RADIATION THERAPY5. Understand broad treatment strategies in the treatment of tumors

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

National Cancer Institute. www.cancer.gov

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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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 single-

and 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 Therapy1. External radiation therapy– 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:• Intraoperative radiation therapy (IORT)

– 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)

– 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 Therapy2. Internal radiation therapy (also called brachytherapy) – 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 • 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 fibrosisproblems

with normal expansion during a later pregnancy.

CHEMOTHERAPY5. Understand broad treatment strategies in the treatment of tumors

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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ChemotherapyAdjuvant 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• 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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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

ANTI-CANCER AGENTS

Combination Chemotherapy• 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.

• 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

• 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:

• 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 American Cancer Society, Inc.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