Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies

A review

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Diffuse intrinsic pontine gliomas constitute ~ 60–75% of tumors found within the pediatric brainstem. These malignant lesions present with rapidly progressive symptoms such as cranial nerve, long tract, or cerebellar dysfunctions. Magnetic resonance imaging is usually sufficient to establish the diagnosis and obviates the need for surgical biopsy in most cases. The prognosis of the disease is dismal, and the median survival is < 12 months. Resection is not a viable option. Standard therapy involves radiotherapy, which produces transient neurological improvement with a progression-free survival benefit, but provides no improvement in overall survival. Clinical trials have been conducted to assess the efficacy of chemotherapeutic and biological agents in the treatment of diffuse pontine gliomas. In this review, the authors discuss recent studies in which systemic therapy was administered prior to, concomitantly with, or after radiotherapy. For future perspective, the discussion includes a rationale for stereotactic biopsies as well as possible therapeutic options of local chemotherapy in these lesions.

Abbreviations used in this paper: BBB = blood-brain barrier; BCNU = carmustine; CED = convection-enhanced delivery; FDG-PET = [18F]fluorodeoxyglucose–PET.

Article Information

Address correspondence to: George I. Jallo, M.D., Division of Pediatric Neurosurgery, Johns Hopkins Hospital, Harvey 811, 600 North Wolfe Street, Baltimore, Maryland 21287. email: gjallo1@jhmi.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Illustration demonstrating various locations of brainstem tumors. A denotes the tectal plate; B, the focal intrinsic midbrain; C, the focal intrinsic pontine; D, the dorsal exophytic pontine; E, the diffuse pontine; F, the focal intrinsic medullary; and G, the dorsal exophytic medullary.

  • View in gallery

    Left: Axial T2-weighted MR image demonstrating a diffuse pontine glioma. Right: Sagittal T1-weighted MR image with Gd contrast showing the pontine glioma. There is mild enhancement.

  • View in gallery

    A and B: Sagittal and axial FDG-PET images coregistered with CT scans demonstrating a focal hypermetabolic area in the pons suggestive of a high-grade glioma. C and D: Sagittal and axial T1-weighted MR images obtained with Gd contrast demonstrating irregular enhancement. The areas of enhancement correspond to the areas of hypermetabolic activity on the FDG-PET coregistered with CT scans.

  • View in gallery

    Left: Artist's illustration showing the position of the rat and angle for tumor implantation. Right: Artist's rendering showing the anatomy of the rat brainstem, the location that is resected, the trajectory of the needle, and the location of tumor implantation. (Reproduced with permission from Lee J, Jallo GI, Guarnieri M, Carson BS, Penno MB: A novel brainstem tumor model: guide screw technology with functional, radiological, and histopathological characterization. Neurosurg Focus 18(6A):E11, 2005, by the American Association of Neurosurgeons. Modified for a typographic correction only.

References

1

Akasaki YBlack KLYu JS: T cell immunity in patients with malignant glioma: recent progress in dendritic cell-based immunotherapeutic approaches. Front Biosci 10:290829212005

2

Alavi JBEck SL: Gene therapy for high grade gliomas. Expert Opin Biol Ther 1:2392522001

3

Albright ALBrain stem gliomas. Youmans J: Neurological Surgery ed 4PhiladelphiaWB Saunders Co1996. 26032611

4

Albright ALPacker RJZimmerman RRorke LBBoyett JHammond GD: Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children's Cancer Group. Neurosurgery 33:102610301993

5

Allen JCSiffert J: Contemporary chemotherapy issues for children with brainstem gliomas. Pediatr Neurosurg 24:98 1021996

6

Allen JSiffert JDonahue BNirenberg AJakacki RRobertson P: A phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas. Cancer 86:106410691999

7

Amano TKajiwara KYoshikawa KMorioka JNomura SFujisawa H: Antitumor effects of vaccination with dendritic cells transfected with modified receptor for hyaluronan-mediated motility mRNA in a mouse glioma model. J Neurosurg 106:6386452007

8

Ashley DMKong FMBigner DDHale LP: Endogenous expression of transforming growth factor beta1 inhibits growth and tumorigenicity and enhances Fas-mediated apoptosis in a murine high-grade glioma model. Cancer Res 58:3023091998

9

Bansal KEngelhard HH: Gene therapy for brain tumors. Curr Oncol Rep 2:4634722000

10

Barkovich AJKrischer JKun LEPacker RZimmerman RAFreeman CR: Brain stem gliomas: a classification system based on magnetic resonance imaging. Pediatr Neurosurg 16:73831990

11

Barzon LZanusso MColombo FPalu G: Clinical trials of gene therapy, virotherapy, and immunotherapy for malignant gliomas. Cancer Gene Ther 13:5395542006

12

Berger MSEdwards MSLaMasters DDavis RLWilson CB: Pediatric brain stem tumors: radiographic, pathological, and clinical correlations. Neurosurgery 12:2983021983

13

Bernier-Chastagner VGrill JDoz FBracard SGentet JCMarie-Cardine A: Topotecan as a radiosensitizer in the treatment of children with malignant diffuse brainstem gliomas: results of a French Society of Paediatric Oncology Phase II Study. Cancer 104:279227972005

14

Bobo RHLaske DWAkbasak AMorrison PFDedrick RLOldfield EH: Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci U S A 91:207620801994

15

Bouffet ERaquin MDoz FGentet JCRodary CDemeocq F: Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 88:685 6922000

16

Brem HGabikian P: Biodegradable polymer implants to treat brain tumors. J Control Release 74:63672001

17

Broniscer AIacono LChintagumpala MFouladi MWallace DBowers DC: Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: results of a multiinstitutional study (SJHG-98). Cancer 103:1331392005

18

Bruce JNFalavigna AJohnson JPHall JSBirch BDYoon JT: Intracerebral clysis in a rat glioma model. Neurosurgery 46:6836912000

19

Carey JPCooper TJallo GICarson BSGuarnieri M: Ototoxicity of carboplatin delivered locally in a monkey brainstem. Int J Toxicol 24:4434492005

20

Carson BS SrWu QTyler BSukay LRaychaudhuri RDi-Meco F: New approach to tumor therapy for inoperable areas of the brain: chronic intraparenchymal drug delivery. J Neurooncol 60:1511582002

21

Choux MLena GDo LBrainstem tumors. Choux MDi Rocco CHockley A: Pediatric Neurosurgery New YorkChurchill Livingstone2000. 471491

22

Culmsee CGasser EHansen STonn JCWagner EGoldbrunner R: Effects of Raf-1 siRNA on human cerebral microvascular endothelial cells: a potential therapeutic strategy for inhibition of tumor angiogenesis. Brain Res 1125:1471542006

23

De Witte OLefranc FLevivier MSalmon IBrotchi JGoldman S: FDG-PET as a prognostic factor in high-grade astrocytoma. J Neurooncol 49:1571632000

24

Debinski WObiri NIPowers SKPastan IPuri RK: Human glioma cells overexpress receptors for interleukin 13 and are extremely sensitive to a novel chimeric protein composed of interleukin 13 and pseudomonas exotoxin. Clin Cancer Res 1:125312581995

25

Degen JWWalbridge SVortmeyer AOOldfield EHLonser RR: Safety and efficacy of convection-enhanced delivery of gemcitabine or carboplatin in a malignant glioma model in rats. J Neurosurg 99:8938982003

26

Delbeke DMeyerowitz CLapidus RLMaciunas RJJennings MTMoots PL: Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET. Radiology 195:47 521995

27

Dhodapkar KMBanerjee DSteinman RM: Harnessing the immune system against human glioma. Ann N Y Acad Sci 1062:13212005

28

Doz FNeuenschwander SBouffet EGentet JCSchneider PKalifa C: Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Societe Francaise d'Oncologie Pediatrique. Eur J Cancer 38:8158192002

29

Dunkel IJGarvin JH JrGoldman SEttinger LJKaplan AMCairo M: High dose chemotherapy with autologous bone marrow rescue for children with diffuse pontine brain stem tumors. Children's Cancer Group. J Neurooncol 37:67731998

30

Edwards MSWara WMUrtasun RCPrados MLevin VAFulton D: Hyperfractionated radiation therapy for brainstem glioma: a phase I-II trial. J Neurosurg 70:6917001989

31

Epstein F: A staging system for brain stem gliomas. Cancer 56:180418061985

32

Epstein FMcCleary EL: Intrinsic brain-stem tumors of childhood: surgical indications. J Neurosurg 64:11151986

33

Epstein FWisoff JH: Intrinsic brainstem tumors in childhood: surgical indications. J Neurooncol 6:3093171988

34

Fenton LZMadden JRForeman NK: Brain stem glioma in a child: false diagnosis of radiation necrosis with FDG PET. Med Pediatr Oncol 40:2602622003

35

Fischbein NJPrados MDWara WRusso CEdwards MSBarkovich AJ: Radiologic classification of brain stem tumors: correlation of magnetic resonance imaging appearance with clinical outcome. Pediatr Neurosurg 24:9231996

36

Fontana AConstam DBFrei KMalipiero UPfister HW: Modulation of the immune response by transforming growth factor beta. Int Arch Allergy Immunol 99:171992

37

Freeman CRKrischer JSanford RABurger PCCohen MNorris D: Hyperfractionated radiotherapy in brain stem tumors: results of a Pediatric Oncology Group study. Int J Radiat Oncol Biol Phys 15:3113181988

38

Freeman CRKrischer JPSanford RACohen MEBurger PCdel Carpio R: Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study. Int J Radiat Oncol Biol Phys 27:1972061993

39

Freeman CRKrischer JSanford RACohen MEBurger PCKun L: Hyperfractionated radiation therapy in brain stem tumors. Results of treatment at the 7020 cGy dose level of Pediatric Oncology Group study #8495. Cancer 68:474 4811991

40

Fujita HKoji TKitagawa NTsutsumi KAbe KKaminogo M: Possible involvement of Fas system in the induction of apoptosis in human astrocytic brain tumors. Cell Mol Neurobiol 22:3934062002

41

Giraud SBessette BBoda CLalloue FPetit DMathonnet M: In vitro apoptotic induction of human glioblastoma cells by Fas ligand plus etoposide and in vivo antitumour activity of combined drugs in xenografted nude rats. Int J Oncol 30:2732812007

42

Gondi CSLakka SSDinh DHOlivero WCGujrati MRao JS: Intraperitoneal injection of a hairpin RNA-expressing plasmid targeting urokinase-type plasminogen activator (uPA) receptor and uPA retards angiogenesis and inhibits intracranial tumor growth in nude mice. Clin Cancer Res 13:405140602007

43

Gratas CTohma YVan Meir EGKlein MTenan MIshii N: Fas ligand expression in glioblastoma cell lines and primary astrocytic brain tumors. Brain Pathol 7:8638691997

44

Greenberg MLFisher PGFreeman CKorones DNBernstein MFriedman H: Etoposide, vincristine, and cyclosporin A with standard-dose radiation therapy in newly diagnosed diffuse intrinsic brainstem gliomas: a pediatric oncology group phase I study. Pediatr Blood Cancer 45:644 6482005

45

Groothuis DR: The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery. Neuro Oncol 2:45592000

46

Groothuis DRWard SItskovich ACDobrescu CAllen CVDills C: Comparison of 14C-sucrose delivery to the brain by intravenous, intraventricular, and convection-enhanced intracerebral infusion. J Neurosurg 90:3213311999

47

Guarnieri MCarson BS Sr: Chronic local therapy for brainstem tumors. Neurosurgery 54:102510272004

48

Guerin COlivi AWeingart JDLawson HCBrem H: Recent advances in brain tumor therapy: local intracerebral drug delivery by polymers. Invest New Drugs 22:27372004

49

Hashizume ROzawa TGryaznov SMBollen AWLamborn KRFrey WH II: New therapeutic approach for brain tumors: intranasal delivery of telomerase inhibitor GRN163. Neuro Oncol 10:1121202008

50

Hatano MEguchi JTatsumi TKuwashima NDusak JEKinch MS: EphA2 as a glioma-associated antigen: a novel target for glioma vaccines. Neoplasia 7:7177222005

51

Helton KJPhillips NSKhan RBBoop FASanford RAZou P: Diffusion tensor imaging of tract involvement in children with pontine tumors. AJNR Am J Neuroradiol 27:7867932006

52

Helton KJWeeks JKPhillips NSZou PKun LEKhan RB: Diffusion tensor imaging of brainstem tumors: axonal degeneration of motor and sensory tracts. J Neurosurg Pediatrics 1:2702762008

53

Ishikawa ETsuboi KYamamoto TMuroi ATakano SEnomoto T: Clinical trial of autologous formalin-fixed tumor vaccine for glioblastoma multiforme patients. Cancer Sci 98:122612332007

54

Jakacki RIJamison CMathews VPHeilman DKDropcho ECornetta K: Dose-intensification of procarbazine, CCNU (lomustine), vincristine (PCV) with peripheral blood stem cell support in young patients with gliomas. Med Pediatr Oncol 31:4834901998

55

Jallo GIBecker MLiu YJCarson BS SrGuarnieri M: Local infusion therapy in the monkey brainstem: technical considerations. Surg Technol Int 15:3113162006

56

Jallo GIPenno MSukay LLiu JYTyler BLee J: Experimental models of brainstem tumors: development of a neonatal rat model. Childs Nerv Syst 21:3994032005

57

Jallo GIVolkov AWong CCarson BS SrPenno MB: A novel brainstem tumor model: functional and histopathological characterization. Childs Nerv Syst 22:151915252006

58

Jenkin RDBoesel CErtel IEvans AHittle ROrtega J: Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the Childrens Cancer Study Group. J Neurosurg 66:2272331987

59

Jennings MTSposto RBoyett JMVezina LGHolmes EBerger MS: Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children's Cancer Group. J Clin Oncol 20:343134372002

60

King GDCurtin JFCandolfi MKroeger KLowenstein PRCastro MG: Gene therapy and targeted toxins for glioma. Curr Gene Ther 5:5355572005

61

Kleinberg LRWeingart JBurger PCarson KGrossman SALi K: Clinical course and pathologic findings after Gliadel and radiotherapy for newly diagnosed malignant glioma: implications for patient management. Cancer Invest 22:192004

62

Kretschmar CSTarbell NJBarnes PDKrischer JPBurger PCKun L: Pre-irradiation chemotherapy and hyperfractionated radiation therapy 66 Gy for children with brain stem tumors. A phase II study of the Pediatric Oncology Group, Protocol 8833. Cancer 72:140414131993

63

Kwon JWKim IOCheon JEKim WSMoon SGKim TJ: Paediatric brain-stem gliomas: MRI, FDG-PET and histological grading correlation. Pediatr Radiol 36:9599642006

64

Lawson HCSampath PBohan EPark MCHussain NOlivi A: Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience. J Neurooncol 83:61702007

65

Lee JJallo GIGuarnieri MCarson BS SrPenno MB: A novel brainstem tumor model: guide screw technology with functional, radiological, and histopathological characterization. Neurosurg Focus 18:6AE112005

66

Lee JJallo GIPenno MBGabrielson KLYoung GDJohnson RM: Intracranial drug-delivery scaffolds: biocompatibility evaluation of sucrose acetate isobutyrate gels. Toxicol Appl Pharmacol 215:64702006

67

Lewis JLucraft HGholkar A: UKCCSG study of accelerated radiotherapy for pediatric brain stem gliomas. United Kingdom Childhood Cancer Study Group. Int J Radiat Oncol Biol Phys 38:9259291997

68

Liau LMBlack KLPrins RMSykes SNDiPatre PLCloughesy TF: Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens. J Neurosurg 90:111511241999

69

Liau LMPrins RMKiertscher SMOdesa SKKremen TJGiovannone AJ: Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res 11:551555252005

70

Littman PJarrett PBilaniuk LTRorke LBZimmerman RABruce DA: Pediatric brain stem gliomas. Cancer 45:278727921980

71

Lonser RRWalbridge SGarmestani KButman JAWalters HAVortmeyer AO: Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion. J Neurosurg 97:9059132002

72

Lonser RRWarren KEButman JAQuezado ZRobison RAWalbridge S: Real-time image-guided direct convective perfusion of intrinsic brainstem lesions. Technical note. J Neurosurg 107:1901972007

73

Lou E: Oncolytic viral therapy and immunotherapy of malignant brain tumors: two potential new approaches of translational research. Ann Med 36:282004

74

Mandell LRKadota RFreeman CDouglass ECFontanesi JCohen ME: There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 43:9599641999

75

Mathupala SPGuthikonda MSloan AE: RNAi based approaches to the treatment of malignant glioma. Technol Cancer Res Treat 5:2612692006

76

May BJGuarnieri MCarson BS SrBachani AJallo GI: Longterm effects of carboplatin brainstem infusions on hearing thresholds in monkeys. Arch Otolaryngol Head Neck Surg 130:141114152004

77

Morrison PFLaske DWBobo HOldfield EHDedrick RL: High-flow microinfusion: tissue penetration and pharmacodynamics. Am J Physiol 266:R292R3051994

78

Murad GJWalbridge SMorrison PFSzerlip NButman JAOldfield EH: Image-guided convection-enhanced delivery of gemcitabine to the brainstem. J Neurosurg 106:351 3562007

79

Occhiogrosso GEdgar MASandberg DISouweidane MM: Prolonged convection-enhanced delivery into the rat brainstem. Neurosurgery 52:3883942003

80

Olivi ABrem H: Interstitial chemotherapy with sustained-release polymer systems for the treatment of malignant gliomas. Recent Results Cancer Res 135:1491541994

81

Packer RJBoyett JMZimmerman RAAlbright ALKaplan AMRorke LB: Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A Childrens Cancer Group Phase I/II Trial. Cancer 74:182718341994

82

Packer RJBoyett JMZimmerman RARorke LBKaplan AMAlbright AL: Hyperfractionated radiation therapy (72 Gy) for children with brain stem gliomas. A Childrens Cancer Group Phase I/II Trial. Cancer 72:141414211993

83

Packer RJKrailo MMehta MWarren KAllen JJakacki R: Phase 1 study of concurrent RMP-7 and carboplatin with radiotherapy for children with newly diagnosed brainstem gliomas. Cancer 104:128112872005

84

Packer RJLittman PASposto RMD'Angio GPriest JRHeideman RL: Results of a pilot study of hyperfractionated radiation therapy for children with brain stem gliomas. Int J Radiat Oncol Biol Phys 13:164716511987

85

Packer RJPrados MPhillips PNicholson HSBoyett JMGoldwein J: Treatment of children with newly diagnosed brain stem gliomas with intravenous recombinant beta-interferon and hyperfractionated radiation therapy: a childrens cancer group phase I/II study. Cancer 77:215021561996

86

Padma MVSaid SJacobs MHwang DRDunigan KSatter M: Prediction of pathology and survival by FDG PET in gliomas. J Neurooncol 64:2272372003

87

Pardridge WM: Intravenous, non-viral RNAi gene therapy of brain cancer. Expert Opin Biol Ther 4:110311132004

88

Pincus DWRichter EOYachnis ATBennett JBhatti MTSmith A: Brainstem stereotactic biopsy sampling in children. J Neurosurg 104:1081142006

89

Prabhu SSBroaddus WCGillies GTLoudon WGChen ZJSmith B: Distribution of macromolecular dyes in brain using positive pressure infusion: a model for direct controlled delivery of therapeutic agents. Surg Neurol 50:3673751998

90

Pulkkanen KJYla-Herttuala S: Gene therapy for malignant glioma: current clinical status. Mol Ther 12:5855982005

91

Rainov NGRen H: Clinical trials with retrovirus mediated gene therapy—what have we learned?. J Neurooncol 65:2272362003

92

Roujeau TMachado GGarnett MRMiquel CPuget SGeoerger B: Stereotactic biopsy of diffuse pontine lesions in children. J Neurosurg 107:142007

93

Saas PWalker PRHahne MQuiquerez ALSchnuriger VPerrin G: Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain?. J Clin Invest 99:117311781997

94

Samadani UStein SMoonis GSonnad SSBonura PJudy KD: Stereotactic biopsy of brain stem masses: decision analysis and literature review. Surg Neurol 66:4844912006

95

Sandberg DIEdgar MASouweidane MM: Convectionenhanced delivery into the rat brainstem. J Neurosurg 96:8858912002

96

Sandberg DIEdgar MASouweidane MM: Effect of hyperosmolar mannitol on convection-enhanced delivery into the rat brain stem. J Neurooncol 58:1871922002

97

Sanghavi SNNeedle MNKrailo MDGeyer JRAter JMehta MP: A phase I study of topotecan as a radiosensitizer for brainstem glioma of childhood: first report of the Children's Cancer Group-0952. Neuro Oncol 5:8132003

98

Schumacher MSchulte-Monting JStoeter PWarmuth-Metz MSolymosi L: Magnetic resonance imaging compared with biopsy in the diagnosis of brainstem diseases of childhood: a multicenter review. J Neurosurg 106:1111192007

99

Shah ACBenos DGillespie GYMarkert JM: Oncolytic viruses: clinical applications as vectors for the treatment of malignant gliomas. J Neurooncol 65:2032262003

100

Sipos EPTyler BPiantadosi SBurger PCBrem H: Optimizing interstitial delivery of BCNU from controlled release polymers for the treatment of brain tumors. Cancer Chemother Pharmacol 39:3833891997

101

Skog J: Glioma-specific antigens for immune tumor therapy. Expert Rev Vaccines 5:7938022006

102

Souweidane MMOcchiogrosso GMark EBEdgar MA: Interstitial infusion of IL13-PE38QQR in the rat brain stem. J Neurooncol 67:2872932004

103

Souweidane MMOcchiogrosso GMark EBEdgar MADunkel IJ: Interstitial infusion of carmustine in the rat brain stem with systemic administration of O6-benzylguanine. J Neurooncol 67:3193262004

104

Storm PBClatterbuck RELiu YJJohnson RMGillis EMGuarnieri M: A surgical technique for safely placing a drug delivery catheter into the pons of primates: preliminary results of carboplatin infusion. Neurosurgery 52:116911772003

105

Strege RJLiu YJKiely AJohnson RMGillis EMStorm P: Toxicity and cerebrospinal fluid levels of carboplatin chronically infused into the brainstem of a primate. J Neurooncol 67:3273342004

106

Stroink ARHoffman HJHendrick EBHumphreys RPDavidson G: Transependymal benign dorsally exophytic brain stem gliomas in childhood: diagnosis and treatment recommendations. Neurosurgery 20:4394441987

107

Tabuchi KShiraishi TToda KKawaguchi S: [Expression of apoptosis-related gene products in human brain tumors and apoptosis-inducing therapy.]. Nippon Rinsho 54:192219281996. (Jpn)

108

Thomale UWTyler BRenard VMDorfman BGuarnieri MHaberl HE: Local chemotherapy in the rat brainstem with multiple catheters: a feasibility study. Childs Nerv Syst 25:21282009

109

Turner CDChi SMarcus KJMacDonald TPacker RJPoussaint TY: Phase II study of thalidomide and radiation in children with newly diagnosed brain stem gliomas and glioblastoma multiforme. J Neurooncol 82:951012007

110

Vecil GGLang FF: Clinical trials of adenoviruses in brain tumors: a review of Ad-p53 and oncolytic adenoviruses. J Neurooncol 65:2372462003

111

Wagner SWarmuth-Metz MEmser AGnekow AKStrater RRutkowski S: Treatment options in childhood pontine gliomas. J Neurooncol 79:2812872006

112

Wakabayashi TYoshida JMizuno MKito ASugita K: Effectiveness of interferon-beta, ACNU, and radiation therapy in pediatric patients with brainstem glioma. Neurol Med Chir (Tokyo) 32:9429461992

113

Walker DAPunt JASokal M: Clinical management of brain stem glioma. Arch Dis Child 80:5585641999

114

Walter AWGajjar AOchs JSLangston JWSanford RAKun LE: Carboplatin and etoposide with hyperfractionated radiotherapy in children with newly diagnosed diffuse pontine gliomas: a phase I/II study. Med Pediatr Oncol 30:28331998

115

Weller MKleihues PDichgans JOhgaki H: CD95 ligand: lethal weapon against malignant glioma?. Brain Pathol 8:2852931998

116

Wheeler CJBlack KL: Dendritic cell vaccines and immunity in glioma patients. Front Biosci 10:286128812005

117

Wheeler CJBlack KL: Dendritic cell vaccines and obstacles to beneficial immunity in glioma patients. Curr Opin Mol Ther 7:35472005

118

Wheeler CJDas ALiu GYu JSBlack KL: Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res 10:531653262004

119

Wheeler CJYu JSBlack KL: Cellular immunity in the treatment of brain tumors. Clin Neurosurg 51:1321392004

120

Wolff JEWestphal SMolenkamp GGnekow AWarmuth-Metz MRating D: Treatment of paediatric pontine glioma with oral trophosphamide and etoposide. Br J Cancer 87:9459492002

121

Wu MPTamada JABrem HLanger R: In vivo versus in vitro degradation of controlled release polymers for intracranial surgical therapy. J Biomed Mater Res 28:3873951994

122

Wu QGuarnieri MTyler BClatterbuck RELiu YCarson BS: Section on tumors: Young Investigator Award: local release of carboplatin via an Alzet mini-osmotic pump prolongs survival in a rat brainstem tumor model. Clin Neurosurg 51:3323392004

123

Wu QTyler BSukay LRhines LDiMeco FClatterbuck RE: Experimental rodent models of brainstem tumors. Vet Pathol 39:2932992002

124

Xia CFZhang YZhang YBoado RJPardridge WM: Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology. Pharm Res 24:230923162007

125

Yamanaka RItoh K: Peptide-based immunotherapeutic approaches to glioma: a review. Expert Opin Biol Ther 7:645 6492007

126

Yamanaka RItoh K: [Peptide vaccination therapy for malignant glioma.]. Brain Nerve 59:2512612007. (Jpn)

127

Yoshida J: Molecular neurosurgery using gene therapy to treat malignant glioma. Nagoya J Med Sci 59:971051996

128

Yu JSLiu GYing HYong WHBlack KLWheeler CJ: Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res 64:497349792004

129

Zhang JGEguchi JKruse CAGomez GGFakhrai HSchroter S: Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics. Clin Cancer Res 13:5665752007

130

Zhao PWang CFu ZYou YCheng YLu X: Lentiviral vector mediated siRNA knock-down of hTERT results in diminished capacity in invasiveness and in vivo growth of human glioma cells in a telomere length-independent manner. Int J Oncol 31:3613682007

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