Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy

Nishikawa,Hiroki; Nishijima,Norihiro; Enomoto,Hirayuki; Sakamoto,Azusa; Nasu,Akihiro; Komekado,Hideyuki; Nishimura,Takashi; Kita,Ryuichi; Kimura,Toru; Iijima,Hiroko; Nishiguchi,Shuhei; Osaki,Yukio

doi:10.3892/ol.2017.6287

Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy

Authors:
- Hiroki Nishikawa
- Norihiro Nishijima
- Hirayuki Enomoto
- Azusa Sakamoto
- Akihiro Nasu
- Hideyuki Komekado
- Takashi Nishimura
- Ryuichi Kita
- Toru Kimura
- Hiroko Iijima
- Shuhei Nishiguchi
- Yukio Osaki
View Affiliations

Affiliations: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663‑8501, Japan, Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka 543‑8555, Japan
Published online on: May 31, 2017 https://doi.org/10.3892/ol.2017.6287
Pages: 1637-1647

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to examine the impact of sarcopenia, defined as low muscle mass on computed tomography (CT), prior to sorafenib therapy on the clinical outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib therapy. In total, 232 patients with unresectable HCC (median age, 72 years) were analyzed, and the extent of sarcopenia was assessed using CT. Cross‑sectional areas (cm2) of the skeletal muscles at the third lumbar vertebra level were determined by manual outlining on the CT images. The cross‑sectional areas were normalized for height [skeletal muscle index (SMI), cm2/m2]. Based on the findings of previous studies, male patients with SMI ≤36.2 cm2/m2 and female patients with SMI ≤29.6 cm2/m2 were defined as having sarcopenia. The baseline characteristics, overall survival (OS) rates, progression‑free survival (PFS) rates and best treatment response of the sarcopenia group were retrospectively compared with those of the non‑sarcopenia group, and the factors associated with OS and PFS were examined. Sarcopenia was observed in 151 patients (65.1%). There were 165 patients with Child‑Pugh A and 67 with Child‑Pugh B cirrhosis. In the sarcopenia group, the median treatment duration was 66 days, whereas in the non‑sarcopenia group it was 103 days (P=0.001). The median OS time was 174 days in the sarcopenia group and 454 days in the non‑sarcopenia group (P<0.0001). The median PFS was 77 days in the sarcopenia group and 106 days in the non‑sarcopenia group (P=0.0131). Multivariate analysis identified sarcopenia to be an independent predictor of OS (hazard ratio, 0.365; P<0.0001). The objective response rate and disease control rate in the sarcopenia group were significantly lower, compared with those in the non‑sarcopenia group (P=0.0146 and P=0.0151, respectively). In conclusion, sarcopenia may be an indicator of poor clinical course in patients with HCC receiving sorafenib.

View Figures

View References

1	El-Serag HB: Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 142:1264–1273.e1. 2012. View Article : Google Scholar : PubMed/NCBI
2	El-Serag HB: Hepatocellular carcinoma. N Engl J Med. 365:1118–1127. 2011. View Article : Google Scholar : PubMed/NCBI
3	McGlynn KA, Petrick JL and London WT: Global epidemiology of hepatocellular carcinoma: An emphasis on demographic and regional variability. Clin Liver Dis. 19:223–238. 2015. View Article : Google Scholar : PubMed/NCBI
4	Singal AG and El-Serag HB: Hepatocellular carcinoma from epidemiology to prevention: Translating knowledge into practice. Clin Gastroenterol Hepatol. 13:2140–2151. 2015. View Article : Google Scholar : PubMed/NCBI
5	Osaki Y and Nishikawa H: Treatment for hepatocellular carcinoma in Japan over the last three decades: Our experience and literature review. Hepatol Res. 45:59–74. 2015. View Article : Google Scholar : PubMed/NCBI
6	Rahbari NN, Mehrabi A, Mollberg NM, Müller SA, Koch M, Büchler MW and Weitz J: Hepatocellular carcinoma: Current management and perspectives for the future. Ann Surg. 253:453–469. 2011. View Article : Google Scholar : PubMed/NCBI
7	Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI
8	Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10:25–34. 2009. View Article : Google Scholar : PubMed/NCBI
9	Di Marco V, De Vita F, Koskinas J, Semela D, Toniutto P and Verslype C: Sorafenib: From literature to clinical practice. Ann Oncol. 24 Suppl 2:ii30–ii37. 2013. View Article : Google Scholar : PubMed/NCBI
10	Sangiovanni A and Colombo M: Treatment of hepatocellular carcinoma: Beyond international guidelines. Liver Int. 36 Suppl 1:S124–S129. 2016. View Article : Google Scholar
11	Arizumi T, Ueshima K, Minami T, Kono M, Chishina H, Takita M, Kitai S, Inoue T, Yada N, Hagiwara S, et al: Effectiveness of sorafenib in patients with transcatheter arterial chemoembolization (TACE) refractory and intermediate-stage hepatocellular carcinoma. Liver Cancer. 4:253–226. 2015. View Article : Google Scholar : PubMed/NCBI
12	Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, Galle PR, Santoro A, Beaugrand M, Sangiovanni A, et al: Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial. J Hepatol. 57:821–829. 2012. View Article : Google Scholar : PubMed/NCBI
13	Llovet JM, Peña CE, Lathia CD, Shan M, Meinhardt G and Bruix J: SHARP Investigators Study Group. Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma. Clin Cancer Res. 18:2290–2300. 2012. View Article : Google Scholar : PubMed/NCBI
14	Ogasawara S, Chiba T, Ooka Y, Suzuki E, Kanogawa N, Saito T, Motoyama T, Tawada A, Kanai F and Yokosuka O: Liver function assessment according to the Albumin-Bilirubin (ALBI) grade in sorafenib-treated patients with advanced hepatocellular carcinoma. Invest New Drugs. 33:1257–1262. 2015. View Article : Google Scholar : PubMed/NCBI
15	Choi GH, Shim JH, Kim MJ, Ryu MH, Ryoo BY, Kang YK, Shin YM, Kim KM, Lim YS and Lee HC: Sorafenib alone versus sorafenib combined with transarterial chemoembolization for advanced-stage hepatocellular carcinoma: Results of propensity score analyses. Radiology. 269:603–611. 2013. View Article : Google Scholar : PubMed/NCBI
16	Kudo M, Matsui O, Izumi N, Kadoya M, Okusaka T, Miyayama S, Yamakado K, Tsuchiya K, Ueshima K, Hiraoka A, et al: Transarterial chemoembolization failure/refractoriness: JSH-LCSGJ criteria 2014 update. Oncology. 87 Suppl 1:S22–S31. 2014. View Article : Google Scholar
17	Printz C: Clinical trials of note. Sorafenib as adjuvant treatment in the prevention of disease recurrence in patients with hepatocellular carcinoma (HCC) (STORM). Cancer. 115:46462009. View Article : Google Scholar : PubMed/NCBI
18	Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L and Baracos VE: Prevalence and clinical implications of sarcopenic obesity in patients with solid tumors of the respiratory and gastrointestinal tracts: A population based study. Lancet Oncol. 9:629–635. 2008. View Article : Google Scholar : PubMed/NCBI
19	Rosenberg IH: Sarcopenia: Origins and clinical relevance. J Nutr. 127:990S–991S. 1997.PubMed/NCBI
20	Wang C and Bai L: Sarcopenia in the elderly: Basic and clinical issues. Geriatr Gerontol Int. 12:388–396. 2012. View Article : Google Scholar : PubMed/NCBI
21	Dasarathy S: Consilience in sarcopenia of cirrhosis. J Cachexia Sarcopenia Muscle. 3:225–237. 2012. View Article : Google Scholar : PubMed/NCBI
22	Periyalwar P and Dasarathy S: Malnutrition in cirrhosis: Contribution and consequences of sarcopenia on metabolic and clinical responses. Clin Liver Dis. 16:95–131. 2012. View Article : Google Scholar : PubMed/NCBI
23	Nishikawa H, Yoh K, Enomoto H, Iwata Y, Kishino K, Shimono Y, Hasegawa K, Nakano C, Takata R, Nishimura T, et al: Factors associated with protein-energy malnutrition in chronic liver disease: Analysis using indirect calorimetry. Medicine (Baltimore). 95:e24422016. View Article : Google Scholar : PubMed/NCBI
24	Fukushima H, Nakanishi Y, Kataoka M, Tobisu K and Koga F: Prognostic significance of sarcopenia in patients with metastatic renal cell carcinoma. J Urol. 195:26–32. 2016. View Article : Google Scholar : PubMed/NCBI
25	Levolger S, van Vugt JL, de Bruin RW and Ijzermans JN: Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies. Br J Surg. 102:1448–1458. 2015. View Article : Google Scholar : PubMed/NCBI
26	Kobayashi A, Kaido T, Hamaguchi Y, Okumura S, Taura K, Hatano E, Okajima H and Uemoto S: Impact of postoperative changes in sarcopenic factors on outcomes after hepatectomy for hepatocellular carcinoma. J Hepatobiliary Pancreat Sci. 23:57–64. 2016. View Article : Google Scholar : PubMed/NCBI
27	Harimoto N, Shirabe K, Yamashita YI, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y, Nishie A and Yamanaka T: Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma. Br J Surg. 100:1523–1530. 2013. View Article : Google Scholar : PubMed/NCBI
28	Takeda H, Nishikawa H, Osaki Y, Tsuchiya K, Joko K, Ogawa C, Taniguchi H, Orito E, Uchida Y and Izumi N; Japanese Red Cross Liver Study Group, : Clinical features associated with radiological response to sorafenib in unresectable hepatocellular carcinoma: A large multicenter study in Japan. Liver Int. 35:1581–1589. 2015. View Article : Google Scholar : PubMed/NCBI
29	Nishikawa H, Takeda H, Tsuchiya K, Joko K, Ogawa C, Taniguchi H, Orito E, Uchida Y, Osaki Y and Izumi N; Japanese Red Cross Liver Study Group, : Sorafenib therapy for BCLC stage B/C hepatocellular carcinoma; clinical outcome and safety in aged patients: A multicenter study in Japan. J. Cancer. 5:499–509. 2014. View Article : Google Scholar
30	Cheng AL, Amarapurkar D, Chao Y, Chen PJ, Geschwind JF, Goh KL, Han KH, Kudo M, Lee HC, Lee RC, et al: Re-evaluating transarterial chemoembolization for the treatment of hepatocellular carcinoma: Consensus recommendations and review by an International Expert Panel. Liver Int. 34:174–183. 2014. View Article : Google Scholar : PubMed/NCBI
31	Fujiwara N, Nakagawa H, Kudo Y, Tateishi R, Taguri M, Watadani T, Nakagomi R, Kondo M, Nakatsuka T, Minami T, et al: Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma. J Hepatol. 63:131–140. 2015. View Article : Google Scholar : PubMed/NCBI
32	Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, Langer C, Murphy B, Cumberlin R, Coleman CN and Rubin P: CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 13:176–181. 2003. View Article : Google Scholar : PubMed/NCBI
33	European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer, . EASL-EORTC Clinical Practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 56:908–943. 2012. View Article : Google Scholar : PubMed/NCBI
34	Lencioni R and Llovet JM: Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 30:52–60. 2010. View Article : Google Scholar : PubMed/NCBI
35	Salvaggio G, Furlan A, Agnello F, Cabibbo G, Marin D, Giannitrapani L, Genco C, Midiri M, Lagalla R and Brancatelli G: Hepatocellular carcinoma enhancement on contrast-enhanced CT and MR imaging: Response assessment after treatment with sorafenib: Preliminary results. Radiol Med. 119:215–221. 2014. View Article : Google Scholar : PubMed/NCBI
36	Albers I, Hartmann H, Bircher J and Creutzfeldt W: Superiority of the Child-Pugh classification to quantitative liver function tests for assessing prognosis of liver cirrhosis. Scand J Gastroenterol. 24:269–276. 1989. View Article : Google Scholar : PubMed/NCBI
37	Saito M, Seo Y, Yano Y, Miki A, Yoshida M and Azuma T: Short-term reductions in non-protein respiratory quotient and prealbumin can be associated with the long-term deterioration of liver function after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. J Gastroenterol. 47:704–714. 2012. View Article : Google Scholar : PubMed/NCBI
38	Hanai T, Shiraki M, Ohnishi S, Miyazaki T, Ideta T, Kochi T, Imai K, Suetsugu A, Takai K, Moriwaki H and Shimizu M: Rapid skeletal muscle wasting predicts worse survival in patients with liver cirrhosis. Hepatol Res. 46:743–751. 2016. View Article : Google Scholar : PubMed/NCBI
39	Chindapasirt J: Sarcopenia in Cancer Patients. Asian Pac J Cancer Prev. 16:8075–8077. 2015. View Article : Google Scholar : PubMed/NCBI
40	Mir O, Coriat R, Blanchet B, Durand JP, Boudou-Rouquette P, Michels J, Ropert S, Vidal M, Pol S, Chaussade S and Goldwasser F: Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PLoS One. 7:e375632012. View Article : Google Scholar : PubMed/NCBI
41	Shiraki M, Nishiguchi S, Saito M, Fukuzawa Y, Mizuta T, Kaibori M, Hanai T, Nishimura K, Shimizu M, Tsurumi H and Moriwaki H: Nutritional status and quality of life in current patients with liver cirrhosis as assessed in 2007–2011. Hepatol Res. 43:106–112. 2013. View Article : Google Scholar : PubMed/NCBI
42	Prado CM, Wells JC, Smith SR, Stephan BC and Siervo M: Sarcopenic obesity: A Critical appraisal of the current evidence. Clin Nutr. 31:583–601. 2012. View Article : Google Scholar : PubMed/NCBI
43	McCurry J: Japan battles with obesity. Lancet. 369:451–452. 2007. View Article : Google Scholar : PubMed/NCBI
44	Examination Committee of Criteria for ‘Obesity Disease’ in Japan; Japan Society for the Study of Obesity, . New criteria for ‘obesity disease’ in Japan. Circ J. 66:987–992. 2002. View Article : Google Scholar : PubMed/NCBI