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CC BY-NC-ND 4.0 · Avicenna J Med 2022; 12(02): 067-072
DOI: 10.1055/s-0042-1749613
Original Article

The Predictive Value of Peripheral Immune Cell Counts for the Presence of Brain Metastases in Stage IV Non-Small-Cell Lung Cancer (NSCLC)

I Abuelbeh
1   Department of General Surgery, Manchester Royal Infirmary, Manchester, United Kingdom
,
O Abu-Shawer
2   Department of Internal Medicine, Cleveland Clinic, Cleveland, United States
,
M Abu-Shawer
3   Department of Internal Medicine, Istiklal Hospital, Amman, Jordan
,
M Alkderat
4   University of Jordan School of Medicine, Amman, Jordan
,
M Safi
5   Department of General Surgery, Barnsley Hospital, Barnsley, United Kingdom
,
A Alwazani
6   University of Jordan School of Medicine, Amman, Jordan
,
A Alkhatib 
7   Department of Surgery, King Hussein Cancer Center, Amman, Jordan
,
B Abu-Hussain 
8   University of Jordan School of Medicine, Amman, Jordan
,
M Aladawi
9   Department of Neurological Sciences, University of Nebraska, Omaha, United States
,
S Ismail
10   University of Jordan School of Medicine, Amman, Jordan
,
T Altamimi
11   Department of Internal Medicine, Rochester General Hospital, New York, United States
,
Taher Abu Hejleh
12   Department of Internal Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, University of Iowa Carver College of Medicine, Iowa City, Iowa
13   Department of Internal Medicine, King Hussein Cancer Center, Amman, Jordan
› Author Affiliations
Funding None.
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Abstract

Background High neutrophil–lymphocyte ratio (NLR) is associated with poor survival in lung cancer. This study evaluates whether NLR is associated with baseline brain metastasis in stage IV non-small cell lung cancer (NSCLC).

Methods Medical records of stage IV NSCLC patients treated at King Hussein Cancer Center (Amman-Jordan) between 2006 and 2016 were reviewed. Patients with baseline brain imaging and complete blood count (CBC) were included. Receiver operating characteristic (ROC) curve was used to identify the optimal cutoff value for the association between NLR and baseline brain metastasis. Association between age, gender, location of the primary tumor, histology, and NLR was assessed using univariate and multivariate logistic regression analyses.

Results A total of 722 stage IV NSCLC patients who had baseline brain imaging were included. Median age was 59 years. Baseline brain metastasis was present in 280 patients (39.3%). Nine patients had inconclusive findings about brain metastasis. The ROC curve value of 4.3 was the best fitting cutoff value for NLR association with baseline brain metastasis. NLR ≥ 4.3 was present in 340 patients (48%). The multivariate analyses showed that high baseline NLR (≥ 4.3) was significantly associated with higher odds of baseline brain metastasis (odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.2–2.2; p = 0.0042). Adenocarcinoma histology was also associated with baseline brain metastasis (OR: 0.4, 95% CI: 0.25–0.6; p = 0.001).

Conclusion High NLR is associated with baseline brain metastasis in advanced-stage NSCLC. In the era of immunotherapy and targeted therapies, whether high NLR predicts response of brain metastasis to treatment is unknown.

Keywords

NSCLC - neutrophil–lymphocyte ratio - brain metastasis - stage IV


Publication History

Article published online:
03 July 2022

© 2022. Syrian American Medical Society. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Schouten LJ, Rutten J, Huveneers HAM, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 2002; 94 (10) 2698-2705
    CrossrefPubMedSearch in Google Scholar
  • 2 Popper HH. Progression and metastasis of lung cancer. Cancer Metastasis Rev 2016; 35 (01) 75-91
    CrossrefPubMedSearch in Google Scholar
  • 3 Stenbygaard LE, Sørensen JB, Larsen H, Dombernowsky P. Metastatic pattern in non-resectable non-small cell lung cancer. Acta Oncol 1999; 38 (08) 993-998
    CrossrefPubMedSearch in Google Scholar
  • 4 Ali A, Goffin JR, Arnold A, Ellis PM. Survival of patients with non-small-cell lung cancer after a diagnosis of brain metastases. Curr Oncol 2013; 20 (04) e300-e306
    CrossrefPubMedSearch in Google Scholar
  • 5 Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140 (06) 883-899
    CrossrefPubMedSearch in Google Scholar
  • 6 Moore MM, Chua W, Charles KA, Clarke SJ. Inflammation and cancer: causes and consequences. Clin Pharmacol Ther 2010; 87 (04) 504-508
    CrossrefPubMedSearch in Google Scholar
  • 7 Abu-Shawer M, Abu-Shawer O, Souleiman M. et al. Hematologic markers of lung metastasis in stage IV colorectal cancer. J Gastrointest Cancer 2019; 50 (03) 428-433
    CrossrefPubMedSearch in Google Scholar
  • 8 Haimour A, Abu-Shawer O, Abu-Shawer M. et al. The clinical potential of circulating immune cell counts in primary gastric lymphoma. J Gastrointest Oncol 2021; 12 (02) 365-376
    CrossrefPubMedSearch in Google Scholar
  • 9 Abu-Shawer O, Abu-Shawer M, Haimour A. et al. Hematologic markers of distant metastases in gastric cancer. J Gastrointest Oncol 2019; 10 (03) 529-536
    CrossrefPubMedSearch in Google Scholar
  • 10 Abu-Shawer O, Abu-Shawer M, Shurman A. et al. The clinical value of peripheral immune cell counts in pancreatic cancer. PLoS One 2020; 15 (06) e0232043
    CrossrefSearch in Google Scholar
  • 11 Xie D, Allen MS, Marks R. et al. Nomogram prediction of overall survival for patients with non-small-cell lung cancer incorporating pretreatment peripheral blood markers. Eur J Cardiothorac Surg 2018; 53 (06) 1214-1222
    CrossrefPubMedSearch in Google Scholar
  • 12 Koh YW, Choi J-H, Ahn MS, Choi YW, Lee HW. Baseline neutrophil-lymphocyte ratio is associated with baseline and subsequent presence of brain metastases in advanced non-small-cell lung cancer. Sci Rep 2016; 6 (01) 38585
    CrossrefPubMedSearch in Google Scholar
  • 13 Swierczak A, Mouchemore KA, Hamilton JA, Anderson RL. Neutrophils: important contributors to tumor progression and metastasis. Cancer Metastasis Rev 2015; 34 (04) 735-751
    CrossrefPubMedSearch in Google Scholar
  • 14 Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow?. Lancet 2001; 357 (9255): 539-545
    CrossrefPubMedSearch in Google Scholar
  • 15 Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity 2013; 39 (01) 1-10
    CrossrefPubMedSearch in Google Scholar
  • 16 Ma J, Xu H, Wang S. Immunosuppressive role of myeloid-derived suppressor cells and therapeutic targeting in lung cancer. J Immunol Res 2018; 2018: 6319649
    CrossrefPubMedSearch in Google Scholar
  • 17 Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J. Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis. Am J Med 1981; 71 (05) 773-778
    PubMedSearch in Google Scholar
  • 18 Nakagawa M, Terashima T, D'yachkova Y, Bondy GP, Hogg JC, van Eeden SF. Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes. Circulation 1998; 98 (21) 2307-2313
    CrossrefPubMedSearch in Google Scholar
  • 19 De Ruysscher D, Dingemans AC, Praag J. et al. Prophylactic cranial irradiation versus observation in radically treated stage III non-small-cell lung cancer: a randomized phase III NVALT-11/DLCRG-02 study. J Clin Oncol 2018; 36 (23) 2366-2377
    CrossrefPubMedSearch in Google Scholar
  • 20 Khunger M, Patil PD, Khunger A. et al. Post-treatment changes in hematological parameters predict response to nivolumab monotherapy in non-small cell lung cancer patients. PLoS One 2018; 13 (10) e0197743
    CrossrefPubMedSearch in Google Scholar
  • 21 Peters S, Camidge DR, Shaw AT. et al; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 2017; 377 (09) 829-838
    CrossrefPubMedSearch in Google Scholar
  • 22 Soria J-C, Ohe Y, Vansteenkiste J. et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018; 378 (02) 113-125
    CrossrefPubMedSearch in Google Scholar
  • 23 Wong A. The emerging role of targeted therapy and immunotherapy in the management of brain metastases in non-small cell lung cancer. Front Oncol 2017; 7: 33
    CrossrefPubMedSearch in Google Scholar
  • 24 Abu-Shawer O, Bushnaq T, Abu-Shawer M. Cancer immunotherapy: an updated overview of current strategies and therapeutic agents. Gulf J Oncolog 2019; 1 (29) 76-82
    PubMedSearch in Google Scholar