Skip to main content
Top
Published in: Supportive Care in Cancer 7/2019

01-07-2019 | Original Article

Early Skeletal Muscle Loss in Non-Small Cell Lung Cancer Patients Receiving Chemoradiation and Relationship to Survival

Authors: Nicole Kiss, Julian Beraldo, Sarah Everitt

Published in: Supportive Care in Cancer | Issue 7/2019

Login to get access

Abstract

Purpose

Sarcopenia is associated with reduced survival in cancer. Currently, data on sarcopenia at presentation and muscle loss throughout treatment are unknown in patients receiving chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). This study evaluated skeletal muscle changes in NSCLC patients receiving CRT and relationship with survival.

Methods

Secondary analysis of 41 patients with NSCLC treated with CRT assessed for skeletal muscle area and muscle density by computed tomography pre-treatment and 3 months post-treatment. Images at week 4 of treatment were available for 32 (78%) patients. Linear mixed models were applied to determine changes in skeletal muscle over time and related to overall survival using Kaplan-Meier plots.

Results

Muscle area and muscle density decreased significantly by week 4 of CRT (− 6.6 cm2, 95% CI − 9.7 to − 3.1, p < 0.001; − 1.3 HU, 95% CI − 1.9 to − 0.64, p < 0.001, respectively), with minimal change between week 4 of CRT and 3 months post-CRT follow-up (− 0.2 cm2, 95% CI − 3.6–3.1, p = 0.91; − 0.27, 95% CI − 0.91–0.36, p = 0.36, respectively). Sarcopenia was present in 25 (61%) and sarcopenic obesity in 6 (14%) of patients prior to CRT, but not associated with poorer survival. Median survival was shorter in patients with low muscle density prior to treatment although not statistically significant (25 months + 8.3 vs 53 months + 13.0, log-rank p = 0.17).

Conclusion

Significant loss of muscle area and muscle density occurs in NSCLC patients early during CRT. A high proportion of patients are sarcopenic prior to CRT; however, this was not significantly associated with poorer survival.
Literature
1.
go back to reference Prado CMM, 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(8):2920–2926CrossRef Prado CMM, 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(8):2920–2926CrossRef
2.
go back to reference Baracos V et al (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–1137SCrossRefPubMed Baracos V et al (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–1137SCrossRefPubMed
3.
go back to reference Awad S, Tan BH, Cui H, Bhalla A, Fearon KCH, Parsons SL, Catton JA, Lobo DN (2012) Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin Nutr 31(1):74–77CrossRef Awad S, Tan BH, Cui H, Bhalla A, Fearon KCH, Parsons SL, Catton JA, Lobo DN (2012) Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin Nutr 31(1):74–77CrossRef
4.
go back to reference Blauwhoff-Buskermolen S, Versteeg KS, de van der Schueren MAE, den Braver NR, Berkhof J, Langius JAE, Verheul HMW (2016) Loss of muscle mass during chemotherapy is predictive for poor survival of patients with metastatic colorectal cancer. J Clin Oncol 34(12):1339–1344CrossRef Blauwhoff-Buskermolen S, Versteeg KS, de van der Schueren MAE, den Braver NR, Berkhof J, Langius JAE, Verheul HMW (2016) Loss of muscle mass during chemotherapy is predictive for poor survival of patients with metastatic colorectal cancer. J Clin Oncol 34(12):1339–1344CrossRef
5.
go back to reference Tan BHL, Birdsell LA, Martin L, Baracos VE, Fearon KCH (2009) Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res 15(22):6973–6979CrossRef Tan BHL, Birdsell LA, Martin L, Baracos VE, Fearon KCH (2009) Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res 15(22):6973–6979CrossRef
6.
go back to reference 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(8):1594–1598CrossRef 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(8):1594–1598CrossRef
7.
go back to reference Antoun S, Lanoy E, Iacovelli R, Albiges-Sauvin L, Loriot Y, Merad-Taoufik M, Fizazi K, di Palma M, Baracos VE, Escudier B (2013) Skeletal muscle density predicts prognosis in patients with metastatic renal cell carcinoma treated with targeted therapies. Cancer 119(18):3377–3384CrossRefPubMed Antoun S, Lanoy E, Iacovelli R, Albiges-Sauvin L, Loriot Y, Merad-Taoufik M, Fizazi K, di Palma M, Baracos VE, Escudier B (2013) Skeletal muscle density predicts prognosis in patients with metastatic renal cell carcinoma treated with targeted therapies. Cancer 119(18):3377–3384CrossRefPubMed
8.
go back to reference 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(12):1539–1547CrossRef 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(12):1539–1547CrossRef
9.
go back to reference Prado CMM, 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(7):629–635CrossRef Prado CMM, 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(7):629–635CrossRef
10.
go back to reference Atlan P, Bayar MA, Lanoy E, Besse B, Planchard D, Ramon J, Raynard B, Antoun S (2017) Factors which modulate the rates of skeletal muscle mass loss in non-small cell lung cancer patients: a pilot study. Support Care Cancer 25(11):3365–3373CrossRef Atlan P, Bayar MA, Lanoy E, Besse B, Planchard D, Ramon J, Raynard B, Antoun S (2017) Factors which modulate the rates of skeletal muscle mass loss in non-small cell lung cancer patients: a pilot study. Support Care Cancer 25(11):3365–3373CrossRef
11.
go back to reference Australian Cancer Network, Clinical Practice Guidelines for the Prevention, Diagnosis and Management of Lung Cancer, T.C.C. Australia, Editor. 2004, National Health and Medical Research Council Australian Cancer Network, Clinical Practice Guidelines for the Prevention, Diagnosis and Management of Lung Cancer, T.C.C. Australia, Editor. 2004, National Health and Medical Research Council
12.
go back to reference Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, Cohen MH, Douglass HO Jr, Engstrom PF, Ezdinli EZ, Horton J, Johnson GJ, Moertel CG, Oken MM, Perlia C, Rosenbaum C, Silverstein MN, Skeel RT, Sponzo RW, Tormey DC (1980) Prognostic effect of weight loss prior tochemotherapy in cancer patients. Am J Med 69(4):491–497CrossRef Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, Cohen MH, Douglass HO Jr, Engstrom PF, Ezdinli EZ, Horton J, Johnson GJ, Moertel CG, Oken MM, Perlia C, Rosenbaum C, Silverstein MN, Skeel RT, Sponzo RW, Tormey DC (1980) Prognostic effect of weight loss prior tochemotherapy in cancer patients. Am J Med 69(4):491–497CrossRef
13.
go back to reference Kiss N, Isenring E, Gough K, Krishnasamy M (2014) The prevalence of weight loss during (chemo)radiotherapy treatment for lung cancer and associated patient- and treatment-related factors. Clin Nutr 33:1074–1080CrossRefPubMed Kiss N, Isenring E, Gough K, Krishnasamy M (2014) The prevalence of weight loss during (chemo)radiotherapy treatment for lung cancer and associated patient- and treatment-related factors. Clin Nutr 33:1074–1080CrossRefPubMed
14.
go back to reference van der Meij BS, Phernambucq ECJ, Fieten GM, Smit EF, Paul MA, van Leeuwen PAM, Oosterhuis JWA (2011) Nutrition during trimodality treatment in stage III non-small cell lung cancer: not only important for underweight patients. J Thorac Oncol 6(9):1563–1568CrossRefPubMed van der Meij BS, Phernambucq ECJ, Fieten GM, Smit EF, Paul MA, van Leeuwen PAM, Oosterhuis JWA (2011) Nutrition during trimodality treatment in stage III non-small cell lung cancer: not only important for underweight patients. J Thorac Oncol 6(9):1563–1568CrossRefPubMed
15.
go back to reference Sanders KJC, Hendriks LE, Troost EGC, Bootsma GP, Houben RMA, Schols AMWJ, Dingemans AMC (2016) Early weight loss during chemoradiotherapy has a detrimental impact on outcome in NSCLC. J Thorac Oncol 11(6):873–879CrossRef Sanders KJC, Hendriks LE, Troost EGC, Bootsma GP, Houben RMA, Schols AMWJ, Dingemans AMC (2016) Early weight loss during chemoradiotherapy has a detrimental impact on outcome in NSCLC. J Thorac Oncol 11(6):873–879CrossRef
16.
go back to reference Prado CMM, Heymsfield SB (2014) Lean tissue imaging: a new era for nutritional assessment and intervention. JPEN. J Parenter Enter Nutr 38(8):940–953CrossRef Prado CMM, Heymsfield SB (2014) Lean tissue imaging: a new era for nutritional assessment and intervention. JPEN. J Parenter Enter Nutr 38(8):940–953CrossRef
17.
go back to reference Everitt S, Ball D, Hicks RJ, Callahan J, Plumridge N, Trinh J, Herschtal A, Kron T, Mac Manus M (2017) Prospective study of serial imagin comparing flurodeoxyglucose position emission tomography (PET) and fluorothymidine PET during radical chemoradiation for non-small cell lung cancer: reducation of detectable proliferation associated with worse survival. Int J Radiat Oncol Biol Phys 99(4):947–955CrossRefPubMed Everitt S, Ball D, Hicks RJ, Callahan J, Plumridge N, Trinh J, Herschtal A, Kron T, Mac Manus M (2017) Prospective study of serial imagin comparing flurodeoxyglucose position emission tomography (PET) and fluorothymidine PET during radical chemoradiation for non-small cell lung cancer: reducation of detectable proliferation associated with worse survival. Int J Radiat Oncol Biol Phys 99(4):947–955CrossRefPubMed
18.
go back to reference Everitt S, Callahan J, Obeid E, Hicks RJ, Mac Manus M, Ball D (2017) Acute radiation oesophagitis associated with 2-deoxy-2-[18F]fluoro-d-glucose uptake on positron emission tomography/CT during chemo-radiation therapy in patients with non-small-cell lung cancer. J Med Imaging Radiat Oncol 61(5):682–688CrossRefPubMed Everitt S, Callahan J, Obeid E, Hicks RJ, Mac Manus M, Ball D (2017) Acute radiation oesophagitis associated with 2-deoxy-2-[18F]fluoro-d-glucose uptake on positron emission tomography/CT during chemo-radiation therapy in patients with non-small-cell lung cancer. J Med Imaging Radiat Oncol 61(5):682–688CrossRefPubMed
19.
go back to reference Mourtzakis M, Prado CMM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE (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(5):997–1006CrossRef Mourtzakis M, Prado CMM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE (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(5):997–1006CrossRef
20.
go back to reference Shen WWZ, Gallagher D, St Onge M, Albu J, Heymsfield S, Heshka S (2004) Total body skeletal muscle and adipose tissue volumes: estimation from a single cross-sectional image. J Appl Physiol 97:2333–2338CrossRef Shen WWZ, Gallagher D, St Onge M, Albu J, Heymsfield S, Heshka S (2004) Total body skeletal muscle and adipose tissue volumes: estimation from a single cross-sectional image. J Appl Physiol 97:2333–2338CrossRef
21.
go back to reference 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(5):489–495CrossRef 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(5):489–495CrossRef
22.
go back to reference Prado CM, Sawyer MB, Ghosh S, Lieffers JR, Esfandiari N, Antoun S, Baracos VE (2013) Central tenet of cancer cachexia therapy: do patients with advanced cancer have exploitable anabolic potential? Am J Clin Nutr 98(4):1012–1019CrossRef Prado CM, Sawyer MB, Ghosh S, Lieffers JR, Esfandiari N, Antoun S, Baracos VE (2013) Central tenet of cancer cachexia therapy: do patients with advanced cancer have exploitable anabolic potential? Am J Clin Nutr 98(4):1012–1019CrossRef
24.
go back to reference Ottery F (1996) Definition of standardized nutritional assessment and interventional pathways in oncology. Nutrition 12(1, Supplement):S15–S19CrossRefPubMed Ottery F (1996) Definition of standardized nutritional assessment and interventional pathways in oncology. Nutrition 12(1, Supplement):S15–S19CrossRefPubMed
25.
go back to reference Cederholm T, Bosaeus I, Barazzoni R, Bauer J, van Gossum A, Klek S, Muscaritoli M, Nyulasi I, Ockenga J, Schneider SM, de van der Schueren MAE, Singer P (2015) Diagnostic criteria for malnutrition – an ESPEN consensus statement. Clin Nutr 34(3):335–340CrossRefPubMed Cederholm T, Bosaeus I, Barazzoni R, Bauer J, van Gossum A, Klek S, Muscaritoli M, Nyulasi I, Ockenga J, Schneider SM, de van der Schueren MAE, Singer P (2015) Diagnostic criteria for malnutrition – an ESPEN consensus statement. Clin Nutr 34(3):335–340CrossRefPubMed
26.
go back to reference White JV, Guenter P, Jensen G, Malone A, Schofield M, Academy Malnutrition Work Group, A.S.P.E.N. Malnutrition Task Force, and the A.S.P.E.N. Board of Directors (2012) Consensus statement: academy of nutrition and dietetics and American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Parenter Enter Nutr 36(3):275–283CrossRef White JV, Guenter P, Jensen G, Malone A, Schofield M, Academy Malnutrition Work Group, A.S.P.E.N. Malnutrition Task Force, and the A.S.P.E.N. Board of Directors (2012) Consensus statement: academy of nutrition and dietetics and American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Parenter Enter Nutr 36(3):275–283CrossRef
27.
go back to reference Lam VK et al (2017) Obesity is associated with long-term improved survival in definitively treated locally advanced non-small cell lung cancer (NSCLC). Lung Cancer 104(Supplement C):52–57CrossRefPubMed Lam VK et al (2017) Obesity is associated with long-term improved survival in definitively treated locally advanced non-small cell lung cancer (NSCLC). Lung Cancer 104(Supplement C):52–57CrossRefPubMed
28.
go back to reference Isenring E, Zabel R, Bannister M, Brown T, Findlay M, Kiss N, Loeliger J, Johnstone C, Camilleri B, Davidson W, Hill J, Bauer J (2013) Updated evidence-based practice guidelines for the nutritional management of patients receiving radiation therapy and/or chemotherapy. Nutr Diet 70(4):312–324CrossRef Isenring E, Zabel R, Bannister M, Brown T, Findlay M, Kiss N, Loeliger J, Johnstone C, Camilleri B, Davidson W, Hill J, Bauer J (2013) Updated evidence-based practice guidelines for the nutritional management of patients receiving radiation therapy and/or chemotherapy. Nutr Diet 70(4):312–324CrossRef
29.
go back to reference Cormie P, Zopf EM, Zhang X, Schmitz KH (2017) The impact of exercise on cancer mortality, recurrence, and treatment-related adverse effects. Epidemiol Rev 39(1):71–92CrossRefPubMed Cormie P, Zopf EM, Zhang X, Schmitz KH (2017) The impact of exercise on cancer mortality, recurrence, and treatment-related adverse effects. Epidemiol Rev 39(1):71–92CrossRefPubMed
30.
go back to reference Gardner JR, Livingston PM, Fraser SF (2014) Effects of exercise on treatment-related adverse effects for patients with prostate cancer receiving androgen-deprivation therapy: a systematic review. J Clin Oncol Off J Am Soc Clin Oncol 32(4):335–346CrossRef Gardner JR, Livingston PM, Fraser SF (2014) Effects of exercise on treatment-related adverse effects for patients with prostate cancer receiving androgen-deprivation therapy: a systematic review. J Clin Oncol Off J Am Soc Clin Oncol 32(4):335–346CrossRef
31.
go back to reference Chasen M, Bhargave R (2010) A rehabilitation program for patients with gastrointestinal cancer - a pilot study. Support Care Cancer 18(Supplement 2):S35–S40CrossRefPubMed Chasen M, Bhargave R (2010) A rehabilitation program for patients with gastrointestinal cancer - a pilot study. Support Care Cancer 18(Supplement 2):S35–S40CrossRefPubMed
32.
go back to reference Gagnon B, Murphy J, Eades M, Lemoignan J, Jelowicki M, Carney S, Amdouni S, di Dio P, Chasen M, MacDonald N (2013) A prospective evaluation of an interdiscipinary nutrition-rehabilitation program for patients with advanced cancer. Curr Oncol 20(6):310–318CrossRefPubMedPubMedCentral Gagnon B, Murphy J, Eades M, Lemoignan J, Jelowicki M, Carney S, Amdouni S, di Dio P, Chasen M, MacDonald N (2013) A prospective evaluation of an interdiscipinary nutrition-rehabilitation program for patients with advanced cancer. Curr Oncol 20(6):310–318CrossRefPubMedPubMedCentral
33.
go back to reference Parmar M, Swanson T, Jagoe RT (2013) Weight changes correlate with alterations in subjective physical function in advanced cancer patients referred to a specialized nutrition and rehabilitation team. Support Care Cancer 21(7):2049–2057CrossRefPubMed Parmar M, Swanson T, Jagoe RT (2013) Weight changes correlate with alterations in subjective physical function in advanced cancer patients referred to a specialized nutrition and rehabilitation team. Support Care Cancer 21(7):2049–2057CrossRefPubMed
Metadata
Title
Early Skeletal Muscle Loss in Non-Small Cell Lung Cancer Patients Receiving Chemoradiation and Relationship to Survival
Authors
Nicole Kiss
Julian Beraldo
Sarah Everitt
Publication date
01-07-2019
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 7/2019
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-018-4563-9

Other articles of this Issue 7/2019

Supportive Care in Cancer 7/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine