Skip to main content
Erschienen in: Journal of Neuro-Oncology 3/2018

30.05.2018 | Clinical Study

Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery

verfasst von: Mudit Chowdhary, Jeffrey M. Switchenko, Robert H. Press, Jaymin Jhaveri, Zachary S. Buchwald, Philip A. Blumenfeld, Gaurav Marwaha, Aidnag Diaz, Dian Wang, Ross A. Abrams, Jeffrey J. Olson, Hui-Kuo G. Shu, Walter J. Curran, Kirtesh R. Patel

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Neutrophil-to-lymphocyte ratio (NLR) is a surrogate for systemic inflammatory response and its elevation has been shown to be a poor prognostic factor in various malignancies. Stereotactic radiosurgery (SRS) can induce a leukocyte-predominant inflammatory response. This study investigates the prognostic impact of post-SRS NLR in patients with brain metastases (BM).

Methods

BM patients treated with SRS from 2003 to 2015 were retrospectively identified. NLR was calculated from the most recent full blood counts post-SRS. Overall survival (OS) and intracranial outcomes were calculated using the Kaplan–Meier method and cumulative incidence with competing risk for death, respectively.

Results

188 patients with 328 BM treated with SRS had calculable post-treatment NLR values. Of these, 51 (27.1%) had a NLR > 6. The overall median imaging follow-up was 13.2 (14.0 vs. 8.7 for NLR ≤ 6.0 vs. > 6.0) months. Baseline patient and treatment characteristics were well balanced, except for lower rate of ECOG performance status 0 in the NLR > 6 cohort (33.3 vs. 44.2%, p = 0.026). NLR > 6 was associated with worse 1- and 2-year OS: 59.9 vs. 72.9% and 24.6 vs. 43.8%, (p = 0.028). On multivariable analysis, NLR > 6 (HR: 1.53; 95% CI 1.03–2.26, p = 0.036) and presence of extracranial metastases (HR: 1.90; 95% CI 1.30–2.78; p < 0.001) were significant predictors for worse OS. No association was seen with NLR and intracranial outcomes.

Conclusion

Post-treatment NLR, a potential marker for post-SRS inflammatory response, is inversely associated with OS in patients with BM. If prospectively validated, NLR is a simple, systemic marker that can be easily used to guide subsequent management.
Literatur
1.
Zurück zum Zitat Nayak L, Lee EQ, Wen PY (2012) Epidemiology of brain metastases. Curr Oncol Rep 14(1):48–54CrossRefPubMed Nayak L, Lee EQ, Wen PY (2012) Epidemiology of brain metastases. Curr Oncol Rep 14(1):48–54CrossRefPubMed
2.
Zurück zum Zitat Patel KR, Lawson DH, Kudchadkar RR et al (2015) Two heads better than one? Ipilimumab immunotherapy and radiation therapy for melanoma brain metastases. Neuro-oncology 17(10):1312–1321CrossRefPubMedPubMedCentral Patel KR, Lawson DH, Kudchadkar RR et al (2015) Two heads better than one? Ipilimumab immunotherapy and radiation therapy for melanoma brain metastases. Neuro-oncology 17(10):1312–1321CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Chowdhary M, Patel KR, Danish HH, Lawson DH, Khan MK (2016) BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy. OncoTargets Ther 9:7149–7159CrossRef Chowdhary M, Patel KR, Danish HH, Lawson DH, Khan MK (2016) BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy. OncoTargets Ther 9:7149–7159CrossRef
4.
Zurück zum Zitat Kocher M, Soffietti R, Abacioglu U et al (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 29(2):134–141CrossRefPubMed Kocher M, Soffietti R, Abacioglu U et al (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 29(2):134–141CrossRefPubMed
5.
Zurück zum Zitat Gaspar L, Scott C, Rotman M et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37(4):745–751CrossRefPubMed Gaspar L, Scott C, Rotman M et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37(4):745–751CrossRefPubMed
6.
Zurück zum Zitat Sperduto CM, Watanabe Y, Mullan J et al (2008) A validation study of a new prognostic index for patients with brain metastases: the Graded Prognostic Assessment. J Neurosurg 109(Suppl):87–89PubMed Sperduto CM, Watanabe Y, Mullan J et al (2008) A validation study of a new prognostic index for patients with brain metastases: the Graded Prognostic Assessment. J Neurosurg 109(Suppl):87–89PubMed
7.
Zurück zum Zitat Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W (2008) A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 70(2):510–514CrossRefPubMed Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W (2008) A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 70(2):510–514CrossRefPubMed
9.
Zurück zum Zitat Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674CrossRefPubMed Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674CrossRefPubMed
10.
Zurück zum Zitat Alagappan M, Pollom EL, von Eyben R et al (2018) Albumin and neutrophil-lymphocyte ratio (NLR) predict survival in patients with pancreatic adenocarcinoma treated with SBRT. Am J Clin Oncol 41(3):242–247PubMed Alagappan M, Pollom EL, von Eyben R et al (2018) Albumin and neutrophil-lymphocyte ratio (NLR) predict survival in patients with pancreatic adenocarcinoma treated with SBRT. Am J Clin Oncol 41(3):242–247PubMed
11.
Zurück zum Zitat Hyder J, Boggs DH, Hanna A, Suntharalingam M, Chuong MD (2016) Changes in neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios during chemoradiation predict for survival and pathologic complete response in trimodality esophageal cancer patients. J Gastrointest Oncol 7(2):189–195PubMedPubMedCentral Hyder J, Boggs DH, Hanna A, Suntharalingam M, Chuong MD (2016) Changes in neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios during chemoradiation predict for survival and pathologic complete response in trimodality esophageal cancer patients. J Gastrointest Oncol 7(2):189–195PubMedPubMedCentral
12.
Zurück zum Zitat Shaverdian N, Veruttipong D, Wang J, Schaue D, Kupelian P, Lee P (2016) Pretreatment immune parameters predict for overall survival and toxicity in early-stage non-small-cell lung cancer patients treated with stereotactic body radiation therapy. Clin Lung Cancer 17(1):39–46CrossRefPubMed Shaverdian N, Veruttipong D, Wang J, Schaue D, Kupelian P, Lee P (2016) Pretreatment immune parameters predict for overall survival and toxicity in early-stage non-small-cell lung cancer patients treated with stereotactic body radiation therapy. Clin Lung Cancer 17(1):39–46CrossRefPubMed
13.
Zurück zum Zitat Louveau A, Smirnov I, Keyes TJ et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523(7560):337–341CrossRefPubMedPubMedCentral Louveau A, Smirnov I, Keyes TJ et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523(7560):337–341CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Bambury RM, Teo MY, Power DG et al (2013) The association of pre-treatment neutrophil to lymphocyte ratio with overall survival in patients with glioblastoma multiforme. J Neurooncol 114(1):149–154CrossRefPubMed Bambury RM, Teo MY, Power DG et al (2013) The association of pre-treatment neutrophil to lymphocyte ratio with overall survival in patients with glioblastoma multiforme. J Neurooncol 114(1):149–154CrossRefPubMed
15.
Zurück zum Zitat Mason M, Maurice C, McNamara MG et al (2017) Neutrophil-lymphocyte ratio dynamics during concurrent chemo-radiotherapy for glioblastoma is an independent predictor for overall survival. J Neurooncol 132(3):463–471CrossRefPubMed Mason M, Maurice C, McNamara MG et al (2017) Neutrophil-lymphocyte ratio dynamics during concurrent chemo-radiotherapy for glioblastoma is an independent predictor for overall survival. J Neurooncol 132(3):463–471CrossRefPubMed
16.
Zurück zum Zitat Patel KR, Prabhu RS, Kandula S et al (2014) Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone. J Neurooncol 120(3):657–663CrossRefPubMed Patel KR, Prabhu RS, Kandula S et al (2014) Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone. J Neurooncol 120(3):657–663CrossRefPubMed
17.
Zurück zum Zitat Eaton BR, LaRiviere MJ, Kim S et al (2015) Hypofractionated radiosurgery has a better safety profile than single fraction radiosurgery for large resected brain metastases. J Neurooncol 123(1):103–111CrossRefPubMed Eaton BR, LaRiviere MJ, Kim S et al (2015) Hypofractionated radiosurgery has a better safety profile than single fraction radiosurgery for large resected brain metastases. J Neurooncol 123(1):103–111CrossRefPubMed
18.
Zurück zum Zitat Shaw E, Scott C, Souhami L et al (2000) Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys 47(2):291–298CrossRefPubMed Shaw E, Scott C, Souhami L et al (2000) Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys 47(2):291–298CrossRefPubMed
19.
Zurück zum Zitat Patel KR, Chowdhary M, Switchenko JM et al (2016) BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis. Melanoma Res 26(4):387–394CrossRefPubMedPubMedCentral Patel KR, Chowdhary M, Switchenko JM et al (2016) BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis. Melanoma Res 26(4):387–394CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Keizman D, Ish-Shalom M, Huang P et al (2012) The association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma. Eur J Cancer 48(2):202–208CrossRefPubMed Keizman D, Ish-Shalom M, Huang P et al (2012) The association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma. Eur J Cancer 48(2):202–208CrossRefPubMed
21.
Zurück zum Zitat Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94(446):496–509CrossRef Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94(446):496–509CrossRef
22.
Zurück zum Zitat de Jager CP, Wever PC, Gemen EF et al (2012) The neutrophil-lymphocyte count ratio in patients with community-acquired pneumonia. PLoS ONE 7(10):e46561CrossRefPubMedPubMedCentral de Jager CP, Wever PC, Gemen EF et al (2012) The neutrophil-lymphocyte count ratio in patients with community-acquired pneumonia. PLoS ONE 7(10):e46561CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Petrie HT, Klassen LW, Kay HD (1985) Inhibition of human cytotoxic T lymphocyte activity in vitro by autologous peripheral blood granulocytes. J Immunol 134(1):230–234PubMed Petrie HT, Klassen LW, Kay HD (1985) Inhibition of human cytotoxic T lymphocyte activity in vitro by autologous peripheral blood granulocytes. J Immunol 134(1):230–234PubMed
24.
Zurück zum Zitat el-Hag A, Clark RA (1987) Immunosuppression by activated human neutrophils. Dependence on the myeloperoxidase system. J Immunol 139(7):2406–2413PubMed el-Hag A, Clark RA (1987) Immunosuppression by activated human neutrophils. Dependence on the myeloperoxidase system. J Immunol 139(7):2406–2413PubMed
25.
Zurück zum Zitat McCourt M, Wang JH, Sookhai S, Redmond HP (1999) Proinflammatory mediators stimulate neutrophil-directed angiogenesis. Arch Surg 134(12):1325–1331CrossRefPubMed McCourt M, Wang JH, Sookhai S, Redmond HP (1999) Proinflammatory mediators stimulate neutrophil-directed angiogenesis. Arch Surg 134(12):1325–1331CrossRefPubMed
26.
Zurück zum Zitat McCourt M, Wang JH, Sookhai S, Redmond HP (2001) Activated human neutrophils release hepatocyte growth factor/scatter factor. Eur J Surg Oncol 27(4):396–403CrossRefPubMed McCourt M, Wang JH, Sookhai S, Redmond HP (2001) Activated human neutrophils release hepatocyte growth factor/scatter factor. Eur J Surg Oncol 27(4):396–403CrossRefPubMed
27.
Zurück zum Zitat Jabłońska E, Kiluk M, Markiewicz W, Piotrowski L, Grabowska Z, Jabłoński J (2001) TNF-alpha, IL-6 and their soluble receptor serum levels and secretion by neutrophils in cancer patients. Arch Immunol Ther Exp 49(1):63–69 Jabłońska E, Kiluk M, Markiewicz W, Piotrowski L, Grabowska Z, Jabłoński J (2001) TNF-alpha, IL-6 and their soluble receptor serum levels and secretion by neutrophils in cancer patients. Arch Immunol Ther Exp 49(1):63–69
28.
Zurück zum Zitat Shamamian P, Schwartz JD, Pocock BJ et al (2001) Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis. J Cell Physiol 189(2):197–206CrossRefPubMed Shamamian P, Schwartz JD, Pocock BJ et al (2001) Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis. J Cell Physiol 189(2):197–206CrossRefPubMed
29.
Zurück zum Zitat Scapini P, Nesi L, Morini M et al (2002) Generation of biologically active angiostatin kringle 1–3 by activated human neutrophils. J Immunol 168(11):5798–5804CrossRefPubMed Scapini P, Nesi L, Morini M et al (2002) Generation of biologically active angiostatin kringle 1–3 by activated human neutrophils. J Immunol 168(11):5798–5804CrossRefPubMed
30.
Zurück zum Zitat Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H (2010) Circulating lymphocyte is in an important determinant of the effectiveness of preoperative radiotherapy in advaced rectal cancer. Radiat Oncol 5:47CrossRefPubMedPubMedCentral Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H (2010) Circulating lymphocyte is in an important determinant of the effectiveness of preoperative radiotherapy in advaced rectal cancer. Radiat Oncol 5:47CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Sharabi AB, Nirschl CJ, Kochel CM et al (2015) Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res 3(4):345–355CrossRefPubMed Sharabi AB, Nirschl CJ, Kochel CM et al (2015) Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res 3(4):345–355CrossRefPubMed
32.
Zurück zum Zitat 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):5458–5468CrossRefPubMed 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):5458–5468CrossRefPubMed
33.
Zurück zum Zitat Shaverdian N, Wang J, Levin-Epstein R et al (2016) Pro-inflammatory state portends poor outcomes with stereotactic radiosurgery for brain metastases. Anticancer Res 36(10):5333–5337CrossRefPubMed Shaverdian N, Wang J, Levin-Epstein R et al (2016) Pro-inflammatory state portends poor outcomes with stereotactic radiosurgery for brain metastases. Anticancer Res 36(10):5333–5337CrossRefPubMed
34.
Zurück zum Zitat Mitsuya K, Nakasu Y, Kurakane T, Hayashi N, Harada H, Nozaki K (2017) Elevated preoperative neutrophil-to-lymphocyte ratio as a predictor of worse survival after resection in patients with brain metastasis. J Neurosurg 127(2):433–437CrossRefPubMed Mitsuya K, Nakasu Y, Kurakane T, Hayashi N, Harada H, Nozaki K (2017) Elevated preoperative neutrophil-to-lymphocyte ratio as a predictor of worse survival after resection in patients with brain metastasis. J Neurosurg 127(2):433–437CrossRefPubMed
Metadaten
Titel
Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery
verfasst von
Mudit Chowdhary
Jeffrey M. Switchenko
Robert H. Press
Jaymin Jhaveri
Zachary S. Buchwald
Philip A. Blumenfeld
Gaurav Marwaha
Aidnag Diaz
Dian Wang
Ross A. Abrams
Jeffrey J. Olson
Hui-Kuo G. Shu
Walter J. Curran
Kirtesh R. Patel
Publikationsdatum
30.05.2018
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 3/2018
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-018-2914-5

Weitere Artikel der Ausgabe 3/2018

Journal of Neuro-Oncology 3/2018 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.