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Principles of radiotherapy and radiobiology
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Seminars in Oneology Nursing, Vol 15, No 4 (November), 1999: pp 250-259
PRINCIPLES OF RADIOTHERAPY AND RADIOBIOLOGY F. DUNNE-DaLr
adiation therapy has been used for a eentury in the treatment of cancer and other diseases. Surgery, radiation therapy, and chemotherapy are the three ajor cancer treatment entities; used alone or in eombination, they determine patient survival. Radiation therapy is used in over 60% of all cancer patients at some point during the course of their disease. It has become a significant therapy due to the growth in the knowledge of radiation physics, radiobiology, treatment planning, refinement of treatment machines (ie, linear accelerator), and the use of three-dimensional computer treatment planning. When a tumor is confined to the site of origin, the local control rates by radiation therapy are higher than when the cancer cells have extended into the adjacent organs. Eaeh eaneer has a unique natural history, biological behavior, mode of tumor growth, and response to radiation therapy. 1 To fully understand radiation therapy and its effectiveness in the treatment of cancer, the principles of radiation therapy and radiobiology need to be understood. This article discusses the principles of radiation therapy, radiobiology, radiation physics, and combined modality treatments; the use of radiosensitizers and radioproteetors; new developments in radiation therapy; and radiation safety prineiples. All of these are essential to better educate, eare for, and manage the adverse effects of treatment in oneology patients undergoing radiation. BIOLOGICAL PRINCIPLES OF RADIATION THERAPY adiation therapy is the treatment of cancer using ionizing radiation. The goal of radiation is to destroy or inactivate cancer cells while preserving the integrity of normal tissues within
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the treatment field. Radiobiology is the study of the sequence of events that follows the absorption of energy from ionizing radiation, the efforts of the organism to compensate for the effects of the energy absorption, and the damage of the organism that may be produced. 1 Radiation with partieles or x-rays eauses ionization within the cell. Ionization is the process by which a neutral atom acquires a positive or negative charge. 2 Electrons, protons, and alpha particles are charged particles that have sufficient kinetic energy to produce ionization by collision as they penetrate matter. Unchanged particles such as neutrons also produce ionization when they interact with matter. High-energy photons that have no mass, such as x-rays or gamma rays, are called electromagnetic radiation; they are generated electrically by machines, such as the linear accelerator, or are produced through spontaneous emission by radioactive materials undergoing nuclear transition, such as radioactive cobalt or cesium. Therapeutic radiation is either electromagnetic or particulate and is capable of the ionization of m a t t e r ) Particulate radiation ineludes electrons, neutrons, protons, helium ions, heavy ions, and alpha particles. 4
DNA, resulting in ionization. In addition, indireet damage to DNA oeeurs when there is an interaction of the radiation with cellular water, forming ion radicals, whieh then attack the DNA. After cells are exposed to radiation, they may die when they attempt to divide (Table 1). Both strands of DNA damaged dose together may cause a double-strand break, which is usually a lethal event for the cell. Damaged DNA may be repaired, although sometimes it is repaired incorrectly, leading to chromosomal abnormalities, mutations, and even a secondary malignancy.
LINEAR ENERGY TRANSFER
SENSITMTY OF THE CELL
OXYGEN EFFECT ll-oxygenated tumors show a much greater esponse to radiation and are therefore more radiosensitive than poorly oxygenated tumors. Theoretieally, the mechanism of the oxygen effeet is related to the ability of oxygen to combine with free radicals formed during ionization, producing new and toxic combinations. In addition, the presence of oxygen at the time of radiation prevents the reversal of some of the ehemieal changes that occur as the result of the oxygen effect.6
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inear energy transfer is the rate at which a
umors, like normal tissue, vary in their particular type of radiation deposits energy as L T sensitivity to radiation; this is reflected in the it travels through matter and varies considerably total dose needed for the eure of refractory between different particles or rays. Electrons are superficial particles that expend their energy after penetrating only a short distance within the treatment field. X-rays are generally described as sparsely ionizing with a low linear energy transfer compared with neutrons or alpha particles. Although certain heavy particles (protons or neutrons) may be more densely ionizing and have a higher number of cells killed per unit dose, there is little evidence of a greater advantage of using them over x-rays (photons) or electrons in treatment. 4 CELLULAR RESPONSE TO RADIATION THERAPY xperimental evidence supports the hypothesis E that the biologieal effects of ionizing radiation result from damage to the DNA of the cell, which is believed to be the target of radiation, s Any type of radiation may deposit its energy direetly in the
tumors. Resistant tumors include head and neck cancers, lung eaneer, esophageal cancer, and anal cancer. The goal of radiation is to deliver a sufficiently high dose of radiation to kill all the
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t u m o r cells with minimal damage to the surrounding normal tissues to allow normal viability and f u n c t i o n / The larger the t r e a t m e n t volume, the more difficult it is to achieve this goal and the lower the tolerated dose before toxicity to normal tissue ensues. TISSUE TOLERANCE he tolerance of normal tissues to radiation depends on the presence of a sufficient n u m b e r of m a t u r e cells or elonogenie cells that can produce m a t u r e cells to allow m a i n t e n a n c e of normal organ function. 4,7,s All normal tissues have a limit with regard to the a m o u n t of radiation they can receive and still remain functional. For this reason, the a m o u n t of radiation used to treat a specific t u m o r is limited by the tolerance of the surrounding normal tissue, not by the tumor. 9 Tolerance can be defined as the total dose at which additional radiation will significantly inerease the probability for the o e e u r r e n e e of severe normal tissue reaetions. 1,9 The response of the tissue or an organ to radiation depends on the sensitivity of the individual cells and kinetics of the population of cells. The relative radiosensitivity of a given t u m o r is closely related to its proliferative aetivity. T h e r e is a variation in sensitivity of eells to radiation depending on their stage in the cell cycle. When radiation is given as a continuous exposure, such as via a p e r m a n e n t implant or in fraetionated doses, cells migrate from the more resistant phases of the cell cycle into the more sensitive phases, making the radiation more effective. 1,9
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FRACTIONATION
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reserving the integrity of normal tissue was recognized early in the development of radiation therapy, which led to dose fractionation techniques. Conventional radiation therapy is delivered in a n u m b e r of fraetions to aehieve b e t t e r t u m o r control and reduce the level of normal tissue toxicity. The daily radiation dose is divided over weeks. The total dose, the size of the fractions, the n u m b e r of fractions, and the time over which the t r e a t m e n t fraetions are given are all i m p o r t a n t to effective radiation therapy.
BIOLOGICAL EFFECT he biological effect of fractionation on tumors and normal tissue is d e p e n d e n t on four factors, known as the four "R's" of radiobiology: repair, reassortment, reoxygenation, and repopulation. Normal tissue is spared by divided doses because it has a greater repair of sublethal damage and repopulation than does tumor tissue. Reassortm e n t or redistribution of cells within the cell cycle occurs after a dose of fractionated radiation. Redistribution brings more of the cells into the most sensitive mitosis phase of the cell cycle with each successive radiation dose. Reoxygenation occurs because the decreased t u m o r b u r d e n leads to better blood flow patterns in the tumor. Repopulation involves the r e p l a c e m e n t of dead or dying cells through cell multiplication. Both normal cells and cancer cells are able to recover from radiation injury (successful mitosis between radiation doses). However, repopulation varies with different tissue types. All tissues within the body have a known degree of radiosensitivity. It is radiosensitivity of the healthy tissues surrounding the t u m o r site that determines the m a x i m u m dose and the expected side effects. When larger fractions are given, late reactions usually are more severe. 1°
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DOSE DELIVERY he unit of dose delivery in radiation therapy is the gray (Gy), which is defined by the a m o u n t of energy delivered to a mass of tissue. The unit also can be referred to as centigray (cGy), which is interchangeable with the rad (radiation absorbed dose). The deposition of this energy within the cell will lead to a series of physical, ehemieal, and biochemical events resulting in formation of free radicals that eause DNA double-strand breaks and delayed cell death. 4
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TREATMENT PLANNING en determining a t r e a t m e n t plan, the hysieist and radiation oneologist will determine a safe and effective dose as well as the exact target tissue and volume. A prescription will be set by the radiation oneologist. The prescription of t r e a t m e n t will include the t r e a t m e n t site, n u m b e r of fields, daily dose fraetionation, total radiation
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dose, total elapsed time, number of fractions, use of beam modifiers, and energy source. Immobilization and positioning deviees are documented if needed to ensure reprodueibility of the exact treatment field. These immobilization and positioning deviees are casts, plastie masks, bite bloeks, tape, or arm boards. For surfaees with an uneven eontour, wedges, tissue compensators, or wax bolus are used to aehieve aeeurate and desired dose distribution. 11 Treatment planning is necessary to have all beams interseet properly within the target area and to ealeulate the dose that ultimately will be achieved inside the tumor from a particular arrangement of beams. With the development of eomputed tomography, radiation therapy treatment planning dramatieally ehanged. Computed tomography images are now the basis for radiation treatment planning as well as a three-dimensional computer treatment planning system. REVIEW OF THE BASIC PROPERTIES OF RADIOACTIVE ISOTOPES fter the initial discovery of x-rays by R6ntgen, 12 radioactive isotopes were found to emit three distinct types of radiation: alpha particles, beta particles, and gamma rays. Since the discovery of these radioactive elements, several other particles have been detected, including neutrons, positrons, neutrinos, w-mesons, Ix-mesons, and K-mesons. 13 The first 92 of the 103 known radioactive elements occur naturally; the remaining elements have been produced artificially. All elements with an atomic number greater than 82 (lead) arc radioactive. The decay constant of a radioactive nucleus is defined as the fraction of the total number of atoms that decay per unit of time. 9,13 Radioactivity is measured as the total number of disintegrations per unit time interval. The curie (Ci) is a unit of activity that is equal to 3.7 x 1010 disintegrations per second. The becquerel (Bq) designates the SI unit for activity and is equal to one disintegration per second. The half-life of a radioactive isotope is the time required for the number of radioactive atoms in a particular sample to decrease by half. Gamma decay occurs when a nucleus undergoes a transition from a higher to a lower energy level. 13 During this process, high-energy photons called x-rays are emitted. In beta decay, a neutron within the nucleus is converted into a proton, which
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results in an electron and anti-neutrino being emitted. Alpha decay occurs when the ratio of neutrons to protons is low and in nuclides with atomic numbers greater than 82.12 Alpha particles have high linear energy transfer and lose their energy quickly when they collide with particles in their path. Because of this high linear energy transfer, alpha particles are unable to penetrate more than 0.04 mm into tissue. Radiation exerts damage to tissue by colliding with and ionizing particles at small intervals along the path through tissue. The extent of radiation injury is partly a function of the ionizing capabilities of the isotope. Gamma emitters have the greatest capacity to produce damage deep in tissue.9,13 RADIOSENSITIZERS AND RADIOPROTECTORS n the past two decades, a number of compounds .have been identified as radiosensitizers or radioproteetors. Radiosensitizers are agents that provide selective enhancement of radiation damage to cancer cells. Radioproteetors are agents that provide protection of normal tissue during radiotherapy. The purpose of these compounds is to increase the number of tumor cells killed without a proportional increase in normal tissue damage.14 Agents that affect nucleoside and nueleotide metabolism are among the most effective and most widely used drugs to sensitize tumor cells to radiation. Known radiosensitizers include 5-fluorouracil, fluorodeoxyuridine, and thymidine analogues, which include bromodeoxyuridine, iodeoxyuridine, and hydroxyurea. Gemeitabine (difluorodeoxyeitidine) and paelitaxel are under investigation. 15,16 A radiation sensitizer must be present at the time of radiation for it to be effective. It is hoped that these drugs can be used in various clinical strategies to achieve selective radiosensitization of tumors relative to normal tissues. 14,17 It should be noted that in some situations the effect of the drug against the tumor, while not acting as a radiosensitizer, may be additive to the effect of the radiation and enhance the antitumor effect. Recent findings suggest that the rational manipulation of drug schedules and combinations has the potential to improve the efficiency of the currently used agents and to establish the benefits of the newer ones. 17-19 Studies, including randomized trials, have shown
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increased local control and survival advantages with systemic 5-fluorouraeil and radiation therapy compared with radiation alone, s It is believed that 5-fluorouraeil kills cells that are in mid S-phase, which is a relatively radioresistant phase of the cell cycle. This interaction is believed to be a form of additivity rather than radiosensitization. Sulfhydryl compounds are known radioprotectors and demonstrate proteetion to eells in culture and to mice exposed to potentially lethal doses of radiation. ~4 It is believed that sulfhydryl compounds act as "radical scavengers," interacting with ionized particles before these particles can damage DNA2 ° To be a useful radioproteetor, the compound must have a seleetive effect on normal tissue (protecting the normal tissue more than the tumor tissue), so that a larger dose of radiation can be delivered without an inerease in normal tissue damage. 14 WR-2721 (amifostine) has been evaluated in a series of clinical trials as a protector of normal tissue against both radiation and chemotherapy. Effectiveness appears to be related to the tissue concentration of the drug at the time of radiation. Success has been limited, although clinical trials continue to evaluate the efficiency of the drug in a variety of clinical environments, including both radiation therapy and chemotherapy. s
COMBINED MODALITY THERAPY urgery offers the best possible prospect of cure for solid tumors eonfined to the primary site. 21 However, 70% of patients with solid tumors may have mierometastases beyond the primary site. 22 In addition, the benefits of surgical intervention in oneology patients must be weighed against the risk of operative mortality and flmetional psyehologieal insult, sueh as the loss of an organ. The combination of surgery with radiation therapy and chemotherapy may allow less-extensive surgery to be performed without eompromising cure rates and offer improved quality of life. Surgery and radiation therapy ean suecessfully eontrol localized tumors, but are limited onee the caneer has beeome widespread. After local and regional tumor is treated by surgery and/or radiation therapy, adjuvant ehemotherapy is administered as part of a multimodality treatment to eradieate undeteetable micrometastases. Neoadjuvant chemotherapy is given before surgery and/or radiation therapy. Neoadjuvant
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chemotherapy is used to achieve several goals: to decrease tumor size to limit the extent or severity of subsequent surgery, to increase the vaseularity and oxygenation of the primary tumor site to improve response to irradiation, and to assess the response of the primary tumor to ehemotherapy agents, which may be used after surgery and/or radiation therapy if a response is observed. Radiation has been used for a long time as the definitive treatment for numerous cancers (Table 2). Multimodality treatments are increasingly used to achieve an effect greater than a single therapy alone. In the past decade, combinations of radiation and chemotherapy have provided local control, with organ conservation equal to surgical resection for several types of cancer. 23 These eancers inelude small cell lung cancer, anal carcinoma (preserving sphincter when possible), bladder cancer (preserving bladder function when possible), carcinoma of the esophagus, and head and neck cancers. It is unclear whether these improved results are due to radiosensitization or the additive effects of the radiation and the systemic control of chemotherapy. RADIOPHARMACEUTICALS FOR METASTATIC BONE PAIN he control of bone pain due to multiple skeletal metastasis is a significant clinical problem in patients with advanced cancer of the breast, lung, and prostate. 13,24 Strontium-89 and phosphorus-32 were investigated as early as the 1940's for treating metastatic cancer to bone. Strontium-89 was approved by the Food and Drug Administration in 1993 for palliative therapy to
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Retinoblastoma Chorodial melanoma Unresectable cancers of the lung and pancreas Un resectable sarcomas
PRINCIPLES OF RADIOTHERAPY AND RADIOBIOLOGY
reduce bone pain associated with metastatic cancer. The results obtained with phosphorus-32 are similar to those obtained with strontium-89, but the associated bone marrow toxicity has been severe; it is therefore not considered a favorable treatment at this time. 2s Strontium-89 has a half-life of 50.5 days. The long physical half-life of strontium-89 and the small range of the beta particles, which travel only a few millimeters, contribute to the longlasting effects of this radiopharmaceutical agent. Because of its strong localizing properties, strontium-89 has been shown to deliver a safe and effective systemic radiation dose. 26 Randomized trials have demonstrated that the combination of strontium-89 and local radiation therapy provides more effective palliation than local radiation alone. 2s Strontium-89 acts like calcium, clearing rapidly from the blood and healthy bone and localizing preferentially at sites of osteoblastie metastasis. Strontium-89 delivers useful doses of beta radiation to the lesions while selectively sparing healthy bone and bone marrow. Patients should receive safety instructions after the injections (Table 3). While results of individual studies have varied, the overall efficacy in terms of patients experieneing pain relief (complete + marked + moderate) appears to be in the range of 54% to 84%.25, 27
Strontium-89 is administered intravenously, usually in an outpatient setting, by a radiation oneologist licensed to administer radiopharmaeeutieal agents or by a tieensed nuclear medicine physician. The usual dose is 4 mCi. If neeessary, the dose can be repeated after 90 days or longer. Not all individuals with metastatic bony metastasis are candidates for strontium-S9 (Table 4). The most common adverse effect is mild bone marrow toxicity, which has a nadir of 4 to 8 weeks following the injection, with a partial return to
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baseline in 12 weeks, s A complete blood cell count with platelets should be monitored weekly until counts return to normal limits. Approximately 10% of patients will experience "flare" pain, which occurs 72 hours after the injection, requiring additional analgesics until pain subsides. "Flare" pain can last up to 1 week following the injeetion, but a decrease in the original pain usually does not occur until the second or third week following the injection. Pain relief has been reported to last from 3 to 6 months. RADIATION SAFETY regulations concerning radiation expoF ederal sure stipulate that the maximum permissible dose for whole-body occupational exposure is 50 mSv per year (National Council on Radiation Proteetion and Measurements, 1990). These standards are set based on risk versus nonoeeupational exposure limits and eritieal organ exposure. The recommendations regarding limits for exposure to ionizing radiation are listed in Table 5. Common radioisotopes and their properties are listed in Table 6. Oeeupational exposure is reeommended to be "as low as reasonably achievable." Low levels of exposure are aehieved by elose collaboration and monitoring by the radiation safety officer within the institution. Nursing eare and safety precautions required for implants are influeneed by the type of radioactive isotope, the dosage, and the method of administration. In practice, nurses working with braehytherapy (implants) may be exposed to beta or gamma ray radioactive sources that may be hazardous (Table 7). The nurse's understanding of radiation biology can help reduce fears and anxieties concerning care for these patients. Radiation exposure must be minimized through proper radiation-protection practices. Nurses as-
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signed to care for implant patients should be rotated daily to prevent any one person from unnecessary exposure to the radioactive isotope. Film badges should be worn to measure the amount of radiation exposure. Isolation preeautions are necessary (Table 8). The three most important, simple, and key principles of radiation protection are time, distance, and shielding. These three factors are the most direct actions that health care workers can personally take to reduce their risk and therefore keep their total effeetive dose as low as reasonably achievable. 2s Knowledge of the specific radioisotopes, whether sealed or unsealed, temporary or permanent, will help the nurse provide the safest care and reduce their own anxiety when earing for these patients.
The shorter the time interval that one is exposed to the radioactive source, the less the amount of radiation that will be absorbed. Distance is the most effective means of reducing radiation exposure. The following rule can be used to calculate the effeet of distance: the amount of radiation exposure is redueed by the square of the increase in distance from the radioactive souree. Thus, a worker who doubles the distance from the source reduces the dose to one fourth and a worker who triples the distance from the souree reduces the dose to one ninth, s The type of shielding deviee reeommended depends on the speeifie radioactive source. Alpha particles cannot penetrate the outermost layers of skin and a thin sheet of paper ean suffieiently shield from alpha particles. Alpha particles are not external hazards. Most beta particles, like alpha
PRINCIPLES
particles, are not external hazards. Those isotopes that are beta and gamma emitters present the most hazardous exposure to health care workers and require protective measures (see Table 6). Lead is the material used in both fixed protective barriers and accessory devices, such as aprons and gloves. 2s,29 If health care workers maintain maximum distance from the radioactive source and demonstrate efficient use of time, they usually can protect themselves even without shielding.3° DISLODGEMENT OF SOURCE f the radioactive source becomes dislodged, it should not be touched with bare hands. Longhandled forceps and a lead container should be left in the patient's room; these are used to retrieve and store the radioactive source should it become dislodged. The nurse should use forceps to place a dislodged implant into the container and then notify the radiation safety officer and the radiation oneologist. For seed implant patients, for 2 to 3 days during hospitalization the urine should be strained to retrieve any radioactive seeds that become dislodged. Dressings should be checked for seeds. If seeds become dislodged, the seeds should be placed into the lead container using the forceps.
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MONITORING DEVICES devices, such as a film badge, a M onitoring thermoluminescent dosimeter, or a ring badge, and the pocket ion chamber are the most commonly used personnel-monitoring devices. Personnel monitoring devices, which record the amount of radiation exposure, are required by law. These devices should only be worn within the hospital or work environment. Occupational exposure rates are closely monitored by the radiation safety officer within the institution. The film badge is the most widely used personnelmonitoring device. It is accurate, reliable, and inexpensive. The film badge is made of photographic emulsion mounted in a plastic holder and provides a measure of whole-body exposure. The film darkens in proportion to exposure to radiation and is changed monthly by the radiation safety officer. For environmental monitoring, a Geiger-Mueller counter is used. The Geiger-Mueller counter does
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not measure exposure; instead, it reacts to the presence of ionizing particles by producing electrical pulses triggered by the transfer of radioisotope energy to electrons in the Geiger-Mueller counter. For implant brachytherapy, the radiation safety officer surveys the room, linen, and garbage with the counter after the source is removed and before the room is cleaned. SEXUALITY ISSUES
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atient teaching before implant insertion is necessary and should include issues related to sexuality. This may be an uncomfortable issue for some patients, but one the nurse should address. Of course, the nurse must be comfortable with answering questions concerning sexuality. In gynecologic implant patients, the biggest concern is vaginal stenosis and/or vaginal shortening, which are late effects. Decreased vaginal lubrication and vaginal sensation also may be a problem long term. Vaginal dilators are usually given to patients during the follow-up visit and are recommended to reduce vaginal stenosis. Vaginal dilators or sexual intercourse prevent the vaginal walls from closing and narrowing. A water-soluble lubricant is recommended when using a dilator and before intercourse. Prostate seed implants, which are permanent, may cause concern about sexual intercourse. Patients need to understand that the radioactive seeds will decay over a period of months and that they will not be radioactive. Sexual intercourse can be resumed when the patient feels comfortable and ready, although a condom is recommended for approximately 2 months after the implant. PATIENT EDUCATION
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atient and family education is extremely important before the insertion or implantation of a radioactive isotope (source). The radiation oneology nurse must educate these patients and their families to help relieve fear and anxiety (Table 9). The patient and his or her family may need clarification of misconceptions and continued reinforcement of this initial teaching. Educational brochures and other materials are available through the American Cancer Society, the National Cancer Institute, and the Oncology Nursing Society.
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ADVANCES AND NEW DEVELOPMENTS IN RADIATION THERAPY dvances and new developments in radiation therapy inelude stereotaetie radioneurosurgery, three-dimensional computer treatment planning and eonformal therapy, aceelerated fractionation or hyperfraetionation, and an increase in research concerning the interaction of chemotherapeutic agents with radiation and the use of proton beam radiation for patients who failed conventional radiation. Stereotactic radioneurosurgery is a method of destroying tumor tissue with single large doses of radiation delivered through stereotaetically directed narrow beams. Presently, the three primary methods of delivering stereotactic irradiation include heavy charged particle beams (protons, helium, neon, ete), gamma irradiation emitted from a fixed array of cobalt-60 sources (ie, gamma knife), and high-energy photon irradiation produced with linear accelerators (modified extant machines or dedicated units)Y Stereotactic radioneurosurgery historically has been used primarily for treating arteriovenous malformation and other benign tumors and presently has been the modality used effectively for treatment of small metastatic brain tumors, brain metastases that progress or recur after external radiation therapy, and small relatively spherical high-grade gliomas. 3 High-speed computers and graphic displays have had an important effect on the aeeuraey of radiation therapy. Three-dimensional treatment planning systems have allowed the radiation
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oncologist, physicist, and dosemetrist to view comprehensive graphic displays of anatomy. Threedimensional computer treatment planning with conformal dose delivery has increased the effectiveness of radiation treatments. It ensures that the intended target is being treated with the full planned dose, restricting the high-dose region to conform more closely to the shape of the target. Therefore, normal tissues receive a smaller percentage of the dose, allowing doses to be escalated to the target (tumor). 3,32 New equipment, including multileaf collimators and computer-controlled treatment machines, along with faster and more sophisticated planning systems, are making three-dimensional planning and treatment delivery increasingly practical. 23 Computer-controlled machines, operating by downloading the dose delivery prescription directly from the three-dimensional treatmentplanning computer, represent an important development that may become more widely available. Laboratory and elinieal studies have shown that the biological effects of radiation are improved by using multiple daily fraetionsY Head and neck cancers have been shown to have more positive outcomes with multiple fractions because these cancers are capable of rapidly proliferating during a 6- to 7-week course of radiation when delivered in standard onee-a-day fraetionation. Accelerated fraetionation uses standard fractions (160 to 200 eGy) given two to three times daily with a 6-hour delay between fractions over a shorter treatment time. Hyperfraetionation uses more frequent (more than one treatment per day) smaller fractions (110 to 120 eGy) to give a higher total dose over a standard treatment time. This technique has been safely used in patients with lung cancers and gliomas23 Finally, particle radiation, such as fast neutrons, deuterons, helium ion beams, and negative ~r-mesons, will continue to be tested and refined for use in situations in which conventional radiation is of little value. 3 These treatments are expensive and presently have only very limited applications for cancer patients. CONCLUSION adiation therapy continues to be an extremely important treatment of eaneer. The goal is to control cancer, spare surrounding normal tissue, preserve organs, and reduce acute and long-term
PRINCIPLES OF RADIOTHERAPY AND RADIOBIOLOGY
toxicity. R e s e a r c h c o n t i n u e s i n r a d i a t i o n p h y s i c s , radiobiology, t h r e e - d i m e n s i o n a l c o m p u t e r treatm e n t p l a n n i n g , a n d e o n f o r m a l t h e r a p y . T h e u s e of c o m b i n e d modality t r e a t m e n t s has m i n i m i z e d radical surgery and promoted organ preservation. N u r s e s e a r i n g for o n e o l o g y p a t i e n t s n e e d to h a v e
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a good u n d e r s t a n d i n g of r a d i o b i o l o g y a n d p h y s i e s , w h i e h is t h e f o u n d a t i o n of this specialty. W i t h a s i g n i f i c a n t u n d e r s t a n d i n g of s e i e n e e , a n o n e o l o g y nurse ean better anticipate the potential problems a patient m a y experienee and better manage the a d v e r s e effects a s s o c i a t e d w i t h r a d i a t i o n t h e r a p y .
REFERENCES 1. Travis EL: Basic biological interactions of radiation, in Travis EL (ed): Medical Radiobiology (ed 2) Chicago, IL, Year Book Medical, 1989, pp 25-44 2. Khan F: Interactions of ionizing radiation, in Khan F (ed): The Physics of Radiation Therapy (ed 2). Baltimore, MA, Williams & Wilkins, 1994, pp 71-91 3. Hilderley L: Radiotherapy, in Groenwald SL, Prop~e MH, Goodman M, Yarbro CH (eds): Cancer Nursing Principles and Practice (ed 4). Sundbury, MA, Jones & Bartlett, 1997, pp 247-282 4. Crocker IR, Popowski Y: Basic physics and biology of radiation therapy. Semin Interv Cardiol 2:89-94, 1997 5. Coleman CN: Radiation and ehemotherapy sensitization and protectors, in Chatner BA, Long DL (eds): Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia, PA, Lippincott Raven, 1996, pp 56-89 6. Hilderley L: Principles of teletherapy, in Dow KH, Buchnoltz JD, Iwamoto RR, Fielder V, Hilderley L (eds): Nursing Care in Radiation Oneology. Philadelphia, PA, Saunders, 1997, pp 6-20 7. Suit HD, Urano M: Radiation biology for radiation therapy, in Wang CC (ed): Clinical Radiation Ontology. Boston, MA, PSG Publishing, 1988, pp 17-55 8. Travis EL: Tissue radiation biology, in Travis EL (ed): Medieal Radiobiology (ed 2). Chieago, IL, Year Book Medical, 1989, pp 65-76 9. Withers HR, McBride WH: Biologic basis of radiation therapy, in Perez CA, Brady LW (eds): Principles and Practiee of Radiation Oneology (ed 3). Philadelphia, PA, LippincottRaven, 1998, 79-118 10. Root KC: Radiation dose, damage, repair, and comparative risk. Semin Radiat Teehnol 4:31-43, 1996 11. Dunne-Daly C: External radiation therapy self-learning module. Cancer Nurs 17:156-169, 1994 12. Purdy J, Lightfoot D, Glasgow G: Principles of radiologic physics, dosimetry, and treatment planning, in Perez, C, Brady L (eds): Prineiples and Practice of Radiation Ontology (ed 3). Philadelphia, PA, Lippineott, 1998, pp 243-369 13. Dunne-Daly C: Principles of braehytherapy, in Dow KH, Bueholtz JD, Iwamoto RR, Fielder V, Hilderley L (eds): Nursing Care in Radiation Ontology (ed 2). Philadelphia, PA, Sannders, 1997, pp 21-35 14. NollL, Riese N: Chemical modifiers of radiation therapy, in Dow KH, Bucholtz JD, Iwamoto RR, Fielder V, Hilderley L (eds): Nursing Care in Radiation Ontology (ed 2). Philadelphia, PA, Saunders, 1997, pp 47-56 15. Rosenthal DI, Carbone DP: Taxol plus radiation for head and neck cancer. J Infus Chemother 5:46-54, 1995
16. Shewach DS, Lawrence TS: Gemcitabine and radiosensitization in human tumor cells. Invest New Drugs 14:257-263, 1996 17. McGinn CJ, Shewach DS, Lawrence TS: Radiosensitizing nueleosides. J Nat Cancer Inst 88:1193-1198, 1996 18. Witt ME: Radiation and chemotherapy as combined treatment for advanced head and neck cancer. Med Surg Nurs 7:159-164, 1999 19. Weiner LM, Colarusso P, Goldberg M, etal: Combinedmodality therapy for esophageal cancer: Phase I trial of escalating doses of paclitaxel combination with cisplatin, 5-Fluorouracil, and high-dose radiation before esophagectomy. Scmin Oneo124:S19-93, 1997 (suppl 19) 20. Hall EJ: Radiobiology for the Radiologist (ed 4). Philadelphia, PA, Lippincott, 1994, pp 134-135 21. Vora AR: Problems assoeiated with treating cancer. J Cancer Care 6:141-149, 1996 22. Rosenberg SA: Principles of surgical ontology, in DeVita VT Jr, Hellman S, Rosenberg SA (eds): Cancer: Principles and Practice of Ontology (ed 4). Philadelphia, PA, Lippincott, 1994, pp 238-247 23. Liehter AS, Lawrence TS: Recent advances in radiation ontology. N Engl J Med 332:371-379, 1995 24. Kent TM: Improvements in bone pain management with strontium-89. Radiat Ther 4:23-29, 1995 25. Atkins H, Srivastava S: Radiopharmaceuticals for bone malignaneytherapy. J Nuel Med Teehno126:80-86, 1998 26. Gifford J: Strontium 89 therapy for palliation of metastatic bone pain. Radiat Ther 4:92-94, 1995 27. Robinson RC, Spioer J, Preston D, etal: Treatment of metastatic bone pain with strontium-89. Int J Radiat Appl Instrum 14:219-222, 1987 28. Passmore GC: A review of radiation protection principles and practices for workers and patients in the radiologic health-care environment. Sernin Radiol Teehnol 4:18-30, 1996 29. Jefferies K: Basic concepts of clinical radiation protection. Semin Radiol Technol 4:5-17, 1996 30. Khan F: Radiation protection, Khan F (ed): The Physics of Radiation Therapy (ed 2). Baltimore, MD, Williams & Wilkins, 1994, 474-502 31. Corn BW, Curran WJ, Shrieve DC, et al: Stereotactic radiosurgery and radiotherapy: New developments and new directions. Semin Onco124:707-714, 1997 32. Lichter AS, TenHaken ILK:Three-dimensionaltreatment planning and conformal radiation dose delivery, in DeVita VT, Hellman S, Rosenberg SA (eds): Important Advances in Oneology. Philadelphia, PA, Lippincott, 1995, pp 95-10
Seminars in Oneology Nursing, Vol 15, No 4 (November), 1999: pp 250-259
PRINCIPLES OF RADIOTHERAPY AND RADIOBIOLOGY F. DUNNE-DaLr
adiation therapy has been used for a eentury in the treatment of cancer and other diseases. Surgery, radiation therapy, and chemotherapy are the three ajor cancer treatment entities; used alone or in eombination, they determine patient survival. Radiation therapy is used in over 60% of all cancer patients at some point during the course of their disease. It has become a significant therapy due to the growth in the knowledge of radiation physics, radiobiology, treatment planning, refinement of treatment machines (ie, linear accelerator), and the use of three-dimensional computer treatment planning. When a tumor is confined to the site of origin, the local control rates by radiation therapy are higher than when the cancer cells have extended into the adjacent organs. Eaeh eaneer has a unique natural history, biological behavior, mode of tumor growth, and response to radiation therapy. 1 To fully understand radiation therapy and its effectiveness in the treatment of cancer, the principles of radiation therapy and radiobiology need to be understood. This article discusses the principles of radiation therapy, radiobiology, radiation physics, and combined modality treatments; the use of radiosensitizers and radioproteetors; new developments in radiation therapy; and radiation safety prineiples. All of these are essential to better educate, eare for, and manage the adverse effects of treatment in oneology patients undergoing radiation. BIOLOGICAL PRINCIPLES OF RADIATION THERAPY adiation therapy is the treatment of cancer using ionizing radiation. The goal of radiation is to destroy or inactivate cancer cells while preserving the integrity of normal tissues within
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the treatment field. Radiobiology is the study of the sequence of events that follows the absorption of energy from ionizing radiation, the efforts of the organism to compensate for the effects of the energy absorption, and the damage of the organism that may be produced. 1 Radiation with partieles or x-rays eauses ionization within the cell. Ionization is the process by which a neutral atom acquires a positive or negative charge. 2 Electrons, protons, and alpha particles are charged particles that have sufficient kinetic energy to produce ionization by collision as they penetrate matter. Unchanged particles such as neutrons also produce ionization when they interact with matter. High-energy photons that have no mass, such as x-rays or gamma rays, are called electromagnetic radiation; they are generated electrically by machines, such as the linear accelerator, or are produced through spontaneous emission by radioactive materials undergoing nuclear transition, such as radioactive cobalt or cesium. Therapeutic radiation is either electromagnetic or particulate and is capable of the ionization of m a t t e r ) Particulate radiation ineludes electrons, neutrons, protons, helium ions, heavy ions, and alpha particles. 4
DNA, resulting in ionization. In addition, indireet damage to DNA oeeurs when there is an interaction of the radiation with cellular water, forming ion radicals, whieh then attack the DNA. After cells are exposed to radiation, they may die when they attempt to divide (Table 1). Both strands of DNA damaged dose together may cause a double-strand break, which is usually a lethal event for the cell. Damaged DNA may be repaired, although sometimes it is repaired incorrectly, leading to chromosomal abnormalities, mutations, and even a secondary malignancy.
LINEAR ENERGY TRANSFER
SENSITMTY OF THE CELL
OXYGEN EFFECT ll-oxygenated tumors show a much greater esponse to radiation and are therefore more radiosensitive than poorly oxygenated tumors. Theoretieally, the mechanism of the oxygen effeet is related to the ability of oxygen to combine with free radicals formed during ionization, producing new and toxic combinations. In addition, the presence of oxygen at the time of radiation prevents the reversal of some of the ehemieal changes that occur as the result of the oxygen effect.6
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inear energy transfer is the rate at which a
umors, like normal tissue, vary in their particular type of radiation deposits energy as L T sensitivity to radiation; this is reflected in the it travels through matter and varies considerably total dose needed for the eure of refractory between different particles or rays. Electrons are superficial particles that expend their energy after penetrating only a short distance within the treatment field. X-rays are generally described as sparsely ionizing with a low linear energy transfer compared with neutrons or alpha particles. Although certain heavy particles (protons or neutrons) may be more densely ionizing and have a higher number of cells killed per unit dose, there is little evidence of a greater advantage of using them over x-rays (photons) or electrons in treatment. 4 CELLULAR RESPONSE TO RADIATION THERAPY xperimental evidence supports the hypothesis E that the biologieal effects of ionizing radiation result from damage to the DNA of the cell, which is believed to be the target of radiation, s Any type of radiation may deposit its energy direetly in the
tumors. Resistant tumors include head and neck cancers, lung eaneer, esophageal cancer, and anal cancer. The goal of radiation is to deliver a sufficiently high dose of radiation to kill all the
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t u m o r cells with minimal damage to the surrounding normal tissues to allow normal viability and f u n c t i o n / The larger the t r e a t m e n t volume, the more difficult it is to achieve this goal and the lower the tolerated dose before toxicity to normal tissue ensues. TISSUE TOLERANCE he tolerance of normal tissues to radiation depends on the presence of a sufficient n u m b e r of m a t u r e cells or elonogenie cells that can produce m a t u r e cells to allow m a i n t e n a n c e of normal organ function. 4,7,s All normal tissues have a limit with regard to the a m o u n t of radiation they can receive and still remain functional. For this reason, the a m o u n t of radiation used to treat a specific t u m o r is limited by the tolerance of the surrounding normal tissue, not by the tumor. 9 Tolerance can be defined as the total dose at which additional radiation will significantly inerease the probability for the o e e u r r e n e e of severe normal tissue reaetions. 1,9 The response of the tissue or an organ to radiation depends on the sensitivity of the individual cells and kinetics of the population of cells. The relative radiosensitivity of a given t u m o r is closely related to its proliferative aetivity. T h e r e is a variation in sensitivity of eells to radiation depending on their stage in the cell cycle. When radiation is given as a continuous exposure, such as via a p e r m a n e n t implant or in fraetionated doses, cells migrate from the more resistant phases of the cell cycle into the more sensitive phases, making the radiation more effective. 1,9
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FRACTIONATION
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reserving the integrity of normal tissue was recognized early in the development of radiation therapy, which led to dose fractionation techniques. Conventional radiation therapy is delivered in a n u m b e r of fraetions to aehieve b e t t e r t u m o r control and reduce the level of normal tissue toxicity. The daily radiation dose is divided over weeks. The total dose, the size of the fractions, the n u m b e r of fractions, and the time over which the t r e a t m e n t fraetions are given are all i m p o r t a n t to effective radiation therapy.
BIOLOGICAL EFFECT he biological effect of fractionation on tumors and normal tissue is d e p e n d e n t on four factors, known as the four "R's" of radiobiology: repair, reassortment, reoxygenation, and repopulation. Normal tissue is spared by divided doses because it has a greater repair of sublethal damage and repopulation than does tumor tissue. Reassortm e n t or redistribution of cells within the cell cycle occurs after a dose of fractionated radiation. Redistribution brings more of the cells into the most sensitive mitosis phase of the cell cycle with each successive radiation dose. Reoxygenation occurs because the decreased t u m o r b u r d e n leads to better blood flow patterns in the tumor. Repopulation involves the r e p l a c e m e n t of dead or dying cells through cell multiplication. Both normal cells and cancer cells are able to recover from radiation injury (successful mitosis between radiation doses). However, repopulation varies with different tissue types. All tissues within the body have a known degree of radiosensitivity. It is radiosensitivity of the healthy tissues surrounding the t u m o r site that determines the m a x i m u m dose and the expected side effects. When larger fractions are given, late reactions usually are more severe. 1°
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DOSE DELIVERY he unit of dose delivery in radiation therapy is the gray (Gy), which is defined by the a m o u n t of energy delivered to a mass of tissue. The unit also can be referred to as centigray (cGy), which is interchangeable with the rad (radiation absorbed dose). The deposition of this energy within the cell will lead to a series of physical, ehemieal, and biochemical events resulting in formation of free radicals that eause DNA double-strand breaks and delayed cell death. 4
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TREATMENT PLANNING en determining a t r e a t m e n t plan, the hysieist and radiation oneologist will determine a safe and effective dose as well as the exact target tissue and volume. A prescription will be set by the radiation oneologist. The prescription of t r e a t m e n t will include the t r e a t m e n t site, n u m b e r of fields, daily dose fraetionation, total radiation
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dose, total elapsed time, number of fractions, use of beam modifiers, and energy source. Immobilization and positioning deviees are documented if needed to ensure reprodueibility of the exact treatment field. These immobilization and positioning deviees are casts, plastie masks, bite bloeks, tape, or arm boards. For surfaees with an uneven eontour, wedges, tissue compensators, or wax bolus are used to aehieve aeeurate and desired dose distribution. 11 Treatment planning is necessary to have all beams interseet properly within the target area and to ealeulate the dose that ultimately will be achieved inside the tumor from a particular arrangement of beams. With the development of eomputed tomography, radiation therapy treatment planning dramatieally ehanged. Computed tomography images are now the basis for radiation treatment planning as well as a three-dimensional computer treatment planning system. REVIEW OF THE BASIC PROPERTIES OF RADIOACTIVE ISOTOPES fter the initial discovery of x-rays by R6ntgen, 12 radioactive isotopes were found to emit three distinct types of radiation: alpha particles, beta particles, and gamma rays. Since the discovery of these radioactive elements, several other particles have been detected, including neutrons, positrons, neutrinos, w-mesons, Ix-mesons, and K-mesons. 13 The first 92 of the 103 known radioactive elements occur naturally; the remaining elements have been produced artificially. All elements with an atomic number greater than 82 (lead) arc radioactive. The decay constant of a radioactive nucleus is defined as the fraction of the total number of atoms that decay per unit of time. 9,13 Radioactivity is measured as the total number of disintegrations per unit time interval. The curie (Ci) is a unit of activity that is equal to 3.7 x 1010 disintegrations per second. The becquerel (Bq) designates the SI unit for activity and is equal to one disintegration per second. The half-life of a radioactive isotope is the time required for the number of radioactive atoms in a particular sample to decrease by half. Gamma decay occurs when a nucleus undergoes a transition from a higher to a lower energy level. 13 During this process, high-energy photons called x-rays are emitted. In beta decay, a neutron within the nucleus is converted into a proton, which
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results in an electron and anti-neutrino being emitted. Alpha decay occurs when the ratio of neutrons to protons is low and in nuclides with atomic numbers greater than 82.12 Alpha particles have high linear energy transfer and lose their energy quickly when they collide with particles in their path. Because of this high linear energy transfer, alpha particles are unable to penetrate more than 0.04 mm into tissue. Radiation exerts damage to tissue by colliding with and ionizing particles at small intervals along the path through tissue. The extent of radiation injury is partly a function of the ionizing capabilities of the isotope. Gamma emitters have the greatest capacity to produce damage deep in tissue.9,13 RADIOSENSITIZERS AND RADIOPROTECTORS n the past two decades, a number of compounds .have been identified as radiosensitizers or radioproteetors. Radiosensitizers are agents that provide selective enhancement of radiation damage to cancer cells. Radioproteetors are agents that provide protection of normal tissue during radiotherapy. The purpose of these compounds is to increase the number of tumor cells killed without a proportional increase in normal tissue damage.14 Agents that affect nucleoside and nueleotide metabolism are among the most effective and most widely used drugs to sensitize tumor cells to radiation. Known radiosensitizers include 5-fluorouracil, fluorodeoxyuridine, and thymidine analogues, which include bromodeoxyuridine, iodeoxyuridine, and hydroxyurea. Gemeitabine (difluorodeoxyeitidine) and paelitaxel are under investigation. 15,16 A radiation sensitizer must be present at the time of radiation for it to be effective. It is hoped that these drugs can be used in various clinical strategies to achieve selective radiosensitization of tumors relative to normal tissues. 14,17 It should be noted that in some situations the effect of the drug against the tumor, while not acting as a radiosensitizer, may be additive to the effect of the radiation and enhance the antitumor effect. Recent findings suggest that the rational manipulation of drug schedules and combinations has the potential to improve the efficiency of the currently used agents and to establish the benefits of the newer ones. 17-19 Studies, including randomized trials, have shown
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increased local control and survival advantages with systemic 5-fluorouraeil and radiation therapy compared with radiation alone, s It is believed that 5-fluorouraeil kills cells that are in mid S-phase, which is a relatively radioresistant phase of the cell cycle. This interaction is believed to be a form of additivity rather than radiosensitization. Sulfhydryl compounds are known radioprotectors and demonstrate proteetion to eells in culture and to mice exposed to potentially lethal doses of radiation. ~4 It is believed that sulfhydryl compounds act as "radical scavengers," interacting with ionized particles before these particles can damage DNA2 ° To be a useful radioproteetor, the compound must have a seleetive effect on normal tissue (protecting the normal tissue more than the tumor tissue), so that a larger dose of radiation can be delivered without an inerease in normal tissue damage. 14 WR-2721 (amifostine) has been evaluated in a series of clinical trials as a protector of normal tissue against both radiation and chemotherapy. Effectiveness appears to be related to the tissue concentration of the drug at the time of radiation. Success has been limited, although clinical trials continue to evaluate the efficiency of the drug in a variety of clinical environments, including both radiation therapy and chemotherapy. s
COMBINED MODALITY THERAPY urgery offers the best possible prospect of cure for solid tumors eonfined to the primary site. 21 However, 70% of patients with solid tumors may have mierometastases beyond the primary site. 22 In addition, the benefits of surgical intervention in oneology patients must be weighed against the risk of operative mortality and flmetional psyehologieal insult, sueh as the loss of an organ. The combination of surgery with radiation therapy and chemotherapy may allow less-extensive surgery to be performed without eompromising cure rates and offer improved quality of life. Surgery and radiation therapy ean suecessfully eontrol localized tumors, but are limited onee the caneer has beeome widespread. After local and regional tumor is treated by surgery and/or radiation therapy, adjuvant ehemotherapy is administered as part of a multimodality treatment to eradieate undeteetable micrometastases. Neoadjuvant chemotherapy is given before surgery and/or radiation therapy. Neoadjuvant
S
chemotherapy is used to achieve several goals: to decrease tumor size to limit the extent or severity of subsequent surgery, to increase the vaseularity and oxygenation of the primary tumor site to improve response to irradiation, and to assess the response of the primary tumor to ehemotherapy agents, which may be used after surgery and/or radiation therapy if a response is observed. Radiation has been used for a long time as the definitive treatment for numerous cancers (Table 2). Multimodality treatments are increasingly used to achieve an effect greater than a single therapy alone. In the past decade, combinations of radiation and chemotherapy have provided local control, with organ conservation equal to surgical resection for several types of cancer. 23 These eancers inelude small cell lung cancer, anal carcinoma (preserving sphincter when possible), bladder cancer (preserving bladder function when possible), carcinoma of the esophagus, and head and neck cancers. It is unclear whether these improved results are due to radiosensitization or the additive effects of the radiation and the systemic control of chemotherapy. RADIOPHARMACEUTICALS FOR METASTATIC BONE PAIN he control of bone pain due to multiple skeletal metastasis is a significant clinical problem in patients with advanced cancer of the breast, lung, and prostate. 13,24 Strontium-89 and phosphorus-32 were investigated as early as the 1940's for treating metastatic cancer to bone. Strontium-89 was approved by the Food and Drug Administration in 1993 for palliative therapy to
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Retinoblastoma Chorodial melanoma Unresectable cancers of the lung and pancreas Un resectable sarcomas
PRINCIPLES OF RADIOTHERAPY AND RADIOBIOLOGY
reduce bone pain associated with metastatic cancer. The results obtained with phosphorus-32 are similar to those obtained with strontium-89, but the associated bone marrow toxicity has been severe; it is therefore not considered a favorable treatment at this time. 2s Strontium-89 has a half-life of 50.5 days. The long physical half-life of strontium-89 and the small range of the beta particles, which travel only a few millimeters, contribute to the longlasting effects of this radiopharmaceutical agent. Because of its strong localizing properties, strontium-89 has been shown to deliver a safe and effective systemic radiation dose. 26 Randomized trials have demonstrated that the combination of strontium-89 and local radiation therapy provides more effective palliation than local radiation alone. 2s Strontium-89 acts like calcium, clearing rapidly from the blood and healthy bone and localizing preferentially at sites of osteoblastie metastasis. Strontium-89 delivers useful doses of beta radiation to the lesions while selectively sparing healthy bone and bone marrow. Patients should receive safety instructions after the injections (Table 3). While results of individual studies have varied, the overall efficacy in terms of patients experieneing pain relief (complete + marked + moderate) appears to be in the range of 54% to 84%.25, 27
Strontium-89 is administered intravenously, usually in an outpatient setting, by a radiation oneologist licensed to administer radiopharmaeeutieal agents or by a tieensed nuclear medicine physician. The usual dose is 4 mCi. If neeessary, the dose can be repeated after 90 days or longer. Not all individuals with metastatic bony metastasis are candidates for strontium-S9 (Table 4). The most common adverse effect is mild bone marrow toxicity, which has a nadir of 4 to 8 weeks following the injection, with a partial return to
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baseline in 12 weeks, s A complete blood cell count with platelets should be monitored weekly until counts return to normal limits. Approximately 10% of patients will experience "flare" pain, which occurs 72 hours after the injection, requiring additional analgesics until pain subsides. "Flare" pain can last up to 1 week following the injeetion, but a decrease in the original pain usually does not occur until the second or third week following the injection. Pain relief has been reported to last from 3 to 6 months. RADIATION SAFETY regulations concerning radiation expoF ederal sure stipulate that the maximum permissible dose for whole-body occupational exposure is 50 mSv per year (National Council on Radiation Proteetion and Measurements, 1990). These standards are set based on risk versus nonoeeupational exposure limits and eritieal organ exposure. The recommendations regarding limits for exposure to ionizing radiation are listed in Table 5. Common radioisotopes and their properties are listed in Table 6. Oeeupational exposure is reeommended to be "as low as reasonably achievable." Low levels of exposure are aehieved by elose collaboration and monitoring by the radiation safety officer within the institution. Nursing eare and safety precautions required for implants are influeneed by the type of radioactive isotope, the dosage, and the method of administration. In practice, nurses working with braehytherapy (implants) may be exposed to beta or gamma ray radioactive sources that may be hazardous (Table 7). The nurse's understanding of radiation biology can help reduce fears and anxieties concerning care for these patients. Radiation exposure must be minimized through proper radiation-protection practices. Nurses as-
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signed to care for implant patients should be rotated daily to prevent any one person from unnecessary exposure to the radioactive isotope. Film badges should be worn to measure the amount of radiation exposure. Isolation preeautions are necessary (Table 8). The three most important, simple, and key principles of radiation protection are time, distance, and shielding. These three factors are the most direct actions that health care workers can personally take to reduce their risk and therefore keep their total effeetive dose as low as reasonably achievable. 2s Knowledge of the specific radioisotopes, whether sealed or unsealed, temporary or permanent, will help the nurse provide the safest care and reduce their own anxiety when earing for these patients.
The shorter the time interval that one is exposed to the radioactive source, the less the amount of radiation that will be absorbed. Distance is the most effective means of reducing radiation exposure. The following rule can be used to calculate the effeet of distance: the amount of radiation exposure is redueed by the square of the increase in distance from the radioactive souree. Thus, a worker who doubles the distance from the source reduces the dose to one fourth and a worker who triples the distance from the souree reduces the dose to one ninth, s The type of shielding deviee reeommended depends on the speeifie radioactive source. Alpha particles cannot penetrate the outermost layers of skin and a thin sheet of paper ean suffieiently shield from alpha particles. Alpha particles are not external hazards. Most beta particles, like alpha
PRINCIPLES
particles, are not external hazards. Those isotopes that are beta and gamma emitters present the most hazardous exposure to health care workers and require protective measures (see Table 6). Lead is the material used in both fixed protective barriers and accessory devices, such as aprons and gloves. 2s,29 If health care workers maintain maximum distance from the radioactive source and demonstrate efficient use of time, they usually can protect themselves even without shielding.3° DISLODGEMENT OF SOURCE f the radioactive source becomes dislodged, it should not be touched with bare hands. Longhandled forceps and a lead container should be left in the patient's room; these are used to retrieve and store the radioactive source should it become dislodged. The nurse should use forceps to place a dislodged implant into the container and then notify the radiation safety officer and the radiation oneologist. For seed implant patients, for 2 to 3 days during hospitalization the urine should be strained to retrieve any radioactive seeds that become dislodged. Dressings should be checked for seeds. If seeds become dislodged, the seeds should be placed into the lead container using the forceps.
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MONITORING DEVICES devices, such as a film badge, a M onitoring thermoluminescent dosimeter, or a ring badge, and the pocket ion chamber are the most commonly used personnel-monitoring devices. Personnel monitoring devices, which record the amount of radiation exposure, are required by law. These devices should only be worn within the hospital or work environment. Occupational exposure rates are closely monitored by the radiation safety officer within the institution. The film badge is the most widely used personnelmonitoring device. It is accurate, reliable, and inexpensive. The film badge is made of photographic emulsion mounted in a plastic holder and provides a measure of whole-body exposure. The film darkens in proportion to exposure to radiation and is changed monthly by the radiation safety officer. For environmental monitoring, a Geiger-Mueller counter is used. The Geiger-Mueller counter does
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not measure exposure; instead, it reacts to the presence of ionizing particles by producing electrical pulses triggered by the transfer of radioisotope energy to electrons in the Geiger-Mueller counter. For implant brachytherapy, the radiation safety officer surveys the room, linen, and garbage with the counter after the source is removed and before the room is cleaned. SEXUALITY ISSUES
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atient teaching before implant insertion is necessary and should include issues related to sexuality. This may be an uncomfortable issue for some patients, but one the nurse should address. Of course, the nurse must be comfortable with answering questions concerning sexuality. In gynecologic implant patients, the biggest concern is vaginal stenosis and/or vaginal shortening, which are late effects. Decreased vaginal lubrication and vaginal sensation also may be a problem long term. Vaginal dilators are usually given to patients during the follow-up visit and are recommended to reduce vaginal stenosis. Vaginal dilators or sexual intercourse prevent the vaginal walls from closing and narrowing. A water-soluble lubricant is recommended when using a dilator and before intercourse. Prostate seed implants, which are permanent, may cause concern about sexual intercourse. Patients need to understand that the radioactive seeds will decay over a period of months and that they will not be radioactive. Sexual intercourse can be resumed when the patient feels comfortable and ready, although a condom is recommended for approximately 2 months after the implant. PATIENT EDUCATION
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atient and family education is extremely important before the insertion or implantation of a radioactive isotope (source). The radiation oneology nurse must educate these patients and their families to help relieve fear and anxiety (Table 9). The patient and his or her family may need clarification of misconceptions and continued reinforcement of this initial teaching. Educational brochures and other materials are available through the American Cancer Society, the National Cancer Institute, and the Oncology Nursing Society.
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ADVANCES AND NEW DEVELOPMENTS IN RADIATION THERAPY dvances and new developments in radiation therapy inelude stereotaetie radioneurosurgery, three-dimensional computer treatment planning and eonformal therapy, aceelerated fractionation or hyperfraetionation, and an increase in research concerning the interaction of chemotherapeutic agents with radiation and the use of proton beam radiation for patients who failed conventional radiation. Stereotactic radioneurosurgery is a method of destroying tumor tissue with single large doses of radiation delivered through stereotaetically directed narrow beams. Presently, the three primary methods of delivering stereotactic irradiation include heavy charged particle beams (protons, helium, neon, ete), gamma irradiation emitted from a fixed array of cobalt-60 sources (ie, gamma knife), and high-energy photon irradiation produced with linear accelerators (modified extant machines or dedicated units)Y Stereotactic radioneurosurgery historically has been used primarily for treating arteriovenous malformation and other benign tumors and presently has been the modality used effectively for treatment of small metastatic brain tumors, brain metastases that progress or recur after external radiation therapy, and small relatively spherical high-grade gliomas. 3 High-speed computers and graphic displays have had an important effect on the aeeuraey of radiation therapy. Three-dimensional treatment planning systems have allowed the radiation
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oncologist, physicist, and dosemetrist to view comprehensive graphic displays of anatomy. Threedimensional computer treatment planning with conformal dose delivery has increased the effectiveness of radiation treatments. It ensures that the intended target is being treated with the full planned dose, restricting the high-dose region to conform more closely to the shape of the target. Therefore, normal tissues receive a smaller percentage of the dose, allowing doses to be escalated to the target (tumor). 3,32 New equipment, including multileaf collimators and computer-controlled treatment machines, along with faster and more sophisticated planning systems, are making three-dimensional planning and treatment delivery increasingly practical. 23 Computer-controlled machines, operating by downloading the dose delivery prescription directly from the three-dimensional treatmentplanning computer, represent an important development that may become more widely available. Laboratory and elinieal studies have shown that the biological effects of radiation are improved by using multiple daily fraetionsY Head and neck cancers have been shown to have more positive outcomes with multiple fractions because these cancers are capable of rapidly proliferating during a 6- to 7-week course of radiation when delivered in standard onee-a-day fraetionation. Accelerated fraetionation uses standard fractions (160 to 200 eGy) given two to three times daily with a 6-hour delay between fractions over a shorter treatment time. Hyperfraetionation uses more frequent (more than one treatment per day) smaller fractions (110 to 120 eGy) to give a higher total dose over a standard treatment time. This technique has been safely used in patients with lung cancers and gliomas23 Finally, particle radiation, such as fast neutrons, deuterons, helium ion beams, and negative ~r-mesons, will continue to be tested and refined for use in situations in which conventional radiation is of little value. 3 These treatments are expensive and presently have only very limited applications for cancer patients. CONCLUSION adiation therapy continues to be an extremely important treatment of eaneer. The goal is to control cancer, spare surrounding normal tissue, preserve organs, and reduce acute and long-term
PRINCIPLES OF RADIOTHERAPY AND RADIOBIOLOGY
toxicity. R e s e a r c h c o n t i n u e s i n r a d i a t i o n p h y s i c s , radiobiology, t h r e e - d i m e n s i o n a l c o m p u t e r treatm e n t p l a n n i n g , a n d e o n f o r m a l t h e r a p y . T h e u s e of c o m b i n e d modality t r e a t m e n t s has m i n i m i z e d radical surgery and promoted organ preservation. N u r s e s e a r i n g for o n e o l o g y p a t i e n t s n e e d to h a v e
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a good u n d e r s t a n d i n g of r a d i o b i o l o g y a n d p h y s i e s , w h i e h is t h e f o u n d a t i o n of this specialty. W i t h a s i g n i f i c a n t u n d e r s t a n d i n g of s e i e n e e , a n o n e o l o g y nurse ean better anticipate the potential problems a patient m a y experienee and better manage the a d v e r s e effects a s s o c i a t e d w i t h r a d i a t i o n t h e r a p y .
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16. Shewach DS, Lawrence TS: Gemcitabine and radiosensitization in human tumor cells. Invest New Drugs 14:257-263, 1996 17. McGinn CJ, Shewach DS, Lawrence TS: Radiosensitizing nueleosides. J Nat Cancer Inst 88:1193-1198, 1996 18. Witt ME: Radiation and chemotherapy as combined treatment for advanced head and neck cancer. Med Surg Nurs 7:159-164, 1999 19. Weiner LM, Colarusso P, Goldberg M, etal: Combinedmodality therapy for esophageal cancer: Phase I trial of escalating doses of paclitaxel combination with cisplatin, 5-Fluorouracil, and high-dose radiation before esophagectomy. Scmin Oneo124:S19-93, 1997 (suppl 19) 20. Hall EJ: Radiobiology for the Radiologist (ed 4). Philadelphia, PA, Lippincott, 1994, pp 134-135 21. Vora AR: Problems assoeiated with treating cancer. J Cancer Care 6:141-149, 1996 22. Rosenberg SA: Principles of surgical ontology, in DeVita VT Jr, Hellman S, Rosenberg SA (eds): Cancer: Principles and Practice of Ontology (ed 4). Philadelphia, PA, Lippincott, 1994, pp 238-247 23. Liehter AS, Lawrence TS: Recent advances in radiation ontology. N Engl J Med 332:371-379, 1995 24. Kent TM: Improvements in bone pain management with strontium-89. Radiat Ther 4:23-29, 1995 25. Atkins H, Srivastava S: Radiopharmaceuticals for bone malignaneytherapy. J Nuel Med Teehno126:80-86, 1998 26. Gifford J: Strontium 89 therapy for palliation of metastatic bone pain. Radiat Ther 4:92-94, 1995 27. Robinson RC, Spioer J, Preston D, etal: Treatment of metastatic bone pain with strontium-89. Int J Radiat Appl Instrum 14:219-222, 1987 28. Passmore GC: A review of radiation protection principles and practices for workers and patients in the radiologic health-care environment. Sernin Radiol Teehnol 4:18-30, 1996 29. Jefferies K: Basic concepts of clinical radiation protection. Semin Radiol Technol 4:5-17, 1996 30. Khan F: Radiation protection, Khan F (ed): The Physics of Radiation Therapy (ed 2). Baltimore, MD, Williams & Wilkins, 1994, 474-502 31. Corn BW, Curran WJ, Shrieve DC, et al: Stereotactic radiosurgery and radiotherapy: New developments and new directions. Semin Onco124:707-714, 1997 32. Lichter AS, TenHaken ILK:Three-dimensionaltreatment planning and conformal radiation dose delivery, in DeVita VT, Hellman S, Rosenberg SA (eds): Important Advances in Oneology. Philadelphia, PA, Lippincott, 1995, pp 95-10