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Poor nutrition and sarcopenia are related to systemic inflammatory response in patients with rectal cancer undergoing preoperative chemoradiotherapy

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

Preoperative chemoradiotherapy (CRT) is the standard therapy for locally advanced rectal cancer (LARC). However, the changes that the patient’s physical status during CRT, such as host systemic inflammatory response, nutritional status, and muscle depletion, are still unclear. We evaluated the clinical significance of malnutrition and sarcopenia for patients with LARC undergoing CRT.

Patients and methods

Patients with LARC treated with CRT following radical surgery at our institution between 2006 and 2016 (N = 225) were retrospectively analyzed. A new prognostic score (PNSI) was devised based on the prognostic nutritional index (PNI) and the psoas muscle mass index (PMI): patients with malnutrition/sarcopenia were scored 2; patients with one and neither abnormality were scored 1 and 0, respectively.

Results

Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and platelet/lymphocyte ratio increased, whereas PNI and PMI decreased after CRT. There were 130, 73, and 22 patients in the PNSI 0, 1, and 2 groups, respectively. Patients with higher PNSI had higher residual tumor size (p = 0.003), yT stage (p = 0.007), ypStage (p < 0.001), post-CRT platelet/lymphocyte ratio (p = 0.027), and post-CRT C-reactive protein/albumin ratio (p < 0.001). Post-CRT PNSI was associated with overall survival and was an independent poor prognosis factor (PNSI 1 to 0, hazard ratio 2.40, p = 0.034, PNSI 2 to 0, hazard ratio 2.66, p = 0.043) together with mesenteric lymph node metastasis, lateral lymph node metastasis, and histology.

Conclusion

A combined score of post-CRT malnutrition/sarcopenia is promising for predicting overall survival in LARC.

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References

  1. Bosset JF, Collette L, Calais G et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355(11):1114–1123

    Article  CAS  PubMed  Google Scholar 

  2. Gérard JP, Conroy T, Bonnetain F et al (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203. J Clin Oncol 24(28):4620–4625

    Article  PubMed  Google Scholar 

  3. de Campos-Lobato LF, Stocchi L, da Luz MA et al (2011) Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence. Ann Surg Oncol 18(6):1590–1598

    Article  PubMed  Google Scholar 

  4. Dinaux AM, Amri R, Bordeianou LG et al (2017) The impact of pathologic complete response in patients with neoadjuvantly treated locally advanced rectal cancer-a large single-center experience. J Gastrointest Surg 21(7):1153–1158

    Article  CAS  PubMed  Google Scholar 

  5. Argilés JM, Busquets S, López-Soriano FJ (2005) The pivotal role of cytokines in muscle wasting during cancer. Int J Biochem Cell Biol 37(10):2036–2046

    Article  PubMed  Google Scholar 

  6. Richards CH, Roxburgh CS, MacMillan MT et al (2012) The relationships between body composition and the systemic inflammatory response in patients with primary operable colorectal cancer. PLoS One 7(8):e41883

  7. Chan JC, Chan DL, Diakos CI et al (2017) The lymphocyte-to-monocyte ratio is a superior predictor of overall survival in comparison to established biomarkers of resectable colorectal cancer. Ann Surg 265(3):539–546

    Article  PubMed  Google Scholar 

  8. Abe S, Kawai K, Nozawa H et al (2018) LMR predicts outcome in patients after preoperative chemoradiotherapy for stage II-III rectal cancer. J Surg Res 222:122–131

    Article  PubMed  Google Scholar 

  9. Zhang J, Zhang HY, Li J et al (2017) The elevated NLR, PLR and PLT may predict the prognosis of patients with colorectal cancer: a systematic review and meta-analysis. Oncotarget 8(40):68837–68846

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ishizuka M, Nagata H, Takagi K et al (2016) Clinical significance of the c-reactive protein to albumin ratio for survival after surgery for colorectal cancer. Ann Surg Oncol 23(3):900–907

    Article  PubMed  Google Scholar 

  11. Geng Y, Qi Q, Sun M et al (2015) Prognostic nutritional index predicts survival and correlates with systemic inflammatory response in advanced pancreatic cancer. Eur J Surg Oncol 41(11):1508–1514

    Article  CAS  PubMed  Google Scholar 

  12. Dolan RD, Almasaudi AS, Dieu LB et al (2019) The relationship between computed tomography-derived body composition, systemic inflammatory response, and survival in patients undergoing surgery for colorectal cancer. J Cachexia Sarcopenia Muscle 10(1):111–122

    Article  PubMed  Google Scholar 

  13. Schiessel DL, Baracos VE (2018) Barriers to cancer nutrition therapy: excess catabolism of muscle and adipose tissues induced by tumour products and chemotherapy. Proc Nutr Soc 77(4):394–402

    Article  CAS  PubMed  Google Scholar 

  14. Lai CC, You JF, Yeh CY et al (2011) Low preoperative serum albumin in colon cancer: a risk factor for poor outcome. Int J Colorectal Dis 26(4):473–481

    Article  PubMed  Google Scholar 

  15. Arends J, Baracos V, Bertz H et al (2017) ESPEN expert group recommendations for action against cancer-related malnutrition. Clin Nutr 36(5):1187–1196

    Article  CAS  PubMed  Google Scholar 

  16. Hu WH, Eisenstein S, Parry L et al (2019) Preoperative malnutrition with mild hypoalbuminemia associated with postoperative mortality and morbidity of colorectal cancer: a propensity score matching study. Nutr J 18(1):33

    Article  PubMed  PubMed Central  Google Scholar 

  17. Yang Y, Gao P, Chen X et al (2016) Prognostic significance of preoperative prognostic nutritional index in colorectal cancer: results from a retrospective cohort study and a meta-analysis. Oncotarget 7(36):58543–58552

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kouzu K, Tsujimoto H, Sugasawa H et al (2021) Modified geriatric nutrition risk index as a prognostic predictor of esophageal cancer. Esophagus 18(2):278–287

    Article  PubMed  Google Scholar 

  19. Yang Y, Gao P, Song Y et al (2016) The prognostic nutritional index is a predictive indicator of prognosis and postoperative complications in gastric cancer: a meta-analysis. Eur J Surg Oncol 42(8):1176–1182

    Article  CAS  PubMed  Google Scholar 

  20. Kanda M, Fujii T, Kodera Y et al (2011) Nutritional predictors of postoperative outcome in pancreatic cancer. Br J Surg 98(2):268–274

    Article  CAS  PubMed  Google Scholar 

  21. Qiu C, Qu X, Shen H et al (2015) Evaluation of prognostic nutritional index in patients undergoing radical surgery with nonsmall cell lung cancer. Nutr Cancer 67(5):741–747

    Article  PubMed  Google Scholar 

  22. McMillan DC, Crozier JE, Canna K et al (2007) Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis 22(8):881–886

    Article  PubMed  Google Scholar 

  23. Okuno M, Ebata T, Yokoyama Y et al (2016) Evaluation of inflammation-based prognostic scores in patients undergoing hepatobiliary resection for perihilar cholangiocarcinoma. J Gastroenterol 51(2):153–161

    Article  PubMed  Google Scholar 

  24. Shachar SS, Williams GR, Muss HB et al (2016) Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review. Eur J Cancer 57:58–67

    Article  PubMed  Google Scholar 

  25. Nagata T, Nakase Y, Nakamura K et al (2016) Prognostic impact of a nutritional index including muscle volume in stage 4 colorectal cancer. In Vivo 30(6):885–891

    Article  CAS  PubMed  Google Scholar 

  26. Chung E, Lee HS, Cho ES et al (2020) Prognostic significance of sarcopenia and skeletal muscle mass change during preoperative chemoradiotherapy in locally advanced rectal cancer. Clin Nutr 39(3):820–828

    Article  PubMed  Google Scholar 

  27. Miyake M, Morizawa Y, Hori S et al (2017) Integrative assessment of pretreatment inflammation-, nutrition-, and muscle-based prognostic markers in patients with muscle-invasive bladder cancer undergoing radical cystectomy. Oncology 93(4):259–269

    Article  PubMed  Google Scholar 

  28. Suzuki Y, Okabayashi K, Hasegawa H et al (2016) Comparison of preoperative inflammation-based prognostic scores in patients with colorectal cancer. Ann Surg

  29. Onodera T, Goseki N, Kosaki G (1984) Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi 85(9):1001–1005

    CAS  PubMed  Google Scholar 

  30. Sugawara K, Yamashita H, Urabe M et al (2020) Poor nutritional status and sarcopenia influences survival outcomes in gastric carcinoma patients undergoing radical surgery. Eur J Surg Oncol 46(10 Pt A):1963–1970

  31. Rectum JSfCotCa (2019) Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma: the 3d English Edition [Secondary Publication]. J Anus Rectum Colon 3(4):175–195

  32. Hashiguchi Y, Muro K, Saito Y et al (2020) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol 25(1):1–42

    Article  Google Scholar 

  33. Taguchi S, Akamatsu N, Nakagawa T et al (2016) Sarcopenia evaluated using the skeletal muscle index is a significant prognostic factor for metastatic urothelial carcinoma. Clin Genitourin Cancer 14(3):237–243

    Article  PubMed  Google Scholar 

  34. Yasui K, Kondou R, Iizuka A et al (2020) Effect of preoperative chemoradiotherapy on the immunological status of rectal cancer patients. J Radiat Res 61(5):766–775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tato-Costa J, Casimiro S, Pacheco T et al (2016) Therapy-induced cellular senescence induces epithelial-to-mesenchymal transition and increases invasiveness in rectal cancer. Clin Colorectal Cancer 15(2):170-178.e3

    Article  PubMed  Google Scholar 

  36. Sung S, Son SH, Park EY et al (2017) Prognosis of locally advanced rectal cancer can be predicted more accurately using pre- and post-chemoradiotherapy neutrophil-lymphocyte ratios in patients who received preoperative chemoradiotherapy. PLoS One 12(3):e0173955

  37. Yamano T, Tomita N, Sato T et al (2020) Influence of chemoradiotherapy on nutritional status in locally advanced rectal cancer: prospective multicenter study. Nutrition 77:110807

  38. Soeters PB, Wolfe RR, Shenkin A (2019) Hypoalbuminemia: pathogenesis and clinical significance. JPEN J Parenter Enteral Nutr 43(2):181–193

    Article  CAS  PubMed  Google Scholar 

  39. Kitayama J, Yasuda K, Kawai K et al (2011) Circulating lymphocyte is an important determinant of the effectiveness of preoperative radiotherapy in advanced rectal cancer. BMC Cancer 11:64

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lee IH, Hwang S, Lee SJ et al (2017) Systemic inflammatory response after preoperative chemoradiotherapy can affect oncologic outcomes in locally advanced rectal cancer. Anticancer Res 37(3):1459–1465

    Article  PubMed  Google Scholar 

  41. Dovedi SJ, Adlard AL, Lipowska-Bhalla G et al (2014) Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res 74(19):5458–5468

    Article  CAS  PubMed  Google Scholar 

  42. Shamseddine A, Zeidan YH, Kreidieh M et al (2020) Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma. BMC Cancer 20(1):831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kong P, Wang J, Song Z et al (2019) Circulating lymphocytes, PD-L1 expression on tumor-infiltrating lymphocytes, and survival of colorectal cancer patients with different mismatch repair gene status. J Cancer 10(7):1745–1754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. McSorley ST, Black DH, Horgan PG et al (2018) The relationship between tumour stage, systemic inflammation, body composition and survival in patients with colorectal cancer. Clin Nutr 37(4):1279–1285

    Article  PubMed  Google Scholar 

  45. Feliciano EMC, Kroenke CH, Meyerhardt JA et al (2017) Association of systemic inflammation and sarcopenia with survival in nonmetastatic colorectal cancer: results from the C SCANS Study. JAMA Oncol 3(12):e172319

  46. Malietzis G, Johns N, Al-Hassi HO et al (2016) Low muscularity and myosteatosis is related to the host systemic inflammatory response in patients undergoing surgery for colorectal cancer. Ann Surg 263(2):320–325

    Article  PubMed  Google Scholar 

  47. Wang Y, Chen L, Zhang B et al (2021) Pretreatment inflammatory-nutritional biomarkers predict responses to neoadjuvant chemoradiotherapy and survival in locally advanced rectal cancer. Front Oncol 11:639909

  48. Ichikawa K, Mizuno S, Hayasaki A et al (2019) Prognostic nutritional index after chemoradiotherapy was the strongest prognostic predictor among biological and conditional factors in localized pancreatic ductal adenocarcinoma patients. Cancers (Basel) 11(4)

  49. Lin JX, Lin JP, Xie JW et al (2019) Prognostic value and association of sarcopenia and systemic inflammation for patients with gastric cancer following radical gastrectomy. Oncologist 24(11):e1091–e1101

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kim SM, Yoon G, Seo AN (2019) What are the most important prognostic factors in patients with residual rectal cancer after preoperative chemoradiotherapy? Yeungnam Univ J Med 36(2):124–135

    Article  PubMed  PubMed Central  Google Scholar 

  51. Wen B, Zhang L, Wang C et al (2015) Prognostic significance of clinical and pathological stages on locally advanced rectal carcinoma after neoadjuvant chemoradiotherapy. Radiat Oncol 10:124

    Article  PubMed  PubMed Central  Google Scholar 

  52. Timudom K, Akaraviputh T, Chinswangwatanakul V et al (2020) Predictive significance of cancer related-inflammatory markers in locally advanced rectal cancer. World J Gastrointest Surg 12(9):390–396

    Article  PubMed  PubMed Central  Google Scholar 

  53. Rödel C, Graeven U, Fietkau R et al (2015) Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 16(8):979–989

    Article  PubMed  Google Scholar 

  54. Klute KA, Brouwer J, Jhawer M et al (2016) Chemotherapy dose intensity predicted by baseline nutrition assessment in gastrointestinal malignancies: a multicentre analysis. Eur J Cancer 63:189–200

    Article  PubMed  Google Scholar 

  55. Hamaguchi Y, Kaido T, Okumura S et al (2016) Proposal for new diagnostic criteria for low skeletal muscle mass based on computed tomography imaging in Asian adults. Nutrition 32(11–12):1200–1205

    Article  PubMed  Google Scholar 

  56. Takada H, Amemiya F, Yasumura T et al (2020) Relationship between presarcopenia and event occurrence in patients with primary hepatocellular carcinoma. Sci Rep 10(1):10186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Itami Y, Miyake M, Tatsumi Y et al (2019) Preoperative predictive factors focused on inflammation-, nutrition-, and muscle-status in patients with upper urinary tract urothelial carcinoma undergoing nephroureterectomy. Int J Clin Oncol 24(5):533–545

    Article  PubMed  Google Scholar 

  58. Ozawa Y, Nakano T, Taniyama Y et al (2019) Evaluation of the impact of psoas muscle index, a parameter of sarcopenia, in patients with esophageal squamous cell carcinoma receiving neoadjuvant therapy. Esophagus 16(4):345–351

    Article  PubMed  Google Scholar 

  59. Ojima Y, Harano M, Sumitani D et al (2019) Impact of preoperative skeletal muscle mass and quality on the survival of elderly patients after curative resection of colorectal cancer. J Anus Rectum Colon 3(4):143–151

    Article  PubMed  PubMed Central  Google Scholar 

  60. Kawakita Y, Motoyama S, Sato Y et al (2020) Decreases in the psoas muscle index correlate more strongly with survival than other prognostic markers in esophageal cancer after neoadjuvant chemoradiotherapy plus esophagectomy. World J Surg 44(5):1559–1568

    Article  PubMed  Google Scholar 

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Funding

This research is supported by Grants-in-Aid for Scientific Research (C: grant number; 18K07194, C: grant number; 19K09114, C: grant number; 19K09115, C: grant number; 20K09051, Challenging Research (Exploratory): grant number; 20K21626) from Japan Society for the promotion of Science. This research is supported by the Project for Cancer Research and Therapeutic Evolution (P-CREATE), grant number: JP 19cm0106502 from the Japan Agency for Medical Research and Development (AMED).

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Authors and Affiliations

  1. Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Shinya Abe, Hiroaki Nozawa, Kazushige Kawai, Kazuhito Sasaki, Koji Murono, Shigenobu Emoto, Junko Kishikawa, Tsuyoshi Ozawa, Yuichiro Yokoyama, Yuzo Nagai, Hiroyuki Anzai, Hirofumi Sonoda & Soichiro Ishihara

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  1. Shinya Abe
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  2. Hiroaki Nozawa
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  3. Kazushige Kawai
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  4. Kazuhito Sasaki
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  5. Koji Murono
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  6. Shigenobu Emoto
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  8. Tsuyoshi Ozawa
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Contributions

Shinya Abe conceptualized and designed the study, acquired, analyzed, and interpreted the data, drafted the article, and approved the final submission. Kazushige Kawai and Hiroaki Nozawa acquired and interpreted the data, critically revised the manuscript, and approved the final submission. Kazuhito Sasaki, Koji Murono, Shigenobu Emoto, Junko Kishikawa, Tsuyoshi Ozawa, Yuichiro Yokoyama, Yuzo Nagai, Hiroyuki Anzai, and Hirofumi Sonoda acquired the data and approved the final submission. Soichiro Ishihara conceptualized and interpreted the data, critically revised the manuscript, and approved the final submission.

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Correspondence to Shinya Abe.

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Abe, S., Nozawa, H., Kawai, K. et al. Poor nutrition and sarcopenia are related to systemic inflammatory response in patients with rectal cancer undergoing preoperative chemoradiotherapy. Int J Colorectal Dis 37, 189–200 (2022). https://doi.org/10.1007/s00384-021-04039-w

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