Skip to main content
Erschienen in: Journal of Neuro-Oncology 3/2017

22.03.2017 | Clinical Study

Neutrophil–lymphocyte ratio dynamics during concurrent chemo-radiotherapy for glioblastoma is an independent predictor for overall survival

verfasst von: Matthew Mason, Catherine Maurice, Mairead G. McNamara, Minh Thi Tieu, Zarnie Lwin, Barbara-Ann Millar, Cynthia Menard, Normand Laperriere, Michael Milosevic, Eshetu G. Atenafu, Warren Mason, Caroline Chung

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

Abstract

Elevated neutrophil–lymphocyte ratio (NLR) may predict worse outcomes in cancer, including glioblastoma (GBM). This study assessed whether change in NLR during focal radiotherapy and concomitant temozolomide (RT-TMZ) provides further prognostic information. This was a retrospective review of patients treated with RT-TMZ for histologically confirmed GBM from January 2004 to September 2010. Variables assessed included age, ECOG performance status (PS), dexamethasone use and extent of surgery. Hematological results were collected at baseline, during and 4 weeks post RT-TMZ. Kaplan–Meier method was used to calculate overall survival (OS). Multivariable analysis (MVA) assessed for joint effect of covariates on OS and Pearson Correlation Coefficients assessed for association between dexamethasone dose and NLR change. With a median age of 55 (range 18–70), 369 patients were included. Median follow up was 15.1 month (range 1.6–134.6). The OS was 66.1% (95% CI 61.2–70.6) and 31.4 (95% CI 26.8–36.1) at 1 and 2 years, respectively. On univariate analysis, both decrease in NLR post RT-TMZ (HR 0.641, p < 0.0001) and baseline NLR < 7.5 (HR 0.628, p < 0.0001) were associated with longer OS. On MVA decrease in NLR (HR 0.727, 95% CI 0.578–0.915), age (HR 1.025, 95% CI 1.012–1.038), baseline neutrophil (<8) (HR 0.689, 95% CI 0.532–0.891), total TMZ cycles (HR 0.89, 95% CI 0.867–0.913) and PS (HR 0.476, 95% CI 0.332–0.683) were independent predictors of OS. These findings suggest that a decrease in NLR during RT-TMZ, accounting for known prognostic factors, is an independent prognostic factor for survival in GBM.
Literatur
1.
Zurück zum Zitat Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol 15(Suppl 2):ii1–56. doi:10.1093/neuonc/not151 CrossRefPubMedPubMedCentral Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol 15(Suppl 2):ii1–56. doi:10.​1093/​neuonc/​not151 CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10):987–996. doi:10.1056/NEJMoa043330 CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10):987–996. doi:10.​1056/​NEJMoa043330 CrossRefPubMed
3.
Zurück zum Zitat Curran WJ Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE et al (1993) Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst 85(9):704–710CrossRefPubMed Curran WJ Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE et al (1993) Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst 85(9):704–710CrossRefPubMed
4.
Zurück zum Zitat Paszat L, Laperriere N, Groome P, Schulze K, Mackillop W, Holowaty E (2001) A population-based study of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 51(1):100–107CrossRefPubMed Paszat L, Laperriere N, Groome P, Schulze K, Mackillop W, Holowaty E (2001) A population-based study of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 51(1):100–107CrossRefPubMed
5.
Zurück zum Zitat Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95(2):190–198. doi:10.3171/jns.2001.95.2.0190 CrossRefPubMed Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95(2):190–198. doi:10.​3171/​jns.​2001.​95.​2.​0190 CrossRefPubMed
6.
Zurück zum Zitat Wick W, Meisner C, Hentschel B, Platten M, Schilling A, Wiestler B, Sabel MC, Koeppen S, Ketter R, Weiler M, Tabatabai G, von Deimling A, Gramatzki D, Westphal M, Schackert G, Loeffler M, Simon M, Reifenberger G, Weller M (2013) Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. Neurology 81(17):1515–1522. doi:10.1212/WNL.0b013e3182a95680 CrossRefPubMed Wick W, Meisner C, Hentschel B, Platten M, Schilling A, Wiestler B, Sabel MC, Koeppen S, Ketter R, Weiler M, Tabatabai G, von Deimling A, Gramatzki D, Westphal M, Schackert G, Loeffler M, Simon M, Reifenberger G, Weller M (2013) Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. Neurology 81(17):1515–1522. doi:10.​1212/​WNL.​0b013e3182a95680​ CrossRefPubMed
9.
Zurück zum Zitat Sato H, Tsubosa Y, Kawano T (2012) Correlation between the pretherapeutic neutrophil to lymphocyte ratio and the pathologic response to neoadjuvant chemotherapy in patients with advanced esophageal cancer. World J Surg 36(3):617–622. doi:10.1007/s00268-011-1411-1 CrossRefPubMed Sato H, Tsubosa Y, Kawano T (2012) Correlation between the pretherapeutic neutrophil to lymphocyte ratio and the pathologic response to neoadjuvant chemotherapy in patients with advanced esophageal cancer. World J Surg 36(3):617–622. doi:10.​1007/​s00268-011-1411-1 CrossRefPubMed
11.
Zurück zum Zitat Cedres S, Torrejon D, Martinez A, Martinez P, Navarro A, Zamora E, Mulet-Margalef N, Felip E (2012) Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer. Clin Transl Oncol 14(11):864–869. doi:10.1007/s12094-012-0872-5 CrossRefPubMed Cedres S, Torrejon D, Martinez A, Martinez P, Navarro A, Zamora E, Mulet-Margalef N, Felip E (2012) Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer. Clin Transl Oncol 14(11):864–869. doi:10.​1007/​s12094-012-0872-5 CrossRefPubMed
12.
Zurück zum Zitat Templeton AJ, Pezaro C, Omlin A, McNamara MG, Leibowitz-Amit R, Vera-Badillo FE, Attard G, de Bono JS, Tannock IF, Amir E (2014) Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio. Cancer. doi:10.1002/cncr.28890 PubMed Templeton AJ, Pezaro C, Omlin A, McNamara MG, Leibowitz-Amit R, Vera-Badillo FE, Attard G, de Bono JS, Tannock IF, Amir E (2014) Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio. Cancer. doi:10.​1002/​cncr.​28890 PubMed
13.
Zurück zum Zitat Malietzis G, Giacometti M, Kennedy RH, Athanasiou T, Aziz O, Jenkins JT (2014) The emerging role of neutrophil to lymphocyte ratio in determining colorectal cancer treatment outcomes: a systematic review and meta-analysis. Ann Surg Oncol 21(12):3938–3946. doi:10.1245/s10434-014-3815-2 CrossRefPubMed Malietzis G, Giacometti M, Kennedy RH, Athanasiou T, Aziz O, Jenkins JT (2014) The emerging role of neutrophil to lymphocyte ratio in determining colorectal cancer treatment outcomes: a systematic review and meta-analysis. Ann Surg Oncol 21(12):3938–3946. doi:10.​1245/​s10434-014-3815-2 CrossRefPubMed
14.
Zurück zum Zitat Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B, Tannock IF, Amir E (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106(6):dju124. doi:10.1093/jnci/dju124 CrossRefPubMed Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B, Tannock IF, Amir E (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106(6):dju124. doi:10.​1093/​jnci/​dju124 CrossRefPubMed
15.
Zurück zum Zitat Bambury RM, Teo MY, Power DG, Yusuf A, Murray S, Battley JE, Drake C, O’Dea P, Bermingham N, Keohane C, Grossman SA, Moylan EJ, O’Reilly S (2013) The association of pre-treatment neutrophil to lymphocyte ratio with overall survival in patients with glioblastoma multiforme. J Neurooncol 114(1):149–154. doi:10.1007/s11060-013-1164-9 CrossRefPubMed Bambury RM, Teo MY, Power DG, Yusuf A, Murray S, Battley JE, Drake C, O’Dea P, Bermingham N, Keohane C, Grossman SA, Moylan EJ, O’Reilly S (2013) The association of pre-treatment neutrophil to lymphocyte ratio with overall survival in patients with glioblastoma multiforme. J Neurooncol 114(1):149–154. doi:10.​1007/​s11060-013-1164-9 CrossRefPubMed
16.
Zurück zum Zitat McNamara MG, Lwin Z, Jiang H, Templeton AJ, Zadeh G, Bernstein M, Chung C, Millar BA, Laperriere N, Mason WP (2014) Factors impacting survival following second surgery in patients with glioblastoma in the temozolomide treatment era, incorporating neutrophil/lymphocyte ratio and time to first progression. J Neurooncol 117(1):147–152. doi:10.1007/s11060-014-1366-9 CrossRefPubMed McNamara MG, Lwin Z, Jiang H, Templeton AJ, Zadeh G, Bernstein M, Chung C, Millar BA, Laperriere N, Mason WP (2014) Factors impacting survival following second surgery in patients with glioblastoma in the temozolomide treatment era, incorporating neutrophil/lymphocyte ratio and time to first progression. J Neurooncol 117(1):147–152. doi:10.​1007/​s11060-014-1366-9 CrossRefPubMed
17.
Zurück zum Zitat Fadul CE, Fisher JL, Gui J, Hampton TH, Cote AL, Ernstoff MS (2011) Immune modulation effects of concomitant temozolomide and radiation therapy on peripheral blood mononuclear cells in patients with glioblastoma multiforme. Neuro Oncol 13(4):393–400. doi:10.1093/neuonc/noq204 CrossRefPubMedPubMedCentral Fadul CE, Fisher JL, Gui J, Hampton TH, Cote AL, Ernstoff MS (2011) Immune modulation effects of concomitant temozolomide and radiation therapy on peripheral blood mononuclear cells in patients with glioblastoma multiforme. Neuro Oncol 13(4):393–400. doi:10.​1093/​neuonc/​noq204 CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Lohr J, Ratliff T, Huppertz A, Ge Y, Dictus C, Ahmadi R, Grau S, Hiraoka N, Eckstein V, Ecker RC, Korff T, von Deimling A, Unterberg A, Beckhove P, Herold-Mende C (2011) Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived TGF-beta. Clin Cancer Res 17(13):4296–4308. doi:10.1158/1078-0432.CCR-10-2557 CrossRefPubMed Lohr J, Ratliff T, Huppertz A, Ge Y, Dictus C, Ahmadi R, Grau S, Hiraoka N, Eckstein V, Ecker RC, Korff T, von Deimling A, Unterberg A, Beckhove P, Herold-Mende C (2011) Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived TGF-beta. Clin Cancer Res 17(13):4296–4308. doi:10.​1158/​1078-0432.​CCR-10-2557 CrossRefPubMed
21.
Zurück zum Zitat Atzpodien J, Reitz M (2008) Peripheral blood neutrophils as independent immunologic predictor of response and long-term survival upon immunotherapy in metastatic renal-cell carcinoma. Cancer Biother Radiopharm 23(1):129–134. doi:10.1089/cbr.2007.0429 CrossRefPubMed Atzpodien J, Reitz M (2008) Peripheral blood neutrophils as independent immunologic predictor of response and long-term survival upon immunotherapy in metastatic renal-cell carcinoma. Cancer Biother Radiopharm 23(1):129–134. doi:10.​1089/​cbr.​2007.​0429 CrossRefPubMed
22.
Zurück zum Zitat Schmidt H, Bastholt L, Geertsen P, Christensen IJ, Larsen S, Gehl J, von der Maase H (2005) Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model. Br J Cancer 93(3):273–278. doi:10.1038/sj.bjc.6602702 CrossRefPubMedPubMedCentral Schmidt H, Bastholt L, Geertsen P, Christensen IJ, Larsen S, Gehl J, von der Maase H (2005) Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model. Br J Cancer 93(3):273–278. doi:10.​1038/​sj.​bjc.​6602702 CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Mabuchi S, Matsumoto Y, Hamasaki T, Kawano M, Hisamatsu T, Mutch DG, Kimura T (2012) Elevated white blood cell count at the time of recurrence diagnosis is an indicator of short survival in patients with recurrent cervical cancer. Int J Gynecol Cancer 22(9):1545–1551. doi:10.1097/IGC.0b013e31826ea0eb PubMed Mabuchi S, Matsumoto Y, Hamasaki T, Kawano M, Hisamatsu T, Mutch DG, Kimura T (2012) Elevated white blood cell count at the time of recurrence diagnosis is an indicator of short survival in patients with recurrent cervical cancer. Int J Gynecol Cancer 22(9):1545–1551. doi:10.​1097/​IGC.​0b013e31826ea0eb​ PubMed
24.
Zurück zum Zitat McGary CT, Miele ME, Welch DR (1995) Highly metastatic 13762NF rat mammary adenocarcinoma cell clones stimulate bone marrow by secretion of granulocyte-macrophage colony-stimulating factor/interleukin-3 activity. Am J Pathol 147(6):1668–1681PubMedPubMedCentral McGary CT, Miele ME, Welch DR (1995) Highly metastatic 13762NF rat mammary adenocarcinoma cell clones stimulate bone marrow by secretion of granulocyte-macrophage colony-stimulating factor/interleukin-3 activity. Am J Pathol 147(6):1668–1681PubMedPubMedCentral
25.
Zurück zum Zitat Fossati G, Ricevuti G, Edwards SW, Walker C, Dalton A, Rossi ML (1999) Neutrophil infiltration into human gliomas. Acta Neuropathol 98(4):349–354CrossRefPubMed Fossati G, Ricevuti G, Edwards SW, Walker C, Dalton A, Rossi ML (1999) Neutrophil infiltration into human gliomas. Acta Neuropathol 98(4):349–354CrossRefPubMed
31.
Zurück zum Zitat Grossman SA, Ellsworth S, Campian J, Wild AT, Herman JM, Laheru D, Brock M, Balmanoukian A, Ye X (2015) Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Canc Netw 13(10):1225–1231CrossRefPubMedPubMedCentral Grossman SA, Ellsworth S, Campian J, Wild AT, Herman JM, Laheru D, Brock M, Balmanoukian A, Ye X (2015) Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Canc Netw 13(10):1225–1231CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Jen JF, Cutler DL, Pai SM, Batra VK, Affrime MB, Zambas DN, Heft S, Hajian G (2000) Population pharmacokinetics of temozolomide in cancer patients. Pharm Res 17(10):1284–1289CrossRefPubMed Jen JF, Cutler DL, Pai SM, Batra VK, Affrime MB, Zambas DN, Heft S, Hajian G (2000) Population pharmacokinetics of temozolomide in cancer patients. Pharm Res 17(10):1284–1289CrossRefPubMed
33.
Zurück zum Zitat Ruiz LM, Bedoya G, Salazar J, Garcia de OD, Patino PJ (2002) Dexamethasone inhibits apoptosis of human neutrophils induced by reactive oxygen species. Inflammation 26(5):215–222CrossRefPubMed Ruiz LM, Bedoya G, Salazar J, Garcia de OD, Patino PJ (2002) Dexamethasone inhibits apoptosis of human neutrophils induced by reactive oxygen species. Inflammation 26(5):215–222CrossRefPubMed
34.
Zurück zum Zitat Liles WC, Dale DC, Klebanoff SJ (1995) Glucocorticoids inhibit apoptosis of human neutrophils. Blood 86(8):3181–3188PubMed Liles WC, Dale DC, Klebanoff SJ (1995) Glucocorticoids inhibit apoptosis of human neutrophils. Blood 86(8):3181–3188PubMed
35.
36.
Zurück zum Zitat Gustafson MP, Lin Y, New KC, Bulur PA, O’Neill BP, Gastineau DA, Dietz AB (2010) Systemic immune suppression in glioblastoma: the interplay between CD14 + HLA-DRlo/neg monocytes, tumor factors, and dexamethasone. Neuro Oncol 12(7):631–644. doi:10.1093/neuonc/noq001 CrossRefPubMedPubMedCentral Gustafson MP, Lin Y, New KC, Bulur PA, O’Neill BP, Gastineau DA, Dietz AB (2010) Systemic immune suppression in glioblastoma: the interplay between CD14 + HLA-DRlo/neg monocytes, tumor factors, and dexamethasone. Neuro Oncol 12(7):631–644. doi:10.​1093/​neuonc/​noq001 CrossRefPubMedPubMedCentral
Metadaten
Titel
Neutrophil–lymphocyte ratio dynamics during concurrent chemo-radiotherapy for glioblastoma is an independent predictor for overall survival
verfasst von
Matthew Mason
Catherine Maurice
Mairead G. McNamara
Minh Thi Tieu
Zarnie Lwin
Barbara-Ann Millar
Cynthia Menard
Normand Laperriere
Michael Milosevic
Eshetu G. Atenafu
Warren Mason
Caroline Chung
Publikationsdatum
22.03.2017
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 3/2017
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-017-2395-y

Weitere Artikel der Ausgabe 3/2017

Journal of Neuro-Oncology 3/2017 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.