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Dorsal Muscle Attenuation May Predict Failure to Respond to Interleukin-2 Therapy in Metastatic Renal Cell Carcinoma

Published:March 21, 2017DOI:https://doi.org/10.1016/j.acra.2017.03.003

      Rationale and Objectives

      To explore whether the sarcopenia body type can help predict response to interleukin-2 (IL-2) therapy in metastatic renal cell carcinoma (RCC).

      Materials and Methods

      Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act-compliant retrospective cohort study of 75 subjects with metastatic RCC who underwent pretreatment contrast-enhanced computed tomography within 1 year of initiating IL-2 therapy. Cross-sectional area and attenuation of normal-density (31–100 Hounsfield units [HU]) and low-density (0–30 HU) dorsal muscles were obtained at the T11 vertebral level. The primary outcome was partial or complete response to IL-2 using RECIST 1.1 criteria at 6 weeks. A conditional inference tree was used to determine an optimal HU cutoff for predicting outcome. Bonferroni-adjusted multivariate logistic regression was conducted to investigate the independent associations between imaging features and response after controlling for demographics, doses of IL-2, and RCC prognostic scales (eg, Heng and the Memorial Sloan Kettering Cancer Center [MSKCC]).

      Results

      Most subjects had intermediate prognosis by Heng (65% [49 of 75]) and the MSKCC (63% [47 of 75]) criteria; 7% had complete response and 12% had partial response. Mean attenuation of low-density dorsal muscles was a significant univariate predictor of IL-2 response after Bonferroni correction (P = 0.03). The odds of responding to treatment were 5.8 times higher for subjects with higher-attenuation low-density dorsal muscles (optimal cutoff: 18.1 HU). This persisted in multivariate analysis (P = 0.02). Body mass index (P = 0.67) and the Heng (P = 0.22) and MSKCC (P = 0.08) clinical prognostic scales were not significant predictors of response.

      Conclusions

      Mean cross-sectional attenuation of low-density dorsal muscles (ie, sarcopenia) may predict IL-2 response in metastatic RCC. Clinical variables are poor predictors of response.

      Key Words

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      References

        • Fearon K.
        • Strasser F.
        • Anker S.D.
        • et al.
        Definition and classification of cancer cachexia: an international consensus.
        Lancet Oncol. 2011; 12: 489-495
        • Lee J.S.
        • He K.
        • Harbaugh C.M.
        • et al.
        Frailty, core muscle size, and mortality in patients undergoing open abdominal aortic aneurysm repair.
        J Vasc Surg. 2011; 53: 912-917
        • Englesbe M.J.
        • Patel S.P.
        • He K.
        • et al.
        Sarcopenia and mortality after liver transplantation.
        J Am Coll Surg. 2010; 211: 271-278
        • Englesbe M.J.
        • Terjimanian M.N.
        • Less J.S.
        • et al.
        Morphometric age and surgical risk.
        J Am Coll Surg. 2013; 216: 976-985
        • Englesbe M.
        • Less J.S.
        • He K.
        • et al.
        Analytic morphomics, core muscle size, and surgical outcomes.
        Ann Surg. 2012; 256: 255-261
        • Canvasser L.D.
        • Mazurek A.A.
        • Cron D.C.
        • et al.
        Paraspinous muscle as a predictor of surgical outcome.
        J Surg Res. 2014; 192: 76-81
        • Lee C.S.
        • Cron D.C.
        • Terjimanian M.N.
        • et al.
        Dorsal muscle group area and surgical outcomes in liver transplantation.
        Clin Transplant. 2014; 28: 1092-1098
        • Miller B.S.
        • Ignatoski K.M.
        • Daignault S.
        • et al.
        Worsening central sarcopenia and increasing intra-abdominal fat correlate with decreased survival in patients with adrenocortical carcinoma.
        World J Surg. 2012; 36: 1509-1516
        • Sabel M.S.
        • Lee J.
        • Cai S.
        • et al.
        Sarcopenia as a prognostic factor among patients with stage III melanoma.
        Ann Surg Oncol. 2011; 18: 3579-3585
        • Lang T.
        • Streeper T.
        • Cawthon P.
        • et al.
        Sarcopenia: etiology, clinical consequences, intervention, and assessment.
        Osteoporos Int. 2010; 21: 543-559
        • Miljkovic I.
        • Kuipers A.L.
        • Cauley J.A.
        • et al.
        Greater skeletal muscle fat infiltration is associated with higher all-cause and cardiovascular mortality in older men.
        J Gerontol A Biol Sci Med Sci. 2015; 70: 1133-1140
        • Anandavadivelan P.
        • Brismar T.B.
        • Nilsson M.
        • et al.
        Sarcopenic obesity: a probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients.
        Clin Nutr. 2016; 35: 724-730
        • Aust S.
        • Knogler T.
        • Pils D.
        • et al.
        Skeletal muscle depletion and markers for cancer cachexia are strong prognostic factors in epithelial ovarian cancer.
        PLoS ONE. 2015; https://doi.org/10.1371/journal.pone.0140403
        • Grossberg A.J.
        • Chamchod S.
        • Fuller C.D.
        • et al.
        Association of body composition with survival and locoregional control of radiotherapy-treated head and neck squamous cell carcinoma.
        JAMA Oncol. 2016; 2: 782-789
        • Tandon P.
        • Ney M.
        • Irwin I.
        • et al.
        Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value.
        Liver Transpl. 2012; 18: 1209-1216
        • Sabel M.S.
        • Lee J.
        • Wang A.
        • et al.
        Morphomics predicts response to ipilimumab in patients with stage IV melanoma.
        J Surg Oncol. 2015; 112: 333-337
        • Schafer A.L.
        • Vittinghoff E.
        • Lang T.F.
        • et al.
        Fat infiltration of muscle, diabetes, and clinical fracture risk in older adults.
        J Clin Endocrinnol Metab. 2010; 95: E368-E372
        • Stenehjem D.D.
        • Toole M.
        • Merriman J.
        • et al.
        Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2.
        Cancer Immunol Immunother. 2016; https://doi.org/10.1007/s00262-106-1854-1
        • Hanzly M.
        • Aboumohamed A.
        • Yarlagadda N.
        • et al.
        High-dose interleukin-2 therapy for metastatic renal cell carcinoma: a contemporary experience.
        Urology. 2014; 83: 1129-1134
        • Klapper J.A.
        • Downey S.G.
        • Smith F.O.
        • et al.
        High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma.
        Cancer. 2008; 113: 293-301
        • McDermott D.F.
        • Cheng S.C.
        • Signoretti S.
        • et al.
        The high-dose aldesluekin “select” trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma.
        Clin Cancer Res. 2015; 21: 561-568
        • Upton M.P.
        • Parker R.A.
        • Youmans A.
        • et al.
        Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy.
        J Immunother. 2005; 28: 488-495
        • Motzer R.J.
        • Mazumdar M.
        • Bacik J.
        • et al.
        Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma.
        J Clin Oncol. 1999; 17: 2530-2540
        • Goodpaster B.H.
        • Kelley D.E.
        • Wing R.R.
        • et al.
        Effects of weight loss on regional fat distribution and insulin sensitivity in obesity.
        Diabetes. 1999; 48: 839-847
        • Goodpaster B.H.
        • Thaete F.L.
        • Kelley D.E.
        Skeletal muscle composition evaluated with computed tomography.
        Ann NY Acad Sci. 2000; 904: 18-24
        • Goodpaster B.H.
        • Kelley D.E.
        • Thaete F.L.
        • et al.
        Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content.
        J Appl Physiol. 2000; 89: 104-110
        • Zoico E.
        • Rossi A.
        • De Francesco V.
        • et al.
        Adipose tissue infiltration in skeletal muscle of healthy, elderly men: relationships with body composition, insulin resistance and inflammation at the systemic and tissue level.
        J Gerontol A Biol Sci Med Sci. 2010; 65: 295-299
        • Eisenhauer E.A.
        • Therasse P.
        • Bogaerts J.
        • et al.
        New response evaluation criteria in solid tumous: revised RECIST guideline (version 1.1).
        Eur J Cancer. 2009; 45: 228-247
        • R Core Team
        R: a language and environment for statistical computing.
        R Foundation for Statistical Computing, Vienna, Austria.2016
        • Hothorn T.
        • Hornik K.
        • Zeileis A.
        Unbiased recursive partitioning: a conditional inference framework.
        J Comput Graph Stat. 2006; 15: 651-674
        • World Health Organization
        Obesity and overweight. Updated 6/2016.
        (Available at:) (Accessed August 28)
        • Steensma D.P.
        • Loprinzi C.L.
        The art and science of prognosis in patients with advanced cancer.
        Eur J Cancer. 2000; 36: 2025-2027
        • Christakis N.A.
        • Lamont E.B.
        Extent and determinants of error in doctors' prognoses in terminally ill patients: prospective cohort study.
        Br Med J. 2000; 320: 469-472