Radiation Therapy Today: Options and Applications
Margaret C. McEntee, DVM, DACVIM (oncology), DACVR (radiation oncology)
Radiation therapy has become both increasingly available and in demand due in part to increased client awareness of treatment options for pets with cancer. Additionally, veterinary oncologists recognize the utility of radiation therapy in a field where a multimodality approach is imperative if we are to control and potentially cure cancer in the vast majority of patients. Significant advances are being made in clinical veterinary radiation oncology. Areas of advancement include utilization of megavoltage radiotherapy equipment, daily radiation therapy protocols with administration of higher total doses of radiation, and the use of computed tomography for both imaging and radiation treatment planning. The following discussion will focus on the various types of radiation therapy available and applications.
External beam radiation sources include beams of x-rays, gamma rays, or electrons. External beam radiation sources (also referred to as teletherapy; tele- referring to radiation applied from a distance from the patient) include orthovoltage, and megavoltage (Cobalt 60, and linear accelerator) equipment.
The following provides relevant information on radiation therapy units in use at veterinary oncology treatment centers across the United States. The trend is toward the installation of linear accelerators both at academic institutions and in the private sector.
The radiation from orthovoltage units is referred to as x-rays, generated by bombarding a metallic target (tungsten) with high-energy electrons. This is a relatively low energy radiation source; typically operated at 250 kV. Maximum dose is deposited at the skin surface and dose falls to 90% at ~2 cm of depth in the tissue. As a result the acute effects to the skin can be severe. It is difficult to treat deep-seated tumors due to the limitations of the radiation tolerance of the overlying tissues; the skin dose becomes prohibitively large when adequate doses are to be delivered to deep-seated tumors. Additionally, there is differential absorption of dose in bone versus soft tissue and there is some risk of bone damage or necrosis. Orthovoltage irradiation is primarily suited for treatment of superficial tumors that do not involve adjacent bone. Applications include primarily skin tumors, and nasal cavity tumors after cytoreductive surgery. Orthovoltage units are operated at a relatively short source-to-skin distance (usually 50 cm) limiting the size of the treatment field; the field size is defined by the use of different sized/shaped attachments or cones (rectangular, circular, slanted). Orthovoltage units are relatively inexpensive machines, relatively easy to repair and maintain, and less shielding and space is required for operation.
With cobalt-60 units gamma rays are emitted from a radioactive source with a 5.26-year half-life (the half-life is the time required for an isotope to decay to half of its original strength). The dose rate is constantly decreasing as the source decays and the source needs to be changed every 5 years. A typical teletherapy 60Co source is a cylinder of diameter ranging from 1.0 to 2.0 cm and is positioned in the cobalt unit with its circular end facing the patient. Both isocentric (Theratron 780) and column-mounted (Eldorado 8) units exist. The advantage of isocentric machines is that the patient is positioned only once for the treatment and then the source located in the head of the machine is rotated around the patient. The 60Co source emits radiation constantly (as opposed to linear accelerators or orthovoltage units) and the source must be shielded when the machine is in the off position. The 60Co source decays to 60Ni with the emission of b particles (Emax = 0.32 MeV and two photons per disintegration of energies 1.17 and 1.33 MeV (average energy 1.25 MeV); the gamma rays constitute the useful treatment beam. With an average energy of 1.25 MeV, there are a number of advantages of cobalt 60 over orthovoltage. There is greater penetrability for more deeply seated tumors due to the higher energy. There is uniform dose deposition in bone and soft tissue (versus orthovoltage). There is a dose build-up region such that maximum dose is not deposited until 0.5 cm below the skin surface resulting in what is termed a "skin-sparing" effect (there is less skin reaction than with orthovoltage). Treatment of superficial tumors and potential tumor cells in surgical incisions requires the placement of a tissue-equivalent material (bolus; superflab; wet gauze) over the site to allow dose build-up to occur and maximum dose deposition at the skin level. In this setting there will then be loss of the skin-sparing effect and increased radiation reaction in the skin. The source-to-skin distance is typically 80 cm so larger field sizes are possible than with orthovoltage.
This is one of the most reliable radiation therapy machines because of their mechanical and electric simplicity. A radioactive material license is required for operation. Also, there is a low level of exposure to radiation with a cobalt 60 unit due to a minor persistent leak of radiation from the source despite the shielding; time spent in the room should be limited to the extent that is possible.
Collimators (two pairs of heavy metal blocks) are use to alter the field size. Other beam modifying devices include the use of lead blocks (preformed or custom made; placed on a tray that is located near the head of the machine and is between the radiation source and the patient) or wedges (used to differentially absorb the photon beam to provide more uniform dose distribution in the tumor and normal tissues; specifically in situations where there is a slope in the patients contour; the use of wedges requires computer planning).
Because the cobalt-60 source is not a point source this results in what is known as the geometric penumbra (penumbra refers to the region at the edge of the radiation beam over which the dose rate changes rapidly). This is one disadvantage of cobalt-60 units compared to linear accelerators.
Cobalt-60 units can be used to treat most tumors in companion animals. The one disadvantage is in the treatment of tumors that overly critical normal tissues. For example treatment of tumors that overly the thorax or abdomen may result in unacceptable normal tissue toxicity and patient morbidity due to delivery of dose at depth in the tissue. In these instances it is more advantageous to use a linear accelerator with electron capability (see discussion below).
Linear Accelerator (linac)
Linear accelerators utilize x-rays (also referred to as photons) or electron beams. Linear accelerators use high-frequency electromagnetic waves to accelerate charged particles, ie, electrons, to high energies through a tube; the electrons can be extracted from the unit and used for the treatment of superficial lesions; or they can be directed to strike a target to produce high-energy x-rays for treatment of deep-seated tumors. The energy is higher and varies depending on the machine specifications with a range of 4-25+ MeV (Note: 4 MV machines do not have electron capability; this typically requires a 6 MV machine or higher energy). With the higher energy there is an even greater skin-sparing effect with maximum dose deposited at a depth related to the energy of the photons (see Table 1). The source-to-skin distance is 80-100 cm, and the relatively large source-to-skin distance allows treatment of large fields. It is also possible to treat large volume tumors more uniformly due to the depth dose characteristics. The relatively small focal spot limits the penumbra of the beam, and results in a relatively sharper edge to the treatment field. High output from the machine shortens the treatment time for individual patients and allows treatment of a larger number of patients per day.
Linear accelerators can potentially be equipped with a multileaf collimator allowing the shape of the field to match the shape of the target. Multileaf collimators consist of a large number of pairs of narrow rods with motors that drive the rods in or out of the treatment field thus creating the desired field shape. Units without multileaf collimators have two sets of jaws that can move independently but basically allow the formation of a square or rectangular field, and further modification of the field requires the use of lead blocks.
TABLE 1 : Depths at Which the Dose is 100%, 80%, and 50% of the Maximum Dose for Common Photon Energies :
Electron beams are used to treat superficial lesions. In human radiation therapy centers approximately 15% of patients are treated with electrons at some time during their therapy. Electron beam dosimetry is different from megavoltage. The percent depth doses fall off rapidly. The range (in cm) of electrons in tissue is approximately one half of their energy in million electron volts (MeV). For example, 12 MeV electrons have a range of about 6 cm. Electrons lose about 2 MeV of energy for each centimeter in tissue traversed. Normally the 80 or 90% depth isodose curve is used to encompass the target volume. The 80% isodose curve lies at a depth (in cm) of tissue that is about one third of the electron energy (MeV). In general, higher energy electron beams exhibit a higher surface dose than lower energy electron beams. With lower energy electron beams (below 15 MeV) there is a significant skin sparing effect and if tumors involve the skin it may be necessary to add bolus to increase the skin dose.
The use of electrons requires cones for collimation; electrons scatter readily in air so the beam collimation must extend as close as possible to the skin surface of the patient; electron cones of variable sizes attached to the collimator and extending to the patient's skin surface are used to collimate the electron beams; secondary beam shaping can be accomplished by adding lead cutouts at the end of a cone.
TABLE 2 : Depths at Which the Dose is 100%, 80%, 50% and 10% of the Maximum Central-Axis Dose for Various Electron Beam Energies
Note : A comparison of the above table to that for various photon energies (Table 1) demonstrates the extent to which the dose drops off in tissue with electrons as opposed to photons. This allows the treatment of tumors over the thorax or abdomen while minimizing the dose delivered the underlying critical normal tissues (e.g., lung, heart, and intestinal tract).
Brachytherapy sources include radionuclides that emit gamma and/or beta rays contained in sealed needles, seeds, etc.; iridium 192 is used most commonly. Brachytherapy refers to the fact that the radioactive source is a short distance from the tumor; interstitial brachytherapy (referring to the fact that the radionuclide is placed within the tissue) includes the use of radionuclides that are permanently implanted (radon-222, gold-196), or temporarily implanted (iridium-192).
There is what is referred to as both high dose rate and low dose rate brachytherapy. A high dose rate remote controlled after-loading system (currently available only at the University of California, Davis) utilizes iridium 192 and allows delivery of a higher total dose of radiation to the tumor and not the surrounding normal tissues. Treatment can be accomplished in a relatively short time period under one general anesthesia, and does not require leaving radioactive sources in the patient; it also does not require handling or exposure to the radiation sources as the movement of the radioactive source is computer controlled. Typically a series of treatments are done once a week over a month+. Low dose rate brachytherapy: low-dose rate iridium sources have been more commonly used in veterinary oncology. The radioactive seeds are implanted in the tumor and left for a period of days (5-7 days). The radiation dose is given by continuous irradiation at a low dose rate (10-15 Gy per day) for a maximum tumor dose of 50-70 Gy. There is some exposure to the radiation both by the radiation oncologist that places and removes the seeds; and by the caretakers during the period of hospitalization.
Brachytherapy has been used primarily in the post-operative setting for the treatment of microscopic residual disease.
Strontium-90 (Sr-90) ß-radiation ophthalmic applicator is used to treat very superficial tumors; referred to as plesiotherapy (plesios- is Greek for close or near). It is a radioactive source that has a 28-year half-life and can be used for many years. The holder for the source is attached to a handle and is fitted with a plexiglass shield that protects the operator. The active diameter of the source is less than 1 cm; a typical treatment entails the delivery of 100-200 Gy in one application. Multiple overlapping applications are done as necessary to treat larger lesions. Dose falls off rapidly with depth in the tissue; 100% of the dose is delivered to the surface; 50% at 1 mm and approximately 25% at 2 mm. Examples of applications include the treatment of feline nasal planum squamous cell carcinoma or squamous cell carcinoma in situ and feline cutaneous mast cell tumors.
Radiation Treatment Planning
The initial step in radiation oncology involves a thorough patient evaluation. A patient with a radiosensitive tumor and localized disease would typically be considered a good candidate for radiation therapy. The decision to prescribe a course of radiation therapy is also contingent upon the ability of a patient to undergo multiple anesthetics and expected longevity based on any concurrent medical problems. Patients with either distant metastasis or a radioresistant tumor can still potentially benefit from radiation therapy but should be considered for palliative radiotherapy or in the latter instance combination therapy to include cytoreductive surgery.
A number of different modalities are used to identify tumor location and extent of disease. The most commonly used imaging tools include radiographs, and computed tomography. Other means of imaging tumors in veterinary radiation oncology include ultrasonography, nuclear scintigraphy and magnetic resonance (MR) imaging. Computed tomography (CT) is the single most important component of tumor imaging and is a critical component of computer assisted radiation treatment planning. Based on a CT scan an initial subjective assessment can be made of the extent of disease, potential inclusion of critical normal tissues in the treatment field, and a risk versus benefit determination can be made. Situations arise wherein due to inclusion of critical normal tissues that radiation therapy cannot be recommended for an individual patient and other treatment options need to be explored.
Radiation Treatment Planning
Treatment planning can be done manually or by computer; when treatment planning is done by hand, ie, calculations are done by hand based based on the field size, depth of treatment, etc., then the only setups that are possible are either single treatment fields, or bilateral parallel opposed treatment fields. It is not possible to do a more complex treatment setup without CT-based computer generated treatment planning. CT images are used most commonly, but MR images can also be used for treatment planning.
For patient positioning for radiation treatment setup the patient should be in the same position for the CT scan as they will be for the radiation treatment such that the CT images can be used for radiation treatment planning. CT images can be directly downloaded into the treatment planning computer for use in treatment planning. The use of immobilization devices, eg, alpha cradles, vac-lok patient positioners, thermoplastic masks, bite blocks, etc., allow the patient to more accurately be repositioned for each treatment over a fractionated course of radiation therapy. It is important to maximize the information obtained from the imaging study. Enhanced patient/tumor imaging is possible through the use of intravenously administered contrast medium, placement of radiopaque catheters in hollow viscera, and use of barium paste or other marker on the skin to identify surgical incisions or other pertinent anatomic landmarks.
CT-based computer assisted radiation treatment planning can be two-dimensional, two1/2-dimensional, or three-dimensional depending on the treatment planning system.
The first step may be treatment simulation. A radiation treatment simulator mimics the geometry of a radiation therapy unit but utilizes an x-ray unit. The patient is under anesthesia and positioned for radiation therapy. A radiograph is made and with the assistance of radiopaque rulers placed or projected on the patient's surface, dimensions of treatment areas on films are ascertained and target volumes are selected. At this time decisions are made regarding the need for and placement of lead blocks.
The next step is portal radiography. A film is made using the radiation source to expose the film; one exposure to delineate the treatment field and a second exposure of a larger field by opening the port to delineate the surrounding normal tissues. Port films are usually made on the first day of treatment and then repeated at least one other time or as necessary to check patient positioning and field position as a quality assurance mechanism. The port film is used to confirm the location of the treatment port both in terms of assessing inclusion of tumor in the treatment field, and documenting normal tissues that are included within the treatment field; the port film is also used to assess whether any blocks that are being used are appropriately placed; when blocks are to be used the block is in place for the first exposure and then removed for the second exposure. Port films are an important and permanent part of a radiation patients' medical record; the port film can be referred to if the patient has tumor recurrence (determine if it is in the radiation field that was treated or if it is outside), develops a secondary problem in the treated field, or develops another tumor in close proximity to the original tumor.
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