Sarkopenie als unabhängiger Prognosefaktor bei Pankreaskarzinom

Zusammenfassung

Einleitung Die Diagnose Pankreaskarzinom zählt trotz modernster Diagnose- und Therapieoptionen zu den häufigsten krebsbedingten globalen Todesursachen. Häufig liegt bei diesen Patienten eine Kachexie und Sarkopenie vor.

Methode In einer retrospektiven Analyse wurde die jeweilige Querschnittsfläche der Skelettmuskulatur auf Höhe des Lendenwirbelkörpers L 3 im axialen CT-Schnittbild von 121 Patienten bestimmt, um so den Skelettmuskelindex (SMI [cm²/m²]) zu erhalten. Es erfolgte außerdem eine Erfassung weiterer Parameter zur zusätzlichen Evaluation deren Assoziation mit der Überlebenswahrscheinlichkeit.

Ergebnisse Die durchschnittliche Überlebenszeit der Gruppe der sarkopenen Patienten war mit 14,4 Monaten im Vergleich zu 17,7 Monaten mittlerer Überlebenszeit bei Patienten ohne Sarkopenie signifikant vermindert (p=0,046). Zusätzlich konnten das Alter (p = 0,006), eine nicht erfolgte Resektion des Tumors (p=0,004), Metastasen bei Erstdiagnose (p=0,002) sowie ein erhöhtes CA 19–9 (p=0,002) als statistisch signifikante negative Prognosefaktoren identifiziert werden.

Schlussfolgerung Sarkopenie ist ein unabhängiger prognostischer Faktor in Bezug auf die Überlebenszeit bei Pankreaskarzinompatienten. Dies legt die standardmäßige Integration des SMI als Prognoseparameter in den klinischen Alltag nahe, um durch entsprechende präventive und therapeutische ernährungs- und bewegungsmedizinische Maßnahmen möglicherweise die Lebensdauer sowie die Lebensqualität von Pankreaskarzinompatienten merklich verbessern zu können.

Abstract

Background Pancreatic cancer is despite modern diagnostic tools and treatment regimen associated with poor outcome. Many patients show cachexia and sarcopenia.

Methods In a retrospective analysis the SMI (cm²/m²) was measured by determining the skelettal muscle area in a computed tomography image at lumbar vertebrae 3. Further clinical parameters were measured to determine the outcome.

Results The mean survival after diagnosis in the population with sarcopenia was significantly lower (14,4 vs 17,7 months, p=0,046). Significantly shorter survival was also seen for higher age (p=0,006), no tumor resection (p=0,004), metastases (p=0,002) and high CA19–9 level (p=0,002)

Conclusion Sarcopenia is an indipendant prognostic factor in patients with pancreatic cancer. SMI should be measured clinical practice and further studies are necessary to asses a potential therapeutic strategy.

Schlüsselwörter

Sarkopenie - Pankreaskarzinom - Kachexie

Keywords

sarcopenia - pancreatic cancer - cancer cachexia

Publication History

Received: 05 May 2022

Accepted: 06 October 2022

Article published online:
08 December 2022

• Literatur

• 1 Basile D, Parnofiello A, Vitale MG. et al. The IMPACT study: early loss of skeletal muscle mass in advanced pancreatic cancer patients. J Cachexia Sarcopenia Muscle 2019; 10: 368-377 DOI: 10.1002/JCSM.12368. (PMID: 30719874)
• 2 Jansen L, Castro FA, Gondos A. et al. Recent cancer survival in Germany: an analysis of common and less common cancers. Int J cancer 2015; 136: 2649-2658 DOI: 10.1002/IJC.29316. (PMID: 25380088)
• 3 Argilés JM, Busquets S, Stemmler B. et al. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer 2014; 14: 754-762 DOI: 10.1038/NRC3829. (PMID: 25291291)
• 4 Bachmann J, Heiligensetzer M, Krakowski-Roosen H. et al. Cachexia worsens prognosis in patients with resectable pancreatic cancer. J Gastrointest Surg 2008; 12: 1193-1201 DOI: 10.1007/S11605-008-0505-Z. (PMID: 18347879)
• 5 Poulia KA, Sarantis P, Antoniadou D. et al. Pancreatic Cancer and Cachexia-Metabolic Mechanisms and Novel Insights. Nutrients 2020; 12 DOI: 10.3390/NU12061543. (PMID: 32466362)
• 6 Reynolds J V, Donohoe CL, Ryan AM. Cancer cachexia: mechanisms and clinical implications. Gastroenterol Res Pract 2011; 2011 DOI: 10.1155/2011/601434. (PMID: 21760776)
• 7 Fearon K, Strasser F, Anker SD. et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12: 489-495 DOI: 10.1016/S1470-2045(10)70218-7. (PMID: 21296615)
• 8 Schmidt SF, Rohm M, Herzig S. et al. Cancer Cachexia: More Than Skeletal Muscle Wasting. Trends in cancer 2018; 4: 849-860 DOI: 10.1016/J.TRECAN.2018.10.001. (PMID: 30470306)
• 9 Park I, Choi SJ, Kim YS. et al. Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy. Cancer Res Treat 2016; 48: 1264-1273 DOI: 10.4143/CRT.2015.250. (PMID: 27034148)
• 10 Bian X, Dai H, Feng J. et al. Prognostic values of abdominal body compositions on survival in advanced pancreatic cancer. Medicine (Baltimore) 2018; 97 DOI: 10.1097/MD.0000000000010988. (PMID: 29851855)
• 11 Bauer J, Morley JE, Schols AMWJ. et al. Sarcopenia: A Time for Action. An SCWD Position Paper. J Cachexia Sarcopenia Muscle 2019; 10: 956-961 DOI: 10.1002/JCSM.12483.
• 12 Cruz-Jentoft AJ, Bahat G, Bauer J. et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019; 48: 16-31 DOI: 10.1093/AGEING/AFY169. (PMID: 30312372)
• 13 Mourtzakis M, Prado CMM, Lieffers JR. et al. 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 DOI: 10.1139/H08-075. (PMID: 18923576)
• 14 Zhang G, Li X, Sui C. et al. Incidence and risk factor analysis for sarcopenia in patients with cancer. Oncol Lett 2016; 11: 1230-1234 DOI: 10.3892/OL.2015.4019. (PMID: 26893724)
• 15 Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev 2009; 89: 381-410 DOI: 10.1152/PHYSREV.00016.2008. (PMID: 19342610)
• 16 Skipworth RJE, Stewart GD, Dejong CHC. et al. Pathophysiology of cancer cachexia: much more than host-tumour interaction?. Clin Nutr 2007; 26: 667-676 DOI: 10.1016/J.CLNU.2007.03.011.
• 17 Biolo G, Cederholm T, Muscaritoli M. Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: from sarcopenic obesity to cachexia. Clin Nutr 2014; 33: 737-748 DOI: 10.1016/J.CLNU.2014.03.007. (PMID: 24785098)
• 18 Ferrando AA, Stuart CA, Sheffield-moore M. et al. Inactivity amplifies the catabolic response of skeletal muscle to cortisol. J Clin Endocrinol Metab 1999; 84: 3515-3521 DOI: 10.1210/JCEM.84.10.6046. (PMID: 10522988)
• 19 Choi MH, Yoon SB, Lee K. et al. Preoperative sarcopenia and post-operative accelerated muscle loss negatively impact survival after resection of pancreatic cancer. J Cachexia Sarcopenia Muscle 2018; 9: 326-334 DOI: 10.1002/JCSM.12274. (PMID: 29399990)
• 20 Cosquéric G, Sebag A, Ducolombier C. et al. Sarcopenia is predictive of nosocomial infection in care of the elderly. 2020; DOI: 10.1017/BJN20061943.
• 21 Prado CMM, Baracos VE, McCargar LJ. 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 DOI: 10.1158/1078-0432.CCR-08-2242. (PMID: 19351764)
• 22 Huillard O, Mir O, Peyromaure M. et al. Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients. Br J Cancer 2013; 108: 1034-1041 DOI: 10.1038/BJC.2013.58. (PMID: 23462722)
• 23 Prado CM, Lieffers JR, McCargar LJ. 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 DOI: 10.1016/S1470-2045(08)70153-0. (PMID: 18539529)
• 24 Martin L, Birdsell L, MacDonald N. 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 DOI: 10.1200/JCO.2012.45.2722. (PMID: 23530101)
• 25 Naumann P, Eberlein J, Farnia B. et al. Continued Weight Loss and Sarcopenia Predict Poor Outcomes in Locally Advanced Pancreatic Cancer Treated with Chemoradiation. Cancers (Basel) 2019; 11: 709 DOI: 10.3390/CANCERS11050709. (PMID: 31126040)
• 26 Okumura S, Kaido T, Hamaguchi Y. et al. Visceral Adiposity and Sarcopenic Visceral Obesity are Associated with Poor Prognosis After Resection of Pancreatic Cancer. Ann Surg Oncol 2017; 24: 3732-3740 DOI: 10.1245/S10434-017-6077-Y. (PMID: 28871520)
• 27 Di Sebastiano KM, Yang L, Zbuk K. et al. Accelerated muscle and adipose tissue loss may predict survival in pancreatic cancer patients: the relationship with diabetes and anaemia. Br J Nutr 2013; 109: 302-312 DOI: 10.1017/S0007114512001067.
• 28 Ninomiya G, Fujii T, Yamada S. et al. Clinical impact of sarcopenia on prognosis in pancreatic ductal adenocarcinoma: A retrospective cohort study. Int J Surg 2017; 39: 45-51 DOI: 10.1016/J.IJSU.2017.01.075. (PMID: 28110029)
• 29 Langius JA, Zandbergen MC, Eerenstein SEJ. et al. Effect of nutritional interventions on nutritional status, quality of life and mortality in patients with head and neck cancer receiving (chemo)radiotherapy: a systematic review. Clin Nutr 2013; 32 DOI: 10.1016/J.CLNU.2013.06.012.
• 30 Roberts KJ, Bannister CA, Schrem H. Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study. Pancreatology 2019; 19: 114-121 DOI: 10.1016/J.PAN.2018.10.010. (PMID: 30385188)
• 31 Ceglia L. Vitamin D and its role in skeletal muscle. Curr Opin Clin Nutr Metab Care 2009; 12: 628-633 DOI: 10.1097/MCO.0B013E328331C707. (PMID: 24508736)
• 32 Paddon-Jones D, Sheffield-Moore M, Zhang XJ. et al. Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol Endocrinol Metab 2004; 286 DOI: 10.1152/AJPENDO.00368.2003. (PMID: 14583440)
• 33 Solheim TS, Fearon KCH, Blum D. et al. Non-steroidal anti-inflammatory treatment in cancer cachexia: a systematic literature review. Acta Oncol 2013; 52: 6-17 DOI: 10.3109/0284186X.2012.724536. (PMID: 23020528)
• 34 Solheim TS, Laird BJA, Balstad TR. et al. A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer. J Cachexia Sarcopenia Muscle 2017; 8: 778-788 DOI: 10.1002/JCSM.12201. (PMID: 28614627)
• 35 Arends J, Bachmann P, Baracos V. et al. ESPEN guidelines on nutrition in cancer patients. Clin Nutr 2017; 36: 11-48 DOI: 10.1016/J.CLNU.2016.07.015. (PMID: 27637832)
• 36 Xing H, Wang J, Wang Y. et al. Diagnostic Value of CA 19–9 and Carcinoembryonic Antigen for Pancreatic Cancer: A Meta-Analysis. Gastroenterol Res Pract 2018; 2018 DOI: 10.1155/2018/8704751. (PMID: 30584422)
• 37 Scarà S, Bottoni P, Scatena R. CA 19–9: Biochemical and Clinical Aspects. Adv Exp Med Biol 2015; 867: 247-260 DOI: 10.1007/978-94-017-7215-0_15. (PMID: 26530370)
• 38 Maréchal R, Demols A, Gay F. et al. Prognostic factors and prognostic index for chemonaïve and gemcitabine-refractory patients with advanced pancreatic cancer. Oncology 2007; 73: 41-51 DOI: 10.1159/000120627. (PMID: 18334830)
• 39 Lee KJ, Yi SW, Chung MJ. et al. Serum CA 19–9 and CEA levels as a prognostic factor in pancreatic adenocarcinoma. Yonsei Med J 2013; 54: 643-649 DOI: 10.3349/YMJ.2013.54.3.643. (PMID: 23549809)
• 40 Inal A, Ciltas A, Yildiz R. et al. Long term survivors with metastatic pancreatic cancer treated with gemcitabine alone or plus cisplatin: a retrospective analysis of an Anatolian Society of Medical Oncology multicenter study. Asian Pac J Cancer Prev 2012; 13: 1841-1844 DOI: 10.7314/APJCP.2012.13.5.1841. (PMID: 22901133)
• 41 Nishigori T, Tsunoda S, Okabe H. et al. Impact of Sarcopenic Obesity on Surgical Site Infection after Laparoscopic Total Gastrectomy. Ann Surg Oncol 2016; 23: 524-531 DOI: 10.1245/S10434-016-5385-Y. (PMID: 27380646)
• 42 Tan BHL, Birdsell LA, Martin L. et al. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res 2009; 15: 6973-6979 DOI: 10.1158/1078-0432.CCR-09-1525. (PMID: 19887488)
• 43 Choi Y, Oh DY, Kim TY. et al. Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index. 2015; DOI: 10.1371/journal.pone.0139749.