What is the role of stereotactic radiosurgery in the treatment of brain metastases?

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Introduction

Stereotactic radiosurgery (SRS) refers to the use of highly conformal radiotherapy delivered with the aid of a stereotactic head frame for precise tumour localisation. This extremely focussed radiotherapy allows a high radiation dose to be delivered to the tumour whilst minimising radiation to surrounding normal tissues.

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SRS in addition to whole brain radiotherapy

An RTOG trial has evaluated the role of additional SRS to whole brain radiotherapy (WBRT) in patients with one to three unresectable brain metastases and stable systemic disease,[1] where 333 patients were treated with WBRT and then randomised to observation or SRS boost. Patients in the SRS arm had significantly reduced steroid use and improvement in performance status at six months compared with the observation group. Overall there was no difference in mean survival (5.7 months in observation arm versus 6.5 months in SRS arm). SRS boost was associated with a significant mean survival benefit in patients with a solitary metastasis (from 4.9 to 6.5 months), RPA Class I and metastases greater than 2cm. However, on multivariate analysis SRS boost was associated with improved local control but not survival. There was no difference in neurological deaths. These findings are supported by a small randomised trial reported by Kondziolka et al.[2]

The dose of SRS used in the RTOG trial was 24Gy for metastases measuring up to 2cm, 18Gy for 3-4cm and 15Gy for 3-4cm in size. The dose of WBRT was 37.5Gy in 15 fractions. There was no significant difference in acute or late toxicities between the arms (Grade 3 and 4 toxicity 3% in SRS arm versus 0% in observation arm, Grade 3 and 4 late toxicity 6% SRS arm versus 3% observation arm).

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SRS as an alternative to surgical resection of brain metastasis

Fuentes et al conducted a systematic review of this topic in patients with solitary brain metastases.[3] They could not show any advantage of one treatment over the other due to lack of randomised evidence.

There is one small randomised trial of SRS versus surgery in the treatment of brain metastases. Roos et al randomised patients with a solitary brain metastasis seen on MRI to SRS + WBRT versus surgery + WBRT . This trial was ceased early due to poor accrual and only 21 patients were randomised. There were no differences in brain relapse, overall survival or quality of life. (Roos 2011) There are single institution retrospective cohort studies which have compared surgery to SRS.[4][5][6][7][8] All of these are subject to bias due to factors determining selection for a particular treatment. Four of the five studies showed similar survival between the two treatments,[4][5][6][7] and three showed better local control with SRS.[5][6][7]

Auchter et al performed a retrospective multicentre study on patients with a solitary metastasis who would have met the eligibility criteria for that Patchell trial of surgical resection.[9][10] Patients could have active or stable systemic disease. All patients received WBRT and SRS boost. The median survival was 56 weeks, and for lung cancer 47 weeks. The median duration of functional independence was 44 weeks. There were no treatment related deaths. These results are not inferior to that reported in randomised trials of surgery in addition to WBRT.[10][11][12]

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Evidence summary and recommendations

Evidence summary Level References
In patients with one to three unresectable brain metastases who have stable systemic disease, the addition of a stereotactic radiosurgery boost to whole brain radiotherapy improves local control and patient performance status and reduces steroid use. II [1]
In patients with one to three brain metastases who have stable systemic disease, the addition of a stereotactic radiosurgery boost to whole brain radiotherapy does not improve survival. II [1]
There is no evidence to suggest an advantage or disadvantage for stereotactic radiosurgery over surgery for the treatment of one to three metastases. III-2 [5], [6], [4]
Recommendation Grade
Patients with one to three unresectable brain metastases and stable systemic disease may be considered for a stereotactic radiosurgery boost in addition to whole brain radiotherapy.
C
Recommendation Grade
Radiosurgery may be used as an alternative to surgery for patients with one to three brain metastases and stable systemic disease.
C

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References

  1. 1.0 1.1 1.2 Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, et al. 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 Lancet 2004 May 22;363(9422):1665-72 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15158627].
  2. Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases Int J Radiat Oncol Biol Phys 1999 Sep 1;45(2):427-34 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10487566].
  3. Fuentes R, Bonfill X, Exposito J.. Surgery versus radiosurgery for patients with a solitary brain metastasis from non-small cell lung cancer Cochrane Database Syst Rev 2010 [Abstract available at http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004840.pub2/pdf].
  4. 4.0 4.1 4.2 Garell PC, Hitchon PW, Wen BC, Mellenberg DE, Torner J.. Stereotactic radiosurgery versus microsurgical resection for the initial treatment of metastatic cancer to the brain. J Radiosurg 1999;2(1):1-5.
  5. 5.0 5.1 5.2 5.3 Schöggl A, Kitz K, Reddy M, Wolfsberger S, Schneider B, Dieckmann K, et al. Defining the role of stereotactic radiosurgery versus microsurgery in the treatment of single brain metastases Acta Neurochir (Wien) 2000;142(6):621-6 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10949435].
  6. 6.0 6.1 6.2 6.3 Rades D, Kueter JD, Veninga T, Gliemroth J, Schild SE. Whole brain radiotherapy plus stereotactic radiosurgery (WBRT+SRS) versus surgery plus whole brain radiotherapy (OP+WBRT) for 1-3 brain metastases: results of a matched pair analysis Eur J Cancer 2009 Feb;45(3):400-4 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19062269].
  7. Bindal AK, Bindal RK, Hess KR, Shiu A, Hassenbusch SJ, Shi WM, et al. Surgery versus radiosurgery in the treatment of brain metastasis J Neurosurg 1996 May;84(5):748-54 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8622147].
  8. Auchter RM, Lamond JP, Alexander E, Buatti JM, Chappell R, Friedman WA, et al. A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis Int J Radiat Oncol Biol Phys 1996 Apr 1;35(1):27-35 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8641923].
  9. 10.0 10.1 Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain N Engl J Med 1990 Feb 22;322(8):494-500 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2405271].
  10. Mintz AH, Kestle J, Rathbone MP, Gaspar L, Hugenholtz H, Fisher B, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis Cancer 1996 Oct 1;78(7):1470-6 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8839553].
  11. Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JH, Hoekstra FH, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 1993 Jun;33(6):583-90 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8498838].

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Appendices

Further resources

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