Comparison of treatment results between 3- and 2-stage Gamma Knife radiosurgery for large brain metastases: a retrospective multi-institutional study

Restricted access

OBJECTIVE

In order to obtain better local tumor control for large (i.e., > 3 cm in diameter or > 10 cm3 in volume) brain metastases (BMs), 3-stage and 2-stage Gamma Knife surgery (GKS) procedures, rather than a palliative dose of stereotactic radiosurgery, have been proposed. Here, authors conducted a retrospective multi-institutional study to compare treatment results between 3-stage and 2-stage GKS for large BMs.

METHODS

This retrospective multi-institutional study involved 335 patients from 19 Gamma Knife facilities in Japan. Major inclusion criteria were 1) newly diagnosed BMs, 2) largest tumor volume of 10.0–33.5 cm3, 3) cumulative intracranial tumor volume ≤ 50 cm3, 4) no leptomeningeal dissemination, 5) no more than 10 tumors, and 6) Karnofsky Performance Status 70% or better. Prescription doses were restricted to between 9.0 and 11.0 Gy in 3-stage GKS and between 11.8 and 14.2 Gy in 2-stage GKS. The total treatment interval had to be within 6 weeks, with at least 12 days between procedures. There were 114 cases in the 3-stage group and 221 in the 2-stage group. Because of the disproportion in patient numbers and the pre-GKS clinical factors between these two GKS groups, a case-matched study was performed using the propensity score matching method. Ultimately, 212 patients (106 from each group) were selected for the case-matched study. Overall survival, tumor progression, neurological death, and radiation-related adverse events were analyzed.

RESULTS

In the case-matched cohort, post-GKS median survival time tended to be longer in the 3-stage group (15.9 months) than in the 2-stage group (11.7 months), but the difference was not statistically significant (p = 0.65). The cumulative incidences of tumor progression (21.6% vs 16.7% at 1 year, p = 0.31), neurological death (5.1% vs 6.0% at 1 year, p = 0.58), or serious radiation-related adverse events (3.0% vs 4.0% at 1 year, p = 0.49) did not differ significantly.

CONCLUSIONS

This retrospective multi-institutional study showed no differences between 3-stage and 2-stage GKS in terms of overall survival, tumor progression, neurological death, and radiation-related adverse events. Both 3-stage and 2-stage GKS performed according to the aforementioned protocols are good treatment options in selected patients with large BMs.

ABBREVIATIONS BM = brain metastasis; CITV = cumulative intracranial tumor volume; CTCAE = Common Terminology Criteria for Adverse Events; GKS = Gamma Knife surgery; JLGKS = Japanese Leksell Gamma Knife Society; KPS = Karnofsky Performance Status; LQ = linear quadratic; MST = median survival time; NPS = neurological prognostic score; OS = overall survival; RPA = recursive partitioning analysis; SRS = stereotactic radiosurgery; SRT = stereotactic radiotherapy; TKI = tyrosine kinase inhibitor; WBRT = whole-brain radiation therapy.

Article Information

Correspondence Toru Serizawa: Tokyo Gamma Unit Center, Tsukiji Neurological Clinic, Tokyo, Japan. gamma-knife.serizawa@nifty.com.

INCLUDE WHEN CITING Published online September 7, 2018; DOI: 10.3171/2018.4.JNS172596.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Trial profile of inclusions and exclusions.

  • View in gallery

    Overall survival: 3-stage versus 2-stage GKS in the 212 case-matched patients. Although the post-GKS MST was shorter in the 2-stage group (11.7 months) than in the 3-stage group (15.9 months), this difference was not statistically significant (HR 1.080, 95% CI 0.777–1.502, p = 0.65).

  • View in gallery

    Tumor progression: 3-stage versus 2-stage GKS in the 212 case-matched patients. Cumulative incidences of tumor progression were slightly higher in the 3-stage group than in the 2-stage group (21.6% vs 16.7% at 1 year, respectively), but these differences did not reach statistical significance (p = 0.31).

References

  • 1

    Angelov LMohammadi AMBennett EEAbbassy MElson PChao ST: Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm. J Neurosurg 129:3663822018

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    Baschnagel AMMeyer KDChen PYKrauss DJOlson REPieper DR: Tumor volume as a predictor of survival and local control in patients with brain metastases treated with Gamma Knife surgery. J Neurosurg 119:113911442013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Chernov MHayashi MIzawa MOchiai TUsukura MAbe K: Differentiation of the radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for brain metastases: importance of multi-voxel proton MRS. Minim Invasive Neurosurg 48:2282342005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Cummings MYoun PBergsma DPUsuki KYWalter KSharma M: Single-fraction radiosurgery using conservative doses for brain metastases: Durable responses in select primaries with limited toxicity. Neurosurgery [epub ahead of print] 2017

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Dohm AMcTyre EROkoukoni CHenson ACramer CKLeCompte MC: Staged stereotactic radiosurgery for large brain metastases: local control and clinical outcomes of a one-two punch technique. Neurosurgery [epub ahead of print] 2017

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Eaton BRGebhardt BPrabhu RShu HKCurran WJ JrCrocker I: Hypofractionated radiosurgery for intact or resected brain metastases: defining the optimal dose and fractionation. Radiat Oncol 8:1352013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Ebner DRava PGorovets DCielo DHepel JT: Stereotactic radiosurgery for large brain metastases. J Clin Neurosci 22:165016542015

  • 8

    Fine JPGray RJ: A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–5091999

  • 9

    Gaspar LScott CRotman MAsbell SPhillips TWasserman T: Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:7457511997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Gerber NKYamada YRimner AShi WRiely GJBeal K: Erlotinib versus radiation therapy for brain metastases in patients with EGFR-mutant lung adenocarcinoma. Int J Radiat Oncol Biol Phys 89:3223292014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Gooley TALeisenring WCrowley JStorer BE: Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18:6957061999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Higuchi YSerizawa TNagano OMatsuda SOno JSato M: Three-staged stereotactic radiotherapy without whole brain irradiation for large metastatic brain tumors. Int J Radiat Oncol Biol Phys 74:154315482009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Iwata HMatsufuji NToshito TAkagi TOtsuka SShibamoto Y: Compatibility of the repairable-conditionally repairable, multi-target and linear-quadratic models in converting hypofractionated radiation doses to single doses. J Radiat Res (Tokyo) 54:3673732013

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Iwata HShibamoto YMurata RTomita NAyakawa SOgino H: Estimation of errors associated with use of linear-quadratic formalism for evaluation of biologic equivalence between single and hypofractionated radiation doses: an in vitro study. Int J Radiat Oncol Biol Phys 75:4824882009

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Kano HKondziolka DLobato-Polo JZorro OFlickinger JCLunsford LD: T1/T2 matching to differentiate tumor growth from radiation effects after stereotactic radiosurgery. Neurosurgery 66:4864922010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Karnofsky DABurchenal JH: The clinical evaluation of chemotherapeutic agents in cancer in MacLeod CM (ed): Evaluation of Chemotherapeutic Agents. New York: Columbia University Press1949 pp 191205

    • Search Google Scholar
    • Export Citation
  • 17

    Kirkpatrick JPBrenner DJOrton CG: Point/Counterpoint. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Med Phys 36:338133842009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Lorenzoni JDevriendt DMassager NDavid PRuíz SVanderlinden B: Radiosurgery for treatment of brain metastases: estimation of patient eligibility using three stratification systems. Int J Radiat Oncol Biol Phys 60:2182242004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Minamimoto RSaginoya TKondo CTomura NIto KMatsuo Y: Differentiation of brain tumor recurrence from post-radiotherapy necrosis with 11C-methionine PET: visual assessment versus quantitative assessment. PLoS One 10:e01325152015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Minniti GD’Angelillo RMScaringi CTrodella LEClarke EMatteucci P: Fractionated stereotactic radiosurgery for patients with brain metastases. J Neurooncol 117:2953012014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Miyakawa AShibamoto YOtsuka SIwata H: Applicability of the linear-quadratic model to single and fractionated radiotherapy schedules: an experimental study. J Radiat Res (Tokyo) 55:4514542014

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Murai TOgino HManabe YIwabuchi MOkumura TMatsushita Y: Fractionated stereotactic radiotherapy using CyberKnife for the treatment of large brain metastases: a dose escalation study. Clin Oncol (R Coll Radiol) 26:151–1582014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Nagai AShibamoto YYoshida MWakamatsu KKikuchi Y: Treatment of single or multiple brain metastases by hypofractionated stereotactic radiotherapy using helical tomotherapy. Int J Mol Sci 15:691069242014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Oermann EKKress MATodd JVCollins BTHoffman RChaudhry H: The impact of radiosurgery fractionation and tumor radiobiology on the local control of brain metastases. J Neurosurg 119:113111382013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Ogura KMizowaki TOgura MSakanaka KArakawa YMiyamoto S: Outcomes of hypofractionated stereotactic radiotherapy for metastatic brain tumors with high risk factors. J Neurooncol 109:4254322012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Otsuka SShibamoto YIwata HMurata RSugie CIto M: 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 81:153815432011

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Parsons LS: Reducing bias in a propensity score matched pair sample using greedy matching techniques. SAS. (http://www2.sas.com/proceedings/sugi26/p214-26.pdf) [Accessed August 24 2018]

    • Export Citation
  • 28

    Patchell RATibbs PARegine WFDempsey RJMohiuddin MKryscio RJ: Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 280:148514891998

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Patchell RATibbs PAWalsh JWDempsey RJMaruyama YKryscio RJ: A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:4945001990

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Prabhu RSPress RHPatel KRBoselli DMSymanowski JTLankford SP: Single-fraction stereotactic radiosurgery (SRS) alone versus surgical resection and SRS for large brain metastases: a multi-institutional analysis. Int J Radiat Oncol Biol Phys 99:4594672017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Serizawa THiguchi YNagano OMatsuda SAoyagi KOno J: Robustness of the neurological prognostic score in brain metastasis patients treated with Gamma Knife radiosurgery. J Neurosurg 127:100010062017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Serizawa THiguchi YNagano OMatsuda SOno JSaeki N: A new grading system focusing on neurological outcomes for brain metastases treated with stereotactic radiosurgery: the modified Basic Score for Brain Metastases. J Neurosurg 121 (Suppl):35432014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Serizawa THiguchi YOno JMatsuda SNagano OIwadate Y: Gamma Knife surgery for metastatic brain tumors without prophylactic whole-brain radiotherapy: results in 1000 consecutive cases. J Neurosurg 105 (Suppl):86902006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Serizawa TSaeki NHiguchi YOno JMatsuda SSato M: Diagnostic value of thallium-201 chloride single-photon emission computerized tomography in differentiating tumor recurrence from radiation injury after gamma knife surgery for metastatic brain tumors. J Neurosurg 102 (Suppl):2662712005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Shibamoto YMiyakawa AOtsuka SIwata H: Radiobiology of hypofractionated stereotactic radiotherapy: what are the optimal fractionation schedules? J Radiat Res (Tokyo) 57 (Suppl 1):i76i822016

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Shibamoto YOtsuka SIwata HSugie COgino HTomita N: Radiobiological evaluation of the radiation dose as used in high-precision radiotherapy: effect of prolonged delivery time and applicability of the linear-quadratic model. J Radiat Res (Tokyo) 53:1–92012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Sperduto PWBerkey BGaspar LEMehta MCurran W: A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 70:5105142008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Sperduto PWKased NRoberge DXu ZShanley RLuo X: Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30:4194252012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Sperduto PWYang TJBeal KPan HBrown PDBangdiwala A: Estimating survival in patients with lung cancer and brain metastases: an update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA). JAMA Oncol 3:8278312017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Tucker SL: Tests for the fit of the linear-quadratic model to radiation isoeffect data. Int J Radiat Oncol Biol Phys 10:1933–19391984

    • Search Google Scholar
    • Export Citation
  • 41

    Wegner RELeeman JEKabolizadeh PRwigema JCMintz AHBurton SA: Fractionated stereotactic radiosurgery for large brain metastases. Am J Clin Oncol 38:1351392015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Weltman ESalvajoli JVBrandt RAde Morais Hanriot RPrisco FECruz JC: Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys 46:115511612000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Yamamoto MSerizawa TSato YKawabe THiguchi YNagano O: Validity of two recently-proposed prognostic grading indices for lung, gastro-intestinal, breast and renal cell cancer patients with radiosurgically-treated brain metastases. J Neurooncol 111:3273352013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Yamamoto MSerizawa TShuto TAkabane AHiguchi YKawagishi J: Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15:3873952014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Yomo SHayashi M: A minimally invasive treatment option for large metastatic brain tumors: long-term results of two-session Gamma Knife stereotactic radiosurgery. Radiat Oncol 9:1322014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46

    Yomo SHayashi MNicholson C: A prospective pilot study of two-session Gamma Knife surgery for large metastatic brain tumors. J Neurooncol 109:1591652012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 56 56 56
Full Text Views 24 24 24
PDF Downloads 32 32 32
EPUB Downloads 0 0 0

PubMed

Google Scholar