Advertisement

Journal of Neuro-Oncology

, Volume 140, Issue 2, pp 413–420 | Cite as

Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery

  • John A. Vargo
  • Kristie M. Sparks
  • Rahul Singh
  • Geraldine M. Jacobson
  • Joshua D. Hack
  • Christopher P. Cifarelli
Clinical Study

Abstract

Background and purpose

Post-operative SRS (stereotactic radiosurgery) for large brain metastases is challenged by risks of radiation necrosis that limit SRS dose. Intraoperative radiotherapy (IORT) is a potential alternative, however standard dose recommendations are lacking.

Methods and materials

Twenty consecutive brain metastases treated with post-operative SRS were retrospectively compared to IORT plans generated for 10–30 Gy in 1 fraction to 0–5 mm by estimating the applicator size and distance from critical organs using pre-operative and post-operative MRI. Additionally, 7 consecutive patients treated with IORT 30 Gy to surface were compared to retrospectively generated SRS plans using the post-operative MRI to 15–20 Gy and 30 Gy in 1 fraction marginal dose.

Results

For the 20 resection cavities treated with SRS and retrospectively compared to IORT, IORT from 10 to 30Gy resulted in lower or not significantly different doses to the optic apparatus and brainstem. Comparatively for the 7 patients treated with IORT 30 Gy to retrospective SRS plans to standard 15–20 Gy and 30 Gy marginal dose, IORT resulted in significantly lower doses to the optic apparatus and brainstem. At a median follow-up of 6.2 months, 86% of patients treated with surgery and IORT achieved local control and 0% developed radiographic or symptomatic radiation necrosis.

Conclusions

Critical organ dosimetry for IORT remains generally lower than that achieved with single fraction SRS following resection of large brain metastases. We recommend 30 Gy to surface as the preferred prescription, consistent with the dose recommendation for IORT in glioblastoma used in the ongoing INTRAGO-II phase-III trial. Early clinical outcomes appear promising for surgery and IORT.

Keywords

Brain metastases Stereotactic radiosurgery GammaKnife Intraoperative radiation Resection cavity 

Notes

Compliance with ethical standards

Conflict of interest

John A Vargo, MD receives speaking honoraria from BrainLAB. All remaining authors declare they have 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.

Informed consent

Informed consent was obtained from all individual participants included in the study for treatment delivery.

References

  1. 1.
    Kocher M, Soffietti R, Abacioglu U 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 29:134–141CrossRefGoogle Scholar
  2. 2.
    Brown PD, Jaeckle K, Ballman KV et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316:401–409CrossRefGoogle Scholar
  3. 3.
    Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomized contolled trial. Lancet 10:1037–1044CrossRefGoogle Scholar
  4. 4.
    Brown PD, Ballman KV, Cerhan J et al (2017) N107C/CEC.3: a Phase III trial of post-operative stereotactic radiosurgery (SRS) compared with whole brain radiotherapy (WBRT) for resected metastatic brain disease. Lancet Oncol 18:1049–1060CrossRefGoogle Scholar
  5. 5.
    Mahajan A, Ahmed S, McAleer MF et al (2017) Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 18:1040–1048CrossRefGoogle Scholar
  6. 6.
    Weil RJ, Mavinkurve CG, Chao ST et al (2015) Intraoperative radiotherapy to treat newly diagnosed solitary brain metastasis: initial experience and long-term outcomes. J Neurosurg 122:825–832CrossRefGoogle Scholar
  7. 7.
    Curry WT Jr, Cosgrove GR, Hochberg FH et al (2005) Stereotactic interstitial radiosurgery for cerebral metastases. J Neurosurg 103:6305CrossRefGoogle Scholar
  8. 8.
    Pantazis G, Trippel M, Birg W et al (2009) Stereotactic interstitial radiosurgery with the photon radiosurgery system (PRS) for metastatic brain tumors: a prospective single-center clinical trial. Int J Radiat Oncol Biol Phys 75:1392–1400CrossRefGoogle Scholar
  9. 9.
    Kalapurakal JA, Goldman S, Stellpfung W et al (2006) Phase I study of intraoperative radiotherapy with photon radiosurgery system in children with recurrent brain tumors: preliminary report of first dose level (10 Gy). Int J Radiat Oncol Biol Phys 65:800–808CrossRefGoogle Scholar
  10. 10.
    Giordano FA, Brehmer S, Abo-Madyan Y et al (2014) INTRAGO: intraoperative radiotherapy in glioblastoma multiforme: a phase I/II dose escalation study. BMC Cancer 14:992CrossRefGoogle Scholar
  11. 11.
    Wernicke AG, Hirschfeld CB, Smith AW et al (2017) Clinical outcomes of large brain metastases treated with neurosurgical resection and intra-operative Cesium-131 brachytherapy: results of a prospective trial. Int J Radiat Oncol Biol Phys 98:1059–1068CrossRefGoogle Scholar
  12. 12.
    Raleigh DR, Seymore ZA, Tomlin B et al (2017) Resection and brain brachytherapy with permanent idodine-125 sources for brain metastasis. J Neurosurg 126:1749–1755Google Scholar
  13. 13.
    Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD (1998) Analysis of neurological sequelae from radiosurgery of arteriovenous malformations: how location affects outcome. Int J Radiat Oncol Biol Phys 40:273–278CrossRefGoogle Scholar
  14. 14.
    Levegrun S, Hof H, Essig M, Sclegel W, Debus J (2004) Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: correlation with dose distribution parameters. Int J Radiat Oncol Biol Phys 59:796–808CrossRefGoogle Scholar
  15. 15.
    Belletti B, Vaidya JS, D’Andrea S et al (2008) Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res 14:1325–1332CrossRefGoogle Scholar
  16. 16.
    Di Lorenzo N, Cavedon C, Paier F et al (2004) Interstitial radiosurgery with the photon radiosurgery system in the minimally-invasive treatment of selected deep-seated brain tumors. J Chemother 16:70–74CrossRefGoogle Scholar
  17. 17.
    Gallina P, Franceson P, Cavedon C et al (2002) Stereotactic interstitial radiosurgery with a miniature X-ray device in the minimally invasive treatment of selected tumors in the thalamus and the basal Ganglia. Stereotact Funt Neurosurg 79:202–213CrossRefGoogle Scholar
  18. 18.
    Vaidya JS, Wenz F, Bulsara M et al (2014) Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet 383:603–613CrossRefGoogle Scholar
  19. 19.
    Siam L, Bleckmann A, Chaung HN et al (2015) The metastatic infiltration at the metastasis/brain parenchyma-interface is very heterogeneous and has a significant impact on survival in a prospective study. Oncotarget 6:29254–29267CrossRefGoogle Scholar
  20. 20.
    Raore B, Schniederjan M, Prabhu R et al (2011) Metastasis infiltration: an investigation of the postoperative brain-tumor interface. Int J Radiat Oncol Biol Phys 81:1075–1080CrossRefGoogle Scholar
  21. 21.
    Baumert BG, Rutten I, Dehing-Oberije C et al (2006) A pathology-based substrate for target definition in radiosurgery of brain metastases. Int J Radiat Oncol Biol Phys 66:187–194CrossRefGoogle Scholar
  22. 22.
    Brennan C, Yang TJ, Hilden P et al (2014) A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys 88:130–136CrossRefGoogle Scholar
  23. 23.
    Choi CY, Chang SD, Gibbs IC et al (2012) Stereotactic radiosurgery of the postoperative resection cavity for brain metastases: prospective evaluation of target margin on tumor control. Int J Radiat Oncol Biol Phys 84:336–342CrossRefGoogle Scholar
  24. 24.
    Chen Y, Souri S, Dian X et al (2016) SU-F-T-56: Dosimetric characterization of the INTRABEAM 50 kV Xray system with a needle applicator in heterogeneous tissues. Med Phys 43:3474CrossRefGoogle Scholar
  25. 25.
    Liu Q, Schneider F, Ma L, Wenz F, Herskind C (2013) Relative biologic effectiveness (RBE) of 50 kV X-rays measured in a phantom for intraoperative tumor-bed irradiation. Int J Radiat Oncol Biol Phys 85:1127–1133CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Radiation OncologyWest Virginia UniversityMorgantownUSA
  2. 2.Department of NeurosurgeryWest Virginia UniversityMorgantownUSA

Personalised recommendations