Outcomes and prognostic stratification of patients with recurrent glioblastoma treated with salvage stereotactic radiosurgery

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OBJECTIVE

Glioblastoma (GBM) is the most malignant form of astrocytoma. The average survival is 6–10 months in patients with recurrent GBM (rGBM). In this study, the authors evaluated the role of stereotactic radiosurgery (SRS) in patients with rGBMs.

METHODS

The authors performed a retrospective review of their brain tumor database (1997–2016). Overall survival (OS) and progression-free survival (PFS) after salvage SRS were the primary endpoints evaluated. Response to SRS was assessed using volumetric MR images.

RESULTS

Fifty-three patients with rGBM underwent salvage SRS targeting 75 lesions. The median tumor diameter and volume were 2.55 cm and 3.80 cm3, respectively. The median prescription dose was 18 Gy (range 12–24 Gy) and the homogeneity index was 1.90 (range 1.11–2.02). The median OS after salvage SRS was estimated to be 11.0 months (95% CI 7.1–12.2) and the median PFS after salvage SRS was 4.4 months (95% CI 3.7–5.0). A Karnofsky Performance Scale score ≥ 80 was independently associated with longer OS, while small tumor volume (< 15 cm3) and less homogeneous treatment plans (homogeneity index > 1.75) were both independently associated with longer OS (p = 0.007 and 0.03) and PFS (p = 0.01 and 0.002, respectively). Based on these factors, 2 prognostic groups were identified for PFS (5.4 vs 3.2 months), while 3 were identified for OS (median OS of 15.2 vs 10.5 vs 5.2 months).

CONCLUSIONS

SRS is associated with longer OS and/or PFS in patients with good performance status, small-volume tumor recurrences, and heterogeneous treatment plans. The authors propose a prognostic model to identify a cohort of rGBM patients who may benefit from SRS.

ABBREVIATIONS EBRT = external-beam radiotherapy; GBM = glioblastoma; GKRS = Gamma Knife radiosurgery; KPS = Karnofsky Performance Scale; LITT = laser interstitial thermal therapy; MGMT = O6-methylguanine-DNA methyltransferase; OS = overall survival; PFS = progression-free survival; rGBM = recurrent GBM; RPA = recursive partitioning analysis; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy.

Article Information

Correspondence Lilyana Angelov: Cleveland Clinic, Cleveland, OH. angelol@ccf.org.

INCLUDE WHEN CITING Published online October 19, 2018; DOI: 10.3171/2018.4.JNS172909.

Disclosures Dr. Barnett is a consultant for Elekta. Dr. Mohammadi is a consultant for Monteris Medical.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Kaplan-Meier curves showing the percentage of PFS and OS in patients following SRS for rGBM.

  • View in gallery

    Kaplan-Meier curves showing PFS (left) in patients stratified into prognostic groups (favorable: homogeneity index > 1.75 and total volume < 15 cm3; unfavorable: index ≤ 1.75 and/or total volume ≥ 15 cm3) and OS (right) in patients stratified into prognostic groups (favorable: 0 poor prognostic features; intermediate: 1 poor prognostic feature; unfavorable: 2 or 3 poor prognostic features) following salvage SRS for rGBM. The poor prognostic features were KPS score < 80, total tumor volume ≥ 15 cm3, and homogeneity index ≤ 1.75.

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    Illustrative case of a 61-year-old man who presented with rGBM following standard concurrent chemoradiotherapy and 3 cycles of adjunct chemotherapy. He exhibited a good response to salvage SRS (22 Gy at 50% isodose line; homogeneity index 2.005) at the 9.4-month follow-up (pretreatment axial [A] and sagittal [B] postgadolinium T1-weighted MR images and postgadolinium axial [C] and sagittal [D] T1-weighted MR images at last follow-up). Figure is available in color online only.

References

1

Abbassy MMissios SBarnett GHBrewer CPeereboom DMAhluwalia M: Phase I trial of radiosurgery dose escalation plus bevacizumab in patients with recurrent/progressive glioblastoma. Neurosurgery [epub ahead of print] 2017

2

Batchelor TTMulholland PNeyns BNabors LBCampone MWick A: Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol 31:321232182013

3

Biswas TOkunieff PSchell MCSmudzin TPilcher WHBakos RS: Stereotactic radiosurgery for glioblastoma: retrospective analysis. Radiat Oncol 4:112009

4

Chan JLLee SWFraass BANormolle DPGreenberg HSJunck LR: Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J Clin Oncol 20:163516422002

5

Chao STAhluwalia MSBarnett GHStevens GHMurphy ESStockham AL: Challenges with the diagnosis and treatment of cerebral radiation necrosis. Int J Radiat Oncol Biol Phys 87:4494572013

6

Combs SEEdler LRausch RWelzel TWick WDebus J: Generation and validation of a prognostic score to predict outcome after re-irradiation of recurrent glioma. Acta Oncol 52:1471522013

7

Ellingson BMKim HJWoodworth DCPope WBCloughesy JNHarris RJ: Recurrent glioblastoma treated with bevacizumab: contrast-enhanced T1-weighted subtraction maps improve tumor delineation and aid prediction of survival in a multicenter clinical trial. Radiology 271:2002102014

8

Elliott REParker ECRush SCKalhorn SPMoshel YANarayana A: Efficacy of Gamma Knife radiosurgery for small-volume recurrent malignant gliomas after initial radical resection. World Neurosurg 76:12814061–62 2011

9

Field KMSimes JNowak AKCher LWheeler HHovey EJ: Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma. Neuro Oncol 17:150415132015

10

Fisher JLSchwartzbaum JAWrensch MWiemels JL: Epidemiology of brain tumors. Neurol Clin 25:867890vii 2007

11

Flickinger JCKondziolka DLunsford LDCoffey RJGoodman MLShaw EG: A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis. Int J Radiat Oncol Biol Phys 28:7978021994

12

Flieger MGanswindt USchwarz SBKreth FWTonn JCla Fougère C: Re-irradiation and bevacizumab in recurrent high-grade glioma: an effective treatment option. J Neurooncol 117:3373452014

13

Friedman HSPrados MDWen PYMikkelsen TSchiff DAbrey LE: Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:473347402009

14

Hsieh PCChandler JPBhangoo SPanagiotopoulos KKalapurakal JAMarymont MH: Adjuvant gamma knife stereotactic radiosurgery at the time of tumor progression potentially improves survival for patients with glioblastoma multiforme. Neurosurgery 57:6846922005

15

Hunn MKBauer EWood CEGasser ODzhelali MAncelet LR: Dendritic cell vaccination combined with temozolomide retreatment: results of a phase I trial in patients with recurrent glioblastoma multiforme. J Neurooncol 121:3193292015

16

Hunter GKSuh JHReuther AMVogelbaum MABarnett GHAngelov L: Treatment of five or more brain metastases with stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 83:139413982012

17

Kano HUrgosik DLiscak RPollock BECohen-Inbar OSheehan JP: Stereotactic radiosurgery for idiopathic glossopharyngeal neuralgia: an international multicenter study. J Neurosurg 125 (Suppl 1):1471532016

18

Kesari SRam Z: Tumor-treating fields plus chemotherapy versus chemotherapy alone for glioblastoma at first recurrence: a post hoc analysis of the EF-14 trial. CNS Oncol 6:1851932017

19

Kim MLee DHKim HJCho YHKim JHKwon DH: Analysis of the results of recurrent intracranial meningiomas treated with re-radiosurgery. Clin Neurol Neurosurg 153:931012017

20

Kondziolka DFlickinger JCBissonette DJBozik MLunsford LD: Survival benefit of stereotactic radiosurgery for patients with malignant glial neoplasms. Neurosurgery 41:7767851997

21

Kondziolka DPatel ALunsford LDKassam AFlickinger JC: Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 45:4274341999

22

Kong DSLee JIPark KKim JHLim DHNam DH: Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas. Cancer 112:204620512008

23

Kreisl TNKim LMoore KDuic PRoyce CStroud I: Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:7407452009

24

Kruyt IJVerheul JBHanssens PEJKunst HPM: Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: a matched cohort study with sporadic vestibular schwannomas. J Neurosurg 128:49592018

25

Lee EWWei LJAmato DALeurgans S: Cox-type regression analysis for large numbers of small groups of correlated failure time observations in Klein JPGoel PK (eds): Survival Analysis: State of the Art. Dordrecht: Springer Netherlands1992 pp 237247

26

Li JWang MWon MShaw EGCoughlin CCurran WJ Jr: Validation and simplification of the Radiation Therapy Oncology Group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 81:6236302011

27

Lin NULee EQAoyama HBarani IJBarboriak DPBaumert BG: Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol 16:e270e2782015

28

Minniti GAgolli LFalco TScaringi CLanzetta GCaporello P: Hypofractionated stereotactic radiotherapy in combination with bevacizumab or fotemustine for patients with progressive malignant gliomas. J Neurooncol 122:5595662015

29

Nagpal JJamoona AGulati NDMohan ABraun AMurali R: Revisiting the role of p53 in primary and secondary glioblastomas. Anticancer Res 26 (6C):463346392006

30

Niranjan AKano HIyer AKondziolka DFlickinger JCLunsford LD: Role of adjuvant or salvage radiosurgery in the management of unresected residual or progressive glioblastoma multiforme in the pre-bevacizumab era. J Neurosurg 122:7577652015

31

Ostrom QTGittleman HXu JKromer CWolinsky YKruchko C: CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro Oncol 18 (Suppl 5):v1v752016

32

Park KJKano HIyer ALiu XNiranjan AFlickinger JC: Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case-control study. J Neurooncol 107:3233332012

33

Patel MSiddiqui FJin JYMikkelsen TRosenblum MMovsas B: Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival. J Neurooncol 92:1851912009

34

Patil CGPricola KSarmiento JMGarg SKBryant ABlack KL: Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Cochrane Database Syst Rev (9):CD0061212012

35

Perry JRBélanger KMason WPFulton DKavan PEasaw J: Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol 28:205120572010

36

Pouratian NCrowley RWSherman JHJagannathan JSheehan JP: Gamma Knife radiosurgery after radiation therapy as an adjunctive treatment for glioblastoma. J Neurooncol 94:4094182009

37

Reardon DADesjardins ASchuster JTran DDFink KLNabors LB: IMCT-08 ReACT: long-term survival from a randomized phase II study of rindopepimut (CDX-110) plus bevacizumab in relapsed glioblastoma. Neuro Oncol 17 (Suppl 5):v1092015 (Abstract)

38

Reardon DANabors LBMason WPPerry JRShapiro WKavan P: Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma. Neuro Oncol 17:4304392015

39

Ryken TCMcDermott MRobinson PDAmmirati MAndrews DWAsher AL: The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 96:1031142010

40

Ryu SBuatti JMMorris AKalkanis SNRyken TCOlson JJ: The role of radiotherapy in the management of progressive glioblastoma: a systematic review and evidence-based clinical practice guideline. J Neurooncol 118:4894992014

41

Sampson JOmuro AVlahovic GSahebjam SBaehring JHafler DA: IMCT-03 Safety and activity of nivolumab monotherapy and nivolumab in combination with ipilimumab in recurrent glioblastoma: updated results from CHECKMATE-143. Neuro Oncol 17 (Suppl 5):v1072015 (Abstract)

42

Seystahl KWick WWeller M: Therapeutic options in recurrent glioblastoma—an update. Crit Rev Oncol Hematol 99:3894082016

43

Sharma MJia XAhluwalia MBarnett GHVogelbaum MAChao ST: Cumulative intracranial tumor volume and number of brain metastasis as predictors of developing new lesions after stereotactic radiosurgery for brain metastasis. World Neurosurg 106:6666752017

44

Sharma MJia XAhluwalia MBarnett GHVogelbaum MAChao ST: First follow-up radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastases. Cancer Med 6:207620862017

45

Shaw EScott CSouhami LDinapoli RKline RLoeffler J: 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 47:2912982000

46

Silva DSharma MBarnett GH: Laser ablation vs open resection for deep-seated tumors: evidence for laser ablation. Neurosurgery 63 (Suppl 1):15262016

47

Silva DSharma MBelsuzarri TBarnett GH: Minimally invasive targeted therapy for glioblastoma: laser interstitial thermal therapy in Brem SAbdullah KG (eds): Glioblastoma. Philadelphia: Elsevier2017

48

Silva DSharma MJuthani RMeola ABarnett GH: Magnetic resonance thermometry and laser interstitial thermal therapy for brain tumors. Neurosurg Clin N Am 28:5255332017

49

Skeie BSEnger POBrøgger JGanz JCThorsen FHeggdal JI: Gamma Knife surgery versus reoperation for recurrent glioblastoma multiforme. World Neurosurg 78:6586692012

50

Soon YYTham IWLim KHKoh WYLu JJ: Surgery or radiosurgery plus whole brain radiotherapy versus surgery or radiosurgery alone for brain metastases. Cochrane Database Syst Rev (3):CD0094542014

51

Souhami LSeiferheld WBrachman DPodgorsak EBWerner-Wasik MLustig R: Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys 60:8538602004

52

Stupp RHegi MEMason WPvan den Bent MJTaphoorn MJJanzer RC: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:4594662009

53

Stupp RIdbaih ASteinberg DMRead WToms SBarnett G: LTBK-01: Prospective, multi-center phase III trial of tumor treating fields together with temozolomide compared to temozolomide alone in patients with newly diagnosed glioblastoma. Neuro Oncol 18 (Suppl 6):i12016 (Abstract)

54

Stupp RMason WPvan den Bent MJWeller MFisher BTaphoorn MJ: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:9879962005

55

Stupp RTaillibert SKanner AAKesari SSteinberg DMToms SA: Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA 314:253525432015

56

Stupp RWong ETKanner AASteinberg DEngelhard HHeidecke V: NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer 48:219222022012

57

Suchorska BWeller MTabatabai GSenft CHau PSabel MC: Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial. Neuro Oncol 18:5495562016

58

Sughrue MESheean TBonney PAMaurer AJTeo C: Aggressive repeat surgery for focally recurrent primary glioblastoma: outcomes and theoretical framework. Neurosurg Focus 38(3):E112015

59

Taal WOosterkamp HMWalenkamp AMDubbink HJBeerepoot LVHanse MC: Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 15:9439532014

60

Thomas JGRao GKew YPrabhu SS: Laser interstitial thermal therapy for newly diagnosed and recurrent glioblastoma. Neurosurg Focus 41(4):E122016

61

Torok JAWegner REMintz AHHeron DEBurton SA: Re-irradiation with radiosurgery for recurrent glioblastoma multiforme. Technol Cancer Res Treat 10:2532582011

62

Trifiletti DMLee CCKano HCohen JJanopaul-Naylor JAlonso-Basanta M: Stereotactic radiosurgery for brainstem metastases: an international cooperative study to define response and toxicity. Int J Radiat Oncol Biol Phys 96:2802882016

63

Tsao MNMehta MPWhelan TJMorris DEHayman JAFlickinger JC: The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma. Int J Radiat Oncol Biol Phys 63:47552005

64

Valery CAFaillot MLamproglou IGolmard JLJenny CPeyre M: Grade II meningiomas and Gamma Knife radiosurgery: analysis of success and failure to improve treatment paradigm. J Neurosurg 125 (Suppl 1):89962016

65

van den Bent MJBrandes AARampling RKouwenhoven MCKros JMCarpentier AF: Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 27:126812742009

66

Weller MTabatabai GKästner BFelsberg JSteinbach JPWick A: MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial. Clin Cancer Res 21:205720642015

67

Wick WBrandes AAGorlia TBendszus MSahm FTaal W: LB-05 Phase III trial exploring the combination of bevacizumab and lomustine in patients with first recurrence of a glioblastoma: the EORTC 26101 trial. Neuro Oncol 17 (Suppl 5):v12015 (Abstract)

68

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

69

Zeng AHu QLiu YWang ZCui XLi R: IDH1/2 mutation status combined with Ki-67 labeling index defines distinct prognostic groups in glioma. Oncotarget 6:30232302382015

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