Neuro-Oncology I Flashcards
1
Q
are malignant tumors in the brain more likely primary or metastases?
A
Metastases
2
Q
Most common primary sites for metastatic spread to the brain
A
lung, breast, melanoma, colon, renal carcinoma
3
Q
Where are most metastatic lesions located?
A
within the cerebrum
4
Q
Most Prevalent brain tumor types in adults
A
- Meningiomas (most common)
- Gliomas (highest mortality rate)
5
Q
WHO Tumor Classification
A
I: benign, slow growing, associated with long term survival
II: Relatively slow growing, cells look abnormal under microscope, can come back as higher grades
III: Malignant, spreads into nearby normal parts of the brain
IV: Malignant, spreads into nearby normal parts of the brain
6
Q
What are gliomas?
A
Morphologically and biologically heterogeneous group of primary CNS
tumors
7
Q
What do gliomas arise from?
A
Arise from precursors of astrocytes or oligodendrocytes –> astrocytomas and oligodendroglioma
Some tumors present with mixed features that include both histologies
8
Q
Is surgical cure of glioma possible?
A
not usually
9
Q
WHO Grade I Glioma
A
Pilocytic astrocytoma
10
Q
WHO Grade II Glioma
A
- low grade astrocytoma
- low grade oligodendroglioma
- low grade oligo-astrocytoma
11
Q
WHO Grade III
A
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Anaplastic oligo-astrocytoma
12
Q
WHO Grade IV
A
Glioblastoma
13
Q
Low grade or diffuse astrocytoma (Grade II)
A
Uncommon, tend to be very slow growing
Found in cerebrum
Tumor progression is highly variable
Surgical resection (plus radiation if incomplete resection)
14
Q
Anaplastic Astrocytoma (Grade III)
A
Malignant tumor, typically located in the cerebral hemisphere
Presents with seizure, symptoms of increased intracranial pressure, focal
neurological dysfunction
Surgical resection followed by radiation and chemotherapy
15
Q
Glioblastoma - Grade IV
A
Most common primary malignant brain tumor; tumor
cells are undifferentiated
Prognosis is poor
Tumor tends to be localized to the cerebral hemispheres
Classic “butterfly” appearance on imaging
Presents with symptoms of increased intracranial pressure and focal neurological dysfunction
Surgical resection to relieve mass effect, radiation and
chemotherapy
16
Q
Oligodendroglioma (Grade II or III)
A
- Primary tumors tend to arise in the frontal lobe or white
matter –> tend to infiltrate the cortex making surgical cure difficult - On imaging, these tumors are not distinguishable from
astrocytomas - Slow growing –> prolonged period of symptoms prior to
diagnosis - Low grade = resectable if in an accessible region of the
brain; if not resectable, controversy over best treatment
17
Q
What occurs to oligodendrogliomas over time?
A
low grade tumors transform into anaplastic tumors = death in most patients
18
Q
What is a meningioma?
A
Intracranial tumors that arise from meningothelial arachnoid cap cells of the meninges
19
Q
the majority of Meningiomas are….
A
benign, slow-growing tumors that compress brain tissue (rarely invade)
Surgical resection is difficult if they invade the sinuses and encase cerebral arteries
Can penetrate bone and present as a scalp mass
20
Q
Presentation of meningiomas
A
- Dependent on location
- Focal seizures, neurological deficits from brain and cranial nerve compression
21
Q
what is the gold standard for meningiomas?
A
surgery
- if unressectable, radiation is utilized
22
Q
Presenting signs and symptoms of Brain tumors
A
- Clinical signs and symptoms of primary brain tumors may be general or focal
- Initial symptoms are often focal –> generalized symptoms as the tumor
increases in size and spreads - General – due to increased intracranial pressure:
Headache: tension type (40-80%) or migraine (10%)
Epileptic seizures
23
Q
Frontal Lobe
A
Thought
Reasoning
Behavior
Memory
24
Q
Parietal Lobe
A
Sensory Perception
Spatial Relations
25
Occipital Lobe
Left: Speech, Motion, Sensation
Right: Abstract Concepts
26
Temporal Lobe
Behavior
Memory
Hearing and Vision Pathways
Emotion
27
Standard of care for diagnosing brain tumors
MRI of brain
28
What does an MRI of the brain tell us
- location, extent of involvement, effect of compression
- IV contrast: enhancement of areas that have had disruption of the blood-brain barrier
- Contrast: differentiate between actual primary mass and peritumoral edema
29
Limitations of MRI
difficulty distinguishing between necrotic tissue and recurrent tumor
30
When is CT used for diagnosis?
When patients have a contraindication to MRI
31
What does CT followed by MRI provide?
structural and anatomical characteristics of the intracranial tumors in question
32
what do MR spectroscopy and PET scans give?
further clues into the nature of intracranial tumors
33
What is used when identification of vascular supply is critical for management?
vascular imaging in the form of CT angiography/magnetic resonance angiography and venous modalities
34
Brain Tumor Diagnosis - Biopsy
Used in cases when diagnosis with imaging is inconclusive or needs to be confirmed
Intraoperative stereotactic
biopsy
Biopsy of intracranial lesions
through a burrhole based on the stereotactic coordinates; minimally invasive
Guided by CT or MRI
35
Management options of brain tumors
* Observation
* Surveillance
* Surgical resection
* Chemotherapy
* Radiation therapy
* Combination treatment
* Must address the tumor itself as well as the neurologic sequelae
36
2 aspects of the initial management of brain tumors
Steroids
Seizure Management
37
What do steroids do?
Minimize symptom burden due to associated vasogenic edema
Edema due to increase in extracellular fluid and plasma --> poorly formed capillaries feeding into the tumor
38
What is the steroid of choice
Dexamethasone
39
Complications/Side effects of Steroids?
Steroid-induced myopathy, anxiety, insomnia, psychosis, delirium, Cushing’s syndrome, steroid-induced hyperglycemia, fractures of the spine and hip, avascular necrosis of the hip
40
Seizure Management
Most common presenting symptoms in patients with brain tumors
Surgical resection of malignancy effectively controls the seizures
Administration of antiepileptic drugs --> standard of care in patients with intracranial malignancy
41
Who is surgical resection considered for?
patient who have significant disease burden and to minimize symptoms
42
Extent of safe tumor resection dependent on:
Tumor location
- Patient performance status
- Patient age
43
Benefits of maximal tumor resection include:
Relief of mass effect
Decreased tumor burden
Improved diagnosis
Possibility of prolonged survival
44
What is radiation therapy used as?
primary treatment or following surgical resection
45
External Beam radiation
- Most common for localized tumors
- Utilizes 3D imaging for radiation planning, allows for precise delivery
46
Gamma Knife Radiosurgery
Treats without an incision
Concentrated radiation dose – 201 beams of radiation
interact to treat a small area of tissue in the brain
Tends to spare the adjacent normal, healthy tissue
47
Radiation Side Effects: Acute Radiation Encephalopathy
◦ Onset: days to weeks after initiation of radiation
◦ Symptoms include: headache, nausea, lethargy, and new onset or worsening focal symptoms --> responds to increase in corticosteroids
48
Radiation Side Effects - Early Delayed Encephalopathy
Decline in status occurring 1 to 6 months after radiation
Produces a somnolence syndrome
Extreme lethargy in conjunction with signs of increased intracranial pressure
May respond to corticosteroids
49
Radiation therapy side effects - Late Delayed Encephalopathy
Occurs 6 months to a year after radiation, especially high doses
Presents as a focal necrosis and can be life threatening
50
Commonly used chemotherapy agents
- Temozolomide
- Bevacizumab
- Irinotecan
51
Temozolomide
Oral alkylating agent used for high grade gliomas and astrocytomas
52
Bevacizumab (Avastin)
- Monoclonal antibody that binds to VEGF
- Used for treatment of recurrent malignant gliomas and management of vasogenic edema
53
Irinotecan
Causes damage to the DNA - cells cannot reproduce or repair themselves
54
Spinal Tumors - Extradural Tumors
- refer to lesions outside the dura mater, in the vertebral bodies and arches
- Osseous structures
- Paravertebral region
- epidural space
55
what is the most common site of osseous metastases?
spinal column
56
Extradural lesions may be....
osteolytic, osteoblastic, or mixed
57
Extradural lesions can alter...
the normal bone architecture and can result in deformity or collapse of the affected vertebral body --> spinal cord compression
58
Clinical Manifestation of epidural spinal cord compression
* Pain: localized, mechanical,
radicular
* Motor weakness
* Sensory impairments
* Autonomic symptoms
* Gait and trunk ataxia
59
Intradural Extramedullary Tumors - Primary Tumors
- located within the dura mater but outside of the spinal cord parenchyma
Tumors arise from peripheral nerves, nerve sheaths and sympathetic ganglion
Most commonly benign
60
Extramedullary metasteses
Common complication of cancer
Most common site of involvement – dorsal aspect of
spinal cord at level of cauda equina
61
What can intradural extra medullary tumors lead to?
spinal cord compression and vascular compromise
62
Intradural Extramedullary Tumors – Spinal Cord Compression Clinical Manifestation
Present similarly to epidural spinal cord compression BUT with a higher incidence of neurologic symptoms
Pain = typically the initial symptom
Weakness
Motor deficits may manifest in the absence of pain
Sensory involvement
- Bowel, bladder and sexual dysfunction can be an early finding
63
Intradural Intramedullary Primary tumors
located within the spinal cord
parenchyma; arise form glial cells, neuronal cells and other connective tissue
Typically benign
Can be found anywhere in the spinal cord, cervical
and cervico-thoracic are more favored locations
64
Intramedullary spinal cord metastases
Diagnosed < 1% of patients with cancer
Usually occurs in the setting of extensive metastatic disease
Rarely the first manifestation of systemic malignancy
65
What do intramedullary lesions cause?
neurologic injury
through direct compression of the surrounding spinal cord and vascular compromise
66
Intradural Intramedullary Tumors – Spinal Cord Compression Clinical Manifestation
Similar to extradural tumors
Pain – most common symptom
Neurologic deficits = common
Sensory deficits
Bowel, bladder and sexual dysfunction
67
Spinal Tumor Diagnosis
- Physical exam (assessment of strength, sensation, reflexes and sphincter function)
- MRI, X Ray, CT
68
MRI for spinal tumor diagnosis
- Gold Standard
- Acurate anatomic assessment of the soft tissue structures
69
X Ray for spinal tumor diagnosis
Useful in screening for lytic or sclerotic lesions, pathologic fractures, spinal deformities and large masses
70
CT for spinal tumor diagnosis
Detailed imaging of the osseous anatomy of the spine and degree of tumor involvement
Suspected metastatic disease - imaging may also include chest, abdomen
and pelvis to establish the extent of disease or identify primary tumor
Provides excellent osseous delineation and can identify bony metastatic lesion 6 months earlier than plain films
71
Surgery is the mainstay of spinal tumor treatment as long as predicted lifespan is...
greater than 3 months
72
Surgical options for spinal tumor
– aimed at preventing or reducing spinal cord compression
Indirect decompression: reduce pressure on spinal cord/nerve roots by removing bone
Direct decompression: removing tumor
73
Indications for surgery
Paraplegia lasting more than 12-24 hours in patients with prior radiation to the
spine
Spinal instability
Boney compression of the spinal cord
74
Goals of surgery
Preserve neurologic function
Reduce pain
Ensure mechanical stability
75
What does Radiation of spinal tumors allow for?
pain relief, prevention of pathologic fracture,
stabilization of neurologic function
76
side effects of radiation on spinal tumors
Damage and fibrosis to the spinal cord itself, exiting roots and nerves and surrounding musculature
Clinical manifestation: myelopathy, radiculopathy, neuropathy,
plexopathy, myopathy
GI toxicity
Mucositis
Fatigue
77
3 subtypes of radiation myelopathy
- acute complete paralysis
- acute transient radiation myelopathy
- chronic progressive radiation myelopathy
78
Radiation myelopathy - Acute complete paralysis
Rare, related to radiation-induced vascular damage resulting in spinal cord
infarction
79
Radiation myelopathy - Acute transient radiation myelopathy
Most common form
Occurs 1 to 29 months after completion of radiation therapy
Due to demyelination of the dorsal columns
Clinical manifestation include: Lhermitte sign without neurologic changes on
examination
Lhermitte sign – shock-like sensation down the spine induced by cervical spine flexion
Treatment is reassurance as symptoms resolve over weeks to months
80
Radiation myelopathy - Chronic progressive radiation myelopathy
Most feared form
Occurs 9 to 15 months after radiation therapy
Characterized by a latent period during which patients are asymptomatic
Clinical manifestation:
Ascending weakness
- Diminished sensation and clumsiness
- Brown-Sequard pattern of deficits
- Tends to be a steady progression of neurologic deficits over the course of weeks to months
- No effective treatmen
81
Corticosteroids for Spinal Tumors
May be an initial part of treatment in spinal tumors
Reduce tumor and spinal cord vasogenic edema resulting in improvement/ stabilization of neurologic deficits
- Provide analgesia for pain
82
Bisphosphate for Spinal Tumors
Inhibit osteoclast activity and suppress bone reabsorption associated with spinal
metastases
Effective in reducing the risk of pathologic fractures, relieving pain, and reducing
malignancy-associated hypercalcemia
