GLIOMAS

Persentase glioma adalah mencapai 26,4% dari semua tumor otak primer, dengan
glioma maligna (stadium III atau IV) terhitung hingga 19,9% dari semua tumor otak primer.
WHO mengklasifikasikan glioma berdasarkan sel-selnya yang menyerupai secara morfologis
(astrosit, oligodendrosit, atau campuran) dan mengelompokkan tumor ke dalam empat
stadium berdasarkan histologi dan agresivitas. Glioma stadium tinggi (stadium WHO III dan
IV) memiliki prognosis yang buruk, dengan kelangsungan hidup rata-rata untuk astrositoma
stadium IV (glioblastoma multiforme [GBM]) kurang dari 15 sampai 20 bulan. Glioma
stadium rendah (stadium WHO I dan II) bersifat heterogen dalam hal prognosis dan
kemungkinan untuk berlanjut menajdi glioma stadium tinggi.

Adult Low-Grade Gliomas

What drives some adult low-grade gliomas to progression whereas
others remain indolent is an area of active investigation. Grade I gliomas,
the majority of which are pilocytic astrocytomas, are histologically benign
tumors with low potential for malignant progression that primarily occur in
the pediatric population and are discussed in detail in the pediatric low-
grade glioma section, which follows. Histologically, WHO grade II gliomas
can be divided into tumors that arise from astrocytes (diffuse
astrocytomas), oligodendrocytes (oligodendrogliomas), or tumors with
elements of both cellular populations (oligoastrocytomas). All three
histologic subtypes have frequent neomorphic driver mutations affecting
the R132 residue of isocitrate dehydrogenase 1 (IDH1), a mutation that
generates the oncometabolite 2-hydroxyglutarate (2HG).5 Ultimately, the
IDH1 R132 mutation drives gliomagenesis through epigenetic
dysregulation, including DNA CpG hypermethylation (G-CIMP phenotype)6
and alterations in histone methylation.79 Despite sharing the IDH1 R132
driver mutation, grade II oligodendrogliomas have improved median
overall survival (11.6 years for grade II oligodendrogliomas versus 5.6
years for grade II astrocytoma),10 and a much lower rate of progression to
a high-grade glioma (45% for oligodendroglioma versus 74% for
astrocytoma). The survival and progression benefit seen in IDH1 mutant
grade II gliomas is likely modified by comutations. Oligodendrogliomas
commonly have a loss of heterozygosity (LOH) on chromosomes 1p and
19q,1113 which is usually the result of a single pericentromeric
translocation event.14 The 1p/19q loss in oligodendrogliomas frequently
co-occurs with somatic mutations in capicua transcriptional repressor
(CIC, located on chr1) or far upstream element (FUSE) binding protein 1
(FUBP1, located on chr19),15 and IDH1-CIC/FUBP1-1p/19q loss gliomas
have a median survival of 8 years. In contrast, grade II astrocytomas
commonly have somatic mutations in the chromatin modifier alpha
thalassemia/mental retardation syndrome X-linked (ATRX), mutations in
tumor protein p53 (TP53),4 and LOH at chr17 (where TP53 is found), and
IDH1-ATRX-TP53 gliomas have a median survival of 5 years.16 This latter
group is likely to progress to form secondary GBMs, a process mediated by
epigenomic dysregulation and deletion of retinoblastoma 1 (RB1), cyclin-
dependent kinase inhibitor 2A (CDKN2A), and phosphatase and tensin
homolog (PTEN).17,18 Oligoastrocytomas have a combination of
mutations and chromosomal LOH found in astrocytomas and
oligoastrocytomas and a median survival of 6.6 years.

Adult High-Grade Gliomas

Glioblastoma multiforme (WHO grade IV) is the most common
malignant brain tumor, accounting for 15.6% of all primary brain tumors
and 60% of all gliomas.1 There are two major routes to GBM formation: de
novo formation (primary GBM, 95% of cases), or progression from low-
grade glioma (secondary GBM, 5% of cases) (Fig. 96.1).17 Secondary
GBMs occur in younger patients, result in improved survival, and bear
IDH1 mutations with common co-mutations in ATRX and TP53 and deletion
of RB1, CDKN2A, and PTEN.1621 In contrast, primary GBMs occur in older
patients, have poor survival, and have dysregulation of three core
pathways: p53, retinoblastoma (Rb), and receptor tyrosine
kinase/Ras/phosphoinositide 3-kinase (PI3K) signaling (RTK/Ras/PI3K
signaling).17,20,2224 A recent large-scale GBM next-generation
sequencing study by The Cancer Genome Atlas (TCGA) found that the p53
pathway is somatically disrupted in 85.3% of GBMs, through p53 loss
(27.9%), homozygous deletion of CDKN2A (57.8%), and amplification of
MDM1/2/4 (15.1%).
The Rb pathway is also impacted by frequent CDKN2A deletion, and
other hits to Rb signaling have been seen via RB1 loss (7.6%) or
amplification of cyclin-dependent kinase 4 or 6(CDK4/6) (15.5%), for a
total of 78.9% alteration of Rb signaling. Somatic alterations in receptor
tyrosine kinases were observed in 67.3% of GBMs, most prominently in
epidermal growth factor receptor (EGFR) (57.4%) and platelet-derived
growth factor receptor alpha (PDGFRA) (13.1%).24 Of GBMs showed either
PTEN loss or PI3K mutation, and neurofibromin 1 (NF1) loss was seen in
10% of tumors.24 In combination, the RTK/Ras/PI3K signaling was hit once
in 89.6% of tumors and hit multiple times in 39% of tumors. Additionally,
83.3% of GBMs were reported to have recurrent telomerase reverse
transcriptase (TERT) promoter mutations (C228T or C250T), and these
mutations are mutually exclusive with ATRX mutations.
Based on gene expression profiling, GBMs cluster into four groups:
classical (chromosome 7 amplification with chromosome 10 loss, deletion
of CDKN2A), mesenchymal (NF1 focal deletions or mutations), proneural
(IDH1 mutant or PDGFRA amplification), and neural (EGFR amplification
with a neural expression signature). These classifications have a utility for
predicting response to therapy; for example, the classical subtype
responds to more intensive therapy whereas the proneural subtype shows
no benefit to this regimen. Another prognostic indicator is the CpG island
methylator phenotype (G-CIMP) demonstrated in IDH1 mutant proneural
tumors, which had a significantly better survival (median of 150 weeks)
compared to proneural G-CIMPnegative patients (median survival of 42
weeks) or other GBM subtypes (median survival 54 weeks). Also clinically
useful to predict response to therapy is O-6-methylguanine-DNA
methyltransferase (MGMT) promoter methylation status, because tumors
with silenced MGMT are unable to remove the alkyl groups deposited on
the O6 position of guanine by alkylating agents such as temozolomide.
Anaplastic (grade III) gliomas, including anaplastic astrocytomas,
anaplastic oligoastrocytomas, and anaplastic oligodendrogliomas, are not
as well characterized genomically as GBMs. Clinically, they can arise
without a prior history of low-grade glioma (presumed de novo) or through
progression from low-grade gliomas (secondary anaplastic glioma). Grade
III gliomas have a high risk of progression to GBM, although the rate of
progression and prognosis varies by histology, with anaplastic
astrocytomas having a 5-year overall survival of 26.5% and anaplastic
oligodendroglioma having a 5-year overall survival of 50.7%. IDH1
mutations have been observed in 75% to 90% of grade III gliomas.
Anaplastic astrocytomas, accounting for 1.7% of primary brain tumors,
commonly have mutations in ATRX, IDH1, and loss of p53 as well as
alterations to the Rb pathway (including RB1 loss, CDKN2A deletion, and
CDK4/6 amplification). It is believed that additional hits in the
RTK/Ras/PI3K pathway, including LOH at chr10q, lead to progression to
frank glioblastoma. Anaplastic oligodendrogliomas are rare (0.5% of
primary brain tumors), and the progression from grade II
oligodendrogliomas (characterized by chr1p/19q loss and IDH1-CIC/FUBP1
mutations) is likely mediated by additional deletion of CDKN2A and PTEN.
Like GBMs, recurrent TERT promoter mutations (C288T or C250T) have
been identified in anaplastic gliomas, reported in 14.8% of anaplastic
astrocytomas, 26.7% of anaplastic oligoastrocytomas, and 88.4% of
anaplastic oligodendrogliomas. The differences in TERT promoter
mutations between the subtypes is probably due to the higher frequency
of ATRX mutations in anaplastic astrocytomas, because TERT promoter
mutations are mutually exclusive with ATRX mutations in GBMs and other
tumors.

Cerebral Glioma
Pathologic Classification
The histologic subtypes of gliomas include tumors of astrocytic,
oligodendroglial, ependymal, and neuroepithelial origin (Table 97.2).
Based on the WHO classification, noninfiltrative gliomas are classified as
grade I, and infiltrating gliomas are subsequently categorized from grades
II to IV. Infiltrative astrocytic tumors are divided into three categories:
astrocytoma (including grade II fibrillary, gemistocytic, and protoplasmic),
anaplastic astrocytoma (grade III), and glioblastoma (including grade IV
giant cell glioblastoma and gliosarcoma). Oligodendrogliomas and
ependymomas are either grade II or anaplastic (grade III).

WHO Grade I: Astrocytoma

Low-grade astrocytomas (WHO grade I) such as pilocytic
astrocytoma, pleomorphic xanthoastrocytoma, and subependymal giant
cell astrocytoma are typically circumscribed and indolent tumors.
Missense mutations of the V600E type in the v-RAF murine sarcoma viral
oncogene homolog B1 (BRAF) gene were identified in these noninfiltrative
neoplasms. The highest frequencies were found in pleomorphic
xanthoastrocytomas (66%; 65% in its anaplastic variant), gangliogliomas
(18%), and pilocytic astrocytomas (9%, especially in tumors with
extracerebellar location).
Complete surgical resection, whenever feasible, is the curative
mainstay therapy for such tumors. Despite aggressive near total
resection, delayed recurrence and eventual malignant transformation are,
unfortunately, common. The resection of a low-grade glioma can be
difficult in locations such as the optic pathway, hypothalamus, and in
those involving deep midline structures. In these instances, asymptomatic
patients can be observed carefully for a prolonged period of time and
undergo a maximally safe resection only at the time of progression.
In patients who have a recurrent tumor that are not amenable to
further resection or who have a residual tumor causing significant
morbidity, adjuvant chemotherapy or radiotherapy can improve
recurrence-free survival, although the role of chemotherapy in adults
remains controversial. Immediate postoperative adjuvant therapies may
be appropriate in some cases depending on the location of the tumor, the
extent of residual disease, the impracticability of repeated surgical
excision, and the availability for follow-up. Generally, radiotherapy is the
primary adjuvant treatment used in older children and adults with low-
grade gliomas. In young children with unresectable, progressive low-grade
gliomas, there is a desire to avoid or delay radiotherapy owing to the long-
term radiation-related sequelae; chemotherapy is often utilized here as
the initial therapeutic option. Some responses from chemotherapy can last
for years, and nearly half of all children treated with chemotherapy
ultimately require radiotherapy for tumor progression.
In terms of radiotherapy used with a curative intent, in children, the
most common situation is with cerebellar and optic-pathway pilocytic
astrocytoma, typically after progression on chemotherapy, whereas in
adults, this tends to occur most commonly with hypothalamic pilocytic
astrocytoma. The typical radiation dose used in this setting is 50.4 to 54.0
Gy, in 1.8 Gy fractions. There is evidence of improved PFS in this situation.
Given the young age and long expected survival of these patients, proton
beam therapy is often considered for these patients, with the desire to
decrease the risk of a second neoplasm, and to treat less normal brain
tissue with radiation.
Subependymal giant cell astrocytomas can be effectively treated
with everolimus. In a prospective randomized study, 35% of patients in
the everolimus group had at least a 50% reduction in the volume of their
tumor versus none in the placebo group, although complete responses
still remain uncommon, even with this therapy.

WHO Grade II: Low-Grade Glioma

Nonpilocytic or diffusely infiltrating low-grade gliomas are classified
as WHO grade II tumors. They may arise from astrocytic, oligodendrocytic,
or mixed lineage. Like astrocytomas, oligodendrogliomas display various
degrees of clinical aggressiveness. Three common genetic alterations,
inactivation of the TP53 tumor suppressor gene, heterozygous point
mutations of the isocitrate dehydrogenase-1 (IDH1), and loss of
chromosome 22q are involved in the formation of WHO grade II
astrocytoma. TP53, located on chromosome 17p, encodes the p53 protein
that has an important role in a number of cellular processes, including cell
cycle arrest, apoptosis, and response to DNA damage.
Somatic mutations at codon 132 in IDH1 are present in 50% to 80%
of WHO grade II and III astrocytic tumors and oligodendroglial tumors, as
well as in secondary grade IV glioblastomas. These IDH mutations
promote the conversion of -ketoglutarate into D-2-hydroxyglutarate, an
oncometabolite that mediates the oncogenic activity of IDH mutations and
can be measured by magnetic spectroscopy. Tumors that have IDH
mutations carry a better prognosis than do IDH wild-type gliomas of the
same histologic grade.
An unbalanced t(1;19)(q10;p10) translocation results in a combined
loss of chromosomal arms 1p and 19q, which leads to the loss of one
hybrid chromosome, and thus, a loss of heterozygosity.
This cytogenetic alteration is usually associated with
oligodendroglial histology and is rarely found in other tumors. Patients
with 1p- and 19q-codeleted tumors have a better prognosis than do
histologically similar tumors of the same grade that do not harbor this
codeletion. In addition to histology and molecular characteristics, several
variables have been found to be of prognostic importance in low- grade
gliomas. Pignatti et al. performed the most comprehensive of these
analyses and developed a scoring system to identify patients at varying
level of risk for mortality. A multivariate analysis showed that age 40 years
or older, astrocytoma histology, maximum diameter 6 cm or greater,
tumor crossing the midline, and presence of neurologic deficits negatively
impacted survival.
Patients with up to two factors were considered low risk (median
survival, 7.7 years) and patients with three or more were considered high
risk (median survival, 3.2 years). Recently, 339 European Organisation for
Research and Treatment of Cancer (EORTC) patients with central-
pathology confirmed LGGs were used to develop a new prognostic model
for PFS and overall survival (OS).
Data from 450 patients with centrally diagnosed LGGs recruited into
two large studies conducted by North American cooperative groups were
used to validate the models. Both PFS and OS were negatively influenced
by the presence of baseline neurologic deficits, a shorter time since first
symptoms, an astrocytic tumor type, and tumors larger than 5 cm in
diameter.

Surgery for Low-Grade Glioma

Retrospective analyses have suggested that the extent of resection
is a significant prognostic variable. The Radiation Therapy Oncology Group
(RTOG) performed a prospective evaluation of the natural history of
completely resected low-grade gliomas (RTOG- 9802), evaluating the
recurrence risk in 111 patients with surgeon-defined gross total resections
(GTR) and found that the extent of postoperative residual disease was an
important variable for time to first relapse. Five-year recurrence rates
were 26% versus 68% for patients with less than 1-cm residual tumors
versus 1- to 2-cm residual tumors.

Radiation Therapy
The role of radiotherapyparticularly the timingremains
somewhat controversial. Early intervention is indicated for patients with
increasing symptoms and radiographic progression. In younger patients
(less than 40 years) who have undergone complete resection, observation
with imaging is an option. In RTOG-9802, median time to progression in
111 good-risk patients defined as younger than 40 years and with a gross
total tumor resection was 5 years. In those who have undergone a
subtotal resection or those with high-risk features, postoperative
radiotherapy may be recommended, typically 50.4 Gy in 1.8 Gy fractions.
Three phase III trials provide the best evidence with respect to the
indications for radiotherapy as well as the dose. In a study by the EORTC
(EORTC-22845), 314 patients were randomized to postoperative
radiotherapy to 54 Gy (n = 157) or radiotherapy at progression (n = 157).
A statistically significant improvement in PFS was associated with early
radiotherapy, 5.3 versus 3.4 years (p <0.0001), without a difference in
median survival, 7.4 versus 7.2 years. Two other trials investigated the
dose question. In EORTC-22844, 379 patients were randomized to 45 Gy
versus 59.4 Gy.
With a median follow-up of 74 months, OS (58% versus 59%) and
PFS (47% versus 50%) were similar. In an Intergroup study, 203 patients
were randomized to 50.4 Gy (n = 101) or 64.8 Gy.
There was no significant difference in PFS or OS. To assess the OS
and cause-specific survival (CSS) impact of early adjuvant radiotherapy
(EART) following the resection of supratentorial LGG in adults (16 to 65
years), 2,021 patients in the SEER database from 1988 to 2007 were
evaluated. Of the 2,021 patients, 871 (43%) received EART, and 1,150
(57%) did not. In the multivariate Cox proportional hazards model, EART
was associated with worse OS and CSS. Using a propensity score and
instrumental variable analyses to account for known and unknown
prognostic factors demonstrated unmeasured confounding variables that
may affect this finding.
Consequently, low-dose radiotherapy, 50.4 to 54.0 Gy in 1.8 Gy
fractions, has become an accepted practice for selected patients with low-
grade gliomas. The target volume is local, with a margin of 2 cm beyond
changes demonstrated on traditional MRI sequences. FLAIR images
usually show considerable abnormality beyond any enhancing or
nonenhancing tumor and whether a smaller margin may be used for
planning if FLAIR sequences are utilized is unknown.
Posttreatment cognition remains an important consideration. Brown
et al. reviewed the results of the Mini-Mental Status Examination for 203
adults irradiated for low-grade gliomas. Most patients maintained stable
neurocognitive status after radiotherapy, and patients with abnormal
baseline results were more likely to have improvement in cognitive
abilities than to deteriorate after therapy; few patients showed cognitive
decline. A more in-depth analysis of formal neurocognitive testing suggest
that the tumor itself may have the most deleterious effect on cognitive
function.
Recognition has been gaining that long-term neurocognitive
functional (NCF) impairment following radiotherapy for benign or low-
grade adult brain tumors could be associated with hippocampal dose. A
dose to 40% of the bilateral hippocampi greater than 7.3 Gy was recently
shown to be associated with long-term impairment in list-learning delayed
recall. Based on such data, the role of proton therapy as a potential
approach to reduce cognitive deficits and other side effects is being
explored.

Chemotherapy
Low-grade gliomas have historically been considered chemotherapy
resistant. With the recent demonstration of the chemotherapy
responsiveness of some low-grade astrocytomas and oligodendrogliomas
has renewed interest in investigating chemotherapy for lowgrade gliomas.
It has been demonstrated that some low-grade gliomas, especially optic
pathway and hypothalamic tumors, can be responsive to chemotherapy. In
children, various single and multichemotherapeutic and biological agents
are effective at controlling the growth of a low-grade glioma in a setting of
a newly progressive lesion,
multiply recurrent, or unresectable residual tumors.102105,129,130
Platinum-containing regimens result in radiographic response rates
greater than 60%.129 Vinblastine has also demonstrated substantial
activity in recurrent low-grade gliomas and is a commonly used
second-line agent after treatment failure with vincristine and carboplatin.
131,132 Other second- and third-line therapies for multiply recurrent
tumors include thioguanine, procarbazine, lomustine, and
vincristine (TPCV) and temozolomide. Irinotecan and bevacizumab
are currently being investigated in a multi-institutional phase II trial

for the treatment of progressive low-grade gliomas. Rapamycin, an

oral immunosuppressive agent, has been effective at reducing the
growth of astrocytomas associated with tuberous sclerosis.133 Most of
the chemotherapy responses seen in children with low-grade gliomas
are for contrast-enhancing masses that probably represent pilocytic
astrocytomas. Some of these responses can last for years, although
nearly half of all children treated with chemotherapy ultimately
require radiotherapy. Nonenhancing, diffusely infiltrating astrocytomas
in children appear to be much less responsive to chemotherapy.
Data on the use of chemotherapy for low-grade glioma in adults
are sparse. In a small Southwest Oncology Group trial, adults with
incompletely excised low-grade gliomas were randomly assigned to
radiation therapy (RT) alone or RT and lomustine ([2-chloroethyl]-
3-cyclohexyl]-1-nitrosourea [CCNU]). There was no difference in
survival between the two arms.134 The role of adjuvant procarbazine,
CCNU, and vincristine (PCV) for high-risk patients (e.g., less than
total resection, age older than 40 years) with low-grade gliomas was
evaluated in RTOG-9802. From 1998 to 2002, 251 patients were
randomly assigned to RT alone or RT followed by six cycles of PCV.
An initial report of this study showed that the 5-year OS rates for RT
versus RT/PCV were 7.5 years versus not reached respectively (hazard
ratio [HR] = 0.72, 95% confidence interval [CI], 0.47 to 1.10;
p = 0.33).135 At the time of that report, however, 65% of the patients
were still alive. A recent National Institute of Health press release
on more mature results of this study reported significant improvement
in OS in the PCV chemotherapy plus RT group (13.3 years)
compared to those assigned to RT alone (7.8 years) at a median follow-
up of 12 years.136 Molecular and cytogenetic analyses (isocitrate
dehydrogenase mutations and loss of heterozygosity of 1p and 19q,
as well as methylation of methylguanine methyltransferase status)
and clinical outcome are pending to identify predictive factors for
patients with LGG.
Several studies have evaluated PCV in the recurrent setting,
and, more recently, temozolomide has also been evaluated
(Tables
97.3 and 97.4).126,127,137146 In general, approximately half
of the patients treated with either temozolomide or PCV experienced
imaging stability or improvement of neurologic symptoms.
Although results are encouraging, the number of patients treated
in these studies was small, and there are questions regarding the
criteria used for radiographic response. In the first report of RTOG
0424, the primary endpoint was to compare the 3-year OS of a
regimen of concurrent and adjuvant temozolomide and RT in a
high-risk low-grade glioma population to the 3-year OS rate of the
high-risk EORTC LGG patients reported by Pignatti et al.116 With
a median follow-up time of 4.1 years and a minimum follow-up
of 3 years, MST has not yet been reached. The 3-year OS rate
was 73.1% (95% CI, 65.3 to 80.8%), significantly improved in
comparison to the prespecified historical control with a p value
<0.0001.147 An ongoing intergroup phase III trial is attempting to
answer this issue more definitively.
Patients with low-grade oligodendroglial tumors with 1p/19q
deletion or t(1p;19q) have longer PFS and OS than those
without.
114 Consequently, 1p/19q determination is important in

patient counseling
and in assessing the results of outcomes in
future
clinical trials. A randomized phase III EORTC trial stratified
patients with low-grade glioma by 1p status prior to randomization
to RT versus temozolomide.148 In the initial results of the
trial presented, PFS was not significantly different, and median OS
was not reached. 1p deletion was a positive prognostic factor irrespective
of treatment (PFS: 0.0003; HR = 0.59; 95% CI, 0.45
to 0.78); OS: 0.002; HR = 0.49; 95% CI, 0.32 to 0.77). First-line
treatment with temozolomide compared to radiotherapy did not
improve PFS in high-risk LGG patients. A molecular and genetic
analysis of LGG has revealed aberrant signaling in the
phosphatidylinositol-
3-kinase (PI3K)/AKT/mammalian target of rapamycin
(mTOR) network; however, a defined role for the inhibition of this
pathway in the treatment of LGG remains to be established.149,150
Targeting this pathway is a therapeutic approach that is being
investigated
in clinical trials in recurrent LGG patients.

Glioma is a type of tumor that occurs in the brain and spinal cord. Gliomas begin in the gluey
supportive cells (glial cells) that surround nerve cells and help them function.

Three types of glial cells can produce tumors. Gliomas are classified according to the type of
glial cell involved in the tumor.

Types of glioma include:

Astrocytomas, including astrocytoma, anaplastic astrocytoma and glioblastoma

Ependymomas, including anaplastic ependymoma, myxopapillary ependymoma and

subependymoma

Oligodendrogliomas, including oligodendroglioma, anaplastic oligodendroglioma

and anaplastic oligoastrocytoma

Gliomas can affect your brain function and be life-threatening depending on their location
and rate of growth.

Gliomas are one of the most common types of primary brain tumors.

The type of glioma you have helps determine your treatment and your prognosis. In general,
glioma treatment options include surgery, radiation therapy, chemotherapy, targeted therapy
and experimental clinical trials.

Grade I: Astrocytoma Pilocytic

Biasanya terjadi pada anak-anak di bagian serebelum atau batang otak, dan kadang-
kadang di hemisfer otak. Tumor ini dapat terjadi pada orang dewasa, tetapi jarang. Grade I
tumor ini tumbuh lambat dan relatif jinak.
Pilihan terapinya termasuk:
- Observasi: untuk tumor kecil dan tumor yang terletak di daerah yang tidak bisa
dilakukan operasi (batang otak) dapat hanya diobservasi dan mungkin tidak akan
pernah tumbuh.
 - Pembedahan: terapi pilihan dalam banyak kasus, pengangkatan tumor lengkap dapat
menjadi kuratif.
- Radiasi: dilakukan untuk tumor yang tidak dapat diangkat dengan operasi, tumor sisa
setelah operasi, atau tumor berulang.

Grade II: Low-grade glioma

Mencakup astrocytoma, oligodendroglioma, dan oligoastrocytma campuran. Glioma
grade II biasanya terjadi pada orang dewasa muda (usia 20-an hingga 50-an) dan yang paling
sering ditemukan di hemisfer otak. Karena sifat infiltratif tumor ini, dapat terjadi
kekambuhan. Beberapa glioma grade II dapat kambuh dan berkembang menjadi tumor yang
lebih agresif (grade III atau IV).
Pilihan terapinya termasuk:
- Observasi: untuk tumor yang terletak di daerah yang tidak dapat untuk operasi atau
berisiko tinggi untuk menyebabkan hilangnya fungsi setelah operasi. Beberapa tumor
mungkin tidak pernah tumbuh, tetapi yang lainnya akan membesar atau berubah
menjadi high-grade tumor yang harus dilakukan pengobatan.
- Pembedahan: terapi pilihan jika tumor dapat diangkat tanpa menyebabkan hilangnya
fungsi. Pengangkatan tumor lengkap dapat menjadi kuratif.
- Radiasi: dapat dilakukan baik setelah operasi untuk memperlambat pertumbuhan
tumor sisa atau dalam kasus di mana bila operasi bukan merupakan pilihan.
- Kemoterapi: tidak sering digunakan kecuali untuk kasus berulang atau beberapa
tumor yang berisiko tinggi.

Grade III: Glioma Maligna

Meliputi astrositoma anaplastik, oligodendroglioma anaplastik, dan oligoastrocytoma
campuran anaplastik. Tumor grade III tumbuh lebih cepat dan
lebih agresif daripada astrocytoma grade II. Tumor ini menyerang jaringan otak terdekat
dengan proyeksi seperti tentakel, yang membuat operasi pengangkatan lengkap menjadi lebih
sulit. Pasien sering datang dengan kejang, defisit neurologis, sakit kepala, atau perubahan
status mental.
Pilihan terapinya termasuk:
- Observasi: biasanya tidak menjadi pilihan karena pertumbuhannya ganas dan cepat.
- Pembedahan: pengangkatan tumor maksimal dianjurkan jika tumor dapat diangkat
tanpa menyebabkan hilangnya fungsi.
- Radiasi: dianjurkan setelah operasi dengan beberapa fraksi selama ~6 minggu.
- Kemoterapi: dilakukan setelah radiasi selama 6-12 bulan; dengan temozolomide
(Temodar).

Clinical trials due to the aggressive nature of malignant gliomas, new

investigative
treatments are being developed and tested. These may include new
chemotherapy drugs,
immunotherapy, vaccines, or combinations. Please check our available
clinical trials.
Recurrence is common for most patients, and typically occurs at the site
of the initial tumor,
usually within 2 cm. Treatment of recurrences can include additional
surgery, radiation,
chemotherapy or combinations.
Grade IV Glioblastoma multiforme (GBM): is a malignant glioma.
GBM is the most aggressive and most common primary brain tumor.
Glioblastoma multiforme usually spreads quickly and invades other parts
of the brain, with tentaclelike projections, making complete surgical
removal more difficult. It is common for GBMs to recur after initial
treatment. Treatment options include:
Observation not typically an option due to malignant and rapid growth.
Surgery maximal removal of the tumor is recommended if tumor can
be removed without
causing loss of function. Radiation seeds may be implanted at the time of
surgery.
Radiation recommended after surgery with multiple fractions over ~6
weeks.
Chemotherapy given during and after radiation for 6-12 months;
temozolomide
(Temodar).
Clinical trials due to the aggressive nature of GBM tumors, new
investigative treatments are being developed and tested. These may
include new chemotherapy drugs, immunotherapy, vaccines, or
combinations. Please check our
available clinical trials.
Recurrence is common, and typically occurs at
the site of the initial tumor, usually within 2 cm.
Treatment of recurrences can include additional
surgery, radiation, chemotherapy or
combinations.