Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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Body Composition as a Prognostic Factor of Neoadjuvant Chemotherapy Toxicity and Outcome in Patients with Locally Advanced Gastric Cancer

  • Palmela, Carolina (Division of Gastroenterology, Surgical Department, Hospital Beatriz Angelo) ;
  • Velho, Sonia (Nutrition Department, Hospital Beatriz Angelo) ;
  • Agostinho, Lisa (Radiology Department, Hospital Beatriz Angelo) ;
  • Branco, Francisco (Oncology Department, Hospital Beatriz Angelo) ;
  • Santos, Marta (General Surgery Department, Hospital Beatriz Angelo) ;
  • Santos, Maria Pia Costa (Division of Gastroenterology, Surgical Department, Hospital Beatriz Angelo) ;
  • Oliveira, Maria Helena (Pathology Department, Hospital Beatriz Angelo) ;
  • Strecht, Joao (Radiology Department, Hospital Beatriz Angelo) ;
  • Maio, Rui (General Surgery Department, Hospital Beatriz Angelo) ;
  • Cravo, Marilia (Division of Gastroenterology, Surgical Department, Hospital Beatriz Angelo) ;
  • Baracos, Vickie E. (Division of Palliative Care Medicine, Department of Oncology, Cross Cancer Institute, University of Alberta)
  • Received : 2017.01.29
  • Accepted : 2017.03.03
  • Published : 2017.03.31
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Abstract

Purpose: Neoadjuvant chemotherapy has been shown to improve survival in locally advanced gastric cancer, but it is associated with significant toxicity. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher chemotherapy toxicity and morbi-mortality. The aim of this study was to assess the prevalence of sarcopenia/sarcopenic obesity in patients with gastric cancer, as well as its association with chemotherapy toxicity and long-term outcomes. Materials and Methods: A retrospective analysis was performed using an academic cancer center patient cohort diagnosed with locally advanced gastric cancer between January 2012 and December 2014 and treated with neoadjuvant chemotherapy. We analyzed body composition (skeletal muscle and visceral fat index) in axial computed tomography images. Results: A total of 48 patients met the inclusion criteria. The mean age was $68{\pm}10years$, and 33 patients (69%) were men. Dose-limiting toxicity was observed in 22 patients (46%), and treatment was terminated early owing to toxicity in 17 patients (35%). Median follow-up was 17 months. Sarcopenia and sarcopenic obesity were found at diagnosis in 23% and 10% of patients, respectively. We observed an association between termination of chemotherapy and both sarcopenia (P=0.069) and sarcopenic obesity (P=0.004). On multivariate analysis, the odds of treatment termination were higher in patients with sarcopenia (odds ratio=4.23; P=0.050). Patients with sarcopenic obesity showed lower overall survival (median survival of 6 months [95% confidence interval {CI}=3.9-8.5] vs. 25 months [95% CI=20.2-38.2]; log-rank test P=0.000). Conclusions: Sarcopenia and sarcopenic obesity were associated with early termination of neoadjuvant chemotherapy in patients with gastric cancer; additionally, sarcopenic obesity was associated with poor survival.

Keywords

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108. https://doi.org/10.3322/caac.21262
  2. Fox JG, Wang TC. Inflammation, atrophy, and gastric cancer. J Clin Invest 2007;117:60-69. https://doi.org/10.1172/JCI30111
  3. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11-20. https://doi.org/10.1056/NEJMoa055531
  4. Tan BH, Brammer K, Randhawa N, Welch NT, Parsons SL, James EJ, et al. Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. Eur J Surg Oncol 2015;41:333-338. https://doi.org/10.1016/j.ejso.2014.11.040
  5. 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. https://doi.org/10.1016/S1470-2045(08)70153-0
  6. 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. https://doi.org/10.1016/j.clnu.2011.08.008
  7. Prado CM, Baracos VE, McCargar LJ, Mourtzakis M, Mulder KE, Reiman T, et al. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res 2007;13:3264-3268. https://doi.org/10.1158/1078-0432.CCR-06-3067
  8. Peng P, Hyder O, Firoozmand A, Kneuertz P, Schulick RD, Huang D, et al. Impact of sarcopenia on outcomes following resection of pancreatic adenocarcinoma. J Gastrointest Surg 2012;16:1478-1486. https://doi.org/10.1007/s11605-012-1923-5
  9. Huang DD, Zhou CJ, Wang SL, et al. Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer. Surgery 2017;161:680-693. https://doi.org/10.1016/j.surg.2016.08.030
  10. Chen FF, Zhang FY, Zhou XY, Shen X, Yu Z, Zhuang CL. Role of frailty and nutritional status in predicting complications following total gastrectomy with D2 lymphadenectomy in patients with gastric cancer: a prospective study. Langenbecks Arch Surg 2016;401:813-822. https://doi.org/10.1007/s00423-016-1490-4
  11. Zhuang CL, Huang DD, Pang WY, Zhou CJ, Wang SL, Lou N, et al. Sarcopenia is an independent predictor of severe postoperative complications and long-term survival after radical gastrectomy for gastric cancer: analysis from a large-scale cohort. Medicine (Baltimore) 2016;95:e3164. https://doi.org/10.1097/MD.0000000000003164
  12. Wang SL, Zhuang CL, Huang DD, Pang WY, Lou N, Chen FF, et al. Sarcopenia adversely impacts postoperative clinical outcomes following gastrectomy in patients with gastric cancer: a prospective study. Ann Surg Oncol 2016;23:556-564. https://doi.org/10.1245/s10434-015-4887-3
  13. Fukuda Y, Yamamoto K, Hirao M, Nishikawa K, Nagatsuma Y, Nakayama T, et al. Sarcopenia is associated with severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy. Gastric Cancer 2016;19:986-993. https://doi.org/10.1007/s10120-015-0546-4
  14. Hayashi N, Ando Y, Gyawali B, Shimokata T, Maeda O, Fukaya M, et al. Low skeletal muscle density is associated with poor survival in patients who receive chemotherapy for metastatic gastric cancer. Oncol Rep 2016;35:1727-1731. https://doi.org/10.3892/or.2015.4475
  15. Huang DD, Chen XX, Chen XY, Wang SL, Shen X, Chen XL, et al. Sarcopenia predicts 1-year mortality in elderly patients undergoing curative gastrectomy for gastric cancer: a prospective study. J Cancer Res Clin Oncol 2016;142:2347-2356. https://doi.org/10.1007/s00432-016-2230-4
  16. Li XT, Tang L, Chen Y, Li YL, Zhang XP, Sun YS. Visceral and subcutaneous fat as new independent predictive factors of survival in locally advanced gastric carcinoma patients treated with neo-adjuvant chemotherapy. J Cancer Res Clin Oncol 2015;141:1237-1247. https://doi.org/10.1007/s00432-014-1893-y
  17. Malietzis G, Currie AC, Athanasiou T, Johns N, Anyamene N, Glynne-Jones R, et al. Influence of body composition profile on outcomes following colorectal cancer surgery. Br J Surg 2016;103:572-580. https://doi.org/10.1002/bjs.10075
  18. Lou N, Chi CH, Chen XD, et al. Sarcopenia in overweight and obese patients is a predictive factor for postoperative complication in gastric cancer: a prospective study. Eur J Surg Oncol 2017;43:188-195. https://doi.org/10.1016/j.ejso.2016.09.006
  19. Nishigori T, Tsunoda S, Okabe H, Tanaka E, Hisamori S, Hosogi H, et al. Impact of sarcopenic obesity on surgical site infection after laparoscopic total gastrectomy. Ann Surg Oncol 2016;23:524-531. https://doi.org/10.1245/s10434-016-5385-y
  20. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247. https://doi.org/10.1016/j.ejca.2008.10.026
  21. 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. https://doi.org/10.1200/JCO.2012.45.2722
  22. Lieffers JR, Bathe OF, Fassbender K, Winget M, Baracos VE. Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery. Br J Cancer 2012;107:931-936. https://doi.org/10.1038/bjc.2012.350
  23. Tan BH, Birdsell LA, Martin L, Baracos VE, Fearon KC. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res 2009;15:6973-6979. https://doi.org/10.1158/1078-0432.CCR-09-1525
  24. Reisinger KW, van Vugt JL, Tegels JJ, Snijders C, Hulsewe KW, Hoofwijk AG, et al. Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery. Ann Surg 2015;261:345-352. https://doi.org/10.1097/SLA.0000000000000628
  25. Joglekar S, Asghar A, Mott SL, Johnson BE, Button AM, Clark E, et al. Sarcopenia is an independent predictor of complications following pancreatectomy for adenocarcinoma. J Surg Oncol 2015;111:771-775. https://doi.org/10.1002/jso.23862
  26. Harimoto N, Shirabe K, Yamashita YI, Ikegami T, Yoshizumi T, Soejima Y, et al. Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma. Br J Surg 2013;100:1523-1530. https://doi.org/10.1002/bjs.9258
  27. Reisinger KW, Bosmans JW, Uittenbogaart M, Alsoumali A, Poeze M, Sosef MN, et al. Loss of skeletal muscle mass during neoadjuvant chemoradiotherapy predicts postoperative mortality in esophageal cancer surgery. Ann Surg Oncol 2015;22:4445-4452. https://doi.org/10.1245/s10434-015-4558-4
  28. 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. https://doi.org/10.1007/s00330-014-3110-4
  29. Wagner D, DeMarco MM, Amini N, Buttner S, Segev D, Gani F, et al. Role of frailty and sarcopenia in predicting outcomes among patients undergoing gastrointestinal surgery. World J Gastrointest Surg 2016;8:27-40. https://doi.org/10.4240/wjgs.v8.i1.27
  30. Huang DD, Wang SL, Zhuang CL, Zheng BS, Lu JX, Chen FF, et al. Sarcopenia, as defined by low muscle mass, strength and physical performance, predicts complications after surgery for colorectal cancer. Colorectal Dis 2015;17:O256-O264. https://doi.org/10.1111/codi.13067
  31. Amini N, Spolverato G, Gupta R, Margonis GA, Kim Y, Wagner D, et al. Impact total psoas volume on short- and long-term outcomes in patients undergoing curative resection for pancreatic adenocarcinoma: a new tool to assess sarcopenia. J Gastrointest Surg 2015;19:1593-1602. https://doi.org/10.1007/s11605-015-2835-y
  32. Hansen RD, Williamson DA, Finnegan TP, Lloyd BD, Grady JN, Diamond TH, et al. Estimation of thigh muscle cross-sectional area by dual-energy X-ray absorptiometry in frail elderly patients. Am J Clin Nutr 2007;86:952-958. https://doi.org/10.1093/ajcn/86.4.952
  33. Kazemi-Bajestani SM, Mazurak VC, Baracos V. Computed tomography-defined muscle and fat wasting are associated with cancer clinical outcomes. Semin Cell Dev Biol 2016;54:2-10. https://doi.org/10.1016/j.semcdb.2015.09.001
  34. Ali R, Baracos VE, Sawyer MB, Bianchi L, Roberts S, Assenat E, et al. Lean body mass as an independent determinant of dose-limiting toxicity and neuropathy in patients with colon cancer treated with FOLFOX regimens. Cancer Med 2016;5:607-616. https://doi.org/10.1002/cam4.621
  35. Sjoblom B, Gronberg BH, Benth JS, Baracos VE, Flotten O, Hjermstad MJ, et al. Low muscle mass is associated with chemotherapy-induced haematological toxicity in advanced non-small cell lung cancer. Lung Cancer 2015;90:85-91. https://doi.org/10.1016/j.lungcan.2015.07.001
  36. Tegels JJ, van Vugt JL, Reisinger KW, Hulsewe KW, Hoofwijk AG, Derikx JP, et al. Sarcopenia is highly prevalent in patients undergoing surgery for gastric cancer but not associated with worse outcomes. J Surg Oncol 2015;112:403-407. https://doi.org/10.1002/jso.24015
  37. Irigaray P, Newby JA, Lacomme S, Belpomme D. Overweight/obesity and cancer genesis: more than a biological link. Biomed Pharmacother 2007;61:665-678. https://doi.org/10.1016/j.biopha.2007.10.008
  38. 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. https://doi.org/10.1136/gut.2009.188946
  39. Gaujoux S, Torres J, Olson S, Winston C, Gonen M, Brennan MF, et al. Impact of obesity and body fat distribution on survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg Oncol 2012;19:2908-2916. https://doi.org/10.1245/s10434-012-2301-y
  40. 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.
  41. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology 2007;132:2169-2180. https://doi.org/10.1053/j.gastro.2007.03.059
  42. Sjoblom B, Benth JS, Gronberg BH, Baracos VE, Sawyer MB, Flotten O, et al. Drug dose per kilogram lean body mass predicts hematologic toxicity from carboplatin-doublet chemotherapy in advanced non-small-cell lung cancer. Clin Lung Cancer 2016 Oct 5. [Epub ahead of print].

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