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| Radiation Therapy and Radiation Damage written and compiled by doctordee May 2001 |
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| NCI publications |
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These give important information in simple, clear language. Your Tax Dollars at Work. http://www.cancer.gov/cancer_information/ |
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| About Choosing Radiation |
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Radiation causes damage, short and long term, and has risks of other complications. So why choose it? Mainly because Cancer kills people. Radiation can kill cancer cells. Given a choice, most people would probably prefer to be alive, with damage that they could live with, or face years later. And radiation does not only save lives from cancer, it can lengthen survival time, decrease pain, and prevent amputations. For Leiomyosarcomas, surgery is almost always the best therapeutic choice, as well as the chance for cure. But in situations where the tumor is inoperable, radiation can be used to shrink it, so the tumor can be surgically removed. For brain tumors, focused radiation as in the 'gamma knife' or proton beam offers a chance of tumor control, or even of killing the tumor completely. In certain selected instances, radiation might be used against other metastases as well. In some situations, when a primary or recurrent tumor is removed, use of radiation might increase the time to next recurrence. When surgical resection does not leave clear margins, radiation therapy might kill the cancer cells left behind. But radiation has its longterm consequences, as well as the short term ones. The tissues that are exposed to radiation are usually not just the cancer. All of the organs around the tumor and in the path of the radiation can be damaged by radiation aimed at the tumor. Some of the longterm consequences can be very serious. It is one of the purposes of this web page to help people understand some of the problems that could develop. This treatment modality can be effective, but is not without risk. And awareness of possible long term complications of radiation may make it easier for cancer survivors to notice the complications sooner, with possibly better outcomes and less suffering. Furthermore, the use of protectants [like amifostine], or radiation sensitizers could, perhaps, ameliorate some of the effects on normal tissue and intensity the effects on the cancerous tissue. The type of radiation will also make a difference to the amount of damage done to surrounding normal tissue, and other risks as well. If it is at all possible, proton beam radiation is the treatment of choice for treating tumors or clearing up dirty margins. Proton beam radiation can be calibrated to "drop" most of its energy in the target area. While the normal tissues on the way in are exposed, proton beam radiation is sparing of skin, and does not penetrate the tissue beyond the target. There are currently three proton beam facilities that treat metastatic disease, Loma Linda in California, the University of Indiana, and Massachusetts General Hospital in Boston. They may decide not to take someone with extensive disease. In which case, IMRT, stereotactic radiosurgery, or the gamma knife, are all relatively concentrated Xray beams that try to spare normal tissue. There is also the possibility of using radioisotopes directly into excised tumor beds, or as Sirspheres, into the capillaries that feed the tumor. High energy neutrons have also been successful at dealing with large LMS tumors. It is worth discussing the different types, and perhaps making the effort to go to another facility, rather than just accept whatever is available at the hospital where you are being treated. |
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| Why This Web Page Was Constructed |
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Because I received the following letter: "When my wife received radiation, pelvic and a vaginal implant, we asked about side effects. We were told possible fatigue and diarrhea. That was it. No one mentioned the long term effects or the impact it would have on future surgeries for a disease that relies on surgery for control." "For my wife these side effects were radiation proctitis, an atrophied vagina, a bladder fistula after surgery. After her last surgery a colostomy was required because of a radiation-damaged colon. I have found that many list members were in the same boat. They enter treatment with little understanding of the long term impact of radiation." AND this letter: "She is still in hospital as recovery is very slow due to the fact that the tumor was in the area of radiation. The radiation therapy was to prevent or significantly reduce the likelihood of a met in that area: I think that there is a real question about the efficacy of radiation. Looking back we wish that my wife did not agree to have it done. Not only was the surgery very difficult [to remove a recurrence in the irradiated area] but the recovery will be slow and difficult, especially in respect of the invasion of the bladder." AND I also received this letter: "There has been very little on the list about IORT*. Not that many hospitals have it. Duke has been doing it for only about 1 year. Most of the papers refer to retroperitoneal sarcomas and conclude that it provides benefit for local control. My wife received it at my request during her last pelvic surgery a couple months when we knew clear margins would not be possible and the recurrence was exactly in the same place. The obvious benefit was that all organs could be moved aside. Still with that and the other radiation, 7 years of CT scans, bone scans, etc., I will be surprised if she does not develop leukemia if she makes it another 5 years. Bottom line, however, is that this should be investigated as a possible better alternative to external beam." *IORT is Intra Operative Radio Therapy. Ultimate Risks of Radiotherapy? Only long-term follow-up can determine the ultimate risks of radiotherapy. One study followed 221 consecutively treated patients for 8 to 42 years after post mastectomy radiation. Complications requiring in-hospital treatment were observed in 24 of 221 patients (11%). There were four sarcomas of the treated chest wall, three squamous carcinomas (two in the esophagus), two angiosarcomas of the swollen arm, nine chronic ulcers, five respiratory insufficiencies, six pathologic fractures of the radiated shoulder or ribs, two fatal cardiomyopathies, one persisting leucopoenia with fatal brain abscess, and one severe neurovascular impairment of the arm. In a comparable group of 394 consecutive post mastectomy patients who were not irradiated, one similar event, a myxosarcoma of an unswollen arm, was observed. Fetch PMID: 6498728 Go to References for this Section |
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| Types of Radiation |
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The absorption of energy from radiation in tissue often leads to ionization. Ionization involves actual ejection of one or more electrons from the atom. Ionizing radiation is electromagnetic (photon, includes gamma rays and Xrays) or particulate radiation (like electrons or protons). X-rays are produced artificially and mechanically while gamma rays are produced by nuclear disintegration [decay of radioactive isotopes.] [Harrison's Principles of Internal Medicine, 14th Edition, page 2559.] Xrays and gamma rays can be thought of as beams of photons [packets of energy] traveling in straight lines. The photons have no weight or charge, and the amount of energy in each determines whether the radiation is ionizing or non-ionizing. Both Xray and gamma ray beams lose their strength [attenuate] continuously and steadily as they pass through tissue [from reacting with the tissue.] Attenuation of the rays indicates use of the energy to create free radicals and other damage in the tissue. Radiation particles include electrons [beta particles], protons, neutrons, and helium nuclei [alpha particles]. Electrons are small, negatively charged, and can be accelerated. They penetrate tissue to a limited depth, and can be used to treat problems near to the surface. Protons are positively charged, and are about 2000 times heavier than electrons, and can be accelerated to increase their energy. Protons tend to stop abruptly when traversing tissue. In their sudden stops, most of their energy is abruptly given up, so there is a compact, enhanced region of ionization. This is called a Bragg Peak. Neutrons are the same weight as protons, but are not charged. Helium nuclei consist of two protons and two neutrons. Their mass and charge are so heavy that unless accelerated to very high energies, they do not penetrate very far into tissue. Other RadioIsotopes are also used to deliver ionizing radiation. Radioisotopes are unstable atoms, whose nuclei decompose, releasing gamma rays and/or electrons, protons, neutrons, or helium nuclei. What is released depends upon the particular radioisotope. Radioisotopes can be placed in suitable containers and left in place either temporarily or permanently, or administered by mouth or intravenously to reach tissues that will preferentially take them up or injected straight into tumors, or placed in beads or resins and injected into liver arteries that feed tumors. Go to References for this Section |
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| How Radiation Works |
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"Radiation must generally produce double-stranded breaks in DNA to kill a cell, owing partly to the high capacity of mammalian cells for repairing single-strand damage. Radiation can also produce effects indirectly by interacting with water (which makes up approximately 80 percent of a cell's volume) to generate free radicals, which can damage the cell. Free radicals are highly reactive chemical entities that lack a stable number of outer-shell electrons. A free radical is not stable and has a life span of a fraction of a second. It is estimated that most x-ray--induced cell damage is due to the formation of hydroxyl radicals..." [Harrison's Principles of Internal Medicine, 14th Edition, page 2560.] What makes a tumor radiosensitive? "It is known that radiation therapy can be successfully used to cure or control some types of human tumors, while consistently failing in others. This has been ascribed to several factors including differences in the intrinsic sensitivity of the tumor cells and in their ability to recover from radiation damage. In this study, human tumor cells from an osteogenic sarcoma, a glioblastoma, and two medulloblastomas, as well as cells from human skin, were established in tissue culture, and ...survival ... determined. No significant differences in ... survival ... could be detected among these human tumors or skin cells, despite the wide variability in their radiocurability. In addition, skin cell strains derived from patients exhibiting markedly sensitive or resistant skin reactions during fractionated radiotherapy showed no differences in survival characteristics from normal controls. It is therefore suggested that the wide range of radiocurabilities seen among various human tumors cannot be explained on the basis of inherent cellular factors responsible for the survival of tumor cells after x-irradiation." J Nucl Med 1998 Sep;39(9):1551-4 Fetch PMID: 1069484 Tumor damage depends upon amount of hypoxic cells [which are radioresistant], radiation dose, doses of chemotherapy and/or other radiosensitizer given, ambient temperature, timing of drug dose and radiation exposures. The effectiveness of oxygenating the hypoxic cells to make them radiosensitive depends upon how densely the tissue is vascularized, hemoglobin concentrations and affinities for oxygen, and levels of carbon dioxide breathed in [causes blood vessels to dilate and deliver more blood to tissues], as well as use of hyperbaric [high pressure] oxygen treatment. Go to References for this Section |
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| Treatment Choices |
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Radiation Treatment is either given externally or internally, and it involves use of either beams or radioisotopes to deliver gamma rays [high energy Xrays], or protons, or neutrons, or electrons, or alpha particles to the tumor. The idea is to get a high dose of radiation to the tumor while the surrounding normal tissue is protected from radiation damage. External Radiation involves beams of either high-energy rays, or neutrons, or electrons or protons. External radiation therapy does not cause your body to become radioactive. |
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Internal radiation therapy allows a higher total dose of radiation in a shorter time than is possible with external treatment and places the radiation source as close as possible to the cancer cells. The radioactive material, sealed in a thin wire, catheter, or tube (implant), is placed directly into the affected tissue. This method of treatment concentrates the radiation on the cancer cells and lessens radiation damage to some of the normal tissue near the cancer. Implants may be removed after a short time, or left in place permanently. The type of implant and the method of placing it depend upon the size and location of the tumor. |
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Go to References for this Section |
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| Prevention of Unwanted Radiation Damage |
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In some post-irradiation studies, radiation damage is present in 90% or more of 10 year survivors. Fetch PMID: 2209839 Since late radiation effects themselves can be lethal, but undertreating cancer also has its risks, prevention of unwanted radiation damage is important. UV radiation damage to membranes, proteins, DNA and other cellular targets is predominantly related to oxidative processes. Vitamin E and possibly other antioxidants partly protect cells from radiation damage. Infection existing in tissues that are irradiated create worse long term effects, including bone necrosis, central nervous system necrosis, and persistent infection. "All patients who developed chronic persistent infection during or shortly after the radiation therapy, increased local tissue sensitivity to late radiation damage. As a result, severe bone, cerebellar and brainstem necrosis was observed at doses that are normally considered safe. We therefore strongly recommend that any infection in a proposed irradiated area should be treated aggressively, with surgical debridement if necessary, before radiotherapy is administered, or that infection developing during or after irradiation is treated promptly." Close observation over function of large nerve trunks and plexuses while the patients are receiving radiation to the area is necessary. Early diagnosis and treatment of radiation plexitis and neuritis is essential for adequate recovery of limb function. Diagnosis of radiation damage to the peripheral nervous system should rest on clinical electrophysiological findings defining the degree of the nerve fiber injury. Hyperbaric oxygen therapy has been useful in restoring nerve function. Fetch PMID: 10465478 Fetch PMID: 8635114 Saline breast implants might be used to displace organs away from the radiation field when treating malignant tumors of the trunk, thereby minimizing the radiation dose to uninvolved organs. In patients with pelvic tumors the bowel can be fixed to the upper abdomen by use of Polyglycolic acid mesh (Devon) to minimize radiation associated small bowel injury. There is no severe disturbance of bowel motility, and after 3 to 4 months the small bowel will again descend into the pelvis. Techniques that concentrate radiation in small areas, like IORT, and implantation radiation, can prevent large areas of healthy tissue from becoming inadvertently damaged. Intraoperative radiotherapy (IORT), with radiation applied directly to the tumor or tumor bed with the abdomen open is a useful process. Stomach and intestines can be easily excluded from the radiation field to avoid late radiation damage. The use of a radiation protectant such as amifostine prior to irradiation might prevent normal tissue damage, while not preventing tumor lysis. For further details, see the section on amifostine in the Chemotherapy web page on this site. Search Pubmed for: radiation treatment protectants References: Radiation Damage Prevention |
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| Radiosensitizers |
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Radiation modifiers, including hyperbaric oxygen, chemical radiosensitizers, normal tissue protective agents, and local and systemic hyperthermia are continually being investigated. A radiosensitizer is a compound that would make tumor cells more sensitive to the effects of radiation, and have no effect upon normal cells. This would allow a given dose of radiation to have a greater effect upon the malignant tissue. Some radiosensitizers lead to an increase in sensitivity of the hypoxic and therefore radioresistant parts of tumours against X- and gamma-radiation. With sufficient concentration within the tumour, they can act where the radiation can reach, even in the deeper parts of the body. A number of chemical compounds that modify radiation effects have been discovered and tested both in the laboratory and clinically over the past 25 years. There are classes of compounds: aminothiol radio-protectors which act on well vascularized oxygenated cells and concentrate in tissues such as skin, gut and marrow; nitromidazole radiosensitizers [metoclopramide derivatives, which cause DNA strand breaks and inhibit DNA repair, and thereby sensitizes radiation and chemotherapeutic drugs in human tumor cell cultures]; pyrimidine analogues which are incorporated into the DNA of cycling cells and cause radiosensitization; and cancer themotherapy agents which, in addition to their ability to kill tumor cells directly, also may sensitize tumor and normal cells to radiation. In addition, 2-deoxy-D-glucose prevents efficient utilization of glucose in cells, and has a greater effect on tumor cells. Not being able to generate energy from glucose inhibits the repair of radiation damage preferentially in tumor cells. Tumor damage depends upon amount of hypoxic cells [which are radioresistant], radiation dose, doses of chemotherapy and/or other radiosensitizer given, ambient temperature, timing of drug dose and radiation exposures. The effectiveness of oxygenating the hypoxic cells to make them radiosensitive depends upon how densely the tissue is vascularized, hemoglobin concentrations and affinities for oxygen, and levels of carbon dioxide breathed in [causes blood vessels to dilate and deliver more blood to tissues], as well as use of hyperbaric [high pressure] oxygen treatment. Radiotherapy combined with razoxane [a radiosensitizer] seems to improve the local control in inoperable, residual, or recurrent Soft Tissue Sarcoma compared to radiotherapy alone. The combined treatment is a fairly well tolerated procedure at low costs. It can be recommended for inoperable primary Soft Tissue Sarcoma or gross disease after incomplete resection, conditions that are associated with limited local control and a grave prognosis COX-2 9 (Cyclooxygenase-2) is overexpressed in many types of malignant tumors. It mediates production of prostaglandins, which in turn may stimulate tumor growth and protect against damage by cytotoxic agents. Treatment with a selective inhibitor of COX-2 [like Vioxx or Celebrex] may greatly enhance tumor radioresponse without markedly affecting normal tissue radioresponse. COX-2 inhibitors might have marked value for increasing the therapy/damage ratio of irradiation. References on Radiosensitivity and Radiation Damage References on Radiosensitivity and Radiochemotherapy |
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| Adding Chemotherapy, Hyperthermia, or Antiangiogenesis |
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Chemoradiotherapy protocols are a recent development in the management of tumours where preservation of organ function is important. It is now recognized that such combined treatment may produce adverse effects above the accepted dose thresholds for either modality, including increased cardiotoxicity with adriamycin. However, there was a study done for inoperable lung cancer that showed local control and survival was improved by combining radiotherapy with daily low-dose cisplatin. As usual, the risk benefit profile requires consideration. The dosages and timing of the chemotherapy agent(s) and the radiation determine the effectiveness of the regimen. Timing between Xray irradiation and chemotherapy dose may be critical. Hyperthermia in combination with chemotherapy has a strong biological rationale based on thermal enhancement of cytotoxicity and partial circumvention of resistance. Weekly locoregional hyperthermia or whole-body hyperthermia using the Aquatherm apparatus, in combination with chemotherapy is feasible. Some results in patients with metastatic sarcomas were promising. The formation of a blood supply (angiogenesis) is critical to the growth of solid tumors. Addition of antiangiogenic agents to treatment with cytotoxic therapies might make standard anticancer therapies more powerful. Interleukin-1 might have a protective effect on normal tissues' response to radiation and chemotherapy damage, while not affecting tumor response to treatment. For some drugs, the protection might be dependent on sequence of administration. References: Radiochemotherapy |
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| Glossary |
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Don't be afraid to ask your health care staff to explain any terms you don't understand. Adjuvant therapy Treatment added to the primary treatment to enhance the effectiveness of the primary treatment. Radiation therapy often is used as an adjuvant to surgery. Alopecia (al-oh-PEE-she-ah) Hair loss. Anesthesia Loss of feeling or sensation to prevent pain. Certain drugs or gases called 'anesthetics' are used to achieve anesthesia so that medical procedures may be performed without pain. A local anesthetic causes loss of feeling in part of the body. A general anesthetic puts the patient to sleep. Antiemetic (an-tee-eh-MET-ik) A medicine that prevents or relieves nausea and vomiting. Biological therapy Treatment to stimulate or restore the ability of the immune system to fight infection and disease; also called immunotherapy. Brachytherapy (BRAK-ee-THER-ah-pee) Internal radiation therapy using an implant of radioactive material placed directly into or near the tumor; also called "internal radiation therapy." Cancer A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread through the bloodstream and lymphatic system to other parts of the body. Catheter A thin, flexible, hollow tube through which fluids enter or leave the body. Radioactive materials may be placed in catheters that are placed near the cancer. Chemotherapy Treatment with anticancer drugs. Cobalt 60 A radioactive substance used as a radiation source to treat cancer. CT (computed tomography) scan An x-ray procedure that uses a computer to produce a series of detailed pictures of a cross section of the body; also called a CAT scan. Dietitian (also "registered dietitian") A professional who plans diet programs for proper nutrition. Dosimetrist (do-SIM-uh-trist) A person who plans and calculates the proper radiation dose for treatment. Electron beam A stream of electrons (small negatively charged particles found in atoms) that can be used for radiation therapy. External radiation The use of radiation from a machine located outside of the body to aim high-energy rays at cancer cells. Fluoride A chemical applied to the teeth to prevent tooth decay. Gamma knife Radiation therapy in which high energy rays are aimed at a brain tumor from many angles in a single treatment session. Gamma rays High-energy rays that come from a radioactive source such as cobalt-60. High dose-rate remote brachytherapy A type of internal radiation treatment in which the radioactive source is removed between treatments; also known as 'high dose-rate remote radiation therapy.' Hyperfractionated radiation Radiation treatment that is given in smaller-than-usual doses two or three times a day. Implant A radioactive source in a small holder that is placed in the body in or near a cancer. Internal radiation Radiation therapy that uses the technique of placing a radioactive source in or near a cancer. Interstitial radiation A radioactive source (implant) placed directly into the cancerous tissue such as the head and neck region or the breast. Intracavitary radiation A radioactive source (implant) placed in a body cavity such as the chest cavity or the vagina. Intraoperative radiation External radiation treatment given during surgery to deliver a large dose of radiation to the tumor bed and surrounding tissue; also called IORT. Linear accelerator A machine that creates high-energy radiation to treat cancers, using electricity to form a stream of fast-moving subatomic particles; also called 'mega-voltage (MeV) linear accelerator' or a "linac." Lumen The cavity or channel within a tube or tubular organ such as a blood vessel or the intestine. Medical oncologist A doctor who specializes in treating cancer with chemotherapy. Neutron A small, uncharged particle of matter found in the atoms of all elements except hydrogen. Streams of neutrons generated by special equipment can be used for radiation treatment. Oncologist A doctor who specializes in treating cancer. Palliative care, palliation Treatment that relieves symptoms but does not cure disease. Palliative care can help people with cancer live more comfortably. Physical therapist A health professional trained in the use of treatments such as exercise and massage. Platelets Blood cells that help stop bleeding by contributing to the formation of clots. Prosthesis An artificial replacement for a body part. Proton A small, positively charged particle of matter found in the atoms of all elements. Streams of protons generated by special equipment can be used for radiation treatment. Radiation Energy carried by waves or a stream of particles. Radiation nurse A nurse who specializes in caring for people who are undergoing radiation therapy. Radiation oncologist A doctor who specializes in treating cancer with radiation. Radiation physicist The person who makes sure that the radiation machine delivers the right amount of radiation to the treatment site. In consultation with the radiation oncologist, the physicist also determines the treatment schedule that will have the best chance of killing the most cancer cells. Radiation therapist The person who runs the equipment that delivers the radiation. Radiation therapy Treatment with high-energy rays (such as x-rays) to kill cancer cells. The radiation may come from outside of the body (external radiation) or from radioactive materials placed directly in the tumor (internal or implant radiation). Types of radiation include x-rays, electron beams, gamma rays, neutron beams, and proton beams. Radioactive substances include cobalt, iridium, and cesium. (See also gamma rays, brachytherapy, and x-ray.) Radioactive Capable of emitting high-energy rays or particles. Radiologist A doctor with special training in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. Reconstructive surgery Surgical procedure done to restore the shape of an area of the body altered by cancer surgery. Recurrent Reappearance of cancer cells at the same site or in another location after a disease-free period. Red blood cells Cells that carry oxygen to all parts of the body. Also called "erythrocytes." Remote brachytherapy See "high dose-rate remote brachytherapy." Simulation The process used to plan radiation therapy so that the target area is precisely located and marked. Telangiectasia A skin lesion that results from dilation of a group of small blood vessels. Treatment port or treatment field The place on the body at which the radiation beam is aimed. Tumor An abnormal mass of excess tissue that results from excessive cell division. Tumors perform no useful body function and may be either benign (not cancerous) or malignant (cancerous). Unsealed internal radiation therapy Internal radiation therapy given by injecting a radioactive substance into the bloodstream or a body cavity. This substance is not sealed in a container. White blood cells Cells that help the body fight infection and disease. X-rays High-energy radiation that is used in low doses to diagnose disease and in high doses to treat cancer. Most of this Glossary comes from Radiation Therapy and You, an NCI publication, available on the National Cancer Institute Website. |
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| The information on this site is not a substitute for professional medical advice. You should not use this information to diagnose or treat a health problem or disease without consulting with your doctor. Please consult your doctor with any questions or concerns you may have regarding your condition. Copyright © 2001-2010 LMSWEBSITE |
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