Skip to main content
SpringerLink
Log in

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

Risikofaktoren für Hirnmetastasen bei Patienten mit kleinzelligem Lungenkarzinom ohne prophylaktische Schädelbestrahlung

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

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.

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

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

References

  1. Aupérin A, Arriagada R, Pignon J, Le Péchoux C, Gregor A, Stephens R, Kristjansen P, Johnson B, Ueoka H, Wagner H, Aisner J (1999) Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic cranial irradiation overview collaborative group. N Engl J Med 341:476–484

    Article  Google Scholar 

  2. Giuliani M, Sun A, Bezjak A, Ma C, Le LW, Brade A, Cho J, Leighl NB, Shepherd FA, Hope AJ (2010) Utilization of prophylactic cranial irradiation in patients with limited stage small cell lung carcinoma. Cancer 116:5694–5699

    Article  Google Scholar 

  3. Sakaguchi M, Maebayashi T, Aizawa T, Ishibashi N, Saito T (2016) Treatment outcomes of patients with small cell lung cancer without prophylactic cranial irradiation. J Thorac Dis 8:2571–2579

    Article  Google Scholar 

  4. Gregory PK, Billy WL, Wallace A, Albert A (2016) NCCN guidelines: small cell lung cancer, version 1.2016. National Comprehensive Cancer Network (NCCN). https://www.nccn.org/professionals/physician_gls/default.aspx

  5. Péchoux C, Sun A, Slotman B, De Ruysscher D, Belderbos J, Gore E (2016) Prophylactic cranial irradiation for patients with lung cancer. Lancet Oncol 17:e277–e293

    Article  Google Scholar 

  6. Patel S, Macdonald OK, Suntharalingam M (2009) Evaluation of the use of prophylactic cranial irradiation in small cell lung cancer. Cancer 115:842–850

    Article  Google Scholar 

  7. Le Pechoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A (2009) Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01). Lancet Oncol 10:467–474 (a randomised clinical trial)

    Article  Google Scholar 

  8. Wolfson AH, Bae K, Komaki R, Meyers C, Movsas B, Le Pechoux C, Werner-Wasik M, Videtic GM, Garces YI, Choy H (2011) Primary analysis of a phase II randomized trial Radiation Therapy Oncology Group (RTOG) 0212. Int J Radiat Oncol Biol Phys 81:77–84 (impact of different total doses and schedules of prophylactic cranial irradiation on chronic neurotoxicity and quality of life for patients with limited-disease small-cell lung cancer)

    Article  Google Scholar 

  9. Lok BH, Ma J, Foster A, Perez CA, Shi W, Zhang Z, Li BT, Rudin CM, Rimner A, Wu AJ (2017) Factors influencing the utilization of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer. Adv Radiat Oncol 2:548–554

    Article  Google Scholar 

  10. Damhuis R, Senan S, Belderbos JS (2017) Usage of prophylactic cranial irradiation in elderly patients with small-cell lung cancer. Clin Lung Cancer 19(2):e263–e267. https://doi.org/10.1016/j.cllc.2017.11.005

    Article  PubMed  Google Scholar 

  11. Arriagada R, Le Chevalier T, Borie F, Riviere A, Chomy P, Monnet I, Tardivon A, Viader F, Tarayre M, Benhamou S (1995) Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst 87:183–190

    Article  CAS  Google Scholar 

  12. Gong L, Wang QI, Zhao L, Yuan Z, Li R, Wang P (2013) Factors affecting the risk of brain metastasis in small cell lung cancer with surgery: is prophylactic cranial irradiation necessary for stage I–III disease? Int J Radiat Oncol Biol Phys 85:196–200

    Article  Google Scholar 

  13. Chen Y, Li J, Zhang Y, Hu Y, Zhang G, Yan X, Lin Z, Zhao Z, Jiao S (2018) Early versus late prophylactic cranial irradiation in patients with extensive small cell lung cancer. Strahlenther Onkol. https://doi.org/10.1007/s00066-018-1307-1

    Article  PubMed  Google Scholar 

  14. Deng M, Ma X, Liang X, Zhu C, Wang M (2017) Are pretreatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio useful in predicting the outcomes of patients with small-cell lung cancer? Oncotarget 8:37200–37207

    PubMed  PubMed Central  Google Scholar 

  15. Wen Q, Meng X, Xie P, Wang S, Sun X, Yu J (2017) Evaluation of factors associated with platinum-sensitivity status and survival in limited-stage small cell lung cancer patients treated with chemoradiotherapy. Oncotarget 8:81405–81418

    PubMed  PubMed Central  Google Scholar 

  16. Mutschelknaus L, Azimzadeh O, Heider T, Winkler K, Vetter M, Kell R, Tapio S, Merl-Pham J, Huber SM, Edalat L, Radulovic V, Anastasov N, Atkinson MJ, Moertl S (2017) Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells. Sci Rep 7:12423

    Article  Google Scholar 

  17. Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904

    Article  CAS  Google Scholar 

  18. Chen G, Huynh M, Chen A, Fehrenbacher L, Gandara D, Lau D (2008) Chemotherapy for brain metastases in small-cell lung cancer. Clin Lung Cancer 9:35–38

    Article  CAS  Google Scholar 

  19. Cao X, Wen ZS, Wang XD, Li Y, Liu KY, Wang X (2017) The clinical effect of metformin on the survival of lung cancer patients with diabetes: a comprehensive systematic review and Meta-analysis of retrospective studies. J Cancer 8:2532–2541

    Article  Google Scholar 

  20. Wang HM, Liao ZX, Komaki R, Welsh JW, O’Reilly MS, Chang JY, Zhuang Y, Levy LB, Lu C, Gomez DR (2013) Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy. Ann Oncol 24:1312–1319

    Article  CAS  Google Scholar 

  21. De Ruysscher D, Lueza B, Le Pechoux C, Johnson DH, O’Brien M, Murray N, Spiro S, Wang X, Takada M, Lebeau B, Blackstock W, Skarlos D, Baas P, Choy H, Price A, Seymour L, Arriagada R, Pignon JP (2016) Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis. Ann Oncol 27:1818–1828

    Article  Google Scholar 

  22. Rusthoven CG, Kavanagh BD (2017) Prophylactic Cranial Irradiation (PCI) versus active MRI surveillance for small cell lung cancer: the case for equipoise. J Thorac Oncol 12:1746–1754

    Article  Google Scholar 

Download references

Acknowledgements

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

Author information

Authors and Affiliations

  1. Department of Oncology, Jinan Central Hospital, Shandong University, 250013, Jinan, Shandong, China

    Yawen Zheng, Weichong Zhao, Yan Dou, Wei Lv, Hongyan Yang & Yuping Sun

  2. Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, No. 440 Jiyan Road, 250117, Jinan, Shandong, China

    Yawen Zheng, Linlin Wang & Ligang Xing

  3. Shandong Academy of Medical Sciences, 250117, Jinan, China

    Yawen Zheng, Linlin Wang & Ligang Xing

Authors
  1. Yawen Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linlin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weichong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Dou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hongyan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuping Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ligang Xing
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ligang Xing.

Ethics declarations

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.

Caption Electronic Supplementary Material

66_2018_1362_MOESM1_ESM.docx

Supplementary 1 The cutoff value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) is 2.55 and 125.7, respectively

Supplementary 2 Univariate and multivariate analysis of the prognostic factors of OS

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, Y., Wang, L., Zhao, W. et al. Risk factors for brain metastasis in patients with small cell lung cancer without prophylactic cranial irradiation. Strahlenther Onkol 194, 1152–1162 (2018). https://doi.org/10.1007/s00066-018-1362-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-018-1362-7

Keywords

Schlüsselwörter

Search

Navigation