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Open Access 01-12-2021 | Sarcopenia | Research

Impact of skeletal muscle mass in patients with unresectable gastric cancer who received palliative first-line chemotherapy based on 5-fluorouracil

Authors: Tomoyuki Matsunaga, Hiroaki Saito, Wataru Miyauchi, Yuji Shishido, Kozo Miyatani, Masaki Morimoto, Yuki Murakami, Takehiko Hanaki, Kyoichi Kihara, Manabu Yamamoto, Naruo Tokuyasu, Shuichi Takano, Teruhisa Sakamoto, Toshimichi Hasegawa, Yoshiyuki Fujiwara

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

The mortality rate of patients with unresectable gastric cancer (UGC) has decreased with the development of chemotherapies and surgical techniques. However, the survival rate remains low. We retrospectively examined the prognostic significance of the pretreatment skeletal muscle mass index (SMI) and nutritional and inflammatory factors in patients with UGC.

Methods

This study included 83 patients diagnosed with UGC at Tottori University Hospital who received palliative chemotherapy based on 5-fluorouracil. Pretreatment computed tomography (CT) measured overall skeletal muscle mass (SMM) and cross-sectional SMM at the third lumbar vertebra (L3). We focused on the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and platelet-to-lymphocyte ratio (PLR) as nutritional and inflammatory factors.

Results

Receiver operating characteristic curve analysis was performed for median survival time (MST) after palliative chemotherapy. SMIs for males and females (43.9 cm²/m² and 34.7 cm²/m², respectively) were the cutoff values, and patients were divided into high (SMI^High; n = 41) and low SMI groups (SMI^Low; n = 42). Body mass index (BMI) was significantly higher in patients in the SMI^High group than in the SMI^Low group (p < 0.001). The number of patients who received third-line chemotherapy was significantly higher in the SMI^High group than in the SMI^Low group (p = 0.037). The MST was significantly higher in the SMI^High group than in the SMI^Low group (17.3 vs. 13.8 months; p = 0.008). The incidence of grade 3 or 4 side effects was significantly higher in patients with SMI^Low UGC (p = 0.028). NLR was significantly higher in patients with SMI^Low than it was in those with SMI^High. (p = 0.047). In the univariate analysis, performance status, SMI, histological type, lines of chemotherapy, and NLR were prognostic indicators. The multivariate analysis identified SMI (p = 0.037), NLR (p = 0.002), and lines of chemotherapy (p < 0.001) as independent prognostic factors.

Conclusions

The SMI^Low group had significantly more grade 3 or 4 side effects, were related to high NLR, and had a significantly worse prognosis than the SMI^High group.

Trial registration

Retrospectively registerd.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.CrossRefPubMed

Zou ZH, Zhao LY, Mou TY, Hu YF, Yu J, Liu H, et al. Laparoscopic vs open D2 gastrectomy for locally advanced gastric cancer: a meta-analysis. World J Gastroenterol. 2014;20(44):16750–64. https://doi.org/10.3748/wjg.v20.i44.16750.CrossRefPubMedPubMedCentral

Digklia A, Wagner AD. Advanced gastric cancer: current treatment landscape and future perspectives. World J Gastroenterol. 2016;22(8):2403–14. https://doi.org/10.3748/wjg.v22.i8.2403.CrossRefPubMedPubMedCentral

Li Z, Shan F, Ying X, Zhang Y, E JY, Wang Y, Ren H, Su X, Ji J: assessment of laparoscopic distal gastrectomy after neoadjuvant chemotherapy for locally advanced gastric Cancer: a randomized clinical trial. JAMA Surg 2019, 154(12):1093–1101, DOI: https://doi.org/10.1001/jamasurg.2019.3473.

Guo X, Zhao F, Ma X, Shen G, Ren D, Zheng F, et al. A comparison between triplet and doublet chemotherapy in improving the survival of patients with advanced gastric cancer: a systematic review and meta-analysis. BMC Cancer. 2019;19(1):1125. https://doi.org/10.1186/s12885-019-6294-9.CrossRefPubMedPubMedCentral

Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9(3):215–21. https://doi.org/10.1016/S1470-2045(08)70035-4.CrossRefPubMed

Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer 2021, 24(1):1–21, DOI: https://doi.org/10.1007/s10120-020-01042-y.

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97. https://doi.org/10.1016/S0140-6736(10)61121-X.CrossRefPubMed

Kanazawa Y, Yamada T, Kakinuma D, Matsuno K, Ando F, Fujita I, et al. Skeletal muscle mass depletion after gastrectomy negatively affects the prognosis of patients with gastric Cancer. Anticancer Res. 2020;40(8):4271–9. https://doi.org/10.21873/anticanres.14429.CrossRefPubMed

10.

Kuwada K, Kuroda S, Kikuchi S, Yoshida R, Nishizaki M, Kagawa S, et al. Clinical impact of sarcopenia on gastric Cancer. Anticancer Res. 2019;39(5):2241–9. https://doi.org/10.21873/anticanres.13340.CrossRefPubMed

11.

Antoun S, Borget I, Lanoy E. Impact of sarcopenia on the prognosis and treatment toxicities in patients diagnosed with cancer. Curr Opin Support Palliat Care. 2013;7(4):383–9. https://doi.org/10.1097/SPC.0000000000000011.CrossRefPubMed

12.

Shachar SS, Deal AM, Weinberg M, Nyrop KA, Williams GR, Nishijima TF, et al. Skeletal muscle measures as predictors of toxicity, hospitalization, and survival in patients with metastatic breast Cancer receiving Taxane-based chemotherapy. Clin Cancer Res. 2017;23(3):658–65. https://doi.org/10.1158/1078-0432.CCR-16-0940.CrossRefPubMed

13.

Saito H, Kono Y, Murakami Y, Shishido Y, Kuroda H, Matsunaga T, et al. Prognostic significance of platelet-based inflammatory indicators in patients with gastric Cancer. World J Surg. 2018;42(8):2542–50. https://doi.org/10.1007/s00268-018-4527-8.CrossRefPubMed

14.

Chen JH, Zhai ET, Yuan YJ, Wu KM, Xu JB, Peng JJ, et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol. 2017;23(34):6261–72. https://doi.org/10.3748/wjg.v23.i34.6261.CrossRefPubMedPubMedCentral

15.

Harada K, Ida S, Baba Y, Ishimoto T, Kosumi K, Tokunaga R, et al. Prognostic and clinical impact of sarcopenia in esophageal squamous cell carcinoma. Dis Esophagus. 2016;29(6):627–33. https://doi.org/10.1111/dote.12381.CrossRefPubMed

16.

Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol (1985). 1998;85(1):115–22.CrossRef

17.

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 (1985). 2004;97(6):2333–8.CrossRef

18.

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(12):1539–47. https://doi.org/10.1200/JCO.2012.45.2722.CrossRefPubMed

19.

Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14(2):113–23. https://doi.org/10.1007/s10120-011-0042-4.

20.

Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer 2017, 20(1):1–19, DOI: https://doi.org/10.1007/s10120-016-0622-4.

21.

Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, et al. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst. 2014;106(9). https://doi.org/10.1093/jnci/dju244.

22.

Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, et al. The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma. Ann Surg Oncol. 2015;22(3):803–10. https://doi.org/10.1245/s10434-014-4048-0.CrossRefPubMed

23.

Saito H, Kono Y, Murakami Y, Shishido Y, Kuroda H, Matsunaga T, et al. Prognostic significance of the preoperative ratio of C-reactive protein to albumin and neutrophil-lymphocyte ratio in gastric Cancer patients. World J Surg. 2018;42(6):1819–25. https://doi.org/10.1007/s00268-017-4400-1.CrossRefPubMed

24.

Onodera T, Goseki N. Kosaki G: [prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients]. Nihon Geka Gakkai Zasshi. 1984;85(9):1001–5.PubMed

25.

Kamarajah SK, Bundred J, Tan BHL. Body composition assessment and sarcopenia in patients with gastric cancer: a systematic review and meta-analysis. Gastric Cancer. 2019;22(1):10–22. https://doi.org/10.1007/s10120-018-0882-2.CrossRefPubMed

26.

Kouzu K, Tsujimoto H, Sugasawa H, Ishibashi Y, Itazaki Y, Tsuchiya S, et al. Impact of postoperative reduced skeletal muscle on prognosis after recurrence in gastric cancer. Mol Clin Oncol. 2021;14(1):3. https://doi.org/10.3892/mco.2020.2165.CrossRefPubMed

27.

Ueno M, Doi A, Sunami T, Takayama H, Mouri H, Mizuno M. Delivery rate of patients with advanced gastric cancer to third-line chemotherapy and those patients' characteristics: an analysis in real-world setting. J Gastrointest Oncol. 2019;10(5):957–64. https://doi.org/10.21037/jgo.2019.05.07.CrossRefPubMedPubMedCentral

28.

Rizzo A, Mollica V, Ricci AD, Maggio I, Massucci M, Rojas Limpe FL, et al. Third- and later-line treatment in advanced or metastatic gastric cancer: a systematic review and meta-analysis. Future Oncol. 2020;16(2):4409–18. https://doi.org/10.2217/fon-2019-0429.CrossRefPubMed

29.

Kurk S, Peeters P, Stellato R, Dorresteijn B, de Jong P, Jourdan M, et al. Skeletal muscle mass loss and dose-limiting toxicities in metastatic colorectal cancer patients. J Cachexia Sarcopenia Muscle. 2019;10(4):803–13. https://doi.org/10.1002/jcsm.12436.CrossRefPubMedPubMedCentral

30.

Matsuura N, Motoori M, Fujitani K, Nishizawa Y, Komatsu H, Miyazaki Y, et al. Correlation between skeletal muscle mass and adverse events of neoadjuvant chemotherapy in patients with gastric Cancer. Oncology. 2020;98(1):29–34. https://doi.org/10.1159/000502613.CrossRefPubMed

31.

Nies AT, Magdy T, Schwab M, Zanger UM. Role of ABC transporters in fluoropyrimidine-based chemotherapy response. Adv Cancer Res. 2015;125:217–43. https://doi.org/10.1016/bs.acr.2014.10.007.CrossRefPubMed

32.

Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, et al. Clinical pharmacogenetics implementation consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther. 2013;94(6):640–5. https://doi.org/10.1038/clpt.2013.172.CrossRefPubMedPubMedCentral

33.

Gusella M, Toso S, Ferrazzi E, Ferrari M, Padrini R. Relationships between body composition parameters and fluorouracil pharmacokinetics. Br J Clin Pharmacol. 2002;54(2):131–9. https://doi.org/10.1046/j.1365-2125.2002.01598.x.CrossRefPubMedPubMedCentral

34.

Hopkins JJ, Sawyer MB. A review of body composition and pharmacokinetics in oncology. Expert Rev Clin Pharmacol. 2017;10(9):947–56. https://doi.org/10.1080/17512433.2017.1347503.CrossRefPubMed

35.

Feliciano EMC, Kroenke CH, Meyerhardt JA, Prado CM, Bradshaw PT, Kwan ML, et al. Association of Systemic Inflammation and Sarcopenia with Survival in nonmetastatic colorectal Cancer: results from the C SCANS study. JAMA Oncol. 2017;3(12):e172319. https://doi.org/10.1001/jamaoncol.2017.2319.CrossRefPubMed

36.

Kim EY, Kim YS, Seo JY, Park I, Ahn HK, Jeong YM, et al. The relationship between sarcopenia and systemic inflammatory response for Cancer Cachexia in small cell lung Cancer. PLoS One. 2016;11(8):e0161125. https://doi.org/10.1371/journal.pone.0161125.CrossRefPubMedPubMedCentral

37.

Rho SY, Hwang HK, Chong JU, Yoon DS, Lee WJ, Kang CM. Association of preoperative total lymphocyte count with prognosis in resected left-sided pancreatic cancer. ANZ J Surg. 2019;89(5):503–8. https://doi.org/10.1111/ans.15030.CrossRefPubMed

38.

Saroha S, Uzzo RG, Plimack ER, Ruth K, Al-Saleem T. Lymphopenia is an independent predictor of inferior outcome in clear cell renal carcinoma. J Urol. 2013;189(2):454–61. https://doi.org/10.1016/j.juro.2012.09.166.CrossRefPubMed

39.

Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN. Cancer Cell. 2009;16(3):183–94. https://doi.org/10.1016/j.ccr.2009.06.017.CrossRefPubMedPubMedCentral

40.

Terzić J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101–2114.e2105.CrossRefPubMed

41.

Rong YD, Bian AL, Hu HY, Ma Y, Zhou XZ. Study on relationship between elderly sarcopenia and inflammatory cytokine IL-6, anti-inflammatory cytokine IL-10. BMC Geriatr. 2018;18(1):308. https://doi.org/10.1186/s12877-018-1007-9.CrossRefPubMedPubMedCentral

Title: Impact of skeletal muscle mass in patients with unresectable gastric cancer who received palliative first-line chemotherapy based on 5-fluorouracil
Authors: Tomoyuki Matsunaga
Hiroaki Saito
Wataru Miyauchi
Yuji Shishido
Kozo Miyatani
Masaki Morimoto
Yuki Murakami
Takehiko Hanaki
Kyoichi Kihara
Manabu Yamamoto
Naruo Tokuyasu
Shuichi Takano
Teruhisa Sakamoto
Toshimichi Hasegawa
Yoshiyuki Fujiwara
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Sarcopenia
Gastric Cancer
Gastric Cancer
Cytostatic Therapy
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08953-8

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Background

Methods

Results

Conclusions

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