifying novel prognostic factors derived from readily available CT scans, and informing the development of future behavioral or pharmacological interventions designed to improve clinical outcomes for the growing population of ccRCC patients.




Radiodensities of Skeletal Muscle and Visceral Adipose Tissues Are Prognostic Factors in Clear-Cell Renal Cell Carcinoma.
Authors: Bradshaw P.T. , Olsson L.T. , Sanchez A. , Knezevic A. , Akin O. , Scott J.M. , Hakimi A.A. , Russo P. , Caan B.J. , Mourtzakis M. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2024-10-02 00:00:00.0; 33(10), p. 1375-1382.
PMID: 39073365
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Skeletal muscle and visceral adipose radiodensities are pre-surgical, non-invasive markers of aggressive kidney cancer.
Authors: Furberg H. , Bradshaw P.T. , Knezevic A. , Olsson L. , Petruzella S. , Stein E. , Paris M. , Scott J. , Akin O. , Hakimi A.A. , et al. .
Source: Journal Of Cachexia, Sarcopenia And Muscle, 2024-01-24 00:00:00.0; , .
EPub date: 2024-01-24 00:00:00.0.
PMID: 38263932
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A comparison of analytic approaches for investigating the obesity paradox in kidney cancer.
Authors: Olsson L.T. , Eberle C.E. , Petruzella S. , Robinson W.R. , Furberg H. .
Source: Cancer Causes & Control : Ccc, 2023-02-14 00:00:00.0; , .
EPub date: 2023-02-14 00:00:00.0.
PMID: 36786871
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Associations between Pretreatment Body Composition Features and Clinical Outcomes among Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Blockade.
Authors: Ged Y. , Sanchez A. , Patil S. , Knezevic A. , Stein E. , Petruzella S. , Weiss K. , Duzgol C. , Chaim J. , Akin O. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2022-12-01 00:00:00.0; 28(23), p. 5180-5189.
PMID: 36190538
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Rectus Abdominis Muscle Thickness is a Valid Measure of Cross-Sectional Area: Implications for Ultrasound.
Authors: Kelly C.R. , Mourtzakis M. , Furberg H. , Tandon P. , Paris M.T. .
Source: Academic Radiology, 2022 03; 29(3), p. 382-387.
EPub date: 2021-07-09 00:00:00.0.
PMID: 34253439
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Impact of body size and body composition on bladder cancer outcomes: Risk stratification and opportunity for novel interventions.
Authors: Sanchez A. , Kissel S. , Coletta A. , Scott J. , Furberg H. .
Source: Urologic Oncology, 2020 09; 38(9), p. 713-718.
EPub date: 2020-04-18 00:00:00.0.
PMID: 32312642
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Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: a cohort study.
Authors: Sanchez A. , Furberg H. , Kuo F. , Vuong L. , Ged Y. , Patil S. , Ostrovnaya I. , Petruzella S. , Reising A. , Patel P. , et al. .
Source: The Lancet. Oncology, 2020 Feb; 21(2), p. 283-293.
EPub date: 2019-12-20 00:00:00.0.
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Automated body composition analysis of clinically acquired computed tomography scans using neural networks.
Authors: Paris M.T. , Tandon P. , Heyland D.K. , Furberg H. , Premji T. , Low G. , Mourtzakis M. .
Source: Clinical Nutrition (edinburgh, Scotland), 2020-01-22 00:00:00.0; , .
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