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Malignant Glioma
1996 del Regato
Progress in the Treatment
of Malignant Gliomas
Juan del Regato, M.D.Lecture - 1996
Theodore L. Phillips, M.D.
Malignant Glioma
1996 del Regato
Focus
• Glioblastoma and Anaplastic Astrocytoma
• Adjuvant Treatments After Surgery
• UCSF Experience
Malignant Glioma
1996 del Regato
Topics to Be CoveredIncidence
Variables influencing outcome
The usefulness of Radiotherapy
Chemoradiation
Radiation Sensitizers
Interstitial Brachytherapy
Hyperthermia
Radiosurgery
Heavy Particles
Boron Neutron Capture Therapy
Future Directions
Malignant Glioma
1996 del Regato
Malignant Gliomas
Incidence and Prognostic
Variables
Malignant Glioma
1996 del Regato
Malignant Glioma Incidence+
Histology Incidence rate/100,000* Prevalence (US)
Anaplastic Astroctyoma 0.4 2,000
Glioblastoma 2.5 10,000
+ CBTRUS 90-92
* Age adjusted
Malignant Glioma
1996 del Regato
5-Year SurvivalEffect of Age and Histology+
<21 21-44 45-64 >65 Total
Astrocytoma 72% 50% 13% 3% 31%
Glioblastoma 21% 13% 2% <1% 3%
+ SEER 81-91
Malignant Glioma
1996 del Regato
Age Specific Rates+
0-24 25-34 35-44 45-54 55-64 65-74
Anaplastic
Astrocytoma 0.2 0.4 0.5 0.6 0.8 1.3
Glioblastoma 0.1 0.5 1.0 3.9 7.9 11.4
+ CBTRUS 90-92
Malignant Glioma
1996 del Regato
Malignant GliomasRTOG 8302 Cox Proportional Hazards Model
Prognostic Factors+ Covariate Coefficient
Age 0.5278 (p < .0001)Histology 1.3976 (p < .0001)KPS 0.3917 (p = .0014)Interval Hours 0.3668 (p = .0011)RX* 0.2068 (p = .1089)Extent of Surgery 0.3703 (p = .0144)
*RX = 64.8 Gy + 72.0 Gy + 76.8 Gy vs. 81.6 Gy
+Nelson et al, 1993
Malignant Glioma
1996 del Regato
Malignant Gliomas
The Major Prognostic Variables Are:
1) Histology - Anaplastic Astrocytoma vs. Glioblastoma Multiforme
2) Performance Status > 80
3) Age: Young is good.
4) Extent of Surgery
Conclusions: Prognostic Variables
Malignant Glioma
1996 del Regato
Is Radiotherapy Useful
in
MALIGNANT GLIOMAS?
Malignant Gliomas
Malignant Glioma
1996 del Regato
Surgery vs. Surgery + RadiotherapyGlioblastoma +
Alive
Procedure Cases 6 Mo 12 Mo
Biopsy Only 65 5% 0%
Partial Resection 93 14% 4%
Biopsy + Radiotherapy (RT) 31 50% 16%
Partial Resection + RT 148 68% 32%
+Taveras et al, 1962
Malignant Glioma
1996 del Regato
Glioma Study - BTSG 69-01Anaplastic Glioma (AA + GBM)
Entered: 303 Valid Study Group: 222
Median Survival (weeks)
+
VSG ATG* P Value
Conventional Care 14 17 ---
BCNU 18.5 25 .12
Radiotherapy 35 37.5 .001
BCNU + Radiotherapy 34.5 40.5 .001+ Walker et al, 1978* ATG=adequately treated group: 50 Gy, 2 courses chemo; min. survival 8 weeks
Malignant Glioma
1996 del Regato
Malignant GliomasDose Response Relationships+
Normal Dose (cGy)
(Whole Brain) #Pts. Median Survival (wks) Wilcoxon Test
0 194 18 *
≤ 4500 61 13.5 .35 *
5000 56 28 .001 .003 *
5500 33 36 .001 .001 0.174 *
6000 270 42 .001 .001 .004 0.11
+Walker, Strike and Sheline, 1979
Malignant Glioma
1996 del Regato
Malignant GliomasHigh Dose Radiation+
Median Survival
Median Dose Grade III Grade IV
5000 cGy 43 wks 30 wks
6000 cGy 82 wks 42 wks
7500 cGy 204 wks 56 wks
+Salazar et al, 1979
Malignant Glioma
1996 del Regato
Malignant GliomasRTOG 8302 Hyperfractionation+
Survival
Dose (Gy) AA AA GBM
Partial Brain 18 mo MST 18 mo
60 (std) (7401) 70% 19%
60 (std) (7918) 75% 24%
64.8 bid 68% 19%
72 bid 85% 50 mo 28%
76.8 bid 70% 30 mo 25%
81.6 bid 59% 33 mo 20%
+Nelson et al, 1993
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) Radiotherapy gives longer survival than surgery alone or surgery plus chemotherapy.
2) There is a dose response relationship up to between 50-70 Gy.
3) Partial Brain is superior to Whole Brain.
4) Hyperfractionation is not of proven value. Most Malignant gliomas probably repair SLD as well as normal brain.
Conclusions: Conventional Radiotherapy
Malignant Glioma
1996 del Regato
The Role of Chemoradiation
Malignant Gliomas
Malignant Glioma
1996 del Regato
Report of BTSG 72-01+
Malignant Gliomas
Total PopulationArm Percent Survival
#Pts. MST 12 mo 24 mo
Semustine 111 31 26 17
Radiotherapy 118 37 37 14
Carmustine + RT 120 49 48 19
Semustine + RT 118 43 41 19
*Walker et al, 1980
Malignant Glioma
1996 del Regato
Report of BTSG 72-01+
Malignant Gliomas
Valid Study GroupArm Percent Survival
#Pts. MST 12 mo 24 mo
Semustine 81 24 15 7.5
Radiotherapy 94 36 35 9.7
Carmustine + RT 92 51 50 15.2
Semustine + RT 91 42 37 12.2
RT vs. RT + Carmustine - Mantel-Haenzel = 0.072
*Walker et al, 1980
Malignant Glioma
1996 del Regato
RTOG - ECOG Study+
Astrocytoma Grades III + IV Survival
Arm 45% K<60 Med (mo) 18 mo%
#Rand #Eval
Radiotherapy (RT) (60Gy) 167 148 AA 15.4 0%
GBM 8.7 9%
RT + Boost 114 105 AA 32.3 62%
GBM 7.7 11%
RT + BCNU 185 165 AA 27.0 71%
GBM 8.0 20%
RT + Semustine + DTIC 160 136 AA 22.0 58%
GBM 9.0 18%
+Chang et al, 1983
Malignant Glioma
1996 del Regato
Malignant GliomasRTOG - ECOG Study
Survival by Performance Status and Age+
Age
< 40 40-60 >60
Performance Median Survival (months)
70-100 32 11.2 8.4
40-60 17 7.4 4.7
20-30 --- 3.1 4.2
+Chang et al, 1983
Malignant Glioma
1996 del Regato
Malignant GliomasRTOG - ECOG Study
Re-Evaluation*Arm Median Survival (months) P
Age 40-60 All Patients
60 Gy 8.7 9.3 mo
70 Gy 8.2 8.2 mo
60 Gy + BCNU 12.0 p < .01 9.7 mo N.S.
60 Gy MeCCNU/DTIC 10.1 10.1 mo
+Nelson et al, 1988
Malignant Glioma
1996 del Regato
Gliomas - ChemotherapyPhase III Comparison of BCNU to PCV after RT with
Hydroxyurea*
# Pts BCNU # Pts PCV P value
Anaplastic
Astrocytoma K 70-100 41 68 wks 39 122 wks 0.2
K 40-60 4 65 wks 5 11 wks --
Glioblastoma
Multiforme K 70-100 36 31 wks 37 29 wks 0.1
K 40-60 14 19.4 wks 12 8.4 wks 0.004
Median Time to Progression
*Levin et al. 1985
Malignant Glioma
1996 del Regato
Malignant GliomasPhase II Evaluation of BFHM+
Schema: Carmustine, 5FU, Hydroxyurea, and 6-MP
Time to Progression
Anaplastic Astrocytoma 46 weeks
Glioblastoma Multiforme 23 weeks
+Levin et al, 1986
Malignant Glioma
1996 del Regato
Malignant GliomasMedian Time to Tumor Progression
(in weeks)+
Stratification BHR BR Significance BHR BRSignificance
(wks) (wks) (wks) (wks)
All Patients 42 31 .04* 50 73 NS
< .05**
Karnofsky rating 60/100 41 31 .04* 50 72 NS
.026**
Karnofsky rating 60/100 49 31 .03* 56 73 NS
Plus subtotal or total < .026**
Resection
Glioblastoma Multiforme Other malignant gliomas (non-glioblastoma)
+BHR = BCNU, hydroxyurea, and radiation; BR=BCNU and radiation.*Gehan modification of the Wilcoxon-rank sum analysis.**Cox analysis based on actual hydroxyurea dose. Levin et al, 1979
VSG 99 Pts.
Malignant Glioma
1996 del Regato
Malignant Gliomas
Percentile (weeks) Treatment 50 25 p
TTPRT + HU + BCNU 62.7 142.3
.025RT + HU + PCV 125.6 317.3
SurvivalRT + HU + BCNU 82.1 214.0
.021RT + HU + PCV 157.1 n.a.
Time to Tumor Progression (TTP) and Survival for Patientswith Anaplastic Gliomas other than GBM+
+Levin et al, 1990
}
}
Malignant Glioma
1996 del Regato
Malignant Gliomas
Percentile (weeks) Treatment 50 25 p
TTPRT + HU + BCNU 34.4 42.7
.106RT + HU + PCV 37.4 72.0
SurvivalRT + HU + BCNU 57.4 71.0
.510RT + HU + PCV 50.4 93.7
Time to Tumor Progression and Survival for Patientswith Glioblastoma Multiforme+
+Levin et al, 1990
}
}
Malignant Glioma
1996 del Regato
Malignant Gliomas
Percentile (weeks) Treatment 50 25 p
TTPRT + HU + BCNU 62.7 142.3
.025RT + HU + PCV 125.6 317.3
SurvivalRT + HU + BCNU 82.1 214.0
.021RT + HU + PCV 157.1 n.a.
Time to Tumor Progression (TTP) and Survival for Patientswith Anaplastic Gliomas other than GBM+
+Levin et al, 1990
}
}
Malignant Glioma
1996 del Regato
Malignant Gliomas
Percentile (weeks) Treatment 50 25 p
TTPRT + HU + BCNU 34.4 42.7
.106RT + HU + PCV 37.4 72.0
SurvivalRT + HU + BCNU 57.4 71.0
.510RT + HU + PCV 50.4 93.7
Time to Tumor Progression and Survival for Patientswith Glioblastoma Multiforme+
+Levin et al, 1990
}
}
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) Various chemotherapies have yielded modest improvements in time to progression and survival.
2) Most early studies are not properly adjusted for prognostic variables.
3) It is impossible to properly compare studies and choose the optimum regimen.
Conclusions: Chemoradiation
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) Hydroxyurea is beneficial during radiotherapy for Glioblastoma.
2) BCNU or PCV after radiotherapy are useful in Glioblastoma.
3) The gain in survival over radiotherapy alone is 2-3 months.
4) Randomized trials with proper selection and stratification are needed.
My Views: Chemoradiation
Malignant Glioma
1996 del Regato
Malignant Gliomas
Radiation
Sensitizers
Malignant Glioma
1996 del Regato
Malignant GliomasPhase III Misonidazole
MRC+
436 Patients
Eligible: Grades III + IV Astrocytoma
Doses:45 Gy in 20 Fractions 600 mg/m2 x 20 days
Results: No significant difference
+Bleehen et al, 1983
Malignant Glioma
1996 del Regato
Malignant GliomasPhase III Misonidazole
MRC+
Miso + RT RT
Number of Patients 188 195
Number Dead 168 179
Median Survival Time - wks 33 36
6 mo survival % 59% 63%
12 mo survival % 25% 28%
+Bleehen et al, 1983
Malignant Glioma
1996 del Regato
Malignant GliomasPhase III Misonidazole
RTOG+
AAF or GBM
Schema - # Pts.
RT + BCNU 60 Gy Whole Brain80 mg/m2/d x 3d q 6-8 wks 146
RT + BCNU + Miso 2.5 g/m2 q wk x 6 wk 147
K > 40 Age < 71
+Nelson et al, 1986
Malignant Glioma
1996 del Regato
Malignant GliomasPhase III Misonidazole
RTOG+
Results Median (Survival - Months
XRT + BCNU AAF 30.3
GBM 10.7
XRT + BCNU + MISO AAF 13.2
GBM 10.3
+ Nelson et al, 1986
Malignant Glioma
1996 del Regato
Results of Protocol 6G91Glioblastoma
Phase II Trial of Chemotherapy and Radiosensitizer
Post Op - Pre Radiation: 5FU, Lomustine
During Radiotherapy: Hydroxyurea + Misonidazole
After Radiotherapy: Procarbazine and Vincristine
alternating with
Carmustine and 5FU
Malignant Glioma
1996 del Regato
Results of Protocol 6G91
Patients Entered: 90
Evaluable: 64
Age: Median = 56
Sex: Male = 75, Female = 25
Karnofsky: 70-100%
Surgery: 95% Total or Subtotal Resection
Malignant Glioma
1996 del Regato
Results of Protocol 6G91
Complete plus partial response 23%
Stable 73%
Progressive 3%
Median Time to Progression 41 weeks
Malignant Glioma
1996 del Regato
Protocol 6G61 vs. 6G91
6G616G91 BCNU PCV
Response n=64 n=40 n=36
Complete + Partial 23% 20% 36%
Stable 73% 72% 58%
Progression 3% 8% 6%
Median Time to Progression 41 wks 32 wks 37 wks
Malignant Glioma
1996 del Regato
Malignant Gliomas
Median TTP Median Survival
WCSGBCNU 73 wksBCNU/HU 56 wks
6G61BCNU 63 wks 82 wksPCV 126 wks 157 wks
NCOG BUdR* 190 wks 208 wksRandomized Trial Null
Comparison of Results in Anaplastic Astrocytoma+
+ K ≥ 70* Limited fields
Malignant Glioma
1996 del Regato
Malignant GliomasComparison of Results in Glioblastoma
Chemotherapy and Halogentated Pyrimidines
Median TTP Median Survival
WCSGBCNU 31 wksBCNU/HU 49 wks
6G61BCNU 34 wks 57 wksPCV 37 wks 50 wks
6G91 37.6 wks 50 wks
NCOG BUdR* 34.5 wks 55.7 wks
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) Nitroimidazoles have proven of no value with fractionated Radiotherapy.
2) Halogenated Pyrimidines had promise - but the RTOG Phase III trial for Anaplastic Astrocytoma showed no benefit.
3) Etanidazole has Potential with Radiosurgery
Conclusions: Radiation Sensitizers
Malignant Glioma
1996 del Regato
Malignant Gliomas
Brachytherapy
Malignant Glioma
1996 del Regato
500400300200100000.0
0.2
0.4
0.6
0.8
1.0
18-29.930-49.9 50
Time (weeks)
Pro
babi
lity Age
Glioblastoma Multiforme Survival From Implant Boost
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) Brachytherapy is of benefit for recurrent Anaplastic Astrocytoma and Glioblastoma Multiforme patients.
2) Boost Brachytherapy is of benefit for Initial Treatment of GBM and leads to cure in some patients, particularly those under age 40.
Conclusions: Brachytherapy
Malignant Glioma
1996 del Regato
Malignant Gliomas
Hyperthermia
Malignant Glioma
1996 del Regato
Results of Hyperthermia for GlioblastomaA Randomized Trial
UCSF P.K. Sneed et al.
TOTAL PATIENTS ARMS
Entered 118 Brachy Boost Brachy & Heat
Eligible 111
Randomized 80 40 40
Treated as Randomized 33 31 (35)+
+Number having Brachytherapy
Malignant Glioma
1996 del Regato
Randomized TrialHyperthermia for Glioblastoma
Thermal Dose Parameters
Median Steady State T90 42.1o C
Thermal Dose Median 12 CEM 43o T90
Malignant Glioma
1996 del Regato
Randomized TrialInterstitial Hyperthermia for Glioblastoma
Median Survival
Group Brachy Alone Brachy & Heat P values
# Pts Median Surv. #Pts. Median Surv.
As Randomized 40 76 weeks 40 89 weeks 0.055
As Treated (Brachy) 33 76 weeks 35(31)* 91 weeks 0.014
* Number heated
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) Phase II trials suggest a benefit in survival with T-90 > 41.5%.
2) Randomized trial proves a survival benefit with interstitial Hyperthermia and Brachytherapy.
Conclusions: Hyperthermia
Malignant Glioma
1996 del Regato
Malignant Gliomas
Radiosurgery
Malignant Glioma
1996 del Regato
UCSF Gamma KnifeBoost Therapy for Glioblastoma
1991-1995
10 females
20 males Median age: 56.6 Median KPS: 90
17 Pts. Alive Median Followup: 42 weeks from diagnosis
30 weeks from Knife Rx
Median Survival Time: 78 weeks from diagnosis
Malignant Glioma
1996 del Regato
Abstract
We performed multivariate analysis on 189 glioma patients treated with the Gamma Knife at 8 different institutions and found that significantly improved survival from the date of radiosurgery was associated with 5 variables: lower pathologic grade, younger age, increased Karnofsky performance status, smaller tumor volume, and unifocal tumor.
We We conclude that groups of patients with glioma treated with radiosurgery or brachytherapy have similar survival, provided their group hazard ratios, which are based on 5 significant variables, are similar. This conclusion might be tested in formal trials which account for the 5 significant variables.
Larson et al.
Malignant Glioma
1996 del Regato
Materials and MethodsVariables Analyzed (N=18)
Clinical age, KPS, gender, complications, chronic steroid
dependency, extent of surgery, radiotherapy,
brachy candidate
Tumor path grade, site, number of lesions treated,
primary/recurrent
Technical tumor volume, number of isocenters, minimum
dose, maximum dose, isodose, inhomogeneity
Other Gamma Knife facility
Malignant Glioma
1996 del Regato
1.00
0.75
0.50
0.25
0.00P<0.001
Pathologic Grade (N=189)I
II
III
IVP<0.001
Age (N=189)
≤45 years
>45 years
P<0.001
>80
≤80
KPS (N=182)
P<0.001>10 cc
≤10 cc
Tumor Volume (N=187)1.00
0.75
0.50
0.25
0.000 1 2 3 4 5 6
Multifocal
Unifocal
P=0.010
Number of Tumors (N=189)
0 1 2 3 4 5 6
Years after radiosurgery
Hazard Ratio (N=180)
3<HR≤12
≤3
>12 P<0.001
0 1 2 3 4 5 6
Results - Survival
Malignant Glioma
1996 del Regato
Results - SurvivalOther Data
Author Tumor Path Treatment Hazard Survival*status ratio 1-yr 2-yr
Sneed primary II brachy 2.6 88% 81%Sneed recurrent II brachy 3.4 64% 46%Sneed primary III brachy 5.5 78% 59%Sneed recurrent III brachy 6.0 54% 29%Shrieve recurrent II-IV radiosurgery 9.8 45% 19%Loeffler primary IV radiosurgery 12.8 74% 24%Sneed primary IV brachy 13.5 73% 30%Sneed recurrent IV brachy 14.7 48% 24%Hall recurrent III-IV radiosurgery 16.7 30% -*survival from date of radiosurgery
Malignant Glioma
1996 del Regato
Conclusions
Survival after radiosurgery depends on 5 selection factors: KPS,
age, pathology, volume, number of tumors.
A hazard ratio model demonstrates that variations in reported
survival following radiosurgery may be attributed mainly to
differences in median values of these 5 factors.
The HR model can be used to separate patients into better,
intermediate, or poor prognosis groups.
Survival following brachytherapy is similar to survival following
radiosurgery, provided the 5 variables are accounted for.
However, formal trials are required to confirm this conclusion.
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) For small tumors, Gamma Knife radiosurgery appears equal to Brachytherapy for recurrent Gliomas.
2) In a limited number of patients, Gamma Knife radiosurgery seems equal to Brachytherapy for initial Boost.
Conclusions: Radiosurgery
Malignant Glioma
1996 del Regato
Malignant Gliomas
Heavy Particles
Malignant Glioma
1996 del Regato
Malignant Gliomas
45-50 Gy Whole Brain Photon + Neutron Boost
Median SurvivalRTOG Study 1: AA GBM
Photon boost 26.3 mo 8.5 moNeutron boost 15.8 mo 9.6 mo
RTOG Study 2:Dose Searching 22.0 mo 9.9 mo3.6-6.0 Gy Boost
*9/12 autopsies showed no tumor or “dead” tumor
Neutron Radiotherapy+
+Laramore et al, 1988
Malignant Glioma
1996 del Regato
Malignant Gliomas
Phase I-II Trial of Heavy Particles+
#Pts Median Survival
Anaplastic Astrocytoma 11 7.6 mo
Glioblastoma Multiforme 17 13.9 mo
Mixed Photon and Helium or Neon
+Castro et al, 1985
Malignant Glioma
1996 del Regato
Malignant Gliomas
15 Patients Randomized to 20 or 25 Gy/16 fx
Time to Failure 7 - 9 mo
Survival 9 - 11 mo
3 patients died w/o tumor; 1 neg. autopsy 19 mo;
1 survived 22 mo., probable necrosis
Neon Ion Treatment of Glioblastoma+
+Castro et al, 1995 (abs)
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) Both Neutrons and Neon Ions can sterilize GBM.
2) Survival is similar to that with conventional radiotherapy for GBM but worse for AA.
3) There appears to be no therapeutic ratio - doses which sterilize tumor cause lethal brain damage.
Conclusions: Heavy Particles
Malignant Glioma
1996 del Regato
Malignant Gliomas
Boron Neutron
Capture Therapy
Malignant Glioma
1996 del Regato
BROOKHAVEN BNCT TRIAL
PHASE 1 TRIAL PART 1
15 PATIENTS treated
BPA Fructose (3-4x Tumor/Blood)
Brain Conc. = Blood
250 mg/m2 slow infusion
Min tumor dose with boron 10.5 Gy
Maximum dose anywhere 10.5 Gy (brain conc)
Median Survival 10.5 mo.
No complications
Malignant Gliomas
Malignant Glioma
1996 del Regato
BNL BNCT TRIAL
PART 2 of PHASE I TRIAL
350 mg/m2 fructose BPA, short infusion
Larger Collimator
Opposed Beams
Min Tumor Dose > 20 Gy
Normal Brain allowed areas of 12.6 Gy
Started in April 96.
Malignant Gliomas
Malignant Glioma
1996 del Regato
BNCT IN GLIOBLASTOMA
1. 3 Phase I Clinical Trials Underway with Epithermal Beams: Brookhaven, MIT and Petten.
2. First two use BPA, Petten BSH.
3. BNL 45 pts, MIT 15 pts, Petten 10 pts treated.
4. MST 12 to 12.9 months, compared to expected (RPA-RTOG) of 8.9-11.1 months.
5. Minimum tumor doses too low. Need better drugs and/or better beams.
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) BNCT has promise but is not proven by any randomized trial.
2) Better drugs and epithermal beams are available now.
3) Clinical trials at BNL, MIT and Petten show encouraging results.
4) Better Beams with higher depth dose are needed as are drugs with higher tumor to blood ratios.
Conclusions: Boron Neutron Capture Therapy
Malignant Glioma
1996 del Regato
Malignant Gliomas
Conclusions
Malignant Glioma
1996 del Regato
Malignant Gliomas
1) Only Modest Progress has been made in the treatment of Malignant Gliomas.
2) Earlier Diagnosis, Improved Histopathology,and Improved Surgical resection have helped.
3) Future improvement depends on genetic and molecular discoveries.
4) Specific Guidelines can be given for treatment today:
Conclusions
Malignant Glioma
1996 del Regato
Malignant GliomasSpecific Guidelines
Anaplastic Astrocytoma
Radiotherapy - 5940 cGy/33 fx, Limited volume+
Followed by PCV chemotherapy
or
Enter Patient in Trial
+spare opposite hemisphere, 3D planning
Malignant Glioma
1996 del Regato
Malignant Gliomas
Specific Guidelines
Glioblastoma Multiforme
Small Tumors (< 3.5 cm Post-Op)
Radiotherapy - 5940 cGy/33 fx with HU to Limited Volume
Boost with Gamma Knife 15-22Gy
Follow with BCNU
or
Enter patient in a Trial
Malignant Glioma
1996 del Regato
Malignant Gliomas
Specific Guidelines
Glioblastoma Multiforme
Larger Tumors:
Radiotherapy - 5940 cGy/33 fx with HU, Limited Volume
Follow with BCNU or PCV
or
Enter in Available Clinical Trial
Malignant Glioma
1996 del Regato
FUTURE DIRECTIONS
MAJOR NEW INITIATIVES INCLUDE:1. UNDERSTANDING THE GENETIC ABNORMALITIES:
CONTROL OF G1/S, CONTROL OF APOPTOSIS
2. UNDERSTANDING DETERMINANTS OF SENSITIVITY TO CHEMO AND RADIATION THERAPY: DELETION OF 1P ETC.
3. DEVELOPMENT OF TUMOR SPECIFIC ANTIGENS.
4. NEW DRUG DELIVERY SYSTEMS.
5. VIRAL GENE THERAPY TO MODIFY GENETIC ABNORMALITIES.