Loss of skeletal muscle during neoadjuvant chemotherapy is related to decreased survival in ovarian cancer patients

Iris J G Rutten, David P J van Dijk, Roy F P M Kruitwagen, Regina G H Beets-Tan, Steven W M Olde Damink, Toon van Gorp, Iris J G Rutten, David P J van Dijk, Roy F P M Kruitwagen, Regina G H Beets-Tan, Steven W M Olde Damink, Toon van Gorp

Abstract

Background: Malnutrition, weight loss, and muscle wasting (sarcopenia) are common among women with advanced ovarian cancer and have been associated with adverse clinical outcomes and survival. Our objective is to investigate overall survival (OS) related to changes in skeletal muscle (SM) for patients with advanced ovarian cancer treated with neoadjuvant chemotherapy and interval debulking.

Methods: Ovarian cancer patients (n = 123) treated with neoadjuvant chemotherapy and interval debulking in the area of Maastricht (the Netherlands) between 2000 and 2014 were included retrospectively. Surface areas of SM and adipose tissue were defined on computed tomography at the level of the third lumbar vertebra. Low SM at baseline and SM changes during chemotherapy were compared with Kaplan Meier curves, and Cox-regression models were applied to test predictors of OS.

Results: Median OS for patients who lost SM (n = 83) was 916 ± 99 days, which was significantly different from median OS for patients who maintained or gained SM (n = 40), which was 1431 ± 470 days (P = 0.004). Loss of SM was also a significant predictor of OS in multivariable Cox-regression analysis (hazard ratio 1.773 (95%CI: 1.018-3.088), P = 0.043). Low baseline SM did not influence survival.

Conclusions: Patients with ovarian cancer have a worse survival when they lose SM during neoadjuvant chemotherapy. Evaluation of low SM at a specific time point is not prognostic for OS. External and prospective validation of these findings is imperative. Nutritional, pharmacological, and/or physical intervention studies are necessary to establish whether SM impairment can be prevented to prolong ovarian cancer survival.

Keywords: Body composition; Computed tomography; Induction chemotherapy; Ovarian neoplasms; Sarcopenia; Survival.

Figures

Figure 1
Figure 1
Body composition analysis with SliceOmatic®.
Figure 2
Figure 2
Flow diagram.
Figure 3
Figure 3
Survival proportions: baseline skeletal muscle index.
Figure 4
Figure 4
Survival proportions: changes in skeletal muscle.

References

    1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11, 2013.
    1. Surveillance, Epidemiology, and End Results (SEER) Program SEER 9 Incidence & U.S. Mortality Research Data (1973–2011). In: National Cancer Institute D, Surveillance Research Program, Surveillance Systems Branch, released April 2014, based on the November 2013 submission, editor.
    1. De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, et al Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE‐‐5‐a population‐based study. Lancet Oncol 2014;15:23–34.
    1. du Bois A, Reuss A, Pujade‐Lauraine E, Harter P, Ray‐Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO‐OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer 2009;115:1234–1244.
    1. Vergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010;363:943–953.
    1. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer 2002;2:862–871.
    1. Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. 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 2008;33:997–1006.
    1. Ross R. Advances in the application of imaging methods in applied and clinical physiology. Acta Diabetol 2003;40 Suppl 1:S45–S50.
    1. Shen W, Punyanitya M, Wang Z, Gallagher D, St‐Onge MP, Albu J, et al Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross‐sectional image. J Appl Physiol 2004;97:2333–2338.
    1. Shen W, Punyanitya M, Wang Z, Gallagher D, St‐Onge MP, Albu J, et al Visceral adipose tissue: relations between single‐slice areas and total volume. Am J Clin Nutr 2004;80:271–278.
    1. Fujiwara N, Nakagawa H, Kudo Y, Tateishi R, Taguri M, Watadani T, et al Sarcopenia, intramuscular Fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma. J Hepatol 2015;doi:.
    1. Lanic H, Kraut‐Tauzia J, Modzelewski R, Clatot F, Mareschal S, Picquenot JM, et al Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B‐cell lymphoma treated with immunochemotherapy. Leuk Lymphoma 2014;55:817–823.
    1. Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, 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;31:1539–1547.
    1. Psutka SP, Carrasco A, Schmit GD, Moynagh MR, Boorjian SA, Frank I, et al Sarcopenia in patients with bladder cancer undergoing radical cystectomy: impact on cancer‐specific and all‐cause mortality. Cancer 2014;120:2910–2918.
    1. Guiu B, Petit JM, Bonnetain F, Ladoire S, Guiu S, Cercueil JP, et al Visceral fat area is an independent predictive biomarker of outcome after first‐line bevacizumab‐based treatment in metastatic colorectal cancer. Gut 2010;59:341–347.
    1. Ladoire S, Bonnetain F, Gauthier M, Zanetta S, Petit JM, Guiu S, et al Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents. Oncologist 2011;16:71–81.
    1. Torres ML, Hartmann LC, Cliby WA, Kalli KR, Young PM, Weaver AL, et al Nutritional status, CT body composition measures and survival in ovarian cancer. Gynecol Oncol 2013;129:548–553.
    1. Awad S, Tan BH, Cui H, Bhalla A, Fearon KC, Parsons SL, et al Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin Nutr 2012;31:74–77.
    1. Yip C, Goh V, Davies A, Gossage J, Mitchell‐Hay R, Hynes O, et al Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer. Eur Radiol 2014;24:998–1005.
    1. Dalal S, Hui D, Bidaut L, Lem K, Del Fabbro E, Crane C, et al Relationships among body mass index, longitudinal body composition alterations, and survival in patients with locally advanced pancreatic cancer receiving chemoradiation: a pilot study. J Pain Symptom Manage 2012;44:181–191.
    1. Stene GB, Helbostad JL, Amundsen T, Sorhaug S, Hjelde H, Kaasa S, et al Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer. Acta Oncol 2015;54:340–348.
    1. World Health Organization . Obesity: Preventing and Managing the Global EpidemicReport of a WHO Consultation (WHO Technical Report Series 894), Geneva, Switzerland: World Health Organization; 2000.
    1. Fearon K, Arends J, Baracos V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol 2013;10:90–99.
    1. Kortebein P, Ferrando A, Lombeida J, Wolfe R, Evans WJ. Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA 2007;297:1772–1774.
    1. Schiesser M, Kirchhoff P, Muller MK, Schafer M, Clavien PA. The correlation of nutrition risk index, nutrition risk score, and bioimpedance analysis with postoperative complications in patients undergoing gastrointestinal surgery. Surgery 2009;145:519–526.
    1. Alphs HH, Zahurak ML, Bristow RE, Diaz‐Montes TP. Predictors of surgical outcome and survival among elderly women diagnosed with ovarian and primary peritoneal cancer. Gynecol Oncol 2006;103:1048–1053.
    1. Baracos V, Kazemi‐Bajestani SM. Clinical outcomes related to muscle mass in humans with cancer and catabolic illnesses. Int J Biochem Cell Biol 2013;45:2302–2308.
    1. Prado CM, Lieffers JR, Bowthorpe L, Baracos VE, Mourtzakis M, McCargar LJ. Sarcopenia and physical function in overweight patients with advanced cancer. Can J Diet Pract Res 2013;74:69–74.
    1. Prado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, et al Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res 2009;15:2920–2926.
    1. Kuroki LM, Mangano M, Allsworth JE, Menias CO, Massad LS, Powell MA, et al Pre‐operative assessment of muscle mass to predict surgical complications and prognosis in patients with endometrial cancer. Ann Surg Oncol 2015;22:972–979.
    1. Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, 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;9:629–635.
    1. Cooper AB, Slack R, Fogelman D, Holmes HM, Petzel M, Parker N, et al Characterization of anthropometric changes that occur during neoadjuvant therapy for potentially resectable pancreatic cancer. Ann Surg Oncol 2014;doi:.
    1. Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer 2011;117:1775–1782.
    1. Jacquelin‐Ravel N, Pichard C. Clinical nutrition, body composition and oncology: a critical literature review of the synergies. Crit Rev Oncol Hematol 2012;84:37–46.
    1. Balogun N, Forbes A, Widschwendter M, Lanceley A. Noninvasive nutritional management of ovarian cancer patients: beyond intestinal obstruction. Int J Gynecol Cancer 2012;22:1089–1095.
    1. von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2015. J Cachexia Sarcopenia Muscle 2015;6:315–316.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다