Annals of Surgical Oncology

, Volume 18, Issue 13, pp 3579–3585 | Cite as

Sarcopenia as a Prognostic Factor among Patients with Stage III Melanoma

  • Michael S. Sabel
  • Jay Lee
  • Shijie Cai
  • Michael J. Englesbe
  • Stephen Holcombe
  • Stewart Wang
Melanomas

Abstract

Background

Several hypotheses proposed to explain the worse prognosis for older melanoma patients include different tumor biology and diminished host response. If the latter were true, then biologic frailty, and not age, should be an independent prognostic factor in melanoma.

Methods

Our prospective institutional review board (IRB)-approved database was queried for stage III patients with computed tomography (CT) scans at time of lymph node dissection (LND). Psoas area (PA) and density (PD) were determined in semi-automated fashion. Kaplan–Meier (K–M) survival estimates and Cox proportional-hazard models were used to determine PA and PD impact on survival and surgical complications.

Results

Among 101 stage III patients, PD was significantly associated with both disease-free survival (DFS) (P = 0.04) and distant disease-free survival (DDFS) (P = 0.0002). Cox multivariate modeling incorporating thickness, age, ulceration, and N stage showed highly significant association with PD and both DFS and DDFS. DDFS was significantly associated with Breslow thickness (P = 0.04), number of positive nodes (P = 0.001), ulceration (P = 0.04), and decreasing muscle density (P = 0.01), with hazard ratio of 0.55 [95% confidence interval (CI) 0.35–0.87]. PD also correlated with surgical complications, with odds ratio (OR) of 1.081 [95% CI 1.016–1.150, P = 0.01].

Conclusions

Decreased psoas muscle density on CT, an objective measure of frailty, was as important a predictor of outcome as tumor factors in a cohort of stage III melanoma patients. On multivariate analysis, frailty, not age, was associated with decreased disease-free survival and distant disease-free survival, and higher rate of surgical complications.

References

  1. 1.
    Balch CM, Soong S-J, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19(16):3622–34.Google Scholar
  2. 2.
    Austin RF, Cruse CW, Lyman GH, et al. Age as a prognostic factor in the malignant melanoma population. Ann Surg Oncol. 1994;1(6):487–94.PubMedCrossRefGoogle Scholar
  3. 3.
    Lasithiotakis K, Leiter U, Meier F, et al. Age and gender are significant independent predictors of survival in primary cutanous melanoma. Cancer. 2008;112:1795–804.PubMedCrossRefGoogle Scholar
  4. 4.
    Paek SC, Griffith KA, Johnson TM, et al. The impact of factors beyond Breslow depth on predicting sentinel lymph node positivity in melanoma. Cancer. 2007;109(1):100-8.PubMedCrossRefGoogle Scholar
  5. 5.
    Statius Muller MG, van Leeuwen PAM, de Lange-De Klerk ES, et al. The sentinel lymph node status is an important factor for predicting clinical outcome in patients with stage I or II cutaneous melanoma. Cancer. 2001;91(12):2401–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Tsai S, Balch CM, Lange J. Epidemiology and treatment of melanoma in elderly patients. Nat Rev Clin Oncol. 2010;7:148–152.PubMedCrossRefGoogle Scholar
  7. 7.
    Englesbe MJ, Patel SP, He K, et al. Sarcopenia and mortality after liver transplantation. JACS. 2010;211(2):271–278.Google Scholar
  8. 8.
    Lang PO, Michel JP, Zekry D. Frailty syndrome: a transitional state in a dynamic process. Gerontology. 2009;55(5):539–49.PubMedCrossRefGoogle Scholar
  9. 9.
    Marcell TJ. Sarcopenia: causes, consequences and preventions. J Gerontol A Biol Sci Med Sci. 2003;58(10):M911–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56.PubMedCrossRefGoogle Scholar
  11. 11.
    Buchman AS, Wilson RS, Bienias JL, et al. Change in frailty and risk of death in older persons. Exp Aging Res. 2009;35(1):61–82.PubMedCrossRefGoogle Scholar
  12. 12.
    Longstreth WT, Bernick C, Fitzpatrick A, et al. Frequency and predictors of stroke death in 5,888 participants in the Cardiovascular Health Study. Neurology. 2001;56(3):368–75.PubMedGoogle Scholar
  13. 13.
    Baumgartner RN, Wayne SJ, Waters DL, et al. Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes Res. 2004;12(12):1995–2004.PubMedCrossRefGoogle Scholar
  14. 14.
    Villareal DT, Banks M, Sinacore DR, et al. Effect of weight loss and exercise on frailty in obese, older adults. Arch Intern Med. 2006;166(8):860–866.PubMedCrossRefGoogle Scholar
  15. 15.
    Goodpaster BH, Thaete FL, Kelley DE. Skeletal muscle composition evaluated with computed tomography. Ann NY Acad Sci. 2000;904:18–24.PubMedCrossRefGoogle Scholar
  16. 16.
    Goodpaster BH, Kelley DE, Thaete FL, et al. Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol. 2000;89:104–110.PubMedGoogle Scholar
  17. 17.
    Hsu M-Y, Meier F, Herlyn M. Melanoma development and progression: a conspiracy between tumor and host. Differentiation. 2002;70:522-536.PubMedCrossRefGoogle Scholar
  18. 18.
    van den Biggelaar AHJ, Huizinga TWJ, de Craen AJM, et al. Impaired innate immunity predicts frailty in old age: the Leiden 85-plus study. Exp Gerontol. 2004;39:1407–1414.PubMedCrossRefGoogle Scholar
  19. 19.
    Paganelli R, Di Iorio A, Cherubini A, et al. Frailty of older age: the role of the endocrine-immune interaction. Curr Pharm Des. 2006;12:3147–3159.PubMedCrossRefGoogle Scholar
  20. 20.
    Yao X, Li H, Leng SX. Inflammation and immune system alterations in frailty. Clin Geriatr Med. 2011;27:79–87.PubMedCrossRefGoogle Scholar
  21. 21.
    Schafer AL, Vittinghoff E, Lang TF, et al. Fat infiltration of muscle, diabetes and clinical fracture risk in older adults. J Clin Endocrin Metab. 2010;95.Google Scholar
  22. 22.
    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;65A(3):295–299.CrossRefGoogle Scholar
  23. 23.
    Gilsanz V, Kremer A, Mo AO, et al. Vitamin D status and its relation to muscle mass and muscle fat in young women. J Clin Endocrin Metab. 2010;95:1595–1601.CrossRefGoogle Scholar
  24. 24.
    Walston J, McBurnie MA, Newman A, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical morbidities: results from the Cardiovascular Health Study. Arch Intern Med. 2002;162:2333–2341.PubMedCrossRefGoogle Scholar
  25. 25.
    Leng S, Chaves P, Koenig KL, et al. Serum IL-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc. 2002;50:1268–1271.PubMedCrossRefGoogle Scholar
  26. 26.
    Tartour E, Dorval T, Mosseri V, et al. Serum interleukin-6 and C-reactive protein levels correlate with resistance to IL-2 therapy and poor survival in melanoma patients. Br J Cancer. 1994;69(5):911–913.PubMedCrossRefGoogle Scholar
  27. 27.
    Holick MF. Vitamin D deficiency. New Engl J Med. 2007;357:266–281.PubMedCrossRefGoogle Scholar
  28. 28.
    Berwick M, Armstrong BK, Ben-Porat L, et al. Sun exposure and mortality from melanoma. J Natl Cancer Inst. 2005;97:195–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Fang JS, Gillies RD, Gatenby RA. Adaptation to hypoxia and acidosis in carcinogenesis and tumor progression. Semin Cancer Biol. 2008;18(5):330–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Kapur P, Rakheja D, Roy LC, et al. Fatty acid synthase expression in cutaneous melanocytic neoplasms. Mod Pathol. 2005;18:1107–12.PubMedCrossRefGoogle Scholar
  31. 31.
    Innocenzi D, Alo PL, Alzani A, et al. Fatty acid synthase expression in melanoma. J Cutan Pathol. 2003;30:23–8.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Michael S. Sabel
    • 1
  • Jay Lee
    • 2
  • Shijie Cai
    • 1
  • Michael J. Englesbe
    • 1
  • Stephen Holcombe
    • 1
  • Stewart Wang
    • 1
  1. 1.Departments of SurgeryUniversity of MichiganAnn ArborUSA
  2. 2.Departments of BiostatisticsUniversity of MichiganAnn ArborUSA

Personalised recommendations