Skip to main content


Log in

Hypofractionated stereotactic radiotherapy for brain metastases from lung cancer

Evaluation of indications and predictors of local control

Hypofraktionierte stereotaktische Strahlentherapie bei Hirnmetastasen eines Lungenkarzinoms

Evaluierung von Indikationen und Prädiktoren der lokalen Kontrolle

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



To evaluate the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for brain metastases (BMs) from lung cancer, and to explore prognostic factors associated with local control (LC) and indication.

Patients and methods

We evaluated patients who were treated with linac-based HSRT for BMs from lung cancer. Lesions treated with stereotactic radiosurgery (SRS) in the same patients during the same periods were analysed and compared with HSRT in terms of LC or toxicity. There were 53 patients with 214 lesions selected for this analysis (HSRT: 76 lesions, SRS: 138 lesions). For HSRT, the median prescribed dose was 35 Gy in 5 fractions.


The 1‑year LC rate was 83.6 % in HSRT; on multivariate analysis, a planning target volume (PTV) of <4 cm3, biologically effective dose (BED10) of ≥51 Gy, and adenocarcinoma were significantly associated with better LC. Moreover, in PTVs ≥ 4 cm3, there was a significant difference in LC between BED10 < 51 Gy and ≥ 51 Gy (p = 0.024). On the other hand, in PTVs < 4 cm3, both HSRT and SRS had good LC with no significant difference (p = 0.195). Radiation necrosis emerged in 5 of 76 lesions (6.6 %) treated with HSRT and 21 of 138 (15.2 %) lesions treated with SRS (p = 0.064).


Linac-based HSRT was safe and effective for BMs from lung cancer, and hence might be particularly useful in or near an eloquent area. PTV, BED10, and pathological type were significant prognostic factors. Furthermore, in BMs ≥ 4 cm3, a dose of BED ≥ 51 Gy should be considered.



Beurteilung von Wirksamkeit und Toxizität einer hypofraktionierten stereotaktischen Strahlentherapie (HSRT) zur Behandlung von Hirnmetastasen (HM) eines Lungenkarzinoms und Erforschung von mit der lokalen Kontrolle (LK) und der Indikation assoziierten Prognosefaktoren.

Patienten und Methoden

Analysiert wurden Daten von Patienten (n = 53), die sich einer Linearbeschleuniger-basierten HSRT unterzogen (mit HSRT behandelte Läsionen n = 76; Median der verordneten Dosis: 35 Gy in 5 Fraktionen). Analysiert wurden ferner bei den gleichen Patienten im gleichen Zeitraum mit stereotaktischer Strahlenchirurgie (SRS) behandelte Läsionen (n = 138). Die Ergebnisse wurden in Bezug auf LK oder Toxizität verglichen.


Nach einem Jahr betrug die LK nach HSRT 83,6 %; bei der multivariaten Analyse zeigte sich, dass ein „planning target volume“ (PTV) < 4 cm3, eine biologisch effektive Dosis (BED10) ≥ 51 Gy und ein Adenokarzinom signifikant mit einer besseren LK assoziiert waren. Darüber hinaus wurde bei einem PTV ≥ 4 cm3 ein signifikanter Unterschied in der LK zwischen BED10 < 51 Gy und ≥ 51 Gy beobachtet (p = 0,024). Andererseits wurde bei einem PTV < 4 cm3 sowohl mit der HSRT als auch mit der SRS eine gute LK erreicht, der Unterschied war nicht signifikant (p = 0,195). Bei 5 der 76 (6,6 %) mit HRST behandelten Läsionen und bei 21 der 138 (15,2 %) mit SRS behandelten Läsionen traten Strahlennekrosen auf (p = 0,064).


Die Linearbeschleuniger-basierte HSRT war eine sichere und effektive Behandlung von HM eines Lungenkarzinoms. Sie kann also besonders hilfreich sein bei Metastasen in einem eloquenten Hirnareal oder in der Nähe eines eloquenten Areals. Signifikante Prognosefaktoren waren PTV, BED 10 und der histopathologische Typ. Bei HM mit einer Ausdehnung ≥ 4 cm3 sollte eine BED ≥ 51 Gy erwogen werden.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others


  1. Patchell RA (2003) The management of brain metastases. Cancer Treat Rev 29:533–540

  2. Sanghavi SN, Miranpuri SS, Chappel R et al (2001) Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method. Int J Radiat Oncol Biol Phys 51:426–434

  3. 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 47:291–298

  4. Fokas E, Henzel M, Surber G et al (2012) Stereotactic radiosurgery and fractionated stereotactic radiotherapy: comparison of efficacy and toxicity in 260 patients with brain metastases. J Neurooncol 109:91–98

  5. Wegner RE, Leeman JE, Kabolizadeh P et al (2015) Fractionated stereotactic radiosurgery for large brain metastases. Am J Clin Oncol 38:135–139

  6. Kwon AK, Dibiase SJ, Wang B et al (2009) Hypofractionated stereotactic radiotherapy for the treatment of brain metastases. Cancer 115:890–889

  7. Jeong WJ, Park JH, Lee EJ et al (2015) Efficacy and safety of fractionated stereotactic radiosurgery for large brain metastases. J Korean Neurosurg Soc 58:217–224

  8. Ahmed KA, Sarangkasiri S, Chinnaiyan P et al (2014) Outcomes following hypofractionated stereotactic radiotherapy in the management of brain metastases. Am J Clin Oncol. doi:10.1097/COC.0000000000000076

  9. Saitoh J, Saito Y, Kazumoto T et al (2010) Therapeutic effects of linac-based stereotactic radiotherapy with a micro-multileaf collimator for the treatment of patients with brain metastases from lung cancer. Jpn J Clin Oncol 40:119–124

  10. Matsuyama T, Kogo K, Oya N. (2013) Clinical outcomes of biological effective dose-based fractionated stereotactic radiation therapy for metastatic brain tumors from non-small cell lung cancer. Int J Radiat Oncol Biol Phys 85:984–990

  11. Minniti G, D’Angelillo RM, Scaringi C et al (2014) Fractionated stereotactic radiosurgery for patients with brain metastases. J Neurooncol 117:295–301

  12. Lischalk JW, Oermann E, Collins SP et al (2015) Five-fraction stereotactic radiosurgery (SRS) for single inoperable high-risk non-small cell lung cancer (NSCLC) brain metastases. Radiat Oncol 10:216

  13. Tian LJ, Zhuang HQ, Yuan ZY (2013) A comparison between cyberknife and neurosurgery in solitary brain metastases from non-small cell lung cancer. Clin Neurol Neurosurg 115:2009–2014

  14. Garsa AA, Badiyan SN, DeWees T et al (2014) Predictors of individual tumor local control after stereotactic radiosurgery for non-small cell lung cancer brain metastases. Int J Radiat Oncol Biol Phys 90:407–413

  15. Dempke WC, Edvardsen K, Lu S et al (2015) Brain metastases in NSCLC – are TKIs changing the treatment strategy? Anticancer Res 35:5797–5806

  16. Johung KL, Yeh N, Desai NB et al (2016) Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis 34:123–129

  17. Cho YH, Lee JM, Lee D et al (2015) Experiences on two different stereotactic radiosurgery modalities of Gamma Knife and Cyberknife in treating brain metastases. Acta Neurochir (Wien) 157:2003–2009

  18. Williams BJ, Suki D, Fox BD et al (2009) Stereotactic radiosurgery for metastatic brain tumor: a comprehensive review of complications. J Neurosurg 111:439–448

  19. Kocher M, Wittig A, Piroth MD et al (2014) Stereotactic radiosurgery for treatment of brain metastases. A report of the DEGRO Working Group on Stereotactic Radiotherapy. Strahlenther Onkol 190:521–532

  20. Fowler JF (2009) Sensitivity analysis of parameters in linear-quadratic radiobiologic modeling. Int J Radiat Oncol Biol Phys 73:1532–1537

  21. Kirkpatrick JP, Meyer JJ, Marks LB (2008) The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol 18:240–243

  22. Courdi A (2010) High doses per fraction and the linear quadratic model. Radiother Oncol 94:121–122

  23. Otsuka S, Shibamoto Y, Iwata H et al (2011) Compatibility of the linear-quadratic formalism and biologically effective dose concept to high-dose-per-fraction irradiation in a murine tumor. Int J Radiat Oncol Biol Phys 81:1538–1543

  24. Wiggenraad R, Verbeek-de Kanter A, Kal HB et al (2011) Dose-effect relation in stereotactic radiotherapy for brain metastases. A systematic review. Radiother Oncol 98:292–297

  25. Garcia LM, Wilkins DE, Raaphorst GP (2007) Alpha/beta ratio: A dose range dependence study. Int J Radiat Oncol Biol Phys 67:587–593

  26. Ma L, Nichol A, Hossain S et al (2014) Variable dose interplay effects across radiosurgical apparatus in treating multiple brain metastases. Int J Comput Assist Radiol Surg 9:1079–1086

  27. Treuer H, Hoevels M, Luyken K et al (2015) Intracranial stereotactic radiosurgery with an adapted linear accelerator vs. robotic radiosurgery: Comparison of dosimetric treatment plan quality. Strahlenther Onkol 191:470–476

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Takeaki Ishihara.

Ethics declarations

Conflict of interest

T. Ishihara, K. Yamada, A. Harada, K. Isogai, Y. Tonosaki, Y. Demizu, D. Miyawaki, K. Yoshida, Y. Ejima, and R. Sasaki state that there are no conflicts of interest.

Ethical standards

The accompanying manuscript does not include studies on humans or animals.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ishihara, T., Yamada, K., Harada, A. et al. Hypofractionated stereotactic radiotherapy for brain metastases from lung cancer. Strahlenther Onkol 192, 386–393 (2016).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: