Advertisement

Musculoskeletal Aging, Sarcopenia, and Cancer

  • Matteo Cesari
  • Riccardo Calvani
  • Emanuele Marzetti
Living reference work entry

Abstract

The decrease in muscle mass and strength represents one of the most relevant descriptor of physiological aging. Sarcopenia is the term coined to indicate the pathologic loss of skeletal muscle mass and strength/function during aging. The skeletal muscle decline has a multifactorial origin, involving lifestyle habits, disease triggers, and age-dependent biological changes. This phenomenon is part of the geriatric background and is today starting to disseminate in other specialties dealing with the complexity of frail older persons. In the oncology field, the interest in muscle wasting has mostly been focused on the clinical entity of cancer cachexia, a complex metabolic syndrome characterized by severe muscle loss, systemic inflammation, and malnutrition. The study of body composition in the oncological setting is crucial and may become one of the main characterizations of the oncogeriatric field, where clinical and research actions have to be designed taking into account the consequences of the aging process.

Keywords

Physical function Cachexia Muscle Body composition Aging 

Notes

Acknowledgments

The authors thank Mr. Francesco Antognarelli for his invaluable assistance with the illustration (Fig. 2).

References

  1. Adamsen L, et al. Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. BMJ. 2009;339:b3410.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Argilés JM. Cancer-associated malnutrition. Eur J Oncol Nurs. 2005;9(Suppl 2):S39–50.PubMedCrossRefGoogle Scholar
  3. Argilés JM, et al. Skeletal muscle regulates metabolism via Interorgan crosstalk: roles in health and disease. J Am Med Dir Assoc. 2016;17:789–96.PubMedCrossRefGoogle Scholar
  4. Balducci L, Ershler WB. Cancer and ageing: a nexus at several levels. Nat Rev Cancer. 2005;5:655–62.PubMedCrossRefGoogle Scholar
  5. Batsis JA, et al. Sarcopenia, sarcopenic obesity and mortality in older adults: results from the National Health and Nutrition Examination Survey III. Eur J Clin Nutr. 2014;68:1001–7.PubMedCrossRefGoogle Scholar
  6. Bauer J, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013;14:542–59.PubMedCrossRefGoogle Scholar
  7. Baumgartner RN, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998;147:755–63.PubMedCrossRefGoogle Scholar
  8. Beaudart C, et al. Sarcopenia in daily practice: assessment and management. BMC Geriatr. 2016;16:170.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Buford TW, et al. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy. Ageing Res Rev. 2010;9:369–83.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Butikofer L, et al. Destabilization of the neuromuscular junction by proteolytic cleavage of agrin results in precocious sarcopenia. FASEB J. 2011;25:4378–93.PubMedCrossRefGoogle Scholar
  11. Calvani R, et al. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy. Biol Chem. 2013a;394:393–414.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Calvani R, et al. Current nutritional recommendations and novel dietary strategies to manage sarcopenia. J Frailty Aging. 2013b;2:38–53.PubMedPubMedCentralGoogle Scholar
  13. Calvani R, et al. Biomarkers for physical frailty and sarcopenia: state of the science and future developments. J Cachexia Sarcopenia Muscle. 2015;6:278–86.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Calvani R, et al. Systemic inflammation, body composition, and physical performance in old community-dwellers. J Cachexia Sarcopenia Muscle. 2016;  https://doi.org/10.1002/jcsm.12134.
  15. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013;75:685–705.PubMedCrossRefGoogle Scholar
  16. Carter CS, et al. Angiotensin-converting enzyme inhibition intervention in elderly persons: effects on body composition and physical performance. J Gerontol A Biol Sci Med Sci. 2005;60:1437–46.PubMedCrossRefGoogle Scholar
  17. Cesari M, Vellas B. Sarcopenia: a novel clinical condition or still a matter for research? J Am Med Dir Assoc. 2012;13:766–7.PubMedCrossRefGoogle Scholar
  18. Cesari M, et al. Skeletal muscle and mortality results from the InCHIANTI Study. J Gerontol A Biol Sci Med Sci. 2009;64:377–84.PubMedCrossRefGoogle Scholar
  19. Cesari M, et al. Vitamin D hormone: a multitude of actions potentially influencing the physical function decline in older persons. Geriatr Gerontol Int. 2011;11:133–42.PubMedCrossRefGoogle Scholar
  20. Cesari M, et al. Biomarkers of sarcopenia in clinical trials-recommendations from the International Working Group on Sarcopenia. J Frailty Aging. 2012;1:102–10.Google Scholar
  21. Cesari M, et al. Functional status and mortality in older women with gynecological cancer. J Gerontol A Biol Sci Med Sci. 2013;68:1129–33.PubMedCrossRefGoogle Scholar
  22. Cesari M, et al. Sarcopenia-related parameters and incident disability in older persons: results from the “Invecchiare in Chianti” Study. J Gerontol A Biol Sci Med Sci. 2015;70:547–58.Google Scholar
  23. Cesari M, et al. The geriatric management of frailty as paradigm of “The end of the disease era”. Eur J Intern Med. 2016a;31:11–4.PubMedCrossRefGoogle Scholar
  24. Cesari M, Nobili A, Vitale G. Frailty and sarcopenia: from theory to clinical implementation and public health relevance. Eur J Intern Med. 2016b;35:1–9.PubMedCrossRefGoogle Scholar
  25. Chahal HS, Drake WM. The endocrine system and ageing. J Pathol. 2007;211:173–80.PubMedCrossRefGoogle Scholar
  26. Christensen JF, et al. Muscle dysfunction in cancer patients. Ann Oncol. 2014;25:947–58.PubMedCrossRefGoogle Scholar
  27. Cleeland CS, et al. Reducing the toxicity of cancer therapy: recognizing needs, taking action. Nat Rev Clin Oncol. 2012;9:471–8.PubMedCrossRefGoogle Scholar
  28. Combaret L, et al. Skeletal muscle proteolysis in aging. Curr Opin Clin Nutr Metab Care. 2009;12:37–41.PubMedCrossRefGoogle Scholar
  29. Cruz-Jentoft AJ, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in older people. Age Ageing. 2010a;39:412–23.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Cruz-Jentoft AJ, et al. Understanding sarcopenia as a geriatric syndrome. Curr Opin Clin Nutr Metab Care. 2010b;13:1–7.PubMedCrossRefGoogle Scholar
  31. Dam TT, et al. An evidence-based comparison of operational criteria for the presence of sarcopenia. J Gerontol A Biol Sci Med Sci. 2014;69:584–90.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Delmonico MJ, et al. Alternative definitions of sarcopenia, lower extremity performance, and functional impairment with aging in older men and women. J Am Geriatr Soc. 2007;55:769–74.PubMedCrossRefGoogle Scholar
  33. Deutz NE, et al. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr. 2014;33:929–36.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Edwards BK, et al. Annual report to the nation on the status of cancer, 1973–1999, featuring implications of age and aging on U.S. cancer burden. Cancer. 2002;94:2766–92.PubMedCrossRefGoogle Scholar
  35. Eijsvogels TM, Thompson PD. Exercise is medicine: at any dose. JAMA. 2015;314:1915–6.PubMedCrossRefGoogle Scholar
  36. (1989) Epidemiologic and methodologic problems in determining nutritional status of older persons. In: Proceedings of a conference. Albuquerque, October 19–21, 1988. Am J Clin Nutr 50:1121–235. https://www.ncbi.nlm.nih.gov/pubmed/2816807.
  37. Evans WJ. Skeletal muscle loss: cachexia, sarcopenia, and inactivity. Am J Clin Nutr. 2010;91:1123S–7S.PubMedCrossRefPubMedCentralGoogle Scholar
  38. Evans WJ, et al. Cachexia: a new definition. Clin Nutr. 2008;27:793–9.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Fearon K, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12:489–95.PubMedCrossRefGoogle Scholar
  40. Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 2012;16:153–66.PubMedCrossRefGoogle Scholar
  41. Ferrucci L, et al. Designing randomized, controlled trials aimed at preventing or delaying functional decline and disability in frail, older persons: a consensus report. J Am Geriatr Soc. 2004;52:625–34.PubMedCrossRefGoogle Scholar
  42. Fielding RA, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 2011;12:249–56.PubMedCrossRefGoogle Scholar
  43. Finkel T, Serrano M, Blasco MA. The common biology of cancer and ageing. Nature. 2007;448:767–74.PubMedCrossRefGoogle Scholar
  44. Forbes GB. Longitudinal changes in adult fat-free mass: influence of body weight. Am J Clin Nutr. 1999;70: 1025–31.PubMedCrossRefGoogle Scholar
  45. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl 1):S4–9.PubMedCrossRefGoogle Scholar
  46. Galvão DA, et al. Exercise can prevent and even reverse adverse effects of androgen suppression treatment in men with prostate cancer. Prostate Cancer Prostatic Dis. 2007;10:340–6.PubMedCrossRefGoogle Scholar
  47. Galvao DA, et al. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. J Clin Oncol. 2010;28:340–7.PubMedCrossRefGoogle Scholar
  48. Gérard S, et al. Body composition and anti-neoplastic treatment in adult and older subjects – a systematic review. J Nutr Health Aging. 2016;20:878–88.PubMedCrossRefGoogle Scholar
  49. Global Burden of Disease Cancer Collaboration, et al. Global, Regional, and National Cancer Incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 Cancer Groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease Study. JAMA Oncol. 2016;  https://doi.org/10.1001/jamaoncol.2016.5688.
  50. Hamaker ME, et al. Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review. Lancet Oncol. 2012;13:e437–44.PubMedCrossRefGoogle Scholar
  51. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.CrossRefGoogle Scholar
  52. Hepple RT, Rice CL. Innervation and neuromuscular control in ageing skeletal muscle. J Physiol. 2016;594:1965–78.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Herndon LA, et al. Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature. 2002;419:808–14.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Hughes VA, et al. Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr. 2002;76:473–81.PubMedCrossRefPubMedCentralGoogle Scholar
  55. Hurria A, et al. Aging, the medical subspecialties, and career development: where we were, Where we are going. J Am Geriatr Soc. 2017;65:680.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Janssen I, et al. Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women. Am J Epidemiol. 2004;159:413–21.PubMedCrossRefPubMedCentralGoogle Scholar
  57. Jo E, et al. Potential mechanisms underlying the role of chronic inflammation in age-related muscle wasting. Aging Clin Exp Res. 2012;24:412–22.PubMedPubMedCentralGoogle Scholar
  58. Justice JN, et al. Comparative approaches to understanding the relation between aging and physical function. J Gerontol A Biol Sci Med Sci. 2016;71:1243–53.PubMedCrossRefGoogle Scholar
  59. Kalinkovich A, Livshits G. Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev. 2016;  https://doi.org/10.1016/j.arr.2016.09.008.
  60. Kazemi-Bajestani SM, Mazurak VC, Baracos V. Computed tomography-defined muscle and fat wasting are associated with cancer clinical outcomes. Semin Cell Dev Biol. 2016;54:2–10.PubMedCrossRefGoogle Scholar
  61. Landi F, et al. Sarcopenia as the biological substrate of physical frailty. Clin Geriatr Med. 2015;31:367–74.PubMedCrossRefGoogle Scholar
  62. Landi F, et al. Age-related variations of muscle mass, strength, and physical performance in community-dwellers: results from the Milan EXPO Survey. J Am Med Dir Assoc. 2016a;  https://doi.org/10.1016/j.jamda.2016.10.007.
  63. Landi F, et al. Sarcopenia and frailty: from theoretical approach into clinical practice. Eur Geriatr Med. 2016b;7:197–200.CrossRefGoogle Scholar
  64. Lauretani F, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol. 2003;95:1851–60.PubMedCrossRefGoogle Scholar
  65. López-Otín C, et al. The hallmarks of aging. Cell. 2013;153:1194–217.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Martin L, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol. 2013;31:1539–47.PubMedCrossRefGoogle Scholar
  67. Martone AM, et al. Treating sarcopenia in older and oldest old. Curr Pharm Des. 2015;21:1715–22.PubMedCrossRefGoogle Scholar
  68. Marzetti E, et al. Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction. Biofactors. 2009;35:28–35.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Marzetti E, et al. Apoptosis in skeletal myocytes: a potential target for interventions against sarcopenia and physical frailty – a mini-review. Gerontology. 2012;58:99–106.PubMedCrossRefGoogle Scholar
  70. Marzetti E, et al. Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials. Int J Biochem Cell Biol. 2013;45:2288–301.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Marzetti E, et al. Patterns of circulating inflammatory biomarkers in older persons with varying levels of physical performance: a partial least squares-discriminant analysis approach. Front Med (Lausanne). 2014;1:27.Google Scholar
  72. Marzetti E, et al. Innovative medicines initiative: the SPRINTT project. J Frailty Aging. 2015;4:207–8.PubMedPubMedCentralGoogle Scholar
  73. Marzetti E, et al. Brand new medicine for an Older Society. J Am Med Dir Assoc. 2016;17:558–9.PubMedCrossRefGoogle Scholar
  74. Miquel J, et al. Mitochondrial role in cell aging. Exp Gerontol. 1980;15:575–91.PubMedCrossRefGoogle Scholar
  75. Morley JE, et al. Sarcopenia with limited mobility: an international consensus. J Am Med Dir Assoc. 2011;12:403–9.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Muscaritoli M, et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”. Clin Nutr. 2010;29:154–9.PubMedCrossRefGoogle Scholar
  77. Newman AB, et al. Sarcopenia: alternative definitions and associations with lower extremity function. J Am Geriatr Soc. 2003;51:1602–9.PubMedCrossRefGoogle Scholar
  78. Nicholson JK, Wilson ID. Opinion: understanding ‘global’ systems biology: metabonomics and the continuum of metabolism. Nat Rev Drug Discov. 2003;2:668–76.PubMedCrossRefGoogle Scholar
  79. Paddon-Jones D, Rasmussen BB. Dietary protein recommendations and the prevention of sarcopenia. Curr Opin Clin Nutr Metab Care. 2009;12:86–90.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Pahor M, Manini T, Cesari M. Sarcopenia: clinical evaluation, biological markers and other evaluation tools. J Nutr Health Aging. 2009;13:724–8.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Pahor M, et al. Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE Study Randomized Clinical Trial. JAMA. 2014;311:2387–96.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Picca A, Lezza AM. Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: useful insights from aging and calorie restriction studies. Mitochondrion. 2015;25:67–75.PubMedCrossRefGoogle Scholar
  83. Picca A, et al. A comparison among the tissue-specific effects of aging and calorie restriction on TFAM amount and TFAM-binding activity to mtDNA in rat. Biochim Biophys Acta. 2014;1840:2184–91.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Prado CM. Body composition in chemotherapy: the promising role of CT scans. Curr Opin Clin Nutr Metab Care. 2013;16:525–33.PubMedCrossRefGoogle Scholar
  85. Prado CM, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9:629–35.PubMedCrossRefGoogle Scholar
  86. Prins JB. Adipose tissue as an endocrine organ. Best Pract Res Clin Endocrinol Metab. 2002;16:639–51.PubMedCrossRefGoogle Scholar
  87. Psutka SP, et al. Sarcopenia in patients with bladder cancer undergoing radical cystectomy: impact on cancer-specific and all-cause mortality. Cancer. 2014;120:2910–8.PubMedCrossRefGoogle Scholar
  88. Rier HN, et al. The prevalence and prognostic value of low muscle mass in Cancer patients: a review of the literature. Oncologist. 2016;21:1396.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Riera CE, Dillin A. Tipping the metabolic scales towards increased longevity in mammals. Nat Cell Biol. 2015;17:196–203.PubMedCrossRefGoogle Scholar
  90. Rolland YM, et al. Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging. 2008;12:433–50.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Rolland Y, et al. Difficulties with physical function associated with obesity, sarcopenia, and sarcopenic-obesity in community-dwelling elderly women: the EPIDOS (EPIDemiologie de l’OSteoporose) Study. Am J Clin Nutr. 2009;89:1895–900.PubMedCrossRefGoogle Scholar
  92. Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127:990S–1S.PubMedCrossRefGoogle Scholar
  93. Rosenberg IH, Roubenoff R. Stalking sarcopenia. Ann Intern Med. 1995;123:727–8.PubMedCrossRefGoogle Scholar
  94. Rozhok AI, DeGregori J. The evolution of lifespan and age-dependent Cancer risk. Trends Cancer. 2016;2:552–60.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Ruiz JR, et al. Muscular strength and adiposity as predictors of adulthood cancer mortality in men. Cancer Epidemiol Biomark Prev. 2009;18:1468–76.CrossRefGoogle Scholar
  96. Sakuma K, Yamaguchi A. Sarcopenia and age-related endocrine function. Int J Endocrinol. 2012a;2012: 127362.PubMedPubMedCentralCrossRefGoogle Scholar
  97. Sakuma K, Yamaguchi A. Sarcopenia and cachexia: the adaptations of negative regulators of skeletal muscle mass. J Cachexia Sarcopenia Muscle. 2012b;3:77–94.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Shachar SS, et al. Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review. Eur J Cancer. 2016;57:58–67.PubMedCrossRefGoogle Scholar
  99. Snyder PJ, et al. Effects of testosterone treatment in Older Men. N Engl J Med. 2016;374:611–24.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Studenski S. Target population for clinical trials. J Nutr Health Aging. 2009;13:729–32.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Studenski SA, et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci. 2014;69:547–58.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Tan BH, et al. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res. 2009;15:6973–9.PubMedCrossRefGoogle Scholar
  103. van Vledder MG, et al. Body composition and outcome in patients undergoing resection of colorectal liver metastases. Br J Surg. 2012;99:550–7.PubMedCrossRefGoogle Scholar
  104. Villaseñor A, et al. Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study. J Cancer Surviv. 2012;6:398–406.PubMedPubMedCentralCrossRefGoogle Scholar
  105. Visser M, et al. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A Biol Sci Med Sci. 2005;60:324–33.PubMedCrossRefGoogle Scholar
  106. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359–407.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Whitham M, Febbraio MA. The ever-expanding myokinome: discovery challenges and therapeutic implications. Nat Rev Drug Discov. 2016;15:719–29.PubMedCrossRefPubMedCentralGoogle Scholar
  108. Woodhouse L, et al. A phase 2 randomized study investigating the efficacy and safety of Myostatin antibody LY2495655 versus placebo in patients undergoing elective Total hip arthroplasty. J Frailty Aging. 2016;5:62–70.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Matteo Cesari
    • 1
    • 2
  • Riccardo Calvani
    • 3
  • Emanuele Marzetti
    • 4
  1. 1.Geriatric UnitFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
  2. 2.Department of Clinical Sciences and Community HealthUniversity of MilanMilanItaly
  3. 3.Department of Geriatrics, Neurosciences and OrthopedicsCatholic University of the Sacred HeartRomeItaly
  4. 4.Department of Geriatrics, Neurosciences and OrthopedicsTeaching Hospital “Agostino Gemelli”RomeItaly

Section editors and affiliations

  • William Dale
    • 1
  1. 1.Department of Supportive Care MedicineCity of Hope Duarte - Comprehensive Cancer CenterDuarteUSA

Personalised recommendations