Identifying candidates for gamma knife radiosurgery among elderly patients with brain metastases

  • Tae Hoon Roh
  • Mi Sun Choi
  • Namkyu You
  • Donghwan Jeong
  • Ae Hwa Jang
  • Mi Ra Seo
  • Sang Ryul Lee
  • Se-Hyuk Kim
Clinical Study

Abstract

We investigated the outcomes of gamma knife radiosurgery (GKRS) for elderly patients (≥ 65 years) with brain metastases, and identified survival-associated factors. We retrospectively analyzed data from 115 patients treated with GKRS for 1–15 brain metastases. The median patient age was 72 years; most primary tumors were pulmonary (n = 83). The mean lesion volume was 2.1 ± 4.8 mL. A mean dose of 19.3 Gy was delivered to the mean 63.9% isodose line. The median overall survival (OS) was 5.3 months (95% confidence interval [CI] 3.5–7.1). During follow-up (median, 5.1 months), 91 patients died of primary cancer progression while 1 died of unknown causes. The 6- and 12-month local control rates were 94.9 and 88.1%, respectively. On multivariate analysis, female sex (p = 0.005, hazard ratio [HR] 0.533, 95% CI 0.343–0.827) and a controlled primary tumor (p < 0.001, HR 0.328, 95% CI 0.180–0.596) were significantly favorable prognostic factors. Of non-small cell lung cancer patients with EGFR mutations, 76.5% were women (p = 0.005). The median OS of EGFR-mutant and EGFR-wildtype patients were 19.1 and 4.7 months, respectively (p = 0.080). Brain metastases < 3 mL showed better local control rates after GKRS (p = 0.005). GKRS produces favorable outcomes in women with brain metastases who are ≥ 65 years and have controlled primary tumors. Such patients are therefore suitable candidates for GKRS.

Keywords

Age Metastasis Radiosurgery Survival 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

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. For this type of study, formal consent is not required.

Supplementary material

11060_2018_2745_MOESM1_ESM.pdf (85 kb)
Supplementary Fig. S1 Kaplan-Meier curves showing overall survival (OS) according to EGFR mutation status. The median OS rates for EGFR-mutant lung cancer vs. EGFR-wildtype lung cancer patients were 19.1 vs. 4.7 months, respectively (p=0.080) (PDF 84 KB)
11060_2018_2745_MOESM2_ESM.pdf (94 kb)
Supplementary Fig. S2 Kaplan-Meier curves showing local tumor control rates according to the tumor volume. The local progression-free survival at 12 months after gamma knife radiosurgery was 88.8% in patients with tumor volumes ≤3 mL and 71.3% in those with tumor volumes &#x003E;3 mL (PDF 93 KB)

References

  1. 1.
    World Population Prospects The 2010 Revision Volume I: Comprehensive Tables (2011) http://www.un.org/en/development/desa/population/publications/pdf/trends/WPP2010/WPP2010_Volume-I_Comprehensive-Tables.pdf
  2. 2.
    World Population Prospects The 2012 Revision Volume II: Demographic Profiles (2013) https://esa.un.org/unpd/wpp/publications/Files/WPP2012_Volume-II-Demographic-Profiles.pdf
  3. 3.
    Kushnirsky M, Nguyen V, Katz JS et al (2016) Time-delayed contrast-enhanced MRI improves detection of brain metastases and apparent treatment volumes. J Neurosurg 124:489–495CrossRefPubMedGoogle Scholar
  4. 4.
    Nagao E, Yoshiura T, Hiwatashi A et al (2011) 3D turbo spin-echo sequence with motion-sensitized driven-equilibrium preparation for detection of brain metastases on 3T MR imaging. Am J Neuroradiol 32:664–670CrossRefPubMedGoogle Scholar
  5. 5.
    Gu X-D, Cai Y-T, Zhou Y-M et al (2015) Prognostic factors and multidisciplinary treatment modalities for brain metastases from colorectal cancer: analysis of 93 patients. BMC Cancer 15:902CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Gans JH, Raper DMS, Shah AH et al (2012) The role of radiosurgery to the tumor bed after resection of brain metastases. Neurosurgery 72:317–326CrossRefGoogle Scholar
  7. 7.
    Chidel MA, Suh JH, Reddy CA et al (2000) Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases. Int J Radiat Oncol Biol Phys 47:993–999CrossRefPubMedGoogle Scholar
  8. 8.
    Sperduto PW, Berkey B, Gaspar LE et al (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 70:510–514CrossRefPubMedGoogle Scholar
  9. 9.
    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 37:745–751CrossRefPubMedGoogle Scholar
  10. 10.
    Peng H, Tan H, Zhao W et al (2016) Computational systems biology in cancer brain metastasis. Front Biosci (Schol Ed) 8:169–186CrossRefGoogle Scholar
  11. 11.
    Hanibuchi M, Kim SJ, Fidler IJ et al (2014) The molecular biology of lung cancer brain metastasis: an overview of current comprehensions and future perspectives. J Med Invest 61:241–253CrossRefPubMedGoogle Scholar
  12. 12.
    Scoccianti S, Ricardi U (2012) Treatment of brain metastases: review of phase III randomized controlled trials. Radiother Oncol 102:168–179CrossRefPubMedGoogle Scholar
  13. 13.
    Lin NU, Lee EQ, Aoyama H et al (2015) Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol 16:e270–e278CrossRefPubMedGoogle Scholar
  14. 14.
    Watanabe S, Yamamoto M, Sato Y et al (2014) Stereotactic radiosurgery for brain metastases: a case-matched study comparing treatment results for patients 80 years of age or older versus patients 65–79 years of age. J Neurosurg 121:1148–1157CrossRefPubMedGoogle Scholar
  15. 15.
    Shim H, Lee D, Park E et al (2011) Histopathologic characteristics of lung adenocarcinomas with epidermal growth factor receptor mutations in the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Lung Adenocarcinoma Classification. Arch Pathol Lab Med 135:1329–1334CrossRefPubMedGoogle Scholar
  16. 16.
    Midha A, Dearden S, McCormack R (2015) EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res 5:2892–2911PubMedPubMedCentralGoogle Scholar
  17. 17.
    Bhatt V, D’Souza SP, Smith LM et al (2016) Epidermal growth factor receptor mutational status and brain metastases in non-small-cell lung cancer. J Glob Oncol.  https://doi.org/10.1200/JGO.2016.003392PubMedPubMedCentralGoogle Scholar
  18. 18.
    Bell DW, Brannigan BW, Matsuo K et al (2008) Increased prevalence of EGFR-mutant lung cancer in women and in East Asian populations: analysis of estrogen-related polymorphisms. Clin Cancer Res 14:4079–4084CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Paez JG, Janne PA, Lee JC et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500CrossRefPubMedGoogle Scholar
  20. 20.
    Inoue A, Yoshida K, Morita S et al (2016) Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patients. Jpn J Clin Oncol 46:462–467CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Eichler AF, Kahle KT, Wang DL et al (2010) EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro-Oncology 12:1193–1199CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kontis V, Bennett JE, Mathers CD et al (2017) Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet 389:1323–1335CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Cho K, Lee M, Kong D-S et al (2015) Outcome of gamma knife radiosurgery for metastatic brain tumors derived from non-small cell lung cancer. J Neurooncol 125:331–338CrossRefPubMedGoogle Scholar
  24. 24.
    Likhacheva A, Pinnix CC, Parikh NR et al (2013) Predictors of survival in contemporary practice after initial radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 85:656–661CrossRefPubMedGoogle Scholar
  25. 25.
    Lee C-K, Lee S, Cho J et al (2011) Therapeutic effect of gamma knife radiosurgery for multiple brain metastases. J Korean Neurosurg Soc 50:179–184CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tae Hoon Roh
    • 1
    • 2
  • Mi Sun Choi
    • 1
  • Namkyu You
    • 1
  • Donghwan Jeong
    • 1
  • Ae Hwa Jang
    • 1
  • Mi Ra Seo
    • 1
  • Sang Ryul Lee
    • 1
  • Se-Hyuk Kim
    • 1
  1. 1.Gamma Knife Center, Department of NeurosurgeryAjou University School of MedicineSuwonSouth Korea
  2. 2.Yonsei University Graduate SchoolSeoulSouth Korea

Personalised recommendations