Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies
Main Article Content
Keywords
adiposity, body composition, obesity, renal cell carcinoma, sarcopenia, targeted therapy, toxicity
Abstract
Treatment of metastatic renal cell cancer (mRCC) currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR) pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI) on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2), and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.
References
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23. Antoun S, Lanoy E, Iacovelli R, Albiges-Sauvin L, Loriot Y, Merad-Taoufik M, et al. Skeletal muscle density predicts prognosis in patients with metastatic renal cell carcinoma treated with targeted therapies. Cancer. 2013;119:3377–3384. http://dx.doi.org/10.1002/cncr.28218
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25. Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol. 2001;3:1014–1019. http://dx.doi.org/10.1038/ncb1101-1014
26. McCabe K, Goh V, Vinaya A, Petruckevitch A, Nathan PD. Body composition and association with treatment toxicity in patients with advanced renal cell carcinoma receiving targeted agents. J Clin Oncol. 2013;31 (suppl; abstr e15608).
27. Huillard O, Mir O, Peyromaure M, Tlemsani C, Tlemsani C, Giroux J, Boudou-Rouquette P, et al. Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients. Br J Cancer 2013;108:1034–1041. http://dx.doi.org/10.1038/bjc.2013.58
28. Cushen SJ, Power DG, Teo MY, Maceneaney P, Maher MM, McDermott R, et al. Body composition by computed tomography as a predictor of toxicity in patients with renal cell carcinoma treated with sunitinib. Am J Clin Oncol. 2014 April 21.
2. Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002;20:289–296.
3. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999;17:2530–2540.
4. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625–1638. http://dx.doi.org/10.1056/NEJMoa021423
5. Chow WH, Dong LM, Devesa SS. Epidemiology and risk factors for kidney cancer Nat Rev Urol. 2010;7:245–257. http://dx.doi.org/10.1038/nrurol.2010.46
6. Chow WH, McLaughlin JK, Mandel JS, Wacholder S, Niwa S, Fraumeni JF Jr. Obesity and risk of renal cell cancer Cancer Epidemiol Biomarkers Prev. 1996;5:17–21.
7. Lindblad P, Wolk A, Bergström R, Persson I, Adami HO. The role of obesity and weight fluctuations in the etiology of renal cell cancer: A population-based case-control study. Cancer Epidemiol Biomarkers Prev. 1994;3:631–639.
8. World Health Organization. In: Obesity: Preventing and managing the global epidemic. WHO Technical Report Series (894th ed.). Geneva, Switzerland: World Health Organization; 2000.
9. Hursting SD, Berger NA. Energy balance, host-related factors, and cancer progression. J Clin Oncol. 2010;28:4058–4065. http://dx.doi.org/10.1200/JCO.2010.27.9935
10. Ceciliani F, Giordano A, Spagnolo V. The systemic reaction during inflammation: The acute- phase proteins. Protein Pept Lett. 2002;9:211–223.
11. Cao Y. Angiogenesis modulates adipogenesis and obesity J Clin Invest. 2007;117:2362–2368. http://dx.doi.org/10.1172/JCI32239
12. Leslie NR. The redox regulation of PI 3-kinase-dependent signaling. Antioxid Redox Signal. 2006;8:1765–1774. http://dx.doi.org/10.1089/ars.2006.8.1765
13. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia Nat Rev Cancer. 2008;8:915–928. http://dx.doi.org/10.1038/nrc2536
14. Awakura Y, Nakamura E, Ito N, Yamasaki T, Kamba T, Kamoto T, et al. Influence of body mass index on prognosis of Japanese patients with renal cell carcinoma. Urology. 2007;70:50–54. http://dx.doi.org/10.1016/j.urology.2007.03.034
15. Kamat AM, Shock RP, Naya Y, Rosser CJ, Slaton JW, Pisters LL. Prognostic value of body mass index in patients undergoing nephrectomy for localized renal tumors. Urology. 2004;63:46–50.
16. Choueiri TK, Xie W, Kollmannsberger CK, Rini BI, McDermott DF, Knox JJ, et al. The impact of body mass index (BMI) and body surface area (BSA) on treatment outcome to vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma: Results from a large international collaboration (abstract 4524). Proc Am Soc Clin Oncol. 2010;28:347s.
17. Albiges LA, Xie W, Lee JL, Rini BI, Srinivas S, Bjarnason GA, et al. The impact of body mass index (BMI) on treatment outcome of targeted therapy in metastatic renal cell carcinoma (mRCC): Results from the International Metastatic Renal Cell Cancer Database Consortium. J Clin Oncol. 2014;32(5s):Abstr 4576.
18. Albiges LA, Hakimi AA, Lin X, Simantov R, Zabor EC, Jacobsen A, et al. The impact of BMI on outcomes of patients with metastatic renal cell carcinoma treated with targeted therapy: An external validation data set and analysis of underlying biology from The Cancer Genome Atlas. J Clin Oncol. 2015;33(7):abstr 405.
19. Flavin R, Peluso S, Nguyen PL, Loda M. Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol. 2010;6(4):551–562. http://dx.doi.org/10.2217/fon.10.11
20. Steffens S, Grunwald V, Ringe K, Seidel C, Eggers H, Schrader M, et al. Does obesity influence the prognosis of metastatic renal cell carcinoma in patients treated with vascular endothelial growth factor–targeted therapy? The Oncologist. 2011;16:1565–1571. http://dx.doi.org/10.1634/theoncologist.2011-0213
21. Ladoire S, Bonnetain F, Gauthier M, Zanetta S, Petit JM, Guiu S, et al. Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents. The Oncologist. 2011;16:71–81. http://dx.doi.org/10.1634/theoncologist.2010-0227
22. Gu W, Zhu Y, Wang H, Zhang H, Shi G, Liu X. Prognostic value of components of body composition in patients treated with targeted therapy for advanced renal cell carcinoma: a retrospective case series. PLoS One. 2015;10(2):e0118022. http://dx.doi.org/10.1371/journal.pone.0118022.
23. Antoun S, Lanoy E, Iacovelli R, Albiges-Sauvin L, Loriot Y, Merad-Taoufik M, et al. Skeletal muscle density predicts prognosis in patients with metastatic renal cell carcinoma treated with targeted therapies. Cancer. 2013;119:3377–3384. http://dx.doi.org/10.1002/cncr.28218
24. Antoun S, Baracos VE, Birdsell L, Escudier B, Sawyer MB. Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol. 2010;21:1594–1598. http://dx.doi.org/10.1093/annonc/mdp605
25. Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol. 2001;3:1014–1019. http://dx.doi.org/10.1038/ncb1101-1014
26. McCabe K, Goh V, Vinaya A, Petruckevitch A, Nathan PD. Body composition and association with treatment toxicity in patients with advanced renal cell carcinoma receiving targeted agents. J Clin Oncol. 2013;31 (suppl; abstr e15608).
27. Huillard O, Mir O, Peyromaure M, Tlemsani C, Tlemsani C, Giroux J, Boudou-Rouquette P, et al. Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients. Br J Cancer 2013;108:1034–1041. http://dx.doi.org/10.1038/bjc.2013.58
28. Cushen SJ, Power DG, Teo MY, Maceneaney P, Maher MM, McDermott R, et al. Body composition by computed tomography as a predictor of toxicity in patients with renal cell carcinoma treated with sunitinib. Am J Clin Oncol. 2014 April 21.
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Published
Mar 22, 2016
Article Details
How to Cite
Yip, S. M., Heng, D. Y., & Tang, P. A. (2016). Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies. Journal of Kidney Cancer and VHL, 3(1), 12–22. https://doi.org/10.15586/jkcvhl.2016.45
Section
Kidney Cancer: Review Articles
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