Supportive Care in Cancer

, Volume 24, Issue 5, pp 2075–2084 | Cite as

Sarcopenia and inflammation are independent predictors of survival in male patients newly diagnosed with small cell lung cancer

  • Se-Il Go
  • Mi Jung Park
  • Haa-Na Song
  • Myoung Hee Kang
  • Hee Jung Park
  • Kyung Nyeo Jeon
  • Seok-Hyun Kim
  • Moon Jin Kim
  • Jung-Hun Kang
  • Gyeong-Won LeeEmail author
Original Article



Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the neutrophil-to-lymphocyte ratio (NLR).


A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non-sarcopenia/high NLR, and non-sarcopenia/low NLR.


Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months, p = 0.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months, p = 0.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively, p < 0.001), as was PFS (median 3.2 vs. 7.7 vs. 7.6 vs. 7.1 months, respectively, p < 0.001). On multivariate analysis, sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (p < 0.001).


In SCLC, sarcopenic male patients with high NLR have a poor prognosis and do not tolerate standard treatment. Intensive supportive care is needed in these patients.


Sarcopenia Cachexia Neutrophil-to-lymphocyte ratio Small cell lung carcinoma Toxicity Prognosis 



No funding was received for the present study.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board and with the 1964 Helsinki declaration and its later amendments.

Informed consent

This study is a retrospective analysis without any intervention and thus did not require informed consent.


  1. 1.
    Morley JE, Baumgartner RN, Roubenoff R, Mayer J, Nair KS (2001) Sarcopenia. J Lab Clin Med 137:231–243CrossRefPubMedGoogle Scholar
  2. 2.
    Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12:489–495CrossRefPubMedGoogle Scholar
  3. 3.
    Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, Garry PJ, Lindeman RD (1998) Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 147:755–763CrossRefPubMedGoogle Scholar
  4. 4.
    Collins J, Noble S, Chester J, Coles B, Byrne A (2014) The assessment and impact of sarcopenia in lung cancer: a systematic literature review. BMJ Open 4, e003697CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, Baracos VE (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9:629–635CrossRefPubMedGoogle Scholar
  6. 6.
    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 capecitabine treatment. Clin Cancer Res 15:2920–2926CrossRefPubMedGoogle Scholar
  7. 7.
    Jung HW, Kim JW, Kim JY, Kim SW, Yang HK, Lee JW, Lee KW, Kim DW, Kang SB, Kim KI, Kim CH, Kim JH (2015) Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy. Support Care Cancer 23:687–694CrossRefPubMedGoogle Scholar
  8. 8.
    Tan BH, Birdsell LA, Martin L, Baracos VE, Fearon KC (2009) Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res 15:6973–6979CrossRefPubMedGoogle Scholar
  9. 9.
    Martin L, Birdsell L, Macdonald N, Reiman 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
  10. 10.
    Stene GB, Helbostad JL, Amundsen T, Sorhaug S, Hjelde H, Kaasa S, Gronberg BH (2014) Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer. Acta Oncol 1–9Google Scholar
  11. 11.
    Alibhai SM, Greenwood C, Payette H (2005) An approach to the management of unintentional weight loss in elderly people. CMAJ 172:773–780CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Toth MJ, Matthews DE, Tracy RP, Previs MJ (2005) Age-related differences in skeletal muscle protein synthesis: relation to markers of immune activation. Am J Physiol Endocrinol Metab 288:E883–891CrossRefPubMedGoogle Scholar
  13. 13.
    Li YP, Schwartz RJ, Waddell ID, Holloway BR, Reid MB (1998) Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-kappaB activation in response to tumor necrosis factor alpha. FASEB J 12:871–880PubMedGoogle Scholar
  14. 14.
    Li YP, Reid MB (2000) NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated skeletal muscle myotubes. Am J Physiol Regul Integr Comp Physiol 279:R1165–1170PubMedGoogle Scholar
  15. 15.
    Baltgalvis KA, Berger FG, Pena MM, Davis JM, Muga SJ, Carson JA (2008) Interleukin-6 and cachexia in ApcMin/+ mice. Am J Physiol Regul Integr Comp Physiol 294:R393–401CrossRefPubMedGoogle Scholar
  16. 16.
    Meng SJ, Yu LJ (2010) Oxidative stress, molecular inflammation and sarcopenia. Int J Mol Sci 11:1509–1526CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Watanabe T, Shibata M, Nishiyama H, Soeda S, Furukawa S, Gonda K, Takenoshita S, Fujimori K (2014) Serum levels of rapid turnover proteins are decreased and related to systemic inflammation in patients with ovarian cancer. Oncol Lett 7:373–377PubMedGoogle Scholar
  18. 18.
    Malietzis G, Johns N, Al-Hassi HO, Knight SC, Kennedy RH, Fearon KC, Aziz O, Jenkins JT (2015) Low muscularity and myosteatosis is related to the host systemic inflammatory response in patients undergoing surgery for colorectal cancer. Ann Surg. doi: 10.1097/SLA.0000000000001113 Google Scholar
  19. 19.
    Kim SI, Kim HS, Kim TH, Suh DH, Kim K, No JH, Chung HH, Kim YB, Song YS (2014) Impact of underweight after treatment on prognosis of advanced-stage ovarian cancer. J Immunol Res 2014:349546CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kang MH, Go SI, Song HN, Lee A, Kim SH, Kang JH, Jeong BK, Kang KM, Ling H, Lee GW (2014) The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer 111:452–460CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N, Japan Clinical Oncology G (2002) Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346:85–91CrossRefPubMedGoogle Scholar
  22. 22.
    Paesmans M, Sculier JP, Lecomte J, Thiriaux J, Libert P, Sergysels R, Bureau G, Dabouis G, Van Cutsem O, Mommen P, Ninane V, Klastersky J (2000) Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years. Cancer 89:523–533CrossRefPubMedGoogle Scholar
  23. 23.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMedGoogle Scholar
  24. 24.
    Consultation WHOE (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363:157–163CrossRefGoogle Scholar
  25. 25.
    Yin Y, Wang J, Wang X, Gu L, Pei H, Kuai S, Zhang Y, Shang Z (2015) Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: a meta-analysis. Clinics (Sao Paulo) 70:524–530CrossRefGoogle Scholar
  26. 26.
    Peng B, Wang YH, Liu YM, Ma LX (2015) Prognostic significance of the neutrophil to lymphocyte ratio in patients with non-small cell lung cancer: a systemic review and meta-analysis. Int J Clin Exp Med 8:3098–3106PubMedPubMedCentralGoogle Scholar
  27. 27.
    Del Fabbro E, Parsons H, Warneke CL, Pulivarthi K, Litton JK, Dev R, Palla SL, Brewster A, Bruera E (2012) The relationship between body composition and response to neoadjuvant chemotherapy in women with operable breast cancer. Oncologist 17:1240–1245CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Mir O, Coriat R, Blanchet B, Durand JP, Boudou-Rouquette P, Michels J, Ropert S, Vidal M, Pol S, Chaussade S, Goldwasser F (2012) Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PLoS One 7, e37563CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Baracos V, Kazemi-Bajestani SM (2013) Clinical outcomes related to muscle mass in humans with cancer and catabolic illnesses. Int J Biochem Cell Biol 45:2302–2308CrossRefPubMedGoogle Scholar
  30. 30.
    Antoun S, Baracos VE, Birdsell L, Escudier B, Sawyer MB (2010) Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol 21:1594–1598CrossRefPubMedGoogle Scholar
  31. 31.
    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
  32. 32.
    Togashi Y, Kogita A, Sakamoto H, Hayashi H, Terashima M, de Velasco MA, Sakai K, Fujita Y, Tomida S, Kitano M, Okuno K, Kudo M, Nishio K (2015) Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer. Cancer Lett 356:819–827CrossRefPubMedGoogle Scholar
  33. 33.
    Acharyya S, Ladner KJ, Nelsen LL, Damrauer J, Reiser PJ, Swoap S, Guttridge DC (2004) Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest 114:370–378CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    McDonald ML, Diaz AA, Ross JC, San Jose Estepar R, Zhou L, Regan EA, Eckbo E, Muralidhar N, Come CE, Cho MH, Hersh CP, Lange C, Wouters E, Casaburi RH, Coxson HO, Macnee W, Rennard SI, Lomas DA, Agusti A, Celli BR, Black-Shinn JL, Kinney GL, Lutz SM, Hokanson JE, Silverman EK, Washko GR (2014) Quantitative computed tomography measures of pectoralis muscle area and disease severity in chronic obstructive pulmonary disease. A cross-sectional study. Ann Am Thorac Soc 11:326–334CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Miyamoto Y, Baba Y, Sakamoto Y, Ohuchi M, Tokunaga R, Kurashige J, Hiyoshi Y, Iwagami S, Yoshida N, Yoshida M, Watanabe M, Baba H (2015) Sarcopenia is a negative prognostic factor after curative resection of colorectal cancer. Ann Surg Oncol 22:2663–2668CrossRefPubMedGoogle Scholar
  36. 36.
    Dodson RM, Firoozmand A, Hyder O, Tacher V, Cosgrove DP, Bhagat N, Herman JM, Wolfgang CL, Geschwind JF, Kamel IR, Pawlik TM (2013) Impact of sarcopenia on outcomes following intra-arterial therapy of hepatic malignancies. J Gastrointest Surg 17:2123–2132CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Fukuoka M, Furuse K, Saijo N, Nishiwaki Y, Ikegami H, Tamura T, Shimoyama M, Suemasu K (1991) Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst 83:855–861CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Se-Il Go
    • 1
  • Mi Jung Park
    • 2
  • Haa-Na Song
    • 1
  • Myoung Hee Kang
    • 1
  • Hee Jung Park
    • 3
  • Kyung Nyeo Jeon
    • 2
  • Seok-Hyun Kim
    • 3
  • Moon Jin Kim
    • 4
  • Jung-Hun Kang
    • 5
  • Gyeong-Won Lee
    • 5
    Email author
  1. 1.Division of Hematology-Oncology, Department of Internal MedicineGyeongsang National University Hospital, Gyeongsang National University School of MedicineJinjuRepublic of Korea
  2. 2.Department of RadiologyGyeongsang National University Hospital, Gyeongsang National University School of MedicineJinjuRepublic of Korea
  3. 3.Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Changwon HospitalSungkyunkwan University School of MedicineChangwonRepublic of Korea
  4. 4.Myongji HospitalGoyangRepublic of Korea
  5. 5.Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang Institute of Health ScienceGyeongsang National University Hospital, Gyeongsang National University School of MedicineJinjuRepublic of Korea

Personalised recommendations