DOI QR코드

DOI QR Code

Nodal tumor response according to the count of peripheral blood lymphocyte subpopulations during preoperative chemoradiotherapy in locally advanced rectal cancer

  • Heo, Jaesung (Department of Radiation Oncology, Ajou University School of Medicine) ;
  • Oh, Young-Taek (Department of Radiation Oncology, Ajou University School of Medicine) ;
  • Noh, O Kyu (Department of Radiation Oncology, Ajou University School of Medicine) ;
  • Chun, Mison (Department of Radiation Oncology, Ajou University School of Medicine) ;
  • Park, Jun-Eun (Department of Pediatrics, Ajou University School of Medicine) ;
  • Cho, Sung-Ran (Department of Laboratory Medicine, Ajou University School of Medicine)
  • Received : 2016.08.12
  • Accepted : 2016.09.12
  • Published : 2016.12.31

Abstract

Purpose: The objective of this prospective study was to evaluate the relationship between the circulating lymphocyte subpopulation counts during preoperative chemoradiotherapy (CRT) and tumor response in locally advanced rectal cancer. Materials and Methods: From August 2015 to June 2016, 10 patients treated with preoperative CRT followed by surgery were enrolled. Patients received conventional fractionated radiotherapy (50.4 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. The absolute blood lymphocyte subpopulation was obtained prior to and after 4 weeks of CRT. We analyzed the association between a tumor response and change in the lymphocyte subpopulation during CRT. Results: Among 10 patients, 2 (20%) had evidence of pathologic complete response. In 8 patients with clinically node positive, 4 (50%) had nodal tumor response. All lymphocyte subpopulation counts at 4 weeks after CRT were significantly lower than those observed during pretreatment (p < 0.01). A high decrease in natural killer (NK) cell, count during CRT (baseline cell count - cell count at 4 weeks) was associated with node down staging (p = 0.034). Conclusion: Our results suggest that the change of lymphocyte subset to preoperative CRT may be a predictive factor for tumor response in rectal cancer.

Keywords

References

  1. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731-40. https://doi.org/10.1056/NEJMoa040694
  2. Walker AS, Zwintscher NP, Johnson EK, et al. Future directions for monitoring treatment response in colorectal cancer. J Cancer 2014;5:44-57. https://doi.org/10.7150/jca.7809
  3. Restivo A, Zorcolo L, Cocco IM, et al. Elevated CEA levels and low distance of the tumor from the anal verge are predictors of incomplete response to chemoradiation in patients with rectal cancer. Ann Surg Oncol 2013;20:864-71. https://doi.org/10.1245/s10434-012-2669-8
  4. Kuremsky JG, Tepper JE, McLeod HL. Biomarkers for response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys 2009;74:673-88. https://doi.org/10.1016/j.ijrobp.2009.03.003
  5. Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H. Circulating lymphocyte is an important determinant of the effectiveness of preoperative radiotherapy in advanced rectal cancer. BMC Cancer 2011;11:64. https://doi.org/10.1186/1471-2407-11-64
  6. Heo J, Chun M, Noh OK, et al. Sustaining blood lymphocyte count during preoperative chemoradiotherapy as a predictive marker for pathologic complete response in locally advanced rectal cancer. Cancer Res Treat 2016;48:232-9. https://doi.org/10.4143/crt.2014.351
  7. Yasuda K, Nirei T, Sunami E, Nagawa H, Kitayama J. Density of CD4(+) and CD8(+) T lymphocytes in biopsy samples can be a predictor of pathological response to chemoradiotherapy (CRT) for rectal cancer. Radiat Oncol 2011;6:49. https://doi.org/10.1186/1748-717X-6-49
  8. Heylmann D, Rodel F, Kindler T, Kaina B. Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells. Biochim Biophys Acta 2014;1846:121-9.
  9. Lissoni P, Brivio F, Fumagalli L, et al. Effects of the conventional antitumor therapies surgery, chemotherapy, radiotherapy and immunotherapy on regulatory T lymphocytes in cancer patients. Anticancer Res 2009;29:1847-52.
  10. Garcia-Martinez E, Gil GL, Benito AC, et al. Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer. Breast Cancer Res 2014;16:488. https://doi.org/10.1186/s13058-014-0488-5
  11. Beets-Tan RG, Lambregts DM, Maas M, et al. Magnetic resonance imaging for the clinical management of rectal cancer patients: recommendations from the 2012 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting. Eur Radiol 2013;23:2522-31 https://doi.org/10.1007/s00330-013-2864-4
  12. Feys J. npIntFactRep: nonparametric interaction tests for factorial designs with repeated measures [Internet]. Vienna, Austria: The R Foundation for Statistical Computing; c2015 [cited 2016 Oct 20]. Available from: https://cran.r-project.org/web/packages/npIntFactRep/npIntFactRep.pdf.
  13. R Core Team. R: a language and environment for the statistical computing [Internet]. Vienna, Austria; The R Foundation for Statistical Computing; c2012 [cited 2016 Oct 20]. Available from: https://cran.r-project.org/doc/manuals/r-release/fullrefman.pdf.
  14. Sage EK, Schmid TE, Sedelmayr M, et al. Comparative analysis of the effects of radiotherapy versus radiotherapy after adjuvant chemotherapy on the composition of lymphocyte subpopulations in breast cancer patients. Radiother Oncol 2016;118:176-80. https://doi.org/10.1016/j.radonc.2015.11.016
  15. He JR, Shen GP, Ren ZF, et al. Pretreatment levels of peripheral neutrophils and lymphocytes as independent prognostic factors in patients with nasopharyngeal carcinoma. Head Neck 2012;34:1769-76. https://doi.org/10.1002/hed.22008
  16. Ishihara S, Iinuma H, Fukushima Y, et al. Radiation-induced apoptosis of peripheral blood lymphocytes is correlated with histological regression of rectal cancer in response to preoperative chemoradiotherapy. Ann Surg Oncol 2012;19:1192-8. https://doi.org/10.1245/s10434-011-2057-9
  17. Tada N, Kawai K, Tsuno NH, et al. Prediction of the preoperative chemoradiotherapy response for rectal cancer by peripheral blood lymphocyte subsets. World J Surg Oncol 2015;13:30. https://doi.org/10.1186/s12957-014-0418-0
  18. Ong ML, Schofield JB. Assessment of lymph node involvement in colorectal cancer. World J Gastrointest Surg 2016;8:179-92. https://doi.org/10.4240/wjgs.v8.i3.179
  19. Sewell HF, Halbert CF, Robins RA, Galvin A, Chan S, Blamey RW. Chemotherapy-induced differential changes in lymphocyte subsets and natural-killer-cell function in patients with advanced breast cancer. Int J Cancer 1993;55:735-8. https://doi.org/10.1002/ijc.2910550506
  20. Marcus A, Gowen BG, Thompson TW, et al. Recognition of tumors by the innate immune system and natural killer cells. Adv Immunol. 2014;122:91-128.
  21. Spurrell EL, Lockley M. Adaptive immunity in cancer immunology and therapeutics. Ecancermedicalscience 2014;8:441.
  22. Knutson KL, Disis ML. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother 2005;54:721-8. https://doi.org/10.1007/s00262-004-0653-2
  23. Hadrup S, Donia M, thor Straten P. Effector CD4 and CD8 T Cells and Their Role in the Tumor Microenvironment. Cancer Microenviron 2013;6:123-33. https://doi.org/10.1007/s12307-012-0127-6

Cited by

  1. Association of markers of systemic and local inflammation with prognosis of patients with rectal cancer who received neoadjuvant radiotherapy vol.11, pp.None, 2016, https://doi.org/10.2147/cmar.s187559
  2. The clinical implication of CD45RA + naïve T cells and CD45RO + memory T cells in advanced pancreatic cancer: a proxy for tumor biology and outcome prediction vol.8, pp.3, 2016, https://doi.org/10.1002/cam4.1988
  3. Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in rectal cancer patients following neoadjuvant chemoradiotherapy vol.105, pp.5, 2016, https://doi.org/10.1177/0300891618792476