Brief description about brain tumors

1. OVERVIEW
OF BRAIN
TUMORS
BY
DR. AYUSH GARG

2. ANATOMY

4. EPIDEMIOLOGY
It is the 20th most common malignancy worldwide and 14th most common in India according to
GLOBOCAN 2020 data.
 whites  males (except meningiomas and schwannomas) .
High mortality upto 75%
Dramatic improvement in children and young adult, mortality  by 50% between 1975 to 2010
Tumors that have a propensity for CSF spread include
◦ Medulloblastomas
◦ Germ cell tumors
◦ CNS lymphoma

5. Neuro Oncol, Volume 22, Issue Supplement_1, October 2020, Pages iv1–iv96, https://doi.org/10.1093/neuonc/noaa200
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Distribution of All Primary Brain and Other CNS Tumors
(Malignant and Non-Malignant Combined)
Site Histology
CBTRUS 2020
Glioblastoma
14.5%
Pituitary
16.9%
Nerve sheath
tumor 8.6%
Meningioma 38.3%

6. Neuro Oncol, Volume 22, Issue Supplement_1, October 2020, Pages iv1–iv96, https://doi.org/10.1093/neuonc/noaa200
The content of this slide may be subject to copyright: please see the slide notes for details.
CBTRUS 2020
Distributionof All Primary Brain and Other CNS Gliomas
Site Histology
Out of all
gliomas
GBM: 57.7%

7. Neuro Oncol, Volume 22, Issue Supplement_1, October 2020, Pages iv1–iv96, https://doi.org/10.1093/neuonc/noaa200
The content of this slide may be subject to copyright: please see the slide notes for details.
CBTRUS 2020
Age adjusted incidence rates of Brain and Other CNS
Tumors

8. ETIOLOGY
Occupational & Environmental factors
 Prior exposure to ionizing and non-ionizing radiation (2.3% incidence of
primary brain tumors in children treated with PCI for acute leukemia, a
22 fold increase expected)
 Farmers and petrochemical workers
 Chemical exposures (formaldehyde, vinyl chloride, acrylonitrile, etc.)
 Cellular telephones ?????
Hereditary Syndromes
 Cowden,Turcot, Lynch & Li-Fraumeni (Gliomas)
 Gorlin(PNET), neurofibromatosis type I&II (meningiomas, optic nerve
glioma, shwannoma)
 VHL (haemangioblastoma)

9. Neuroepithelial Tumors :
Glial cell origin: Astrocytoma, Oligodendroglioma, Ependymoma, Choroid plexus
Neuronal and mixed neuro–glial origin: Gangliocytoma, Neurocytoma, Papillary
glioneuronal tumor, Rosette-forming glioneural tumor of the fourth ventricle
Embryonal Tumors : Medulloblastoma, PNET
Classification of Adult Brain
Tumors

10. Tumors of specialized anatomic structures:
 Pituitary Adenoma
 Craniopharyngioma
 Pineocytoma
 Chordoma
 Haemangiopericytoma
 Germ Cell Tumors
 Choroid Plexus Tumors
Classification of Adult Brain
Tumors

11.  Tumors of meninges (meningoepithilial cells, mesenchymal)
 Tumors of haematopoitic system
 Lymphoma
 Plasmacytoma
 Metastatic
Classification of Adult Brain
Tumors

12. WHO grade I = low proliferative potential, a frequently discrete nature,
and the possibility of cure following surgical resection alone.
WHO grade II = generally infiltrating and low in mitotic activity but recur
more frequently than grade I malignant tumors after local therapy. Some
tumor types tend to progress to higher grades of malignancy.
WHO grade III = anaplastic histology & infiltrative, usually treated with
aggressive adjuvant therapy.
WHO grade IV = mitotically active, necrosis-prone , micro-vascular
proliferation & generally associated with a rapid pre & post-operative
progression & fatal outcomes, usually treated with aggressive adjuvant
therapy.
Grading of Adult Brain Tumors

13. PATHOLOGY
Primary intracranial tumors are of ecto- and mesodermal origin and arise from the brain, cranial nerves,
meninges, pituitary, pineal, and vascular elements.
In 2016, the WHO revised its classification system for pathologic subtypes of CNS tumors to combine
histology with molecular parameters such as:
 IDH1 mutation
 1p19q codeletion for gliomas
 H3 K27M mutation
 RELA fusion for ependymoma
 WNT and SHH activation for medulloblastoma

14. But in 2021…..

15. Gliomas, glioneuronal tumors, and neuronal tumors
1) Adult-type diffuse gliomas
 Astrocytoma, IDH-mutant
 Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted
 Glioblastoma, IDH-wildtype
2) Pediatric-type diffuse low-grade gliomas
3) Pediatric-type diffuse high-grade gliomas
4) Circumscribed astrocytic gliomas
5) Glioneuronal and neuronal tumors
6) Ependymal tumors

16. Two major changes:
 Roman numerals have been changed to Arabic numerals (I → 1, II → 2, III →
3, IV → 4)
 Grading within tumor types
(1) to provide more flexibility in using grade relative to the tumor type
(2) to emphasize biological similarities within tumor types rather than
approximate clinical behavior
(3) to conform with WHO grading in non-CNS tumor types.

17. Increased
intracranial
pressure
Seizures
Physiological
deficits specific
to location
Neurocognitive
deficits
Endocrinal
dysfunction
CLINICAL PRESENTATION

18. SITE WISE CLINICAL PRESENTATION
Tumors Symptoms
GBM /
Astrocytoma
Headache, seizure, unilateral weakness, mental changes
Meningioma Localized Headache
Cerebral Headache, seizure, unilateral weakness, mental changes
Cerebellar Occipital Headache
Brainstem or
thalamus
Nausea, vomiting, ataxia

19. CLINICAL PRESENTATION
Tumors Symptoms
Optic nerve Ocular changes
Medulloblastoma Morning headaches, nausea, vomiting
Ependymoma Morning headaches, nausea, vomiting
Neurilemoma,
schwannoma,
Neurinomas
Unilateral deafness, vertigo
Craniopharyngioma Headache, mental changes, hemiplegia, seizure, vomiting, visual
impairment
CLINICAL PRESENTATION

20. DIAGNOSTIC WORK UP
 Complete history and physical examination
 Magnetic Resonance Imaging
 CT Scan
 Newer Imaging Modalities
 FDG PET-CT is approved in USA, FLT and F-DOPA are being evaluated
 Cerebrospinal Fluid Examination
 Medulloblastoma, ependymoma, choroid plexus carcinoma, lymphoma, and some
embryonal pineal and suprasellar region tumors have high likelihood of spreading to CSF.
 Biopsy (craniotomy / stereotactic)
 IHC & Cyto-genetics

21. T1WI T2WI
FLAIR
Cerebrospinal fluid Dark Bright Dark
Fat Bright Dark Bright
Solid mass (tumor) Dark Bright Bright
Edema Dark Bright Bright
Cyst Dark Bright Dark
MRI

22. High-grade glioma — High-grade gliomas are typically hypointense masses on T1-
weighted images that enhance heterogeneously following contrast infusion

23. Low-grade glioma — Low-grade gliomas in adults generally appear as T2/FLAIR
hyperintense, expansile lesions involving both cortex and underlying white matter
matter

24. Meningioma — On MRI, a typical meningioma is an
extra-axial, dural-based mass that is isointense or
hypointense to gray matter on T1 and isointense or
hyperintense on T2-weighted images

25. Brain metastases — Brain metastases typically appear as rounded, well-
circumscribed masses that enhance after administration of contrast

26. Biopsy
When biopsy is not indicated
 Known active systemic cancer and multiple lesions that are radiographically
consistent with brain metastases
 Brainstem glioma
 Optic nerve meningioma
 HIV positive patients with CT or MRI findings consistent with primary CNS
lymphoma (PCNSL)
 Positive Epstein-Barr virus PCR in the CSF
 Patients with secretory germ cell tumors

27. Common Adult Tumors Frequent Gene and Chromosomal Alterations
Astrocytoma, IDH-mutant IDH1, IDH2, ATRX, TP53, CDKN2A/B
Oligodendroglioma, IDH-mutant, and
1p/19q-codeleted
IDH1, IDH2, 1p/19q, TERT promoter, CIC, FUBP1, NOTCH1
Glioblastoma, IDH-wildtype IDH-wildtype, TERT promoter, chromosomes 7/10, EGFR
Medulloblastoma, WNT-activated CTNNB1, APC
Medulloblastoma, SHH-activated TP53, PTCH1, SUFU, SMO, MYCN, GLI2 (methylome)
Meningioma NF2, AKT1, TRAF7, SMO, PIK3CA; KLF4, SMARCE1,
BAP1 in subtypes; H3K27me3; TERT promoter, CDKN2A/B
in CNS WHO grade 3
IHC & CYTOGENETICS

28. IDH 1/2 Mutation 1p/19q Co-deletion MGMT promoter
methylation
Diffuse astro (GRII) 70%-80% 15% 40%-50%
Oligod/astro (GRII) 70%-80% 30%-60% 60%-80%
Astro(GR III) 50%-70% 15% 50%
Oligod/astro (GR III) 50%-80% 50%-80% 70%
GBM (GR IV) 5% - 10% <5% 35%
Diagnostic role DD glioma vs.gliosis
Typical for transformed
LGG
Pathognomonic for
oligodendroglioma
None
Prognostic role Protracted natural history
in IDH-mutated tumors
Protracted natural history
in 1p/19q codeleted
tumours
Prognostic for AG (+/-
with IDH mutations)
treated with RT / CT
Predictive role Absence of mutation
suggests predictive role
for MGMT promoter
methylation
Prolongation of survival
with early chemotherapy
in 1p/19-co-deleted OD
Predictive in GBM for benefit
from alkalating CT Elderly
GBM: MGMT-methyl = TMZ
MGMT – unmethyl=RT

29. MANAGEMENT
Medical management
•Increased intracranial
pressure
•Seizures
•Venous thromboembolic
disease
Surgery Radiation
Therapy
Chemotherapy
and targeted
agents

30. GENERAL MANAGEMENT
Cerebral Edema
Glucocorticoids are used to control neurologic signs and symptoms
Dexamethasone 2-4mg twice daily
Seizures
Anticonvulsants, such as levetiracetam, lacosamide, lamotrigine, and
pregabalin are preferred
Prophylactic anticonvulsant use (in patients who have never experienced a
seizure) remains controversial because there is lack of data.

31. SURGERY
Surgical Procedures
 Biopsy
 Total Resection
 Surgical Debulking
 CSF Diversion
 Re-resection

32. RADIATION THERAPY
Radiobiologic Considerations Underlying Tissue Injury
The process of radiation injury depends on
Technical factors: Dose, Volume, Fraction size, Specific target cell population,
Secondary mechanisms: blood vessel injury resulting in hypoxia, edema
Reactive gliosis
Host factors: Inherent Radiosensitivity of different organs within brain (Ex. Optic
chiasm, hypothalamus, Lacrimal gland, Lenses are sensitive to radiation than
others)

33. RADIATION THERAPY
Partial-brain irradiation, 3DCRT, IMRT, IGRT
Whole-brain radiotherapy (WBRT)
Cranio-spinal irradiation (CSI)
Stereotactic radiosurgery (SRS)
Fractionated stereotactic radiotherapy (FSRT)
Brachytherapy (less common)
Proton beam therapy (3DPT, IMPT)

34. CT SIMULATION ADVANTAGE : Coverage of meninges in
subfrontal region and sparing of lens in CSI.

35. CT SIMULATION
•Contouring of the cord and
overlying meninges that
extend laterally to the lateral
aspect of the spinal ganglia
results in a  field width than
one based on bony anatomy.
•The addition of shielding
further reduces the volume of
normal tissues included in the
treated volume.

38. Surgery :
Except deep seated lesions such as pontine glioma
Complete resection not achievable frequently
Radiotherapy :
RT immediately or after progression
EORTC TRIAL 22845 – 7.4 vs .7.2 yrs OS. but PFS 5.3 vs. 3.4
Conclusion in doubt
No difference in survival of dose escalation
Surveillance
General principle of treatment in
adult Low Grade Gliomas (LGG)

39. Risk factors for survival in Low Grade Gliomas
 Age (<40 vs, > 40 years old)
 Tumor largest diameter (<6 cm vs. > 6 cm)
 Tumor crossing midline (yes vs. no)
 HPE tumor type (oligodendroglioma or mixed vs. astrocytoma)
 Neurologic deficit present preoperatively (absent vs. present)
Survival
 Low risk (0-2) 7.8 (6.8 - 8.9) yrs.
 High risk (3-5) 3.7 (2.9 - 4.7) yrs.
General principle of treatment in
adult Low Grade Gliomas (LGG)

40. General principle of treatment in
adult High Grade Gliomas (HGG)

41. General principle of treatment in
adult High Grade Gliomas (HGG)

42. General principle of treatment in
adult High Grade Gliomas (HGG)

43. BRACHYTHERAPY
Selection criteria:
 Tumor confined to one hemisphere
 No transcallosal or subependymal spread
 Small size (<5 to 6 cm)
 Well circumscribed on CT or MRI
 Accessible location for the implant.

44. Procedure:
 A balloon based system, GliaSite, placed into the cavity at the time of surgery
 Balloon is filled with organically bound iodine-125 (125I)
 Treatment is completed within 3 to 7 days
 Direct infusion of radioimmunoglobulins has been used in primary and
recurrent brain gliomas

45. CHEMOTHERAPY AND
TARGETED AGENTS
CNS tumors are resistant to most chemotherapeutic agents as they are unable to
cross BBB.
Alkylating agents such as BCNU (carmustine) and CCNU (lomustine) cross the
BBB, but prolonged use causes myelotoxicity and pulmonary fibrosis
Procarbazine has similar efficacy but is better tolerated
Temozolomide (TMZ), has excellent bioavailability and is the only agent to
demonstrate a survival benefit for glioblastoma and anaplastic astrocytoma

46. Radiation therapy with immediate chemotherapy (PCV) prolongs survival in patients
with anaplastic oligodendroglioma and high-risk low-grade gliomas.
Implantation of slow-release chemotherapy wafers into a tumor resection cavity or
convection-enhanced drug (CED) delivery have been used to bypass BBB.
VEGF pathway inhibitor bevacizumab is the only targeted agent approved for GBM
Two large randomized trials of bevacizumab for the treatment of newly diagnosed GBM
improved PFS but failed to improve OS

47. Vaccines under development:
 Rindopepimut (EGFRvIII-targeted peptide vaccine)
 DC Vax (autologous tumor lysate-pulsed dendritic cell vaccine)
 ICT-107 (dendritic cells prepared from autologous mononuclear cells that are
pulsed with six synthetic peptides)
 HSPPC-96 (autologous tumor-derived heat shock protein [glycoprotein 96])

48. TOXICITY
General symptoms:
 Fatigue
 Headache
 Drowsiness
 Dermatitis
 Alopecia
 Nausea and vomiting (raised ICP, posterior fossa or brainstem irradiation)
 Otitis externa (if ear in the field)

49. Acute Toxicity
Transient worsening of pretreatment deficits may develop during the course of
radiotherapy, and further acute toxicities may manifest up to 6 weeks following
completion of irradiation.
These symptoms are consequence of a transient peritumoral edema and usually
respond to a short-term increase of corticosteroids

50. Sub Acute Toxicity
Toxicity that develops during the 6-week to 6-month period following irradiation is
is attributed to changes in capillary permeability as well as transient demyelination
demyelination due to damage to oligodendroglial cells.
Symptoms include: headache, somnolence and fatigability

51. Late Toxicity
Late sequelae of radiotherapy appear from 6 months to many years following
treatment and are usually irreversible and progressive
They are thought to be due to white matter damage from vascular injury,
demyelination, and necrosis
The most serious late reaction to radiotherapy is radiation necrosis, which has a
peak incidence at 3 years

52. FOLLOW UP
Periodic MRIs are used to detect tumor recurrence/ treatment response
Assessment of cognitive functioning and quality of life
Monitoring of for neuroendocrine and ophthalmologic side effects

53. Type Location Clinical F Survival RT CT
A Supratent slow growing 5 yr MS Res At recc.
AA Supratent Rapid growing 2.5 yr MS Yes Yes
GBM Supratent  Malignant 1 yr MS Yes Yes
OG Supratent  Seizures 5 yr MS Yes Yes
MN convexity  Women Long term Yes Rare
clival (Gr II& III, res Gr I)
LYMP Multifocal  CSF/ ocular 3-5 Yr MS Yes Yes
periventricular Diss.
A=Astrocytoma (adult>child), AA=Anaplastic astrocytoma, GBM=Glioblastoma (elderly), OG=Oligodendroglioma (any
age), MN= Meningioma, Res= residual, Recc= recurrence

54. Type Location Clinical F Survival RT CT
BSG Pons Fatal 1 Yr MS Yes Seldom
PA Cerebellum Cure with TR 80% 10 yr Res Yes
hypothalamus
EPDM 4th ventricle Cure with TR 70% 5 yr Yes# Seldom
cauda equina can diss. in CSF
MDBM Cerebellum likely to 70% - 80% Yes Yes
diss. in CSF
GERM Pineal & Sensitive to CT 80% 5Yr Yes Yes
suprasellar & RT
BSG=brain stem glioma,PA=Pilocytic astrocytoma (child>adult), EPDM=Ependymoma (child, adult), MDBM=
medulloblastoma (child>adult), GERM = Germinoma, #= Gr II & III, Res

55. SUMMARY
 Metastases from a systemic cancer are the most common brain tumors in
adults
 Among primary brain tumors, meningiomas and gliomas together account for
more than two-thirds of all adult primary brain tumors
 Pignatti scoring, RPA and GPA used for prognosis grading
 MRI with contrast is the optimal study for evaluation of brain tumors
 Histopathology is gold standard for final diagnosis until or unless eloquent
area

56. SUMMARY
 Molecular markers important aspect of diagnosis
 Glucocorticoids are used to decrease peritumoral edema and elevated ICP
 Conformal radiotherapy better spares OAR as compared to conventional
techniques
 Hippocampal avoidance may improve neurocognitive function

57. Your best quote that reflects your
approach… “It’s one small step for
man, one giant leap for mankind.”
- NEIL ARMSTRONG