SpringerLink
Log in

Single-fraction radiosurgery versus fractionated stereotactic radiotherapy in patients with brain metastases: a comparative study

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

To compare the local control and brain radionecrosis in patients with brain metastasis primarily treated by single-fraction radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). Between January 2012 and December 2017, 179 patients with only 1–3 brain metastases (total: 287) primarily treated by SRS (14 Gy) or HFSRT (23.1 Gy in 3 fractions of 7.7 Gy, every other day) were retrospectively analyzed in a single center. Follow-up imaging data were available in 152 patients with 246 lesions. The corresponding Biological Effective Dose (BED) were 33.6 Gy and 40.9 Gy respectively for SRS and HFSRT group, assuming an α/β of 10 Gy. Local control (LC) and risk of radionecrosis (RN) were calculated by the Kaplan–Meier method. The actuarial local control rates at 6 and 12 months were 94% and 88.1% in SRS group, and 87.6% and 78.4%, in HFSRT group (p = 0.06), respectively. Only the total volume of edema was associated with worse LC (p = 0.01, HR 1.02, 95% CI [1.004–1.03]) in multivariate analysis. Brain radionecrosis occurred in 1 lesion in SRS group and 9 in HFSRT group. Median time to necrosis was 5.5 months (range 1–9). Only the volume of GTV was associated with RN (p = 0.02, HR 1.09, 95% CI [1.01–1.18]) in multivariate analysis. Multi-fraction SRT dose of 23.31 Gy in 3 fractions has similar efficacy to single-fraction SRT dose of 14 Gy in patients with brain metastases. A slightly higher occurrence of radionecrosis appeared in HFSRT group.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Soffietti R, Abacioglu U, Baumert B, Combs SE, Kinhult S, Kros JM et al (2017) Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO). Neuro-Oncol févr 19(2):162–174

    Article  CAS  Google Scholar 

  2. Auchter RM, Lamond JP, Alexander E, Buatti JM, Chappell R, Friedman WA et al (1996) A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis. Int J Radiat Oncol Biol Phys 35(1):27–35

    Article  CAS  PubMed  Google Scholar 

  3. Muacevic A, Wowra B, Siefert A, Tonn J-C, Steiger H-J, Kreth FW (2008) Microsurgery plus whole brain irradiation versus Gamma Knife surgery alone for treatment of single metastases to the brain: a randomized controlled multicentre phase III trial. J Neurooncol 87(3):299–307

    Article  PubMed  Google Scholar 

  4. Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10(11):1037–1044

    Article  PubMed  Google Scholar 

  5. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC et al (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. The Lancet 363(9422):1665–1672

    Article  Google Scholar 

  6. Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG et al (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol 29(2):134–141

    Article  PubMed  Google Scholar 

  7. Minniti G, D’Angelillo RM, Scaringi C, Trodella LE, Clarke E, Matteucci P et al (2014) Fractionated stereotactic radiosurgery for patients with brain metastases. J Neurooncol avr 117(2):295–301

    Article  CAS  Google Scholar 

  8. Ernst-Stecken A, Ganslandt O, Lambrecht U, Sauer R, Grabenbauer G (2006) Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity. Radiother Oncol J Eur Soc Ther Radiol Oncol 81(1):18–24

    Article  Google Scholar 

  9. Narayana A, Chang J, Yenice K, Chan K, Lymberis S, Brennan C et al (2007) Hypofractionated stereotactic radiotherapy using intensity-modulated radiotherapy in patients with one or two brain metastases. Stereotact Funct Neurosurg 85(2–3):82–87

    Article  PubMed  Google Scholar 

  10. Kwon AK, Dibiase SJ, Wang B, Hughes SL, Milcarek B, Zhu Y (2009) Hypofractionated stereotactic radiotherapy for the treatment of brain metastases. Cancer 115(4):890–898

    Article  PubMed  Google Scholar 

  11. Saitoh JI, Saito Y, Kazumoto T, Kudo S, Ichikawa A, Hayase N et al (2010) Therapeutic effect 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(2):119–124

    Article  PubMed  Google Scholar 

  12. Rajakesari S, Arvold ND, Jimenez RB, Christianson LW, Horvath MC, Claus EB et al (2014) Local control after fractionated stereotactic radiation therapy for brain metastases. J Neurooncol 120(2):339–346

    Article  CAS  PubMed  Google Scholar 

  13. Higuchi Y, Serizawa T, Nagano O, Matsuda S, Ono J, Sato M et al (2009) Three-staged stereotactic radiotherapy without whole brain irradiation for large metastatic brain tumors. Int J Radiat Oncol Biol Phys 74(5):1543–1548

    Article  PubMed  Google Scholar 

  14. Lehrer EJ, Peterson JL, Zaorsky NG, Brown PD, Sahgal A, Chiang VL et al (2019) Single versus multifraction stereotactic radiosurgery for large brain metastases: an international meta-analysis of 24 trials. Int J Radiat Oncol Biol Phys 103(3):618–630

    Article  PubMed  Google Scholar 

  15. Kim Y-J, Cho KH, Kim J-Y, Lim YK, Min HS, Lee SH et al (2011) Single-dose versus fractionated stereotactic radiotherapy for brain metastases. Int J Radiat Oncol 81(2):483–489

    Article  Google Scholar 

  16. Feuvret L, Vinchon S, Martin V, Lamproglou I, Halley A, Calugaru V et al (2014) Stereotactic radiotherapy for large solitary brain metastases. Cancer/Radiothérapie 18(2):97–106

    Article  CAS  Google Scholar 

  17. Fokas E, Henzel M, Surber G, Kleinert G, Hamm K, Engenhart-Cabillic R (2012) Stereotactic radiosurgery and fractionated stereotactic radiotherapy: comparison of efficacy and toxicity in 260 patients with brain metastases. J Neurooncol 109(1):91–98

    Article  PubMed  Google Scholar 

  18. Minniti G, Scaringi C, Paolini S, Lanzetta G, Romano A, Cicone F et al (2016) Single-fraction versus multifraction (3 × 9 Gy) stereotactic radiosurgery for large (%3e 2 cm) brain metastases: a comparative analysis of local control and risk of radiation-induced brain necrosis. Int J Radiat Oncol 95(4):1142–1148

    Article  Google Scholar 

  19. Ishihara T, Yamada K, Harada A, Isogai K, Tonosaki Y, Demizu Y et al (2016) Hypofractionated stereotactic radiotherapy for brain metastases from lung cancer: Evaluation of indications and predictors of local control. Strahlenther Onkol 192(6):386–393

    Article  PubMed  Google Scholar 

  20. Kirkpatrick JP, Soltys SG, Lo SS, Beal K, Shrieve DC, Brown PD (2017) The radiosurgery fractionation quandary: single fraction or hypofractionation? Neuro-Oncol 19(suppl_2):ii38–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shuryak I, Carlson DJ, Brown JM, Brenner DJ (2015) High-dose and fractionation effects in stereotactic radiation therapy: analysis of tumor control data from 2965 patients. Radiother Oncol 115(3):327–334

    Article  PubMed  Google Scholar 

  22. Wiggenraad R, Kanter AV, Kal HB, Taphoorn M, Vissers T, Struikmans H (2011) Dose–effect relation in stereotactic radiotherapy for brain metastases. A systematic review Radiother Oncol 98(3):292–297

    Article  PubMed  Google Scholar 

  23. Baliga S, Garg MK, Fox J, Kalnicki S, Lasala PA, Welch MR et al (2017) Fractionated stereotactic radiation therapy for brain metastases: a systematic review with tumour control probability modelling. Br J Radiol 90(1070):20160666

    Article  PubMed  PubMed Central  Google Scholar 

  24. Rodrigues G, Warner A, Bauman G, Senan S, Lagerwaard F (2014) Systematic review of fractionated brain metastases radiotherapy. J Radiat Oncol 3(1):29–41

    Article  CAS  Google Scholar 

  25. 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(4):984–990

    Article  PubMed  Google Scholar 

  26. 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(4):240–243

    Article  PubMed  Google Scholar 

  27. Brenner DJ (2008) The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction. Semin Radiat Oncol 18(4):234–239

    Article  PubMed  PubMed Central  Google Scholar 

  28. Brown JM, Carlson DJ, Brenner DJ (2014) The tumor radiobiology of SRS and SBRT: are more than the 5 R’s Involved? Int J Radiat Oncol Biol Phys 88(2):254–262

    Article  PubMed  PubMed Central  Google Scholar 

  29. Song CW, Lee Y-J, Griffin RJ, Park I, Koonce NA, Hui S et al (2015) Indirect tumor cell death after high-dose hypofractionated irradiation: implications for stereotactic body radiation therapy and stereotactic radiation surgery. Int J Radiat Oncol Biol Phys 93(1):166–172

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pin Y, Antoni D, Keller A, Truntzer P, Clavier JB, Schaeffer O, et al. Clinical evaluation of a semi-automated contouring tool for edema surrounding brain metastasis: the Metabrain software. In submission [Internet]. 2018; Available on: https://github.com/yvanpin/Metabrain

  31. Lucia F, Key S, Dissaux G, Goasduff G, Lucia A-S, Ollivier L et al (2019) Inhomogeneous tumor dose distribution provides better local control than homogeneous distribution in stereotactic radiotherapy for brain metastases. Radiother Oncol 130:132–138

    Article  PubMed  Google Scholar 

  32. Nataf F, Schlienger M, Liu Z, Foulquier JN, Grès B, Orthuon A et al (2008) Radiosurgery with or without A 2-mm margin for 93 single brain metastases. Int J Radiat Oncol Biol Phys 70(3):766–772

    Article  PubMed  Google Scholar 

  33. Noël G, Simon JM, Valery CA, Cornu P, Boisserie G, Hasboun D et al (2003) Radiosurgery for brain metastasis: impact of CTV on local control. Radiother Oncol 68(1):15–21

    Article  PubMed  Google Scholar 

  34. Kirkpatrick JP, Wang Z, Sampson JH, McSherry F, Herndon JE, Allen KJ et al (2015) Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial. Int J Radiat Oncol Biol Phys 91(1):100–108

    Article  PubMed  Google Scholar 

  35. Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J 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(2):291–298

    Article  CAS  PubMed  Google Scholar 

  36. Vogelbaum MA, Angelov L, Lee S-Y, Li L, Barnett GH, Suh JH (2006) Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin. J Neurosurg 104(6):907–912

    Article  PubMed  Google Scholar 

  37. Chao ST, Barnett GH, Vogelbaum MA, Angelov L, Weil RJ, Neyman G et al (2008) Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy. Cancer 113(8):2198–2204

    Article  PubMed  Google Scholar 

  38. Molenaar R, Wiggenraad R, Verbeek-de Kanter A, Walchenbach R, Vecht C (2009) Relationship between volume, dose and local control in stereotactic radiosurgery of brain metastasis. Br J Neurosurg 23(2):170–178

    Article  PubMed  Google Scholar 

  39. Schomas DA, Roeske JC, MacDonald RL, Sweeney PJ, Mehta N, Mundt AJ (2005) Predictors of tumor control in patients treated with linac-based stereotactic radiosurgery for metastatic disease to the brain. Am J Clin Oncol 28(2):180–187

    Article  PubMed  Google Scholar 

  40. Jiang X, **ao J, Zhang Y, Xu Y, Li X, Chen X et al (2012) Hypofractionated stereotactic radiotherapy for brain metastases larger than three centimeters. Radiat Oncol Lond Engl 7:36

    Article  Google Scholar 

  41. Wegner R, Leeman J, Kabolizadeh P, Rwigema J-C, Mintz A, Burton S et al (2015) Fractionated stereotactic radiosurgery for large brain metastases. Am J Clin Oncol 38(2):135–139

    Article  PubMed  Google Scholar 

  42. Murai T, Ogino H, Manabe Y, Iwabuchi M, Okumura T, Matsushita Y et al (2014) Fractionated stereotactic radiotherapy using cyberKnife for the treatment of large brain metastases: a dose escalation study. Clin Oncol 26(3):151–158

    Article  CAS  Google Scholar 

  43. Bilger A, Frenzel F, Oehlke O, Wiehle R, Milanovic D, Prokic V et al (2017) Local control and overall survival after frameless radiosurgery: a single center experience. Clin Transl Radiat Oncol 7:55–61

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tini P, Nardone V, Pastina P, Battaglia G, Vinciguerra C, Carfagno T et al (2017) Perilesional edema in brain metastasis from non-small cell lung cancer (NSCLC) as predictor of response to radiosurgery (SRS). Neurol Sci 38(6):975–982

    Article  PubMed  Google Scholar 

  45. Berghoff AS, Ilhan-Mutlu A, Wöhrer A, Hackl M, Widhalm G, Hainfellner JA et al (2014) Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases. Strahlenther Onkol Organ Dtsch Rontgengesellschaft Al 190(7):676–685

    Article  CAS  Google Scholar 

  46. Spanberger T, Berghoff AS, Dinhof C, Ilhan-Mutlu A, Magerle M, Hutterer M et al (2013) Extent of peritumoral brain edema correlates with prognosis, tumoral growth pattern, HIF1a expression and angiogenic activity in patients with single brain metastases. Clin Exp Metastasis 30(4):357–368

    Article  CAS  PubMed  Google Scholar 

  47. Aoyama H, Shirato H, Onimaru R, Kagei K, Ikeda J, Ishii N et al (2003) Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull. Int J Radiat Oncol Biol Phys 56(3):793–800

    Article  PubMed  Google Scholar 

  48. Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Breneman JC (2010) Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 77(4):996–1001

    Article  PubMed  Google Scholar 

  49. Navarria P, Clerici E, Carta G, Attuati L, Picozzi P, Franzese C et al (2018) Randomized phase III trial comparing gamma knife and linac based (EDGE) approaches for brain metastases radiosurgery: results from the gadget trial. Int J Radiat Oncol Biol Phys 102(3):S143–S144

    Article  Google Scholar 

  50. Inoue HK, Seto K, Nozaki A, Torikai K, Suzuki Y, Saitoh J et al (2013) Three-fraction CyberKnife radiotherapy for brain metastases in critical areas: referring to the risk evaluating radiation necrosis and the surrounding brain volumes circumscribed with a single dose equivalence of 14 Gy (V14). J Radiat Res 54(4):727–735

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Radiotherapy Department, Centre Paul Strauss, Strasbourg Cedex, 67065, France

    Maxime Loo, Yvan Pin & Jean-Baptiste Clavier

  2. Public Health and Statistics Department, Centre Paul Strauss, Strasbourg Cedex, 67065, France

    Alicia Thierry

Authors
  1. Maxime Loo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yvan Pin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alicia Thierry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jean-Baptiste Clavier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maxime Loo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Loo, M., Pin, Y., Thierry, A. et al. Single-fraction radiosurgery versus fractionated stereotactic radiotherapy in patients with brain metastases: a comparative study. Clin Exp Metastasis 37, 425–434 (2020). https://doi.org/10.1007/s10585-020-10031-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-020-10031-5

Keywords

Search

Navigation