Pre-operative Stereotactic Radiosurgery for Cerebral Metastatic Disease: A Retrospective Dose-Volume Study


      • Neoadjuvant SRS is associated with decreased radiation dosage and improved conformality profile due to enhanced target delineation.
      • Pre-operative SRS can decrease delivery of radiation to important structures such as optic apparatus, hippocampal cortex and brain stem.
      • These findings better characterize the role of neoadjuvant SRS in brain metastatic disease and could support further clinical trials.


      Background and purpose

      Stereotactic radiosurgery (SRS) after maximal safe resection is an accepted treatment strategy for patients with cerebral metastatic disease. Despite its high conformality profile, the incidence of radionecrosis (RN) remains high. SRS delivered pre-operatively could be associated with a reduced incidence of RN. We sought to evaluate whether neoadjuvant SRS could reduce radiotherapy doses in a cohort of patients treated with post-operative SRS.


      A cohort of 47 brain metastases (BM) treated at 2 academic institutions was retrospectively analyzed. Subjects underwent surgical extirpation of BMs and subsequent SRS to surgical bed. Post-operative volumetric and dosimetric data was collected from records or recreations of delivered plans; pre-operative data were derived from hypothetical radiotherapy courses and compared using Wilcoxon signed-rank tests.


      Higher planned tumor volume post-operatively (median[IQR] 12.28 [6.54, 18.69]cc vs. 10.20 [4.53, 21.70]cc respectively, p=0.4150) was observed. The median prescribed radiotherapy dose (DRx) was 16Gy pre-operatively and 24Gy post-operatively(p<0.0001). Further investigations revealed improved pre-operative conformity index (1.23[1.20, 1.29] vs. 1.29[1.23, 1.39], p=0.0098) and gradient index (2.72[2.59, 2.98] vs. 2.94[2.69, 3.47], p=0.0004). A significant difference was found in normal brain tissue exposed to 10Gy (12.97[6.78, 25.54]cc vs. 32.13[19.42, 48.40]cc, p<0.0001), 12Gy (9.31[4.56, 17.43]cc vs. 23.80[14.74, 36.56]cc, p<0.0001), and 14Gy (5.62[3.23, 11.61]cc vs. 17.47[9.00, 28.31]cc, p<0.0001), favoring pre-operative SRS.


      Neoadjuvant SRS is associated reduced DRx, better conformality profile and decreased radiation to normal tissue. These findings could support the use of neoadjuvant SRS for the treatment of BMs.



      BM (brain metastasis), DRx (prescribed radiation dosage), GTV (gross tumor volume), NBT (normal brain tissue), PostSRS (post-operative stereotactic radiosurgery), PreSRS (pre-operative stereotactic radiosurgery), PTV (planned tumor volume), RN (radionecrosis), SRS (stereotactic radiosurgery)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Radiotherapy and Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Nayak L.
        • Lee E.Q.
        • Wen P.Y.
        Epidemiology of brain metastases.
        Current Oncology Reports. 2012; 14: 48-54
        • Molenaar R.
        • Wiggenraad R.
        • Verbeek-De Kanter A.
        • Walchenbach R.
        • Vecht C.
        Relationship between volume, dose and local control in stereotactic radiosurgery of brain metastasis.
        British Journal of Neurosurgery. 2009; 23: 170-178
        • Soltys S.G.
        • Adler J.R.
        • Lipani J.D.
        • Jackson P.S.
        • Choi C.Y.H.
        • Puataweepong P.
        • et al.
        Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases.
        International Journal of Radiation Oncology Biology Physics. 2008; 70: 187-193
        • Adler J.R.
        • Cox R.S.
        • Kaplan I.
        • Martin D.P.
        Stereotactic radiosurgical treatment of brain metastases.
        Journal of Neurosurgery. 1992; 76: 444-449
      1. Donovan EK, Parpia S, Greenspoon JN. Incidence of radionecrosis in single-fraction radiosurgery compared with fractionated radiotherapy in the treatment of brain metastasis. Current Oncology 2019;26:e328.

        • Minniti G.
        • Clarke E.
        • Lanzetta G.
        • Osti M.F.
        • Trasimeni G.
        • Bozzao A.
        • et al.
        Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis.
        Radiat Oncol. 2011; 6
        • McCutcheon I.E.
        Stereotactic Radiosurgery to Prevent Local Recurrence of Brain Metastasis After Surgery: Neoadjuvant Versus Adjuvant.
        Acta Neurochirurgica, Supplementum. 2021; 128: 85-100
        • Patel K.R.
        • Burri S.H.
        • Asher A.L.
        • Crocker I.R.
        • Fraser R.W.
        • Zhang C.
        • et al.
        Comparing preoperative with postoperative stereotactic radiosurgery for resectable brain metastases: A multi-institutional analysis.
        Neurosurgery. 2016; 79: 279-285
        • Prabhu R.S.
        • Patel K.R.
        • Press R.H.
        • Soltys S.G.
        • Brown P.D.
        • Mehta M.P.
        • et al.
        Preoperative vs postoperative radiosurgery for resected brain metastases: A review.
        Clinical Neurosurgery. 2019; 84: 19-29
        • Paddick I.
        • Lippitz B.
        A simple dose gradient measurement tool to complement the conformity index.
        J Neurosurg. 2006; 105: 194-201
      2. ICRU Report 62, Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU 50) – ICRU n.d. (accessed June 15, 2022).

        • Lawrence Y.R.
        • Li X.A.
        • el Naqa I.
        • Hahn C.A.
        • Marks L.B.
        • Merchant T.E.
        • et al.
        Radiation Dose-Volume Effects in the Brain.
        International Journal of Radiation Oncology Biology Physics. 2010; 76: S20-S27
        • Blonigen B.J.
        • Steinmetz R.D.
        • Levin L.
        • Lamba M.A.
        • Warnick R.E.
        • Breneman J.C.
        Irradiated Volume as a Predictor of Brain Radionecrosis After Linear Accelerator Stereotactic Radiosurgery.
        International Journal of Radiation Oncology Biology Physics. 2010; 77: 996-1001
        • Kohutek Z.A.
        • Yamada Y.
        • Chan T.A.
        • Brennan C.W.
        • Tabar V.
        • Gutin P.H.
        • et al.
        Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases.
        J Neurooncol. 2015; 125: 149-156
      3. Loo M, Clavier JB, Khalifa JA, Moyal E, Khalifa J. Dose-Response Effect and Dose-Toxicity in Stereotactic Radiotherapy for Brain Metastases: A Review. Cancers (Basel) 2021;13.

        • Marchan E.M.
        • Peterson J.
        • Sio T.T.
        • Chaichana K.L.
        • Harrell A.C.
        • Ruiz-Garcia H.
        • et al.
        Postoperative cavity stereotactic radiosurgery for brain metastases.
        Frontiers in Oncology. 2018; 8
        • Patel K.R.
        • Burri S.H.
        • Boselli D.
        • Symanowski J.T.
        • Asher A.L.
        • Sumrall A.
        • et al.
        Comparing pre-operative stereotactic radiosurgery (SRS) to post-operative whole brain radiation therapy (WBRT) for resectable brain metastases: a multi-institutional analysis.
        Journal of Neuro-Oncology. 2017; 131: 611-618
        • Kocher M.
        • Wittig A.
        • Piroth M.D.
        • Treuer H.
        • Seegenschmiedt H.
        • Ruge M.
        • et al.
        Stereotactic radiosurgery for treatment of brain metastases: A report of the DEGRO Working Group on Stereotactic RadiotherapyStereotaktische Radiochirurgie zur Behandlung von Hirnmetastasen: Ein Bericht der Deutschen Gesellschaft für Radioonkologie (DEGRO).
        Strahlentherapie Und Onkologie. 2014; 190: 521-532
        • Sanghavi S.N.
        • Miranpuri S.S.
        • Chappell R.
        • Buatti J.M.
        • Sneed P.K.
        • Suh J.H.
        • et al.
        Radiosurgery for patients with brain metastases: A multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method.
        International Journal of Radiation Oncology Biology Physics. 2001; 51: 426-434
        • Balagamwala E.H.
        • Chao S.T.
        • Suh J.H.
        Principles of radiobiology of stereotactic radiosurgery and clinical applications in the central nervous system.
        Technology in Cancer Research and Treatment. 2012; 11: 3-13
      4. Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD. Radiation-induced brain injury: A review. Frontiers in Oncology 2012;2 JUL:73.

        • Mayo C.
        • Yorke E.
        • Merchant T.E.
        Int J Radiat Oncol Biol Phys. 2010; 76: S36-S41
        • Brown P.D.
        • Gondi V.
        • Pugh S.
        • Tome W.A.
        • Wefel J.S.
        • Armstrong T.S.
        • et al.
        Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001.
        Journal of Clinical Oncology. 2020; 38: 1019-1029
        • Burgess L.
        • Nair V.
        • Gratton J.
        • Doody J.
        • Chang L.
        • Malone S.
        Stereotactic radiosurgery optimization with hippocampal-sparing in patients treated for brain metastases.
        Physics and Imaging in Radiation Oncology. 2021; 17: 106-110