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Risk factors for brain metastasis in patients with small cell lung cancer without prophylactic cranial irradiation

  • Yawen Zheng
  • Linlin Wang
  • Weichong Zhao
  • Yan Dou
  • Wei Lv
  • Hongyan Yang
  • Yuping Sun
  • Ligang Xing
Original Article
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Abstract

Background

This study aimed to determine the risk factors for brain metastasis (BM) and the prognostic factors for overall survival (OS) in patients with small cell lung cancer without prophylactic cranial irradiation (PCI).

Patients and methods

Limited stage small cell lung cancer (LS-SCLC) patients achieving a complete response (CR) or partial response (PR) were enrolled into this study between January 2010 and December 2016. We retrospectively evaluated the influencing factors for time to BM and overall survival (OS).

Results

A total of 153 patients were enrolled into this study. Sixty-eight developed BM during the follow-up period. For the whole cohort, the 1‑ and 2‑year BM rates were 29.4 and 41.2%, respectively. Multivariate analysis showed that T stage (hazard ratio [HR] = 2.27, P = 0.024), neutrophil-to-lymphocyte ratio (NLR; HR = 2.07, P = 0.029), time to thoracic radiotherapy (HR = 0.34, P = 0.002) and chemotherapy cycles (HR = 0.49, P = 0.036) were the independent influencing factors of time to BM. Only NLR (HR = 2.11, P = 0.005) and time to thoracic radiotherapy (HR = 1.95, P = 0.011) were independent prognostic factors of OS. Of the 68 patients developing BM, those with BM occurring as the first relapse (42/68) had better OS than the others (39.5 months vs 23.0 months, P = 0.016).

Conclusion

LS-SCLC patients without PCI had a high risk of BM. High T stage, high NLR, early thoracic radiotherapy and fewer chemotherapy cycles were the risk factors of BM. Further research is needed to confirm the results.

Keywords

Small cell lung cancer Brain metastasis Prophylactic cranial irradiation Risk factor Neutrophil-to-lymphocyte ratio 

Abbreviations

3D-CRT

Three-dimensional conformal radiotherapy

AUC

Area under the curve

BM

Brain metastasis

BMI

Body mass index

CEA

Carcinoembryonic antigen

CFRT

Conventional fractionated radiotherapy

CR

Complete response

GTV

Gross tumor volume

HFRT

Hyperfractionated radiotherapy

IMRT

Intensity-modulated radiotherapy

LS-SCLC

Limited stage small cell lung cancer

NLR

Neutrophil-to-lymphocyte ratio

NSE

Neuron-specific enolase

OS

Overall survival

PCI

Prophylactic cranial irradiation

PFS

Progression-free survival

PLR

Platelet-to-lymphocyte ratio

PR

Partial response

ROC

Receiver operating characteristic

Risikofaktoren für Hirnmetastasen bei Patienten mit kleinzelligem Lungenkarzinom ohne prophylaktische Schädelbestrahlung

Zusammenfassung

Hintergrund

Ziel dieser Studie war es, Risikofaktoren für eine Hirnmetastasierung („brain metastasis“, BM) und prognostische Faktoren des Gesamtüberlebens („overall survival“, OS) bei Patienten mit kleinzelligem Lungenkarzinom („small cell lung cancer“, SCLC) ohne prophylaktische Schädelbestrahlung („prophylactic cranial irradiation“, PCI) zu ermitteln.

Patienten und Methoden

Von Januar 2010 bis Dezember 2016 wurden Patienten mit SCLC im limitierten Stadium („limited-stage“, LS-SCLC) mit kompletter („complete response“, CR) oder partieller Remission („partial response“, PR) in die Studie aufgenommen. Einflussfaktoren auf die Zeit bis zur BM und das OS wurden retrospektiv ausgewertet.

Ergebnisse

Von 153 Patienten entwickelten 68 während der Nachbeobachtungszeit eine BM. Bei 29,4 bzw. 41,2 % aller Patienten kam es binnen eines bzw. 2 Jahren zur BM. Gemäß der multivariaten Analyse waren T‑Stadium (Hazard Ratio, HR = 2,27; p = 0,024), Neutrophilen-Lymphozyten-Quotient („neutrophil-to-lymphocyte ratio“, NLR; HR = 2,07; p = 0,029), Zeit bis zur Strahlentherapie des Thorax (HR = 0,34; p = 0,002) und Anzahl der Chemotherapiezyklen (HR = 0,49; p = 0,036) unabhängige Einflussfaktoren auf die Zeit bis zur BM. Nur NLR (HR = 2,11; p = 0,005) und Zeit bis zur Strahlentherapie des Thorax (HR = 1,95; p = 0,011) stellten unabhängige prognostische Faktoren des OS dar. Unter den 68 Patienten mit BM wiesen diejenigen, bei denen die BM als Erstrezidiv auftrat (42/68), ein längeres OS auf die übrigen (39,5 vs. 23,0 Monate; p = 0,016).

Schlussfolgerung

Bei Patienten mit LS-SCLC ohne PCI bestand ein hohes Risiko für BM. Hohes T‑Stadium, hoher NLR, frühe Strahlentherapie des Thorax und weniger Chemotherapiezyklen waren Risikofaktoren für BM. Weitere Untersuchungen sind erforderlich, um die Ergebnisse zu verifizieren.

Schlüsselwörter

Kleinzelliges Lungenkarzinom Hirnmetastasierung Prophylaktische Schädelbestrahlung Risikofaktor Neutrophilen-Lymphozyten-Quotient 

Notes

Acknowledgements

The authors are thankful to all the patients included and their clinicians in charge.

Compliance with ethical guidelines

Conflict of interest

Y. Zheng, L. Wang, W. Zhao, Y. Dou, W. Lv, H. Yang, Y. Sun and L. Xing declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Supplementary material

66_2018_1362_MOESM1_ESM.docx (212 kb)
Supplementary 1 The cutoff value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) is 2.55 and 125.7, respectively
66_2018_1362_MOESM2_ESM.docx (25 kb)
Supplementary 2 Univariate and multivariate analysis of the prognostic factors of OS

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Oncology, Jinan Central HospitalShandong UniversityJinanChina
  2. 2.Department of Radiation Oncology, Shandong Key Laboratory of Radiation OncologyShandong Cancer Hospital Affiliated to Shandong UniversityJinanChina
  3. 3.Shandong Academy of Medical SciencesJinanChina

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