Skip to main content
Top
Published in: Radiation Oncology 1/2010

Open Access 01-12-2010 | Short report

Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer

Authors: Joji Kitayama, Koji Yasuda, Kazushige Kawai, Eiji Sunami, Hirokazu Nagawa

Published in: Radiation Oncology | Issue 1/2010

Login to get access

Abstract

Although neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer (RC), markers to predict the treatment response have not been fully established. In 73 patients with advanced RC who underwent CRT in a neoadjuvant setting, we retrospectively examined the associations between the clinical effects of CRT and blood cell counts before and after CRT. Clinical or pathological complete response (CR) was observed in 10 (14%) cases. The CR rate correlated significantly with the size and the circumferential extent of the tumor. Hemoglobin level, white blood cell (WBC) count and platelet count before CRT did not show a significant difference between CR and non-CR cases. Interestingly, however, lymphocyte ratio in WBC was significantly higher (p = 0.020), while neutrophil ratio tended to be lower (p = 0.099), in CR cases, which was shown to be an independent association by multivariate analysis. When all the blood data obtained in the entire treatment period were evaluated, circulating lymphocyte count was most markedly decreased in the CRT period and gradually recovered by the time of surgery, while the numbers of neutrophils and monocytes were comparatively stable. Moreover, the lymphocyte percentage in samples obtained from CR patients was maintained at a relatively higher level than that from non-CR patients. Since tumor shrinkage is known to be dependent not only on the characteristics of tumor cells but also on various host conditions, our data raise the possibility that a lymphocyte-mediated immune reaction may have a positive role in achieving complete eradication of tumor cells. Maintenance of circulating lymphocyte number may improve the response to CRT in rectal cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004,351(17):1731-1740. 10.1056/NEJMoa040694CrossRefPubMed Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004,351(17):1731-1740. 10.1056/NEJMoa040694CrossRefPubMed
2.
go back to reference Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC: Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006,355(11):1114-1123. 10.1056/NEJMoa060829CrossRefPubMed Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC: Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006,355(11):1114-1123. 10.1056/NEJMoa060829CrossRefPubMed
3.
go back to reference Ortholan C, Francois E, Thomas O, Benchimol D, Baulieux J, Bosset JF, Gerard JP: Role of radiotherapy with surgery for T3 and resectable T4 rectal cancer: evidence from randomized trials. Dis Colon Rectum 2006,49(3):302-310. 10.1007/s10350-005-0263-xCrossRefPubMed Ortholan C, Francois E, Thomas O, Benchimol D, Baulieux J, Bosset JF, Gerard JP: Role of radiotherapy with surgery for T3 and resectable T4 rectal cancer: evidence from randomized trials. Dis Colon Rectum 2006,49(3):302-310. 10.1007/s10350-005-0263-xCrossRefPubMed
4.
go back to reference Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA, Eng C, Krishnan S, Janjan NA, Crane CH: Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer 2007,109(9):1750-1755. 10.1002/cncr.22625CrossRefPubMed Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA, Eng C, Krishnan S, Janjan NA, Crane CH: Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer 2007,109(9):1750-1755. 10.1002/cncr.22625CrossRefPubMed
5.
go back to reference Park HC, Janjan NA, Mendoza TR, Lin EH, Vadhan-Raj S, Hundal M, Zhang Y, Delclos ME, Crane CH, Das P, Wang XS, Cleeland CS, Krishnan S: Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated with Preoperative Chemoradiation Therapy for Rectal Cancer. Int J Radiat Oncol Biol Phys 2009. Park HC, Janjan NA, Mendoza TR, Lin EH, Vadhan-Raj S, Hundal M, Zhang Y, Delclos ME, Crane CH, Das P, Wang XS, Cleeland CS, Krishnan S: Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated with Preoperative Chemoradiation Therapy for Rectal Cancer. Int J Radiat Oncol Biol Phys 2009.
6.
go back to reference Kremser C, Trieb T, Rudisch A, Judmaier W, de Vries A: Dynamic T(1) mapping predicts outcome of chemoradiation therapy in primary rectal carcinoma: sequence implementation and data analysis. J Magn Reson Imaging 2007,26(3):662-671. 10.1002/jmri.21034CrossRefPubMed Kremser C, Trieb T, Rudisch A, Judmaier W, de Vries A: Dynamic T(1) mapping predicts outcome of chemoradiation therapy in primary rectal carcinoma: sequence implementation and data analysis. J Magn Reson Imaging 2007,26(3):662-671. 10.1002/jmri.21034CrossRefPubMed
7.
go back to reference Konski A, Li T, Sigurdson E, Cohen SJ, Small W Jr, Spies S, Yu JQ, Wahl A, Stryker S, Meropol NJ: Use of molecular imaging to predict clinical outcome in patients with rectal cancer after preoperative chemotherapy and radiation. Int J Radiat Oncol Biol Phys 2009,74(1):55-59. 10.1016/j.ijrobp.2008.07.050PubMedCentralCrossRefPubMed Konski A, Li T, Sigurdson E, Cohen SJ, Small W Jr, Spies S, Yu JQ, Wahl A, Stryker S, Meropol NJ: Use of molecular imaging to predict clinical outcome in patients with rectal cancer after preoperative chemotherapy and radiation. Int J Radiat Oncol Biol Phys 2009,74(1):55-59. 10.1016/j.ijrobp.2008.07.050PubMedCentralCrossRefPubMed
8.
go back to reference Jiang SM, Wang RB, Yu JM, Zhu KL, Mu DB, Xu ZF: Correlation of VEGF and Ki67 expression with sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma. Zhonghua Zhong Liu Za Zhi 2008,30(8):602-605.PubMed Jiang SM, Wang RB, Yu JM, Zhu KL, Mu DB, Xu ZF: Correlation of VEGF and Ki67 expression with sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma. Zhonghua Zhong Liu Za Zhi 2008,30(8):602-605.PubMed
9.
go back to reference Kikuchi M, Mikami T, Sato T, Tokuyama W, Araki K, Watanabe M, Saigenji K, Okayasu I: High Ki67, Bax, and thymidylate synthase expression well correlates with response to chemoradiation therapy in locally advanced rectal cancers: proposal of a logistic model for prediction. Br J Cancer 2009,101(1):116-123. 10.1038/sj.bjc.6605105PubMedCentralCrossRefPubMed Kikuchi M, Mikami T, Sato T, Tokuyama W, Araki K, Watanabe M, Saigenji K, Okayasu I: High Ki67, Bax, and thymidylate synthase expression well correlates with response to chemoradiation therapy in locally advanced rectal cancers: proposal of a logistic model for prediction. Br J Cancer 2009,101(1):116-123. 10.1038/sj.bjc.6605105PubMedCentralCrossRefPubMed
10.
go back to reference Kuremsky JG, Tepper JE, McLeod HL: Biomarkers for response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys 2009,74(3):673-688. 10.1016/j.ijrobp.2009.03.003CrossRefPubMed Kuremsky JG, Tepper JE, McLeod HL: Biomarkers for response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys 2009,74(3):673-688. 10.1016/j.ijrobp.2009.03.003CrossRefPubMed
11.
go back to reference Stjernsward J, Jondal M, Vanky F, Wigzell H, Sealy R: Lymphopenia and change in distribution of human B and T lymphocytes in peripheral blood induced by irradiation for mammary carcinoma. Lancet 1972,1(7765):1352-1356. 10.1016/S0140-6736(72)91091-4CrossRefPubMed Stjernsward J, Jondal M, Vanky F, Wigzell H, Sealy R: Lymphopenia and change in distribution of human B and T lymphocytes in peripheral blood induced by irradiation for mammary carcinoma. Lancet 1972,1(7765):1352-1356. 10.1016/S0140-6736(72)91091-4CrossRefPubMed
12.
go back to reference Stratton JA, Byfield PE, Byfield JE, Small RC, Benfield J, Pilch Y: A comparison of the acute effects of radiation therapy, including or excluding the thymus, on the lymphocyte subpopulations of cancer patients. J Clin Invest 1975,56(1):88-97. 10.1172/JCI108084PubMedCentralCrossRefPubMed Stratton JA, Byfield PE, Byfield JE, Small RC, Benfield J, Pilch Y: A comparison of the acute effects of radiation therapy, including or excluding the thymus, on the lymphocyte subpopulations of cancer patients. J Clin Invest 1975,56(1):88-97. 10.1172/JCI108084PubMedCentralCrossRefPubMed
13.
go back to reference O'Toole C, Unsgaard B: Clinical status and rate of recovery of blood lymphocyte levels after radiotherapy for bladder cancer. Cancer Res 1979,39(3):840-843.PubMed O'Toole C, Unsgaard B: Clinical status and rate of recovery of blood lymphocyte levels after radiotherapy for bladder cancer. Cancer Res 1979,39(3):840-843.PubMed
14.
go back to reference Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL: Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Cancer Res 2004,10(11):3755-3762. 10.1158/1078-0432.CCR-04-0054CrossRefPubMed Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL: Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Cancer Res 2004,10(11):3755-3762. 10.1158/1078-0432.CCR-04-0054CrossRefPubMed
15.
go back to reference Barcellos-Hoff MH, Park C, Wright EG: Radiation and the microenvironment - tumorigenesis and therapy. Nat Rev Cancer 2005,5(11):867-875. 10.1038/nrc1735CrossRefPubMed Barcellos-Hoff MH, Park C, Wright EG: Radiation and the microenvironment - tumorigenesis and therapy. Nat Rev Cancer 2005,5(11):867-875. 10.1038/nrc1735CrossRefPubMed
16.
go back to reference Prise KM, Schettino G, Folkard M, Held KD: New insights on cell death from radiation exposure. Lancet Oncol 2005,6(7):520-528. 10.1016/S1470-2045(05)70246-1CrossRefPubMed Prise KM, Schettino G, Folkard M, Held KD: New insights on cell death from radiation exposure. Lancet Oncol 2005,6(7):520-528. 10.1016/S1470-2045(05)70246-1CrossRefPubMed
17.
go back to reference Stone HB, Peters LJ, Milas L: Effect of host immune capability on radiocurability and subsequent transplantability of a murine fibrosarcoma. J Natl Cancer Inst 1979,63(5):1229-1235.PubMed Stone HB, Peters LJ, Milas L: Effect of host immune capability on radiocurability and subsequent transplantability of a murine fibrosarcoma. J Natl Cancer Inst 1979,63(5):1229-1235.PubMed
18.
go back to reference Demaria S, Formenti SC: Sensors of ionizing radiation effects on the immunological microenvironment of cancer. Int J Radiat Biol 2007,83(11-12):819-825. 10.1080/09553000701481816CrossRefPubMed Demaria S, Formenti SC: Sensors of ionizing radiation effects on the immunological microenvironment of cancer. Int J Radiat Biol 2007,83(11-12):819-825. 10.1080/09553000701481816CrossRefPubMed
19.
go back to reference Lorimore SA, Coates PJ, Scobie GE, Milne G, Wright EG: Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects? Oncogene 2001,20(48):7085-7095. 10.1038/sj.onc.1204903CrossRefPubMed Lorimore SA, Coates PJ, Scobie GE, Milne G, Wright EG: Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects? Oncogene 2001,20(48):7085-7095. 10.1038/sj.onc.1204903CrossRefPubMed
20.
go back to reference Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, Ryffel B, Barrat FJ, Saftig P, Levi F, Lidereau R, Nogues C, Mira JP, Chompret A, Joulin V, Clavel-Chapelon F, Bourhis J, Andre F, Delaloge S, Tursz T, Kroemer G, Zitvogel L: Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 2007,13(9):1050-1059. 10.1038/nm1622CrossRefPubMed Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, Ryffel B, Barrat FJ, Saftig P, Levi F, Lidereau R, Nogues C, Mira JP, Chompret A, Joulin V, Clavel-Chapelon F, Bourhis J, Andre F, Delaloge S, Tursz T, Kroemer G, Zitvogel L: Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 2007,13(9):1050-1059. 10.1038/nm1622CrossRefPubMed
21.
go back to reference Nesslinger NJ, Sahota RA, Stone B, Johnson K, Chima N, King C, Rasmussen D, Bishop D, Rennie PS, Gleave M, Blood P, Pai H, Ludgate C, Nelson BH: Standard treatments induce antigen-specific immune responses in prostate cancer. Clin Cancer Res 2007,13(5):1493-1502. 10.1158/1078-0432.CCR-06-1772CrossRefPubMed Nesslinger NJ, Sahota RA, Stone B, Johnson K, Chima N, King C, Rasmussen D, Bishop D, Rennie PS, Gleave M, Blood P, Pai H, Ludgate C, Nelson BH: Standard treatments induce antigen-specific immune responses in prostate cancer. Clin Cancer Res 2007,13(5):1493-1502. 10.1158/1078-0432.CCR-06-1772CrossRefPubMed
22.
go back to reference Schaue D, Comin-Anduix B, Ribas A, Zhang L, Goodglick L, Sayre JW, Debucquoy A, Haustermans K, McBride WH: T-cell responses to survivin in cancer patients undergoing radiation therapy. Clin Cancer Res 2008,14(15):4883-4890. 10.1158/1078-0432.CCR-07-4462PubMedCentralCrossRefPubMed Schaue D, Comin-Anduix B, Ribas A, Zhang L, Goodglick L, Sayre JW, Debucquoy A, Haustermans K, McBride WH: T-cell responses to survivin in cancer patients undergoing radiation therapy. Clin Cancer Res 2008,14(15):4883-4890. 10.1158/1078-0432.CCR-07-4462PubMedCentralCrossRefPubMed
23.
go back to reference Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC: Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 2009,69(4):1553-1560. 10.1158/0008-5472.CAN-08-1921PubMedCentralCrossRefPubMed Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC: Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 2009,69(4):1553-1560. 10.1158/0008-5472.CAN-08-1921PubMedCentralCrossRefPubMed
24.
go back to reference Muller I, Munder M, Kropf P, Hansch GM: Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms? Trends Immunol 2009,30(11):522-530. 10.1016/j.it.2009.07.007CrossRefPubMed Muller I, Munder M, Kropf P, Hansch GM: Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms? Trends Immunol 2009,30(11):522-530. 10.1016/j.it.2009.07.007CrossRefPubMed
Metadata
Title
Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer
Authors
Joji Kitayama
Koji Yasuda
Kazushige Kawai
Eiji Sunami
Hirokazu Nagawa
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2010
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-5-47

Other articles of this Issue 1/2010

Radiation Oncology 1/2010 Go to the issue