Biology 207 Biology of Cancer

Lecture 17 "Brain Cancers"Spring 2004

Reading: Lemonick, “The tumor war”TIME 150, 46-53

Web sites: American Brain Tumor Association:

Oncolink:

Lecture Outline

1. Statistics and Risk factors

2. Classification

3. Astrocytomas

4. Diagnosis

5. Treatment/Blood-Brain Barrier

Lecture:

1. A. Statistics:

In 1997, 18,000 new brain tumors diagnosed; 50% increase from 10 years ago
Account for only 1.4% of cancers in U.S.
Not a major cancer, however most deadly because they interfere with essential life functions
Do not metastasize to other parts of the body

B. Risk factors

Radiation exposure
Impaired immune systems, HIV, other cancers
Heredity
Head trauma NOT a risk factor

2. Classification

Primary brain tumors: those that start in the brain

Secondary brain tumors: due to metastasis of other cancers to the brain

Primary tumors are classed based on cell type of origin

Most common brain tumors:

Astrocytomas=gliomas
Arise from astrocytes, which are glial cells
These make up the blood-brain barrier and contribute to nutrition of the central nervous system
Glial cells do divide in adults; nerve cells do not divide in adult
Cancers of nerve cells only occur in children and are called Neuroblastomas

Secondary brain tumors:

Most commonly spread from breast and lung
Colon cancers and melanomas can also spread to the brain
Cells of secondary tumor resemble the cells of the organ where the tumor started, not brain cells

3. Astrocytomas

World Health Organization tumor grading system

Tumor grades 1 4

1= slowest growing

4= fastest growing

Grade 1

Astrocytic tumor cells usually normal looking
Observe cell proliferation
Produce epileptic seizures as their only symptom
Can become quite large and increased pressure inside skull can lead to headaches, paralysis, personality change, coma and death
Prognosis good
Radiation therapy not recommended

Grade 2

Tumor cells slightly abnormal in appearance as well as number
No mitotic (dividing) cells usually observed
No necrosis (dead tissue)
Usually biopsied, not removed
Radiation treatment usually recommended to shrink tumor

Grade 3

"Malignant astrocytomas"--Can spread to other regions of brain or spine but not to other parts of the body
Observe "contrast enhancement" on CT and MRI scans
Cells are abnormal in appearance
Show evidence of mitosis
Cells in the tumor invade brain tissue
Confirm diagnosis with surgery or stereotactic biopsy
Follow up with radiation or chemotherapy
Average survival 18 months without treatment

Grade 4

Called glioblastomas
Most malignant form
Made of cells that infiltrate brain tissue
Mitotic cells frequently observed
Regions of dead tissue seen especially where growth of tumor has outpaced blood supply
Tumors induce angiogenesis, however new blood vessels may be abnormal
Obvious mass seen on CT and MRI scans
Very poor prognosis: survival 17 weeks with no treatment, about 1 year with certain treatments
Prognosis depends on age and performance status

4. Diagnosis of brain tumors:

Signs and symptoms of brain tumors:

Depend on location in brain
Size of tumor

May include:

Paralysis/numbness
Mood swings
Seizures
Loss of balance
Impaired vision

Generally a tumor on one side causes symptoms and impairment on opposite side; exception is cerebellum

Tumor may place pressure on the brain or cause build-up of fluid, leading to headaches. Headaches are most common presenting symptom

Neurological exam: Office visit to specialist doctor (Neurologist) to assess reflexes and brain function.

Scans: CT and MRI

Inject a dye to make abnormal tissue more obvious
Dyes concentrate more in disease tissues due to leakiness of blood vessels in and around brain tumors
CT better for tumors showing calcification (calcium deposits due to erosion of bone)
MRI better for small tumors, tumors next to bone, brain stem tumors
Low grade and metastatic tumors

CT scan=Computerized tomography

X-ray device combined with a computer
Patient lays on a table that slides into an opening like a doughnut hole in the scanner
X-rays penetrate brain from many directions, thousands of thin cross sections are fed into a computer that constructs a picture

MRI scan=Magnetic resonance imaging

Tunnel shaped piece of equipment
Magnetic field surrounds the head
Radio frequency pulse introduced; does not involve X-rays
Magnetic field causes atoms in brain to change direction
Radio frequency pulse causes another change in direction
Pulse stops; during relaxation, atoms give off energy in different amounts and at different intervals
Antennas pick up signals and feed them into a computer that assembles an image

Follow-up may involve biopsy

Surgery to remove tumor
Stereotactic biopsy=remove small piece of tissue with thin needle

5. Treatment options

Survival depends on

Type of tumor
Location of tumor

Therapy for Astrocytomas:

Generally not curable
Surgery often done after MRI or CT scan
Radiation: External beam or internal implants
Chemotherapy: Options still in clinical trials
Experimental therapies: immunotherapies, gene therapies

Problems with chemotherapies and other experimental therapies:

Blood--brain barrier--Blood vessels in the brain are not leaky because of connections between endothelial cells lining the blood vessels.

Most drugs can't diffuse from blood to get to tumor.

New drugs make blood vessels leaky so they can take up drugs

Example: Bradykinin analog RMP-7.

Bradykinin is naturally occurring body peptide with hormone action.
Analog can make blood-brain barrier leaky as site of tumors but not in normal regions of brain.
Combine RMP-7 with chemotherapeutic drug to deliver to brain tumor

Other strategies involve delivery of drugs with liposomes (lipid coat around drug molecules); fats (lipids) can cross the blood-brain barrier

Other approaches try to recruit patient's own immune system to attack brain cancer="immunotherapy"