Transcript Radiation therapy

5. Understand broad treatment strategies in the treatment of tumors
RADIATION THERAPY
Clinical Use of Radiation Therapy
• used to treat almost every type of solid tumor, including
cancers of the brain, breast, cervix, larynx, lung, pancreas,
prostate, skin, spine, stomach, uterus, or soft tissue
sarcomas.
• can also be used to treat leukemia and lymphoma (cancers
of the blood-forming cells and lymphatic system,
respectively).
• prophylactic radiation therapy
– to prevent cancer cells from growing in the area receiving the
radiation
• palliative radiation therapy
– to help reduce symptoms such as pain from cancer that has
spread to the bones or other parts of the body
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Goals of Therapy
• To cure or shrink early stage cancer
– Radiation may be used by itself in these cases to make the cancer
shrink or disappear completely.
– before surgery (pre-operative therapy) to shrink the tumor,
– after surgery to prevent the cancer from coming back (adjuvant
therapy).
– It may also be used along with chemotherapy
• To stop cancer from recurring (coming back) in another area
– That area may be treated to keep these cells from growing into tumors
– preventive (or prophylactic) radiation
• To treat symptoms caused by advanced cancer
– Radiation may help to relieve symptoms such as pain, trouble
swallowing or breathing, or bowel problems that can be caused by
advanced cancer. This is often referred to as palliative radiation.
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06/17/2009
Radiation Therapy
• also called radiotherapy, x-ray therapy, or irradiation
• It is the use of a certain type of energy (called ionizing
radiation) to kill cancer cells and shrink tumors.
• It injures or destroys cells in the area being treated (the
“target tissue”) by damaging their genetic material,
making it impossible for these cells to continue to grow
and divide.
• considered a local treatment because only cells in and
around the cancer are affected. It is not useful against
cancer that has already spread to distant parts of the
body, because most forms of radiation therapy do not
reach all parts of the body.
Physical basis of Radiation Therapy
• Radiation therapy is delivered primarily as high-energy
photons (gamma rays and x-rays) and charged particles
(electrons).
• Ionizing radiation can be sorted into 2 major types:
– photons (x-rays and gamma rays), which are most widely
used
• Gamma rays are released from the nucleus of a radioactive atom.
• X-rays are created electronically, such as with a clinical linear
accelerator.
– particle radiation (electrons, protons, neutrons, alpha
particles, and beta particles)
• Currently, high-energy radiation is delivered to tumors
primarily with linear accelerators.
Biologic Basis of Radiation Therapy
• Radiation deposition results in DNA damage manifested by singleand double-strand breaks in the sugar phosphate backbone of the
DNA molecule.
• The mechanism of DNA damage differs by the type of radiation
delivered.
• Electromagnetic radiation is indirectly ionizing through short-lived
hydroxyl radicals produced primarily by the ionization of cellular
hydrogen peroxide (H2O2).
• Protons and other heavy particles are directly ionizing and directly
damage DNA.
• Radiation damage is manifested primarily by the loss of cellular
reproductive integrity.
• Most cell types do not show signs of radiation damage until they
attempt to divide, so slowly proliferating tumors may persist for
months and appear viable.
• Some cell types, however, undergo apoptosis.
Types of Radiation Therapy
1. External radiation therapy
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radiation comes from a machine outside the body
usually is given on an outpatient basis
used to treat most types of cancer, including cancer of the
bladder, brain, breast, cervix, larynx, lung, prostate, and vagina
may be used to relieve pain or ease other problems when
cancer spreads to other parts of the body from the primary
site
Examples:
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Intraoperative radiation therapy (IORT)
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given during surgery
used to treat localized cancers that cannot be completely removed or that
have a high risk of recurring (coming back) in nearby tissues
Prophylactic cranial irradiation (PCI)
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given to the brain when the primary cancer (for example, small cell lung
cancer) has a high risk of spreading to the brain.
Types of Radiation Therapy
2. Internal radiation therapy (also called brachytherapy)
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uses radiation that is placed very close to or inside the
tumor.
– The radiation source is usually sealed in a small holder
called an implant.
– Internal radiation therapy may require a hospital stay.
– Forms:
• Interstitial radiation therapy
– inserted into tissue at or near the tumor site
– tumors of the head and neck, prostate, cervix, ovary, breast, and perianal
and pelvic regions.
• Intracavitary or intraluminal radiation therapy
– inserted into the body with an applicator
– used in the treatment of uterine cancer
Types of Radiation Therapy
3. Systemic radiation therapy
– uses radioactive materials such as iodine 131 and
strontium 89
– The materials may be taken by mouth or injected
into the body.
– sometimes used to treat cancer of the thyroid and
adult non-Hodgkin lymphoma.
Side Effects of Radiation Therapy
• Most common side effects:
– Tiredness
– skin reactions (such as a rash or redness, permanent
pigmentation, and scarring) in the treated area
– loss of appetite
• Radiation therapy can cause inflammation of tissues and
organs in and around the body site radiated.
• This can cause symptoms that depend on what organs are
affected and to what degree.
– inflame skin to cause a burn or permanent pigmentation
– irritate the colon and cause diarrhea
– decrease in the number of white blood cells and weaken the
body’s protection from infection
Side effects when certain areas are treated
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Brain
– memory loss, lower sexual desire, or poor tolerance for cold weather
– Nausea, unsteady walking, and changes in vision
– radiation necrosis
Lung
– decrease in the levels of a substance, called surfactant  shortness of breath or
cough.
– fibrosis (stiffening or scarring)  reduces the ability of the lungs to inflate and take in
air
Digestive tract
– swelling and inflammation in the esophagus (swallowing tube), stomach, or intestine
 pain, nausea, vomiting, or diarrhea
Reproductive/sex organs
– Fertility: Radiation to the testicles can cause permanent loss of sperm production.
– If both ovaries are exposed to radiation, early menopause and permanent infertility
can result.
– If the uterus (womb) is exposed, radiation can cause scarring and fibrosisproblems
with normal expansion during a later pregnancy.
5. Understand broad treatment strategies in the treatment of tumors
CHEMOTHERAPY
Clinical Use of Chemotherapy
• usually the primary modality of therapy in
patients with documented distant metastatic
disease
• goal of therapy : to decrease the tumor
burden, thus prolonging survival
Schwartz’s Principles of Surgery 8/e
Goals of Therapy
• Cure: If possible, chemotherapy is used to cure
the cancer, meaning that the tumor or cancer
disappears and does not return.
• Control: If cure is not possible, the goal may be to
control the disease - to shrink any tumors and to
stop the cancer from growing and spreading.
• Palliation: When the cancer is at an advanced
stage, chemotherapy drugs may be used to
relieve symptoms caused by the cancer. When
the only goal of treatment is to improve the
quality of life, it is called palliation.
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Chemotherapy
Adjuvant Chemotherapy
• Postoperative chemotherapy
• When drugs are used to kill
those unseen cancer cells after
surgery has been performed
• can also be given after using
radiation to kill the cancer
• eradication of micrometastatic
disease, with the intent of
decreasing relapse rates and
improving survival rates
Neoadjuvant Chemotherapy
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preoperative chemotherapy or
induction therapy
chemotherapy is given before the
main cancer treatment (such as
surgery or radiation)
can shrink a large tumor, making it
easier to remove with surgery or
may also allow it to be treated
more easily with radiation.
also kills small deposits of cancer
cells that cannot be seen on scans
or x-rays
ability to assess a cancer's response
to treatment clinically, after a
number of courses of
chemotherapy, and pathologically,
after surgical resection.
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06/17/2009
Schwartz’s Principles of Surgery 8/e
Principles of Chemotherapy
• It destroys cancer cells by first-order kinetics, meaning
that with the administration of a drug a constant
percentage of cells are killed, not a constant number of
cells.
• It differs from surgery or radiation in that it is almost
always used as a systemic treatment.
• Chemotherapeutic agents can be classified according
to the phase of the cell cycle they are effective in.
– Cell-cycle phase–nonspecific agents
• linear dose-response curve
– cell-cycle phase–specific drugs
• plateau
Schwartz’s Principles of Surgery 8/e
ANTI-CANCER AGENTS
Alkylating
Agents
• cell-cycle–nonspecific agents
• act by cross-linking the two strands of the DNA helix
or by other direct damage to the DNA  prevents
cell division  apoptosis
• classic alkylators, nitrosoureas, and miscellaneous
DNA-binding agents
• products of fermentation of microbial organisms
• cell-cycle nonspecific
Antitumor
Antibiotics • damage the cell by interfering with DNA or RNA
synthesis, although the exact mechanism of action
may differ by agent
ANTI-CANCER AGENTS
Anti-metabolites
Mitotic inhibitors
• cell-cycle–specific (S phase of the cell cycle &
little effect on cells in G0)
• most effective in tumors that have a high
growth fraction.
• structural analogues of naturally occurring
metabolites involved in DNA and RNA
synthesis
• interfere with normal synthesis of nucleic
acids by substituting for purines or
pyrimidines in the metabolic pathway to
inhibit critical enzymes in nucleic acid
synthesis
• include folate antagonists, purine
antagonists, and pyrimidine antagonists
• Mostly plant alkaloids
• periwinkle plant, Vinca rose (vincristine, a
vinca alkaloid)
• root of mandrake, Podophyllum peltatum
(e.g., etoposide, a podophyllotoxin).
• Vinca alkaloids affect the cell by binding to
tubulin in the S phaseblocks
microtubule polymerization impaired
mitotic spindle formation in the M phase.
• Taxanes such a paclitaxel, on the other
hand, cause excess polymerization and
stability of microtubules, blocking the cell
cycle in mitosis.
• epipodophyllotoxins act to inhibit a DNA
enzyme called topoisomerase II by
stabilizing the DNA–topoisomerase II
complex. This results in an inability to
synthesize DNA, thus the cell cycle is
stopped in G1 phase.
Combination Chemotherapy
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may provide greater efficacy than single-agent therapy by three mechanisms:
1. provides maximum cell kill within the range of toxicity for each drug that can be
tolerated by the host
2. offers a broader range of coverage of resistant cell lines in a heterogeneous
population,
3. it prevents or delays the emergence of drug-resistant cell lines.
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Drugs with different mechanisms of action are combined to allow for additive or
synergistic effects.
– Combining cell-cycle–specific and cell-cycle–nonspecific agents
– Drugs with differing dose-limiting toxic effects
– Drugs with different patterns of resistance
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Sometimes used not to cure but to reduce symptoms and prolong life.
can be useful for people with advanced cancers that are not suitable for radiation
therapy or surgical treatment
Factors to consider in choosing which drugs to
use for a chemotherapy regimen include:
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the type of cancer
the stage of the cancer (how far it has spread)
the patient's age
the patient's general state of health
other serious health problems (such as heart,
liver, or kidney diseases)
• other types of anti-cancer treatments given in
the past
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06/17/2009
Side effects of Chemotherapy
• Although chemotherapy is given to kill cancer
cells, it also can damage normal cells. The normal
cells most likely to be damaged are those that
divide rapidly:
– bone marrow/blood cells (bone marrow suppression,
leucopenia, anemia, thrombocytopenia)
– cells of hair follicles (hair loss)
– cells lining the digestive tract (nausea & vomiting,
diarrhea)
– cells lining the reproductive tract (fertility problems &
birth defects)
Other side effects
• Nausea and vomiting
• Appetite loss and weight
changes
• Taste changes
• Sores in mouth and or
throat
• Diarrhea
• Fatigue
• Constipation
• Heart damage
• Nervous system changes
• Changes in thinking and
memory
• Lung / liver/ kidney &
urinary system damage
• Reproduction and sexuality
• LONG TERM SIDE EFFECT
– Permanent organ damage
– Delayed development inc
children
– Nerve damage
– Another cancer