This document discusses high grade gliomas, which include anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and glioblastoma multiforme. It describes the epidemiology, clinical features, prognosis, and management of these tumors. The optimal treatment involves maximal safe surgical resection followed by concurrent chemoradiation and adjuvant chemotherapy. Radiotherapy techniques such as 3D conformal radiation therapy and intensity-modulated radiation therapy aim to deliver a dose of 60 Gy to the tumor volume while sparing surrounding normal brain tissue. However, dose escalation above standard doses has not shown a survival benefit.

2. HIGH GRADE GLIOMAS
 Anaplastic astrocytoma (WHO grade III)
 Anaplastic oligodendroglioma (WHO III)
 Anaplastic oligoastrocytoma (WHO grade III)
 Glioblastoma multiforme (GBM) (WHO grade IV)

3.  Malignant or high-grade gliomas account for
approximately half of all primary brain tumors in
adults
 70% of all gliomas and predominantly affect
patients between 40-70 years of age.
 They are rapidly growing tumors that directly
invade the brain parenchyma

4.  They are commonly located in or near to eloquent
brain regions, i.e. motor, language, visuo-spatial and
memory.
 These tumours continue to have growth potential,
there is no stable tumour and recurrence tends to be at
the site of the original disease
 Death is usually due to recurrence and disease
progression and the optimal treatment of HGG is
tailored to individual patients

5. Clinical features
 Features of raised intracranial pressure
 focal neurological deficit are the commonest
presenting complaint

7. PROGNOSIS
 Due to their infiltrative nature high grade gliomas
are not curable

8. Prognostic Factors Age
 tumor type
 tumor grade
 seizure symptoms
 duration of symptoms
 performance status
 extent of surgery performed and irradiation dose

10.  Using nonparametric recursive partitioning analysis
(RPA)
 a statistical tool that allows for the identification of
significant prognostic factors and subsequent
classification of patients into groups with similar
outcomes
 showed that age was the most important predictor of
survival, with patients <50 years faring better than
older patients.
 KPS (KPS >70 more favorable than <70) was the next
most significant prognostic factor in patients with
GBM

13. Aim of treatment
 maintain quality of life
 minimise tumour volume
 stabilise disease

14. Glioblastoma Multiforme
 accounts for approximately 75% of all high-grade
gliomas.
 The histopathologic features of GBM include
nuclear atypia, mitotic activity, vascular
proliferation, and necrosis
 GBM is typically diffusely infiltrative, involving
large portions of the brain

15.  The prognosis for patients with GBM is poor
 a median survival without treatment of only 3–6
months.

16. MANAGEMENT
 SURGERY
 CONCURRENT CHEMORT
 ADJUVANT CHEMOTHERAPY

17. SURGERY surgical procedures
 biopsy for diagnosis only
 Maximum safe surgical resection
 surgical debulking for management of mass effect
related symptoms
 CSF diversion procedures to relieve acute symptoms
caused by increased intracranial pressure or
hydrocephalus

18.  Surgical options depend on
 clinical condition
 performance status
 tumour location
 patient choice

19. AIM
 Optimal goal of glioma surgery is to resect completely
 Tumor bulk reduction alleviates symptoms of raised
ICT
 Also provides adequate tissue for HPE evaluation
 Also removes hypoxic tissues resistant to chemo
 Due to lower number of tumor cells left in the surgical
cavity
 increased chances of response to adjuvant treatment

20. TECHNIQUES
 CT- and MRI-guidance systems provide surgeons with
intraoperative navigation based upon preoperative
and/or intraoperative imaging studies.
 these systems consist of a computer workstation
operated by the surgeon into which the relevant
imaging studies have been loaded
 together with infrared or ultrasound detectors that
recognize the 3D orientation and position in space of
various tools

21.  the tumor's margins are visualized below the scalp so
that the surgeon can plan the smallest and safest,
approach
 Resection is assisted by use of the intraoperative
microscope
 guided by the appearance and consistency of tumor
tissue compared with surrounding normal brain
 In the case of lesions that are in or near suspected
functional cortex
 cortical mapping can be performed to localize areas
that are critical for motor or speech function

22.  Stereotactic biopsy
 CT or MRI is performed and the imaging data loaded into
an image guidance system.
 A target and entry points are selected
 the trajectory is visualized on the computer workstation.
 The entry point is located on the patient's scalp and a small
burr hole or twist drill hole is made.
 The biopsy needle is oriented using the image guidance
system, passed to the appropriate depth, and tissue
samples are obtained

23. Extend of surgery and survival
 An analysis of an RTOG database of 645 patients
with malignant gliomas
 revealed a median survival of 11.3 months with
total resection
 10.4 months with subtotal resection
 6.6 months with biopsy alone

24.  A biopsy is preferred for tumors located in
functionally important or inaccessible areas of the
brain.
 In addition, surgical resection is not practical for
patients with significant tumor infiltration across
the midline and around the ventricular system, or
for those with diffuse, non focal lesions.

25. SEQUELAE OF SURGERY
 With appropriate patient selection
 diligent surgical technique
 use of surgical adjuncts such as speech and/or motor
mapping, the rate of complications can be minimized
 new temporary neurological deficits can be seen in
15% or more of patients
 rate of permanent new deficits is <5%

26.  The most common complications associated with
surgery are bleeding and infection
 Transient perioperative edema, within about 48 hours
of surgery-early postoperative neurologic worsening
 The incidence and types of deficits seen following
surgery depend upon the location of the tumor and
the deficits present preoperatively

27. Role of radiotherapy
 Randomized trials conducted by the Brain Tumor
Cooperative Group (BTCG) and the Scandinavian
Glioblastoma Study Group (SGSG)
 provided seminal evidence that external-beam
irradiation favorably affects the outcome of
malignant gliomas

29. DOSE?
 Walker et al. reported a dose response analysis using
data from 420 patients treated on Brain Tumor
Cooperative Group protocols.
 Doses ranged from <45 to 60 Gy using daily fractions
of 1.7 to 2 Gy
 only one third of the patients received <60 Gy.
 A significant improvement in median survival from 28
to 42 weeks in the groups treated with doses of 50 to
60 Gy was found.

30.  A Medical Research Council study of 443 patients
also showed a significant survival advantage in
patients who received 60 Gy compared to those
who received 45 Gy (12 vs. 9 months; p = .007)

31. Fractionation same for all patients?
 For patients with poor pretreatment prognostic factors
 a limited expected survival who are not able to tolerate
conventional treatment
 a shorter course of treatment may provide good palliation

32.  Older patients (>65 years) with poor performance
status, have been shown to have limited post
treatment improvement
 rapid neurological deterioration following
conventional radiotherapy
 Phillips et al. randomized 68 such patients to standard
radiotherapy to 60 Gy in 30 fractions or a shorter
course to 35 Gy in 10 fractions.
 There was no significant survival difference between
the two arms.

33.  Roa et al.randomized 100 patients with GBM over
60 years to receive standard radiotherapy of 60 Gy
in 30 fractions
 or an shorter course of 40 Gy in 15 fractions.
 Overall survival between the two arms was not
significantly different

34. Radiotherapy cont..
 Surgery can be followed by radiotherapy within 4–
6 weeks of uncomplicated recovery.
 Radiotherapy following surgery extends median
survival to 9–12 months.

35. RADIOTHERPY TECHNIQUES

36. DATA AQUISITION
 Immobilisation
 The patient lies supine with the head immobilised
in an individualised(e.g., headrest, Aquaplast, tilt
boards)
 The head position depends on the location of the
tumor and the patient’s ability to tolerate
positioning

37.  CT scanning-
 Since MRI cannot be used for planning treatment alone,
CT planning scans using intravenous contrast are taken
with 1–3 mm slices from the vault to the base of the skull
 Treatment-planning CT should be obtained in the
treatment position

39. TARGET VOLUMES
 The GTV is delineated at the contrast-enhancing
edge of the tumour (not oedema) on postsurgical
gadolinium enhanced T1-weighted MRI scans
fused with planning CT

40. fused T1-weighted contrast-enhanced MR/CT
images for high grade glioma

41. GTV-CTV MARGIN
 GRADE 3
 CTV45=GTV + 25 mm
 CTV60=GTV + 15 mm
 GRADE 4
 CTV50=GTV + 25mm
 CTV60=GTV + 15mm

42. Volumes outlined from MRI displayed on fused
treatment-planning CT

43.  PTV A 5 mm margin is added to the CTV taking
into account departmental measurements of set-
up accuracy
 Volumes must be tailored to minimise dose to
OAR, such as optic chiasm, and take account of
natural barriers to spread such as bone and falx.

45.  Using CT scanning and MLCs, volumes are tailored to
avoid as much normal tissue as possible.
 Isodose distributions for the PTVs should be generated and
evaluated for homogeneity and normal tissue tolerance
 The inhomogeneity within the target volume should be
kept to ≤10%
 minimum dose to the target volume should be kept within
5–10% of the dose at the center of the volume

46.  Treatment should be delivered with multiple fields in
an attempt to achieve homogeneity throughout the
volume
 to spare dose to uninvolved brain
 This can be accomplished by using 3 D CRTor by IMRT

47. Isodoses and beam arrangement displayed on the
treatment-planning CT

48. Dose constraints

49. DOSE ESCALATION EFFECTIVE? The RTOG and Eastern Cooperative Oncology Group
(ECOG) randomized 253 patients to either whole-brain
irradiation to 60 Gy given in 6 to 7 week
 60 Gy plus a 10-Gy boost to a limited volume given in 7
to 8 weeks
 There was no benefit for the higher irradiation dose.
 Median survival was 9.3 months for patients receiving
60 Gy and 8.2 months for those receiving 70 Gy

50.  Chan et al. published the results of 34 patients
with high-grade gliomas treated using 3D
conformal IMRT to a dose of 90 Gy.
 At median follow-up of 11.7 months, median
survival was found to be 11.7 months and 1- and 2-
year survivals of 47.1% and 12.9%, respectively,
 Which was comparable to historical controls

51. ROLE OF HYPERFRACTINATION
 RTOG 83-02 examined dose escalation using twice
daily fractionation in patients with malignant
gliomas.
 comparing conventional radiotherapy to 60 Gy in
30 daily fractions to hyperfractionated
radiotherapy to 72 Gy in 60 fractions of 1.2 Gy
given twice daily
 No difference in survival was found

52. Dose Escalation Using Radiosurgery
and FSRT a retrospective analysis of 115 patients treated at
three institutions (75 from the Joint Center for
Radiation Therapy, 30 from the University of
Wisconsin, and 10 from the University of Florida)
 with a combination of surgery, external-beam
radiotherapy, and LINAC-based radiosurgery on
similar institutional protocols
 patients treated with radiosurgery had
significantly improved 2-year and median survival

53.  This improvement in survival was seen
predominantly for the worse prognostic classes
(RPA classes 3 to 6)
 2-year survival for the patients treated with
radiosurgery vs conventionally treated patients
 81 vs 76 for class I n 2
 75 vs 35% for class3
 34% versus 15% for class 4
 21% versus 6% for RPA classes 5 and 6

54.  Patient selection may in part account for these
results
 The use of a boost using FSRT was tested
prospectively in RTOG 0023
 Seventy-six patients with GBM with postoperative
residual tumor plus tumor cavity diameter <60
mm
 treated with 50 Gy standard radiotherapy in daily 2
Gy fractions, plus four FSRT treatments given once
weekly during weeks 3 to 6 of radiotherapy

55.  The FSRT dose was either 5 Gy or 7 Gy per fraction for
a cumulative dose of 70 or 78 Gy in 29 treatments over
6 weeks
 Overall, no survival advantage was seen when
compared to the RTOG historical database
 However, subset analysis showed that patients who
had undergone gross total resection had a median
survival time of 16.6 compared with 12.0 months for
historic controls (p = .14)
 suggesting that patients with minimal disease burden
may benefit from this form of treatment

56. Dose Escalation Using
Brachytherapy Laperriere et al.used brachytherapy as a boost to
conventional radiotherapy in patients with malignant
gliomas
 randomized to external-beam radiotherapy (50 Gy in 25
fractions) alone (n = 69)
 or external-beam radiotherapy plus a temporary
stereotactic 125I implant delivering a minimum peripheral
tumor dose of 60 Gy (n = 71).
 Median survival was not significantly different between the
two arms (13.8 vs. 13.2 months

57.  Brain Tumor Cooperative Group National Institutes of
Health Trial 87-01 reported by Selker et al
 299 patients with newly diagnosed malignant glioma
received surgery, external-beam radiotherapy, and BCNU
with or without an interstitial radiotherapy boost with 125I
 Median survival was 68.1 versus 58.8 weeks (p = .101)

58.  GliaSite Radiation Therapy System
 Radiotherapy delivered by an inflatable balloon catheter
 Tatter et al. evaluated the safety and performance of one
such
 Twenty-one patients with recurrent malignant gliomas
underwent surgical resection and implantation of a
subcutaneous port.
 At 1 to 2 weeks following implantation, the catheter was
filled with an aqueous solution of organically bound 125I for
delivering a minimum of 40 to 60 Gy over 3 to 6 days

59.  This treatment was well tolerated with no serious adverse
effects.
 Median survival was 12.7 months.
 Prospective, randomized trials are needed for further
evaluation

60. Radiosensitizers
 to overcome the hypoxia present in malignant gliomas
 Studies using radiation modifiers in conjunction with
radiotherapy have been tried
 Chang reported on 38 patients treated with hyperbaric
oxygen and irradiation using fractionation schedules
 compared them with 42 patients treated with radiotherapy
alone.

61.  An improvement in 18-month survival rate from 10% to
28%
 increase of median survival from 31 to 38 weeks was noted
 The increased cost and difficulty of the widespread
application of this treatment make this approach
impractical
 Miralbell et al. reported the results of (EORTC) trial
examining the addition of carbogen and nicotinamide
 to overcome the effects of proliferation and hypoxia
presumed responsible for radioresistance in GBM
 Overall survival does not differ with RT alone

62.  Redox modulating radiosensitizer motexafin
gadolinium encouraging results in phase 1 clinical
trial
 RTOG O515 A single arm phase 2 trial failed to
show any advantage of its use in newly diagnosed
GBM

63. Particle Therapy
 Alternate radiation modalities are used
 neutrons, protons, helium ions, other heavy nuclei,
negative pi-mesons
 Despite theoretical advantages with respect to dose
distribution and/or radiobiologic effect, most trials have
failed to demonstrate improved survival.

64.  Studies have shown no benefit from dose
escalation, hyperfractionation, addition of
radiosensitiser, or wide compared with local
irradiation;

65. Role of chemotherapy
 Historically, the nitrosoureas, especially carmustine (bis-
chloroethyl-nitrosourea [BCNU] was the most common
agent to be used
 procarbazine, lomustine (CCNU), and vincristine (PCV)
regimen.
 a retrospective analysis of RTOG data and a phase III trial
conducted at the Medical Research Council (MRC) showed
no benefit in survival with the PCV regimen
 Treatment with these agents is associated with increased
toxicity

66.  The role of chemotherapy in GBM has been
redefined on the basis of a phase III cooperative
group trial published by Stupp et al

67.  EORTC/NCIC (Stupp et al. 2005, 2009)
 573 patients with newly diagnosed glioblastoma (16%
biopsy only, 40% GTR, 44% STR)
 randomized to RT alone vs. RT + concurrent and
adjuvant temozolomide.
 RT was 60 Gy/30 fx.
 Temozolomide was concurrentdaily (75 mg/m2/day)
 adjuvant (150–200 mg/m2/day × 5days) q4 weeks × 6
month.

68.  RESULT
 Concurrent and adjuvant temozolomide
significantly improved MS (14.6 vs. 12.1 month)
 improved median survival and 2-year survival rates
of 26% and 10%,
 5-year OS (9.8 vs. 1.9%).

69. temozolamide
 It is a derivative of dacarbazine and an inactive
prodrug
 undergoes hydrolysis to active metabolite
monomethyl triazeno imidazole carboximide
 when absorbed and results in methylation of
guanine at the O6 and N7 positions at the
deoxyribonucleic acid.

70.  Advantages
 oral administration
 rapid absorption
 100% bioavailability
 ability to cross the blood-brain barrier
 linear pharmacokinetics
 minimal delayed myelosuppression.

71. DOES TMZ INFLUENCE ALL?
 a large proportion of patients benefited only marginally from
this regimen.
 Different levels of expression of O6-methylguanine-DNA
methyltransferase (MGMT)
 responsible for DNA repair, have been proposed as a possible
explanation for differing responses to chemoradiotherapy
 Hegi et al. evaluated the methylation status of the MGMT gene
promoter region in patients with available and adequate
specimens

72.  MGMT promoter methylation was found in 45% of assessable
patients
 Median overall survival was better with patients with
methylated MGMT promoter regions
 18.2 months and 12.2 months, respectively; p < .001
 survival benefit from the addition of temozolomide to
radiotherapy was seen only in patients with MGMT promoter
methylation.
 MEDIAN OVERALL SURVIVA 21.7 VS 15.3 MONTHS
 In patients without MGMT promoter methylation
 12.7 VS 11.8 months

73. DOES DOSE INTENSE TMZ
IMPROVES SURVIVAL?
 RTOG conducted RCT comparing standard adjuvant TMZ
vs dose intense TMZ in newly diagnosed GBM
 In adjuvant setting TMZ 5/28 VS 21/28
 OVERALL SURVIVAL 14.9 VS 16.6 months
 Dose intense regimen had more toxicity

74. INVESTIGATIONAL MODALITIES

75. Radioimmunotherapy
 using monoclonal antibodies against EGFR tagged with 125I
 In a phase II trial by Brady et al.
 25 patients with malignant gliomas (10 with anaplastic
astrocytoma and 15 with GBM) were treated with surgical
resection or biopsy followed by definitive external-beam
radiotherapy and
 one or multiple doses (35 to 90 mCi per intravenous or
intra-arterial infusion) of 125I-labeled monoclonal antibody

76.  At 1 year, 60% of patients were alive, and the median
survival was 15.6 months.
 In an updated report of this study that included a total of
180 patients with a minimum follow-up of 5 years, median
survival was 13.4 months for those with GBM
 Another potential target is tenascin, an extracellular
protein overexpressed in malignant gliomas but not found
in normal tissue.
 Radiolabeled monoclonal antibodies to tenascin have been
evaluated in phase I or II trials showing activity against
newly diagnosed and recurrent malignant gliomas

77. Targeted Therapies
 EGFR gene amplification is seen in approximately 40% to
50% of patients with GBM
 Inhibitors of EGFR tyrosine kinase such as gefitinib and
erlotinib and EGFR antibodies have shown activity against
GBM in early clinical trials
 The presence of an EGFR deletion mutant variant III
 the presence of intact PTEN have been found to be
significantly associated to clinical response

78.  Neovascularization is a major feature of GBM
 many studies demonstrate that GBM secrete VEGF in
abundance
 Bevacizumab an anti VEGF antibody is used
 Multiple phase 2 trial has shown radiographic response rate
and reduction in peri tumoral edema

79. IMPLANTED WAFERS
 Local administration of carmustine using a
biodegradable polymer place intra operatively in
the surgical cavity
 Phase 3 trial n=240 newly diagnosed malignant
glioma
 Improved survival in wafer + RT arm vs RT alone
 13.9 vs 11.6 median survival

80. EVIDENCE BASED TRAETMENT
SUMMARY Maximal surgical resection is generally associated with
more favorable outcome and is recommended whenever
feasible
 Postoperative radiotherapy has been shown to provide a
survival advantage in several clinical trials. The typical
radiotherapy dose is 60 Gy in 6 weeks
 Temozolomide, given during and after radiotherapy,
provides a significant survival advantage
 greatest in patients with methylation of the promoter
region of the MGMT gene

81. Anaplastic Glioma
 Anaplastic gliomas constitute approximately 25%
of high-grade gliomas in adults( WHO GRADE 3)
 anaplastic astrocytomas
 anaplastic oligodendrogliomas
 anaplastic mixed oligoastrocytomas

82.  anaplastic astrocytoma have a median survival of
approximately 3 years following diagnosis
 Patients with anaplastic oligodendroglioma have a
better prognosis
 The prognosis for patients with a mixed tumor,
anaplastic oligoastrocytoma, varies depending on
the dominant histological cell type

83.  Combined 1p and 19q deletions have been found in
63% anaplastic oligodendroglioma
 52% of patients with mixed anaplastic
oligoastrocytoma
 astrocytic tumors have a low incidence (8% to 11%)
 Patients with co deletions of 1p and 19q had
significantly longer overall survival irrespective of
treatment

84. Anaplastic Astrocytoma
 Surgery
 Radiotherapy
 Chemotherapy

85. Role of chemotherapy
 prospective phase III trial by the United Kingdom Medical
Research Council randomized 674 patients of whom 117
(17%) had anaplastic astrocytoma
 after surgery to radiotherapy alone or radiotherapy
followed by PCV
 There was no advantage for adjuvant PCV in any subgroup

86.  A phase II trial by Levin et al. investigated the safety of
accelerated fractionated radiotherapy combined with
carboplatin followed by PCV in patients with anaplastic
gliomas.
 A total of 90 patients (76.7% with anaplastic astrocytoma)
were enrolled.
 Median survival for anaplastic glioma patients was 28.7
months.
 Neurologic deterioration and/or dementia were seen in
10% of patients.
 inferior median survival due to excessive CNS toxicity from
this intense regimen

87. Anaplastic
Oligodendroglioma/Oligoastrocyto
ma
 Surgery
 Radiotherapy
 Chemotherapy

88. Role of chemotherapy

89.  EORTC 26951: RT alone versus RT followed by PCV
 368 patients were randomized to receive either
radiotherapy alone or radiotherapy, followed by 6
cycles of adjuvant PCV
 At median follow up of 140 months overall survival was
longer in combination arm
 42.3 vs 30.6
 No survival advantage with addition of PCV among
patients without co deletion

90. Evidence-Based Treatment Summary
for grade 3 tumors
 Maximal surgical resection is generally associated with more
favorable outcome and is recommended whenever feasible.
 Postoperative radiotherapy has been shown to provide a survival
advantage in several clinical trials
 Trials included WHO grade III and IV tumors; no trial for only
grade III tumors has been conducted
 The role and which chemotherapy to be used remains
undefined.
 Patients with co deletions of 1p and 19q have a more favorable
prognosis and respond better to both chemotherapy and
radiotherapy

92. NCCN GUIDELINES

93. Recurrent glioma
 High grade gliomas all tend to recur and treatment is
tailored to individual patients according to clinical status
 a) revision surgery +/- Gliadel
 b) revision surgery +/- further radiotherapy
 c) 2nd line chemotherapy with CCNU
 d) re-challenge chemotherapy with temozolomide
 e) stereotactic radiosurgery (SRS) in highly selected cases
 f) participation in clinical trials

94.  Palliative debulking relieves mass effect and extend
survival by 4-6 months
 Bevacizumab as single agent can used
 Polymer based local chemotherapy(carmustine wafers) has
been tested
 Survival increase from 44% to 64% at 6 months
 Repeat RT using radiosurgery, brachytherapy ,gliasite
balloon brachytherapy , EBRT using IMRT

95. BRAIN STEM GLIOMAS
 Brainstem gliomas are highly aggressive brain tumors.
 Brainstem gliomas have been reported to make up
2.4% of all intracranial tumors in adults
 9.4% of intracranial tumors in children

96.  Bimodal age distribution has been noted
 with a peak incidence in the latter half of the first
decade of life and a second peak in the fourth decade.
 Approximately three fourths of patients are younger
than 20 years.

97.  DEPENDS ON SITE
 diffuse intrinsic pontine
 Tectal
 Cervicomedullary
 Intrinsic pontine gliomas carry a grave prognosis

98. CLINICAL PRESENTATION
 Pontine lesions
 double vision, weakness, unsteady gait, difficulty in
swallowing, dysarthria, headache, drowsiness, nausea,
and vomiting
 Tectal lesions typically present with headache, nausea,
and vomiting
 Hydrocephalus is a common presentation, especially
for tumors in periaqueductal or fourth ventricle
outflow locations

99.  Cervicomedullary lesions usually present with
dysphagia, unsteadiness, nasal speech, vomiting, and
weakness
 Common clinical findings can be summarized as
constituting a triad of
 cranial nerve deficits
 long tract signs (clonus, muscle spasticity, or bladder
involvement)
 ataxia of trunk and limbs

100. Work up
 Tissue confirmation is frequently not feasible with
infiltrating, expansile tumors unless an exophytic
component exists
 Histopathologically it may vary from grade 1-4

101. MRI
 MRI of the head is the diagnostic test of choice.
 MRI can differentiate vascular malformations and
other processes that can be misdiagnosed as a
brainstem glioma on CT scan
 an expansile, infiltrative process with low-to-normal
signal intensity on T1-weighted images
 heterogeneous high-signal intensity on T2-weighted
images, with or without contrast enhancement

102. T2-weighted image of a diffuse intrinsic pontine glioma

103.  MANAGEMENT
 Surgery
 most appropriate in tumors of the cervicomedullary
junctiondorsal exophytic tumors protruding into the
fourth ventricle
 cystic tumors
 enhancing tumors with clear margins that exert a space-
occupying effect

104.  Typically, biopsy and/or surgery are not required for
diagnosis or treatment of diffuse intrinsic pontine or
tectal gliomas
 cannot be recommended routinely due to high risk
 For dorsally exophytic tumors, judicious incomplete
resection will establish the diagnosis
 reduce the obstructing mass in the fourth ventricular
region

105.  Radiation Therapy
 Children with diffusely infiltrating pontine gliomas
often respond impressively to irradiation initially
 Approximately 70% show improvement in neurologic
symptoms and signs over the several weeks during and
after irradiation.
 Improvement in MRI has been reported in 30–70% of
children
 objective response is almost always followed by signs
of progressive disease within 8 to 12 months

106.  tegmental midbrain lesions and tumors of the medulla
 radiation therapy is more likely to achieve long-term
disease control
 tectal plate or dorsally exophytic pontomedullary
astrocytomas
 irradiation is safely deferred until signs of disease
progression are apparent on imaging
 The conventional dose of radiotherapy ranges from 54-
60 Gy

107.  CHEMOTHERAPY
 there is little evidence of efficacy for chemotherapy in
brainstem tumors
 For focal, low-grade gliomas, the use of chemotherapy
before irradiation is an extrapolation from
diencephalic low-grade tumors, which may be rational
in selected settings
 No significant advantage in delaying definitive RT with
intervening chemotherapy.