reference slideshare perez 7th edition

1. Presented by – Dr. Pushpendra Kumar Patel
3rd year Post Graduate student
Dept. of Radiation Oncology
Regional cancer centre raipur

2. INTRODUCTION-
• A wide variety of tumours affect the brain and spine.
• Primary benign and malignant tumours arise from the various elements of the
CNS, including neurons, glia and meninges. Tumours metastasize to the CNS from
many primary sources.
• Presentation varies widely depending on relevant neuroanatomy. Prognosis
depends on histology and anatomy.
• Modern brain tumour centers use team approaches to CNS tumours, as patient
may require a combination of surgery, radiation therapy, chemotherapy and
research protocol enrollment.

3. ANATOMY OF BRAIN-
• Nervous system may be divided into-
Central nervous system –
1. Brain
2. Spinal cord
Peripheral nervous system-
1. Peripheral nerves
2. Ganglia
• The brain consist of
1. The cerebrum comprising 2 large cerebral hemisphere
2. The cerebellum
3. Diencephalon
4. Brainstem
- Midbrain
- Pons
- Medulla

4. Covering layers & CSF-
Central nervous system enveloped by- Duramatter (Pachymeninges)
Arachnoid & Piamatter (combined called as
Leptomeninges)
within them, there is subarachnoid space filled with cerebrospinal fluid.
 CSF flows- Lateral ventricles
Foramen of monro
3rd ventricle
Aquiduct of sylvius (narrowest canal m.c. site of obstruction)
4th ventricle m.c location for tumor deposits
spinal canal
foramen of luschka & magendie venous circulation

5. Covering layers of the brain

6. THE CEREBRUM-
• The cerebrum made up of 2 cerebral hemisphere, partially separated from each
other by the median longitudinal fissure.
• The 2 hemisphere are connected to each other by corpus callosum.
• Each hemispere contains a cavity, called the lateral ventricle.
• Each cerebral hemisphere is divided into 4 lobes-
Frontal
Parietal
Occipital
Temporal

7. THE CEREBRUM-
Dural folds separate the two hemispheres of cerebrum (Falx cerebri) & the
cerebrum from the cerebellum & brainstem(Tentorium or Falx cerebelli)
Frontal & parietal lobes separated by sulcus – central sulcus
Frontal & temporal lobes are separated by – Sylvian fissure
Parietal & occipital lobes – calcarine sulcus

24. Diencephalon
Dienchephalon consist of thalamus & pineal region
situated between the cerebrum & mesencephalon.
Lateral to thalamus there is internal capsule that
carries motor fibers from cortex to brainstem – spinal
cord.
Partners with the cerebrum and cerebellum to
1. Coordinate motor functions
2. Play a role in consciousness
3. Control and integrate the autonomic nervous
system
4. Regulate eating and thirst
5. Control body temperature and circadian
rhythm.

25. Cerebellum
Functions-
1. Coordinates skeletal muscle contractions
2. Regulates balance and posture
3. May have a role in language processing and recognition

26. Brainstem
1. Midbrain-
contains tracks for nerve impulses between motor areas of the cerebral cortex to the
spinal cord. Some of the other functions that relay through the midbrain include
reflexes for the head, eyes and trunk response to visual stimuli, and impulses for
auditory stimuli (eg, the startle reflex)

27. Brainstem
2. Pons-
Serves as a bridge to connect areas of the brain to one another. The pons contains
areas that relay signals for voluntary movements, equilibrium information from the inner
ear, and areas that ( together with the medulla oblongata) help control breathing.

28. Brainstem
3. Medulla oblongata-
contains areas that control
key vital body functions:
• The cardiovascular center,
which regulates the rate
and force of the heartbeat
and the diameter of blood
vessels
• The respiratory center,
which adjust basic rhythm
of breathing.
• Reflexes for swallowing ,
sneezing, vomiting,
hiccupping, and coughing.

29. Arterial supply

30. Arterial supply

31. Dural venous sinus
• The cerebrum, cerebellum and
brainstem are drained by numerous
veins, which empty into the dural
venous sinuses.
• Dural venous sinuses lie between the
periosteal and meningeal layers of the
dura matter.
• All the dural venous sinuses ultimately
drain into the internal jugular vein.
• There are eleven venous sinuses in
total. The straight, superior, and inferior
sagittal sinuses are found in the falx
crebri of the dura matter.they converge
at the confluence of sinuses. The
straight sinus is a continuation of the
great cerebral and inferior saggital
sinus.

32. Dural venous sinus
• From ther confluence, the transverse
sinus continues bilaterally and curves
into sigmoid sinus to meet the
opening of the internal jugular vein.
• The cavernous sinus drains the
ophthalmic veins and can be found on
either side of the sella turcica. From
here, the blood returns to the internal
jugular vein via the superior or
inferior petrosal sinuses.

33. Tissue constituting nervous system
• The specialized cells that
constitute the nervous
system are called – neuron(
Neuron consist of cell body
gives off variable number of
processes – short branching
called dendrites and one
longer process axon.
• Neurons are supported by
special kind of connective
tissue called – neuroglia.

34. Neuroglial cells-
• Astrocytes
• Microglia
• Oligodendrocytes
Astrocytes:
These are star shaped cells present in all part
of the brain.concerned with nutrition and
blood brain barrier.
1. Fibrous astrocytes – present in white
matter
2. Protoplasmic astrocytes- present in grey
matter
Microglia:
These are the phagocytic cells which enters
the tissue of nervous system from blood.
Oligodendrocytes:
these are the cells forming myelin sheath
around the nerve fibres in central nervous
system.

35. Neuroglial cells-
Ependymal cells- columnar cells lining
the cavities of the CNS.
Schwann cells- mylinate the peripheral
system.
Satellite cells- cover the surface of
nerve cell bodies in sensory,
sympathetic and parasympathetic
ganglia.

36. Peripheral nervous system-
12 pairs of cranial nerve (brain stem)
31 pairs of spinal nerve (spinal cord)

37. Peripheral nervous system-

38. Peripheral nervous system-
Origin of cranial nerve in brain -

39. Functions of cranial nerve -

40. Base of skull with clinically important foramen and
fissure-
 The optic canals are
situated anteriorly in the
MCF.
 They transmit the optic
nerves (CN II) and
ophthalmic arteries into
orbital cavities.
 The superior orbital fissure
opens anteriorly into the
orbit. It transmits the CN
III, CN IV, ophthalmic
branch of the CN V1, CN
VI, ophthalmic veins and
sympathetic fibres.

41. Base of skull with clinically important foramen and
fissure-
 The foramen rotundum opens into
the pterygopalatine fossa and
transmits the maxillary branch of the
trigeminal nerve.
 The foamen ovale opens into the
infratemporal fossa, transmitting the
mandibular branche of trigeminal
nerve and accessory meningeal
artery.
 The foramen spinosum also opens
into the infratemporal fossa. It
transmits the middle meningeal
artery, middle meningeal vein and a
meningeal branch of trigeminal nerve
(CN V3)

42. Base of skull with clinically important foramen and
fissure-
 Hiatus for greater petrosal
nerve – transmit the greater
petrosal nerve(facial nerve)
 Hiatus lesser petrosal nerve –
transmit the lesser petrosal
nerve (glossopharyngeal
nerve)
 Carotid canal- located
posteriorly and medially to
the foramen ovale and it is
transversed by the internal
carotid artery.
 The formen lacerum,wehich
is pierced by small blood
vessels.

43. Base of skull with clinically important foramen and
fissure-
Ct images-

44. Base of skull with clinically important foramen and
fissure-
Ct images-

45. Intracranial tumours-
• Although either benign or malignant, almost all brain tumours are
malignant in the sense that they may lead eventually to death if not
treated.
• In general, the incidence of primary brain tumours is higher in whites
than in blacks, and mortality Is higher in males than in females.
• It is the 20th most common malignancy worldwide and 14th most
common in india according to GLOBOCAN 2020 data.
• High mortility upto 75%.

46. Intracranial tumours-
• Intracranial tumours can be classified in different ways: primary versus secondary,
pediatric versus adult, by a cell of origin, or by location in the nervous system.
• Classification of brain tumor ( according to cell of origin)
 Neuroepithelial tumor
• Glial cell origin: Astrocytoma, Oligodendroglioma, Ependymoma, Choroid plexus.
• Neuronal and mixed neuro-glial origin: Gangliocytoma, Neurocytoma, Papillary
gliomeuronal tumor, Rosette-forming glioneural tumor of the fourth ventricle.
• Embryonal tumors: Medulloblastoma, PNET.
 Meningioma tumour (meningothelial cells, mesenchymal)
 Tumors of hematopoietic system
• Lymphoma
• Plasmacytoma
 Metastatic

47. Tumors of specialized anatomic structures
• Pitutary adenoma
• Craniopharyngioma
• Pinealoblastoma
• Chordoma
• Haemangiopericytoma
• Germ cell tumors
• Choroid plexus tumors

48. 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
over expected)
• Farmers and petrochemical workers
• Chemical exposures (formaldehyde, vinyl chloride,acrylonitrile etc.)
• Cellular telephones- WHO classified radiofrequency electromagnetic fields those
emitted by wireless phones, as possibly carcinogens to humans based on limited
clinicians evidence. Increase incidence of glioma individual with greatest
cumulative lifetimes cell phone use (> 1620 hours in one study)
Hereditary syndromes
• Cowden, Turcot, Lynch & Li-Fraumeni (Gliomas)
• Gorlin(PNET), Neurofibromatosis type I & II (meningiomas, optiv nerve glioma,
schwannoma) & retinoblastoma.
• VHL (haemangioblastoma)

49. Natural history
Determined by location, grade & histology.
Majority of adult gliomas spread invasively with out forming natural capsule &
causes edema usually vasogenic but may be cytotoxic seen best on T2 weighted
images.
Edema is consequence of altered Blood-Brain-Barrier permeability.
Amount of edema is variable( in desending order- Mets, astrocytoma,
meningioma, oligodendroglioma.
High grade neoplasm metastasize by seeding the subarachnoid and ventricular
spaces. Because of gravity or flow.these metastatic deposits are often present in
the caudal portion of the spinal canal.
Tumors that have propensity for csf spread – medulloblastoma, germ cell tumors
& CNS lymphoma.
Extracranial mets from primary brain tumours are rare but can occure –
medulloblastoma, germonomas & high grade astrocytomas.

50. Grading of adult brain tumors
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 tumor
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, microvascular
proliferation & generally associated with a rapid pre
& post- operative progression & fatal outcomes,
usually treated with aggressive adjuvant therapy.

51. 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 parameter such as:
• IDH 1 mutation
• 1p19q codeletion
• H3 K27M mutation
• RELA fusion for ependymoma
WNT and SHH activation for medulloblastoma

56. Clinical presentation
Classified as generalised & focal-
1. Focal neurologic deficit- weakness ,laryngeal dysfunction etc.
2. Headache (classically morning headache) & sensory loss more
prevalent in fast growing high grade tumors.
3. Seizures – low grade tumors
4. Increased ICT – cushing triade(HTN, bradycardia & respiratory
irregularity). Long term raised ICT causes optic atrophy blindness.

57. Site wise clinical presentation

58. Site wise clinical presentation

59. Diagnostic work up
Complete history and physical examination
Solitery brain lesion with lung cancer, breast cancer, colon cancer or melanoma
can be metastatic.
Magnetic resonance imaging with gadolinium is IOC.
• T1 images – demonstrating anatomy & areas of contrast enhancement.
• T2 images & FLAIR(Fluid atenuated Inversion Recovery) – sensitive for detecting
edema & infiltrative tumor.
• Diffusion, perfusion & spectroscopic sequence- post treatment
pseudoprogression. Used to distinguish tumour from necrosis or
pseudoprogression.
Neuraxis imaging – for high risk of CSF spread. Post operative period- arachnoiditis
& blood products in the CSF can mimic leptomeningeal mets. So MRI should be
done after 3 weeks of surgery.

60. MRI
T1WI T2WI FLAIR
CSF DARK BRIGHT DARK
FAT BRIGHT DARK BRIGHT
SOLID MASS DARK BRIGHT BRIGHT
EDEMA DARK BRIGHT BRIGHT
CYST DARK BRIGHT DARK

61. MRI
High-grade glioma –high-grade gliomas are typically hypointense masses on
T1- weighted images that enhance heterogeneously following contrast infusion.

62. MRI
Low-grade glioma –low-grade gliomas in adult generally appear as T2/FLAIR
hyperintense, expansile lesion involving both cortex and underlying white
matter .

63. MRI
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.

64. MRI
Brain metastases – brain metastases typically appear as rounded, well-
circumscribed masses that enhance after administration of contrast.

65. Diagnostic work up
CT scan where MRI is contraindicated
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 high likelihood of
spreading to CSF.
• Done for staging in medulloblastoma, germ cell tumour & primary CNS
lymphoma. Done after 3 weeks of surgery.
• CSF spread findings- CSF pressure- >150 mm of H2O at the lumber level in
laterally positioned patient
Elevated protein level- >40 mg/dl
Reduced glucose level – below <50 mg/ml

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

68. IHC & Cytogenetics

69. IHC & Cytogenetics

70. Management

71. General management
Cerebral edema
 Glucocorticoid are used to control neurologic signs and symptoms
 Dexamethasone 2-4 mg twice daily. It is preferred due its minimal
mineralocorticoid activity. It should be tapered to prevent rebound cerebral
edema.(allows pituitary adrenal axis to recover)
Seizures
 Anticonvulsants, such as levetiracetum, lacosamide, lamotrigine, and
pregabalin are preferred. Carbamazepine, phenobarbital & phenytoin also
used.
 Prophylactic anticonvulsants use (In patients who have never experienced a
seizure) remains controversial because there is lack of data.
For raised ICT
Venous thromboembolic disease

72. Surgery
Surgical procedures
 Biopsy
 Total resection for cure
 Surgical debulking
 CSF diversion
 Re-resection
 Others- placement of chemothereupy, brachytherapy devices & catheters for
interstitial drug delivery.
 Note that some radio/chemosensitive such as PCNSL aggressive resection is
unnecessary.
 Operative technique-
• ultrasound, CT & MRI guidance system.
• Endoscopic flouroscent tumour localising by usisng 5 aminolevulenic acid.
• Sterotactic biopsy/Intra operative diagnosis
• LASER interstitial thermal therapy (LITT)

73. Surgery
Extent of surgery
 Gross total resection
>90% : Total or near total
51-90% : Subtotal resection
11-50% : Partial resection
<10% : Biopsy

74. 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 mechanism of expression of injury- vascular leak causing edema,
vascular epithelial loss- resulting hypoxia injury, resulting gliosis.
• Host factor- inherent radiosensitivity of different organs within brain(ex. Optic
chiasm, hypothalamus, lacrimal gland, lenses are sensitive to radiation than
others)

75. Radiation therapy
Radiobiologic considerations underlying tissue injury
 Functional perturbation- endothelial cells often becomes manifeste as early T2
signal abnormality on MRI – possibly due to disruption of Blood-Brain-Barrier
& edema formation.
 Metabolic perturbation- observed in PET CT may reflect oligodendroglioma
demylination.
 Vascular perturbation
 Late injury reported as tolerance dose at either 5% or 50% risk level at 5
yrs.(TD 5/5 or 50/5)
 For whole brain fractionated radiotherapy at 2Gy/fraction it is 60 & 70Gy.
 For partial brain radiation – 70 & 80Gy
 QUANTEC(quantitative analysis of normal tissue effect in the clinic)- estimated
5% & 10% rate of symptomatic necrosis at 72 & 90Gy (2Gy/fraction)

76. Radiation therapy
Klatzo specified two categories of cerebral edema – vasogenic and cytotoxic edema. The term
cellular edema refers to cytotoxic edema and is preferable to the latter; Fishman accepts these two
categories but adds a third, which he calls interstitial cerebral edema. Rarely is the separation into
distinct categories possible, there is often overlap between the various types of edema.
Vasogenic cerebral edema refers to the influx of fluid and solutes into the brain through an
incompetent blood-brain-barrier (BBB). This is the most common type of brain edema and results
from increased permeability of the capillary endothelial cells, the white matter is primarily affected.
Breakdown in the blood-brain barrier allows movement of proteins from the intravascular space
through the capillary wall into the extracellular space.
Cellular (cytotoxic) cerebral edema refers to a cellular swelling. It is seen in conditions like head
injury and hypoxia. It results from the swelling of brain cells, most likely due to the release of toxic
factors from neutrophils and/bacteria. Cytotoxic edema is caused by swelling of glia, neurons,
endothelial cells and begins within minutes after an insult. Cytotoxic edema affects predominantly
the gray matter.
Interstitial edema is seen in hydrocephalus when outflow of CSF is obstructed and
intraventricular pressure increases. The result is movement of sodium and water across the
ventricular wall into the paraventricular space. Interstitial cerebral edema occurring during
meningitis is due largely to obstruction of normal CSF pathways, with a resulting increase in the
resistance to CSF outflow.

77. Radiation therapy
 General concept- pertinent anatomic landmark:
External auditory meatus define anatomic reference points- reid base line &
Frankfort horizontal plane.
• Reid base line- drawn from the inferior margine of the orbit(orbitale point) to
the auricular point (center of the orifice of the external acoustic meatus) and
extending backward to the center of the occipital bone.
• Frankfort horizontal plane- plane determined the highest point on the upper
margine of the opening of each external auditory canal and the low point on
the lower margine of the orbit.

79. Radiation therapy
 General concept- pertinent anatomic landmark:
 Lateral radiograph- sella turcica is centrally located marks the lower border of
the medial telencephalon & diencephalon.
 Hypothalamic structure- 1cm superior to sellar floor & optic canal runs at
most 1 cm superior & 1 cm anterior to that point.
 Pineal body- (tentorial notch) 1cm posterior & 3 cm superior to ext.auditory
meatus.
 Cribriform plate- most inferior part of anterior cranial fossa.(inferior border of
WBRT fields)

80. Radiation therapy
 Treatment setup- head preferably fully flex /extended neck or use
noncoplanar fields & IMRT.
• Target volume definition – CTV expansion should not transverse anatomically.
Inclusion of bony skull is unnecessary unless direct tumour extension.

81. 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)

82. Radiation therapy
Partial brain irradiation- which includes treatment of the tumor or tumor
bed and surrounding margin, and some healthy brain tissue subject to
incidental irradiation.
Whole beain radiotherapy- in which the entire brain and brainstem are
irradiated. In case of brain mets also in PCNSL & component of CSI.
Parallel opposed lateral portals used. Inferior field border- inferior to
cribriform plate, the middle cranial fossa & foramen magnum.safty margine
1 cm taken.
Anterior border- 3 cm posterior to the ipsilateral eyelid to exclude
contralateral lense.

83. Radiation therapy
Cranio-spinal irradiation- Craniospinal Irradiation (CSI) is a technique used
in radiation therapy to deliver a prescribed amount of radiaion to the entire cranial-
spinal axis used in treatment of medulloblastoma and other brain tumors, which
tend to spread via Cerebrospinal Fluid (CSF). Generally in CSI for
medulloblastoma of two laterally opposed cranial fields, are matched to a posterior
spine field with the potential for dose in homogeneity at the junctions. Hence,
elder children and adults frequently require two posterior spine fields which lead
to additional junctions and planning complexity.treatment fields include the brain
to thecal sac.
Stereotactic radiosurgery (SRS)- very precise form of therapeutic
radiation that can be used to treat abnormalities in the brain and spine,
including cancer, epilepsy, trigeminal neuralgia and arteriovenous
malformations.
Fractionated stereotactic radiotherapy- process in which the total dose
of stereotactic radiation is divided into several smaller doses of radiation,
on separate days of treatment.

84. Radiation therapy
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
Procedure :
 A ballon based system, gliasite, placed into the cavity at the time of surgery
 Ballon is filled with organically bound iodine-125.
 Treatment is completed within 3 to 7 days.
 Direct infusion of radioimmunoglobulins has been used in primary and
recurrent brain gliomas.

85. Chemotherapy and targeted agents
CNS tumors are resistent to most chemotheraoeutic 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
Temozolamide (TMZ), has excellent bioavailability and is the only agent to
demonstrate a survival benefit for glioblastoma and anaplastic astrocytoma.
Radiation therapy with immediate chemotherapy (PCV) prolongs survival in
patients with anaplastic oligodendroglioma and high-risk low-grade gliomas.
Implantation of slow-release chemotherapy waters into a tumor resection cavity
or convection-enhanced drug (CED) delivery have been used to bypass BBB.
VEGF pathway inhibitor bevacizumab is the only targated agent approved for
GBM.
Two large randomized trials of bevacizumab for the treatment of newely
diagmosed GBM improved PFS but failed to improve OS.

86. 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)

87. Acute toxicity
Transient worsening of pretreatment deficits may develop during the course of
radiotherapy, and further acute toxicities may manifiest up to 6 weeks following
completion of irradiation.
These symptoms are consequence of a transient peritumoral edema and usually
respond to a short increase of corticosteroids.
Sub acute toxicity
Toxicity that develops during the 6-week to 6-month period following irradiation
is attributed to changes in capillary permeability as well as transient
demyelination due to damage to oligodendroglial cells.
Symptom include : headache, somnolence and fatigability

88. Late toxicity
Late sequele 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.

89. 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.