Supportive Care in Cancer

, Volume 24, Issue 11, pp 4495–4502 | Cite as

Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer—chemotherapy toxicity and prognostic value

  • Drazena SrdicEmail author
  • Sanja Plestina
  • Ana Sverko-Peternac
  • Nora Nikolac
  • Ana-Maria Simundic
  • Miroslav Samarzija
Original Article



Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer.

The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment.


Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases “Jordanovac,” was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively.


One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 %, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients demonstrated statistically significant difference (p = 0.020, p = 0.040, p = 0.003). Cachexia and sarcopenia were not found to be predictors of chemotoxicity nor was time to tumor progression. On the contrary, albumin concentration with established cutoff point of 37.5 g/L was clearly proved as the predictive factor of both chemotoxicity (OR (95 % CI) = 0.85; p < 0.001) and survival (HR (95 % CI) = 0.55).


Albumin level has been shown to be more important predictive marker of chemotherapy toxicity and survival than cachexia and sarcopenia are. This approach in clinical settings can be used to guide the choice of oncologic treatment.


Cancer cachexia Sarcopenia Non-small cell lung cancer Chemotherapy toxicity 


Compliance with ethical standards

The study was approved by the University Hospital Ethics Board.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Fearon K, Strasser F, Anker DS (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12:489–495CrossRefPubMedGoogle Scholar
  2. 2.
    Prado CM, Lieffers JR, McCargar LJ, Reinman T, Sawyer MB, Martin L, Baracos VE (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumors of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9:629–635CrossRefPubMedGoogle Scholar
  3. 3.
    Moses AWG, Slater C, Preston T, Barber MD, Fearon KCH (2004) Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. Br J Cancer 90:996–1002CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Prado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, Mackey JR, Koski S, Pituskin E, Sawyer MB (2009) Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabin treatment. Clin Cancer Res 15:2920–2926CrossRefPubMedGoogle Scholar
  5. 5.
    Mir O, Coriat R, Blanchet B et al (2012) Sarcopenia predicts early dose-limiting toxicities pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PLoS One 7, e37563CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Dewys WD, Begg C, Lavin PT et al (1980) Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 69:491–497CrossRefPubMedGoogle Scholar
  7. 7.
    Fearon KHC, Voss AC, Hustead DS on the bahalf of the Cancer Cachexia Study Group (2006) Definition of cancer cachexia: effect of weight loss, reduced food intake and systemic inflammation on functional status and prognosis. Am J Clin Nutr 83:1345–1350Google Scholar
  8. 8.
    von Haehling S, Anker SD (2010) Cachexia as a major underestimated and unmet medical need: facts and numbers. J Cachex Sarcopenia Muscle 1:1–5CrossRefGoogle Scholar
  9. 9.
    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vanderwoude M, Zamboni M (2010) Sarcopenia: European concensus on definition and diagnosis: report of the European Working Group on sarcopenia in older people. Age Aging 39:412–423CrossRefGoogle Scholar
  10. 10.
    Baracos VE, Reiman T, Mourtzakis M, Gioulbasanis I, Antoun S (2010) Body composition in patients with non-small cell lung cancer: a contemporary view of cancer cachexia with the use of computed tomography image analysis. Am J Clin Nutr 91:1133S–1137SCrossRefPubMedGoogle Scholar
  11. 11.
    Bistrian B (2007) Systemic response to inflammation. Nutr Rev 65(12 Pt 2):S170–S172CrossRefPubMedGoogle Scholar
  12. 12.
    Delano MJ, Moldawer LL (2006) The origins of cachexia in acute and chronic inflammatory diseases. Nutr Clin Pract 21(1):68–81CrossRefPubMedGoogle Scholar
  13. 13.
    Argiles JM, Lopez-Soriano FJ (1998) Catabolic proinflammatory cytokines. Curr Opin Clin Nutr Metab Care 1:245–251CrossRefPubMedGoogle Scholar
  14. 14.
    Walsh D, Mahmoud F, Barna B (2003) Assessment of nutritional status and prognosis in advanced cancer: interleukin-6, C-reactive protein, and the prognostic and inflammatory nutritional index. Support Care Cancer 11(1):60–62PubMedGoogle Scholar
  15. 15.
    Deans C, Wigmore SJ (2005) Systemic inflammation, cachexia and prognosis in patients with cancer. Curr Opin Clin Nutr Metab Care 8:265–269CrossRefPubMedGoogle Scholar
  16. 16.
    Heymsfield SB, Wang Z, Baumgartner RN, Ross R (1997) Human body composition: advances in models and methods. Annu Rev Nutr 17:527–558CrossRefPubMedGoogle Scholar
  17. 17.
    Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R (1998) Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol 85:115–122PubMedGoogle Scholar
  18. 18.
    Shen W, Punyanitya M, Wang Z et al (2004) Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross sectional image. J Apl Physiol 97:2333–2338CrossRefGoogle Scholar
  19. 19.
    Miller KD, Jones E, Yanovski JA, Shankar R, Feuerstein I, Falloon J (1998) Visceral abdominal-fat accumulation associated with use of indinavir. Lancet 351:871–875CrossRefPubMedGoogle Scholar
  20. 20.
    Mourtzakis M, Prado CM, Lieffers JR et al (2008) A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab 33:997–1006CrossRefPubMedGoogle Scholar
  21. 21.
    Lieffers JR, Mourtzakis M, Hall KD et al (2009) A viscerally driven cachexia syndrome in patients with advanced colorectal cancer: contributions of organ and tumor mass to whole-body energy demands. Am J Clin Nutr 89:1173–1179CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Prado CM, Baracos VE, McCargar LJ, Mourtzakis M, Mulder KE, Reiman T, Butts CA, Scarfe AG, Sawyer MB (2007) Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res 13:3264–3268CrossRefPubMedGoogle Scholar
  23. 23.
    WHO (2000) Obesity: preventing and managing the global epidemic. World Health Organization, Geneva, SwitzerlandGoogle Scholar
  24. 24.
    Martin L, Birdsell L, Macdonald N, Reinman T, Clandinin MT, McCargar LJ, Murphy R, Ghosh S, Sawyer MB, Baracos VE (2013) Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol 31:1539–1547CrossRefPubMedGoogle Scholar
  25. 25.
    Kimura M, Naito T, Kenmotsu H, Taira T, Wakuda K, Oyakawa T, Hisamatsu Z, Tokito T, Imai H, Akamatsu H, Ono A, Kaira K, Murakami H, Endo M, Mori K, Takahashi T, Yamamoto N (2015) Prognostic impact of cancer cachexia in patients with advanced non-small cell lung cancer. Support Care Cancer 23:1699–1708CrossRefPubMedGoogle Scholar
  26. 26.
    Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB (2003) Years of life lost due to obesity. JAMA 289:187–193CrossRefPubMedGoogle Scholar
  27. 27.
    Morley JE, Baumgartner RN, Roubenoff R, Mayer J, Nair KS (2001) Sarcopenia. J Lab Clin Med 137:231–243CrossRefPubMedGoogle Scholar
  28. 28.
    Cosqueric G, Sebag A, Ducolombier C, Thomas C, Piette F, Weill-Engerer S (2006) Sarcopenia is predictive of nosocomial infection in care of elderly. Br J Nutr 96:895–901CrossRefPubMedGoogle Scholar
  29. 29.
    Baumgartner RN, Koehler KM, Gallagher D, Romero L, Hezmsfield SB, Ross RR, Garrz PJ, Lindeman RD (1998) Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 147:755–763CrossRefPubMedGoogle Scholar
  30. 30.
    Kim EY, Ys K, Park I, Ahn HK, Cho EK, Jeong YM (2015) Prognostic significance of CT-determined sarcopenia in patients with small-cell lung cancer. J Thorac Oncol 10:1795–1799CrossRefPubMedGoogle Scholar
  31. 31.
    Kim YS, Lee Y, Chung Y et al (2012) Prevalence of sarcopenia and sarcopenic obesity in the Korean population based on the Fourth Korean National Health and Nutritional Examination Surveys. J Gerontol A Biol Sci Med Sci 67:1107–1233CrossRefPubMedGoogle Scholar
  32. 32.
    Simmons CP, Koinis F, Fallon MT, Fearon KC, Bowden J, Solheim TS, Gronberg BH, McMillan DC, Gioulbasanis I, Laird BJ (2015) Prognosis in advanced lung cancer—a prospective study examining key clinicopathological factors. Lung Cancer 88:304–309CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Drazena Srdic
    • 1
    Email author
  • Sanja Plestina
    • 2
  • Ana Sverko-Peternac
    • 3
  • Nora Nikolac
    • 4
  • Ana-Maria Simundic
    • 5
  • Miroslav Samarzija
    • 6
  1. 1.Department for Respiratory Diseases “Jordanovac”University Hospital Centre ZagrebZagrebCroatia
  2. 2.Medical School University of Rijeka, Department for Respiratory Diseases “Jordanovac”University Hospital Centre ZagrebZagrebCroatia
  3. 3.Department for Diagnostic and Interventional RadiologyUniversity Hospital Centre Sestre MilosrdniceZagrebCroatia
  4. 4.University Department of ChemistryMedical School University Hospital Sestre MilosrdniceZagrebCroatia
  5. 5.Department of Medical Laboratory DiagnosticsUniversity Hospital “Sveti Duh”ZagrebCroatia
  6. 6.Medical School University of Zagreb, Department for Respiratory Diseases “Jordanovac”University Hospital Centre ZagrebZagrebCroatia

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