The incidence of brain tumors is increasing rapidly, particularly in the older population. Advances in molecular biology help to explain differences in biologic behavior and response to therapy of brain tumors in the elderly compared with younger patients. The number of elderly patients who desire and receive therapy for brain tumors and are included in clinical trials is increasing.
Methods
This article reviews the literature on the epidemiology, clinical aspects, and therapy of brain tumors, with emphasis on the older patient population.
Results
The increased incidence of brain tumors in the elderly is principally due to the increasing number of people who comprise the older population. Age and performance status are important independent prognostic indicators, together with tumor histology. Surgery, radiation therapy, and chemotherapy can benefit elderly patients with brain tumors with favorable histologies, tumor location, and good performance status. The response rates to available therapies are less favorable than in younger patients, and only a small number of elderly patients are enrolled in clinical studies addressing new treatment modalities.
Conclusions
Brain tumors in the elderly have specific characteristics that determine their biologic behavior and response to therapy. There is a need for clinical studies designed for treatment of brain tumors in older patients, and requirements for rehabilitation and support systems for the elderly need to be addressed.
References
1.
MahaleyMSJr, MettlinC., NatarajanN.. National survey of patterns of care for brain tumor patients.J Neurosurg.1989; 71: 826–835.
2.
LawsERJr, ThaparK.. Brain tumors.CA Cancer J Clin.1993; 43: 263–271. Review.
3.
BoringC.C., SquiresT.S., TongT.. Cancer statistics, 1991.CA Cancer J Clin.1991; 41: 19–36.
4.
BoringC.C., SquiresT.S., TongT.. Cancer statistics, 1993.CA Cancer J Clin.1993; 43: 7–26.
5.
CrawfordJ., CohenH.J.. Relationship of cancer and aging.Clin Geriatr Med.1987; 3: 419–432.
6.
LarsenN.S.. Experts divided over rising incidence of brain tumors.Prim Care Cancer.1993; 13: 26–29.
7.
LeglerJ.M., RiesL.A., SmithM.A.. Cancer surveillance series [corrected]: brain and other central nervous system cancers. Recent trends in incidence and mortality.J Natl Cancer Inst.1999; 91: 1382–1390.
8.
GriegN.H., RiesL.G., YancikR.. Increasing annual incidence of primary malignant brain tumors in the elderly.J Natl Cancer Inst.1990; 82: 1621–1624.
9.
DavisD.L., HoelD., PercyC.. Is brain cancer mortality increasing in industrial countries?Ann N Y Acad Sci.1990; 609: 191–204.
10.
RadhakrishnanK., MokriB., ParisiJ.E.. The trends in incidence of primary brain tumors in the population of Rochester, Minnesota.Ann Neurol.1995; 37: 67–73.
11.
LowryJ.K., SnyderJ.J., LowryP.W.. Brain tumors in the elderly: recent trends in a Minnesota cohort study.Arch Neurol.1998; 55: 922–928.
12.
PolednakA.P.. Time trends in incidence of brain and central nervous system cancers in Connecticut.J Natl Cancer Inst.1991; 83: 1679–1681.
13.
WernerM.H., PhuphanichS., LymanG.H.. Increasing incidence of primary brain tumors in the elderly in Florida.Cancer Control.1995; 2: 309–314.
14.
SantM., CrosignaniP., BordoB.M.. Incidence and survival of brain tumors: a population-based study.Tumori.1988; 74: 243–252.
15.
FleuryA., MenegozF., GrosclaudeP.. Descriptive epidemiology of cerebral gliomas in France.Cancer.1997; 79: 1195–1202.
16.
van der SandenG.A., SchoutenL.J., CoeberghJ.W.. Incidence of primary cancer of the central nervous system in southeastern Netherlands during the period 1980-94: specialists in neuro-oncology in southeastern Netherlands.Cancer Causes Control.1998; 9: 225–228.
17.
DesmeulesM., MikkelsenT., MaoY.. Increasing incidence of primary malignant brain tumors: influence of diagnostic methods.J Natl Cancer Inst.1992; 84: 442–445.
18.
ModanB., WagenerD.K., FeldmanJ.J.. Increased mortality from brain tumors: a combined outcome of diagnostic technology and change of attitude towards the elderly.Am J Epidemiol.1992; 135: 1349–1357.
19.
VelemaJ.P., WalkerA.M.. The age curve of nervous system tumour incidence in adults: common shape but changing levels by sex, race and geographical location.Int J Epidemiol.1987; 16: 177–183.
20.
BoyleP., MaisonneuveP., SaracciR.. Is the increased incidence of primary malignant brain tumors in the elderly real?J Natl Cancer Inst.1990; 82: 1594–1596.
21.
RiggsJ.E.. Rising primary malignant brain tumor mortality in the elderly: a manifestation of differential survival.Arch Neurol.1995; 52: 571–575.
22.
SalcmanM.. Brain tumors and the geriatric patient.J Am Geriatr Soc.1982; 30: 501–508.
23.
GilesG.G., GonzalesM.F.. Epidemiology of brain tumors and factors in prognosis. In: KayeA.H., LawsE.R., eds. Brain Tumors: An Encyclopedic Approach.Edinborough: Churchill Livingstone;1995: 47–68.
24.
BondyM.L., WrenschM.. Update on brain cancer epidemiology.Bull Cancer.1993; 45: 365–369.
25.
MackW., Preston-MartinS., PetersJ.M.. Astrocytoma risk related to job exposure to electric and magnetic fields.Bioelectromagnetics.1991; 12: 57–66.
26.
SchoenbergB.S., ChristineB.W., WhisnantJ.P.. Nervous system neoplasms and primary malignancies of other sites: the unique association between meningiomas and breast cancer.Neurology.1975; 25: 705–712.
27.
AhsanH., NeugutA.I., BruceJ.N.. Association of malignant brain tumors and cancers of other sites.J Clin Oncol.1995; 13: 2931–2935.
28.
TsangR.W., LaperriereN.J., SimpsonW.J.. Glioma arising after radiation therapy for pituitary adenoma: a report of four patients and estimation of risk.Cancer.1993; 72: 2227–2233.
29.
BurgerP.C., GreenS.B.. Patient age, histologic features, and length of survival in patients with glioblastoma multiforme.Cancer.1987; 59: 1617–1625.
30.
HildebrandJ., ThomasD.G.. Report of a workshop sponsored by the European Organisation for Research and Treatment of Cancer (EORTC) on the treatment of primary malignant brain tumours.J Neurol Neurosurg Psych.1991; 54: 182–183.
31.
DavisF.G., FreelsS., GrutschJ.. Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on Surveillance, Epidemiology, and End Results (SEER) data, 1973-1991.J Neurosurg.1998; 88: 1–10.
32.
DavisF.G., McCarthyB.J., FreelsS.. The conditional probability of survival of patients with primary malignant brain tumors: surveillance, epidemiology, and end results (SEER) data.Cancer.1999; 85: 489–491.
33.
McDermottM.W.. How to diagnose and manage adult astrocytomas.Contemp Oncol.1993; 12: 11–21.
AlexanderE.M., WagnerE.H., BuchnerD.M.. Do surgical brain lesions present as isolated dementia? A population-based study.J Am Geriatr Soc.1995; 43: 138–143.
36.
PatronasN.J., MooreW.D., SchellingerD.R.. Brain imaging in the diagnosis of intracranial neoplasms. In: KornblithP.L., WalkerM.D., eds. Advances in Neuro-Oncology.Mount Kisco, NY: Futura Publishing Co;1988: 197–247.
37.
MineuraK., SasajimaT., KowadaM.. Perfusion and metabolism in predicting the survival of patients with central gliomas.Cancer.1994; 73: 2386–2394.
38.
VertosickFTJr, SelkerR.G., GrossmanS.J.. Correlation of thallium-201 single photon emission computed tomography and survival after treatment failure in patients with glioblastoma multiforme.Neurosurgery.1994; 34: 396–401.
39.
KernohanJ.N., MabonR.F., SuienH.S.. A simplified classification of gliomas.Proc Staff Mtg Mayo Clinic.1949; 24: 71–74.
40.
Daumas-DuportC., ScheitauerB., O'FallonJ.. Grading of astrocytomas: a simple and reproducible method.Cancer.1988; 62: 2152–2165.
41.
ZulchK.J. ed. Histological Typing of Tumours of the Central Nervous System.Geneva: World Health Organization;1979.
42.
RingertzN.. Grading of gliomas.Acta Pathol Microbiol Scand.1950; 27: 57–65.
43.
KimT.S., HallidayA.L., Hedley-WhyteE.T.. Correlates of survival and the Daumas-Duport grading system for astrocytomas.J Neurosurg.1991; 74: 27–37.
44.
NelsonD.F., NelsonJ.S., DavisD.R.. Survival and prognosis of patients with astrocytoma with atypical anaplastic features.J Neurooncol.1985; 3: 99–103.
45.
ShawE.G., ScheitauerB.W., O'FallonJ.R.. Mixed oligoastrocytomas: a survival and prognostic factor analysis.Neurosurgery.1994; 34: 577–582.
46.
Medical Research Council Brain Tumor Working Party.Prognostic factors for high-grade malignant glioma: development of a prognostic index. A report of the Medical Research Council Brain Tumor Working Party.J Neurooncol.1990; 9: 47–55.
47.
SalmonI., DewitteO., PasteelsJ.L.. Prognostic scoring in adult astrocytic tumors using patient age, histopathologic grade and DNA histogram type.J Neurosurg.1994; 80: 877–883.
SteckP.A., BrunerJ.M., PershouseM.A.. Molecular, genetic and biologic aspects of primary brain tumors.Bull Cancer.1993; 45: 365–369.
50.
McKeeverP.E., StrawdermanM.S., YaminiB.. MIB-1 proliferation index predicts survival among patients with grade II astrocytoma.J Neuropathol Exp Neurol.1998; 57: 931–936.
51.
ChozickB.S., PezzulloJ.C., EpsteinM.H.. Prognostic implications of p53 overexpression in supratentorial astrocytic tumors.Neurosurgery.1994; 35: 831–8378.
52.
KyritsisA.P., BondyM.L., HessK.R.. Prognostic significance of p53 immunoreactivity in patients with glioma.Clin Cancer Res.1995; 1: 1617–1622.
53.
KorkolopoulouP., ChristodoulouP., KonzelisK.. MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor.Br J Cancer.1997; 75: 1269–1278.
54.
RasheedB.K., StenzelT.T., McLendonR.E.. PTEN gene mutations are seen in high-grade but not in low-grade gliomas.Cancer Res.1997; 57: 4187–4190.
55.
FernandezP.M., BremS.. Malignant brain tumors in the elderly.Clin Geriatr Med.1997; 13: 327–338. Review.
56.
PhilipponJ.H., ClemenceauS.H., FauchonF.H.. Supratentorial low-grade astrocytomas in adults.Neurosurgery.1993; 32: 554–559.
57.
LoteK., EgelandT., HagerB.. Survival, prognostic factors, and therapeutic efficacy in low-grade glioma: a retrospective study in 379 patients.J Clin Oncol.1997; 15: 3129–3140.
58.
VechtC.J.. Effect of age on treatment decisions in low-grade glioma.J Neurol Neurosurg Psychiatry.1993; 56: 1259–1264.
59.
KallioM.. Therapy and survival of adult patients with intracranial glioma in a defined population.Acta Neurol Scand.1990; 81: 541–549.
60.
HalperinE.C.. Malignant gliomas in older adults with poor prognostic signs: getting nowhere, and taking a long time to do it.Oncology.1995; 9: 229–234.
61.
LayonA.J., GeorgeB.E., HambyB.. Do elderly patients overutilize healthcare resources and benefit less from them than younger patients? A study of patients who underwent craniotomy for treatment of neoplasm.Crit Care Med.1995; 23: 829–834.
62.
CaudryM., MaireJ.P., GuerinJ.. Supratentorial malignant glioma in adults: adjustment of the treatment of 3 groups according to a clinical classification [French].Sem Hop.1983; 59: 453–458.
63.
TomitaT., RaimondiA.J.. Brain tumors in the elderly.JAMA.1981; 246: 53–55.
64.
SalcmanM.. Surgery for malignant glioma. In: MorantzR.A., WalshJ.W., eds. Brain Tumors: A Comprehensive Text.New York, NY: M. Dekker;1994: 417–427.
65.
DevauxB.C., O'FallonJ.R., KellyP.J.. Resection, biopsy and survival in malignant glial neoplasms: a retrospective study of clinical parameters, therapy and outcome.J Neurosurg.1993; 8: 767–775.
66.
AmmiratiM., VickN., LiaoY.L.. Effect of the extent of surgical resection on survival and quality of life in patients with supratentorial glioblastomas and anaplastic astrocytomas.Neurosurgery.1987; 21: 201–206.
67.
BergerM.S., DeliganisA.V., DobbinsJ.. The effect of extent of resection on recurrence in patients with low grade cerebral hemispheric gliomas.Cancer.1994; 74: 1784–1791.
68.
AndreouJ., GeorgeA.E., WiseA.. CT prognostic criteria of survival after malignant glioma surgery.AJNR Am J Neuroradiol.1983; 4: 488–490.
69.
AlbertF.K., ForstingM., SartorK.. Early postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis.Neurosurgery.1994; 34: 45–60.
70.
PietilaT.A., StendelR., HasslerW.E.. Brain tumor surgery in geriatric patients: a critical analysis in 44 patients over 80 years.Surg Neurol.1999; 52: 259–264.
71.
WingerM.J., MacdonaldD.R., CairncrossJ.G.. Supratentorial anaplastic gliomas in adults: the prognostic importance of extent of resection and prior low-grade glioma.J Neurosurg.1989; 71: 487–493.
72.
SalcmanM., KaplanR.S., DuckerT.B.. Effect of age and reoperation on survival in the combined modality treatment of malignant astrocytomas.Neurosurgery.1982; 10: 454–463.
73.
BarnettG.H., KormosD.W., SteinerC.P.. Use of a frameless, armless stereotactic wand for brain tumor localization with two-dimensional and three-dimensional neuroimaging.Neurosurgery.1993; 33: 674–678.
74.
ShelineG.E.. Radiation therapy of brain tumors.Cancer.1977; 39: 873–881.
75.
ShawE.G.. Low-grade gliomas: to treat or not to treat? A radiation oncologist's viewpoint.Arch Neurol.1990; 47: 1138–1140.
76.
LeibelS.A., ShelineG.E., WaraW.M.. The role of radiation therapy in the treatment of astrocytomas.Cancer.1975; 35: 1551–1557.
77.
KrethF.W., WarnkeP.C., ScheremetR.. Surgical resection and radiation therapy versus biopsy and radiation therapy in the treatment of glioblastoma multiforme.J Neurosurg.1993; 78: 762–766.
78.
MecklingS., DoldO., ForsythP.A.. Malignant supratentorial glioma in the elderly: is radiotherapy useful?Neurology.1996; 47: 901–905.
79.
PeschelR.E., WilsonL., HafftyB.. The effect of advanced age on the efficacy of radiation therapy for early breast cancer, local prostate cancer and grade III-IV gliomas.Int J Radiat Oncol Biol Phys.1993; 26: 539–544.
80.
ShibamotoY., YamashitaJ., TakahashiM.. Supratentorial malignant glioma: an analysis of radiation therapy in 178 cases.Radiother Oncol.1990; 18: 9–17.
81.
VillaS., VinolasN., VergerE.. Efficacy of radiotherapy for malignant gliomas in elderly patients.Int J Radiat Oncol Biol Phys.1998; 42: 977–980.
82.
BaumanG.S., GasparL.E., FisherB.J.. A prospective study of short-course radiotherapy in poor prognosis glioblastoma multiforme.Int J Radiat Oncol Biol Phys.1994; 29: 835–839.
83.
HercbergsA.A., TadmorR., FindlerG.. Hypofractionated radiation therapy and concurrent cisplatin in malignant cerebral gliomas: rapid palliation in low performance status patients.Cancer.1989; 64: 816–820.
84.
HernandezJ.C., MaruyamaY., YaesR.. Accelerated fractionation radiotherapy for hospitalized glioblastoma multiforme patients with poor prognostic factors.J Neurooncol.1990; 9: 41–45.
85.
KleinbergL., GrossmanS., PiantadosS.. Preliminary results of a phase II trial of RSR13 in newly diagnosed GBM.Neuro-oncology.1999; 3: A318.
BradaM., LaingR.. Radiotherapy/stereotactic external beam radiotherapy for malignant brain tumours: the Royal Marsden Hospital experience.Recent Results Cancer Res.1994; 135: 91–104. Review.
88.
ShrieveD.C., AlexanderEIII, BlackP.M.. Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome.J Neurosurg.1999; 90: 72–77.
89.
WenP.Y., AlexanderEIII, BlackP.M.. Long term results of stereotactic brachytherapy used in the initial treatment of patients with glioblastomas.Cancer.1994; 73: 3029–3036.
90.
KitchenN.D., HughesS.W., TaubN.A.. Survival following interstitial brachytherapy for recurrent malignant glioma.J Neurooncol.1994; 18: 33–39.
91.
RivaP., AristaA., SturialeC.. Intralesional radioimmunotherapy of malignant gliomas: an effective treatment in recurrent tumors.Cancer.1994; 73: 1076–1082.
TsurudaJ.S., KortmanK.E., BradleyW.G.. Radiation effects on cerebral white matter: MR evaluation.AJR Am J Roentgenol.1987; 149: 165–171.
96.
ForsythP.A., KellyP.J., CascinoT.L.. Radiation necrosis or glioma recurrence: is computer-assisted stereotactic biopsy useful?J Neurosurg.1995; 82: 436–444.
97.
ArmstrongC., RufferJ., CornB.. Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms.J Clin Oncol.1995; 13: 2263–2271.
98.
TrouetteR., CaudryM., MaireJ.P.. Adult mental deterioration, the main limiting factor in cerebral radiotherapy? [French]Bull Cancer Radiother.1993; 80: 209–221.
99.
CrossenJ.R., GarwoodD., GlatsteinE.. Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy.J Clin Oncol.1994; 12: 627–642. Review.
100.
YungW.K.. Chemotherapy for malignant brain tumors.Curr Opin Oncol.1990; 2: 673–678.
101.
KyritsisA.P.. Chemotherapy for malignant gliomas.Oncology (Huntingt).1993; 7: 93–100.
102.
FlowersA., LevinV.A.. Chemotherapy for brain tumors. In: KayeA.H., LawsE.R., eds. Brain Tumors: An Encyclopedic Approach.Edinborough: Churchill Livingstone;1995: 349–360.
103.
VendrickC.P., BergersJ.J., De JongW.H.. Resistance to cytostatic drugs at the cellular level.Cancer Chemother Pharmacol.1992; 29: 413–429. Review.
104.
BelanichM., PastorM., RandallT.. Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine.Cancer Res.1996; 56: 783–788.
105.
FriedmanH.S., McLendonR.E., KerbyT.. DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma.J Clin Oncol.1998; 16: 3851–3857.
106.
DonelliM.G., ZucchettiM., D'IncalciM.. Do anticancer agents reach the tumor target in the human brain?Cancer Chemother Pharmacol.1992; 30: 251–260. Review.
107.
BoazizC., BreauJ.L., MorereJ.F.. The blood-brain barrier: implications for chemotherapy in brain tumors [French].Path Biol (Paris).1991; 39: 789–795.
108.
VickN.A., KhandekarJ.D., BignerD.D.. Chemotherapy of brain tumors.Arch Neurol.1997; 34: 523–526.
109.
YungW.K., JanusT.J., MaorM.. Adjuvant chemotherapy with carmustine and cisplatin for patients with malignant gliomas.J Neurooncol.1992; 12: 131–135.
110.
RogersL.R., PurvisJ.B., LedermanR.J.. Alternating sequential intracarotid BCNU and cisplatin in recurrent malignant glioma.Cancer.1991; 68: 15–21.
111.
NewtonH.B., JunckL., BrombergJ.. Procarbazine chemotherapy in the treatment of recurrent malignant astrocytomas after radiation and nitrosourea failure.Neurology.1990; 40: 1743–1746.
112.
NewtonH.B., BrombergJ., JunckL.. Comparison between BCNU and procarbazine chemotherapy for treatment of gliomas.J Neurooncol.1993; 15: 257–263.
113.
LevinV.A., SilverP., HanniganJ.. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report.Int J Radiat Oncol Biol Phys.1990; 18: 321–324.
114.
Sandberg-WollheimM., MalmstromP., StrombaldL.G.. A randomized study of chemotherapy with procarbazine, vincristine and lomustine with and without radiation therapy for astrocytoma grades 3 and/or 4.Cancer.1991; 68: 22–29.
115.
PradosM.D., ScottC., CurranW.J.. Procarbazine, lomustine and vincristine (PCV) chemotherapy for anaplastic astrocytoma: a retrospective review of radiation therapy oncology group protocols comparing survival with carmustine or PCV adjuvant chemotherapy.J Clin Oncol.1999; 17: 3389–3395.
116.
MasonW.P., KrolG.S., DeAngelisL.M.. Low-grade oligodendroglioma responds to chemotherapy.Neurology.1996; 46: 203–207.
117.
YungW.K., PradosM.D., Yaya-TurR.. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group.J Clin Oncol.1999; 17: 2762–2771.
118.
ChangC.H., HortonJ., SchoenfeldD.. Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas: a joint Radiation Therapy Oncology Group and Eastern Cooperative Group Study.Cancer.1983; 52: 997–1007.
119.
FineH.A., DearK.B., LoefflerJ.S.. Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults.Cancer.1993; 71: 2585–2597.
120.
WalkerM.D., GreenS.B., ByarD.P.. Randomized comparison of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery.N Engl J Med.1980; 303: 1323–1329.
121.
KrishnasamyS., VokesE.E., DohrmannG.J.. Concomitant chemoradiotherapy, neutron boost, and adjuvant chemotherapy for anaplastic astrocytoma and glioblastoma multiforme.Cancer Invest.1995; 13: 453–459.
122.
WatneK., NomeO., HagerB.. Pre-irradiation chemotherapy in glioma patients with poor prognostic factors.J Neurooncol.1992; 13: 261–264.
123.
VertosickFTJr, SelkerR.G., PollackI.F.. The treatment of intracranial malignant gliomas using orally administered tamoxifen therapy: preliminary results in a series of “failed” patients.Neuro-surgery.1992; 30: 897–903.
124.
CouldwellW.T., WeissM.H., DeGiorgioC.M.. Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen.Neurosurgery.1993; 32: 485–490.
125.
SchneiderJ., HofmanF.M., ApuzzoM.L.. Cytokines and immunoregulatory molecules in malignant glial neoplasms.J Neurosurg.1992; 77: 265–273.
126.
ChatelM., LebrunC., FrenayM.. Chemotherapy and immunotherapy in adult malignant gliomas.Curr Opin Oncol.1993; 5: 464–473. Review.
127.
LippmanS.M., KesslerJ.F., MeyskensFLJr. Retinoids as preventive and therapeutic anticancer agents (part II).Cancer Treat Rep.1987; 71: 493–515. Review.
128.
YungW.K., LotanD., LeeP.. Modulation of growth and epidermal growth factor receptor activity by retinoic acid in human glioma cells.Cancer Res.1989; 49: 1014–1019.
129.
YungW.K., SimagaM., LevinV.A.. 13-Cis-retinoic acid: a new and potentially effective agent for recurrent malignant astrocytomas.Proc Annu Meet Am Soc Clin Oncol.1993; 12: A175.
130.
Acevedo-DuncanN., ZhangR., ByvoetP.. Interferon modulates human glioma protein kinase C II.Proc Annu Meet Am Assoc Cancer Res.1993; 34: A176.
131.
NagaiM., AraiT.. Clinical effect of interferon in malignant brain tumours.Neurosurg Rev.1984; 7: 55–64.
132.
DuffT.A., BordenE., BayJ.. Phase II trial of interferon-beta for treatment of recurrent glioblastoma multiforme.J Neurosurg.1986; 64: 408–413.
133.
YungW.K., CastellanosA.M., Van TasselP.. A pilot study of recombinant interferon beta (IFN-beta ser) in patients with recurrent glioma.J Neurooncol.1990; 9: 29–34.
134.
BucknerJ.C., BrownL.D., KuglerJ.W.. Phase II evaluation of recombinant interferon alpha and BCNU in recurrent glioma.J Neurosurg.1995; 82: 430–435.
NeuweltE.A., FrenkelE.P., DiehlJ.. Reversible osmotic blood-brain barrier disruption in humans: implications for the chemotherapy of malignant brain tumors.Neurosurgery.1980; 7: 44–52.
137.
GumerlockM.K., BelsheB.D., MasdenR.. Osmotic blood-brain barrier disruption and chemotherapy in the treatment of high grade malignant glioma: patient series and literature review.J Neurooncol.1992; 12: 33–46.
138.
BremH., MahaleyMSJr, VickN.A.. Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas.J Neurosurg.1991; 74: 441–446.
139.
MarkertJ.M., CoenD.M., MalickA.. Expanded spectrum of viral therapy in the treatment of nervous system tumors.J Neurosurg.1992; 77: 590–594.
140.
ZerbeL.K., HughesT.L., JosephsS.A.. Rapid cytotoxicity with gancyclovir following adenovirus transduction of glioma cells with herpes virus thymidine kinase.Proc Annu Meet Am Assoc Cancer Res.1995; A423.
141.
HallW.A., FodstadO.. Immunotoxins and central nervous system neoplasia.J Neurosurg.1992; 76: 1–12. Review.
142.
JohnsonV.G., WrobelC., WilsonD.. Improved tumor-specific immunotoxins in the treatment of CNS and leptomeningeal neoplasia.J Neurosurg.1989; 70: 240–248.
143.
ShackS., PrasannaP., HudginsW.R.. Experimental therapies for malignant gliomas: targeting the mevalonate pathway of cholesterol synthesis.Proc Annu Meet Am Assoc Cancer Res.1994; 35: A409.
144.
SamidD., ShackS., LiuL.. Phenylacetate and related non-toxic differentiation inducers in treatment of prostate, brain and skin cancer.Proc Annu Meet Am Assoc Cancer Res.1993; 34: 377.
145.
IngberD., FujitaT., KishimotoS.. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth.Nature.1990; 348: 555–557.
146.
TeicherB.A., HoldenS.A., AraG.. Potentiation of cytotoxic cancer therapies by AGM-1470 (AGM) alone and with other angiogenic antiangiogenic agents.Proc Annu Meet Am Assoc Cancer Res.1994; 35: 324.
147.
O'NeillB.P., O'FallonJ.R., EarleJ.D.. Primary central nervous system non-Hodgkin's lymphoma: survival advantages with combined initial therapy?Int J Radiat Oncol Biol Phys.1995; 33: 663–673.
148.
SawayaR., LigonB.L., FlowersA.. Management of metastatic brain tumors: a review.Neurosurg Q.1994; 4: 140–157.
149.
NoordijkE.M., VechtC.J., Haaxma-ReicheH.. The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age.Int J Radiat Oncol Biol Phys.1994; 29: 711–717.
150.
NiederC., NiewaldM., SchnabelK.. The results of the radiotherapy of brain metastases in patients at an advanced age [German].Strahlenther Onkol.1995; 171: 646–648.
151.
HutchinsL.F., UngerJ.M., CrowleyJ.J.. Underrepresentation of patients 65 years of age or older in cancer-treatment trials.N Engl J Med.1999; 341: 2061–2067.
152.
GrantR., LiangB.C., PageM.A.. Age influences chemotherapy response in astrocytomas.Neurology.1995; 45: 929–933.
153.
RosenblumM.L., GerosaM., DoughertyD.V.. Age-related chemosensitivity of stem cells from human malignant brain tumors.Lancet.1982; 1: 885–887.
154.
TrojanowskiT., PeszynskiJ., TurowskiK.. Quality of survival in patients with brain gliomas treated with postoperative CCNU and radiation therapy.J Neurosurg.1989; 70: 18–23.
155.
WeitznerM.A., MeyersC.A., GelkeC.K.. The Functional Assessment of Cancer Therapy (FACT) scale: development of a brain subscale and revalidation of the general version (FACT-G) in patients with primary brain tumors.Cancer.1995; 75: 1151–1161.
