Chapter 1

Overview of Brachytherapy Physics

Ravinder Nath, Ph.D. Department of Therapeutic Radiology Yale University School of Medicine New Haven, Connecticut
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Different Types of Brachytherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Intracavitary Brachytherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Interstitial Brachytherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Intraluminal Brachytherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Surface Molds and Plaques for Brachytherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Different Types of Brachytherapy Loading Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Manual Hot Loading Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Manual Afterloading Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Remote Afterloading Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Image-Guided Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Different Types of Brachytherapy Based on Dose Rate and Duration of Brachytherapy . . . . . . 4 Different Durations of Brachytherapy Typically Used . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Permanent Implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Temporary Implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Dose Rates Used in Brachytherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Introduction
Brachytherapy is a special procedure in therapeutic radiology that utilizes the irradiation of a target with radioactive sources placed at short distances from the target. Typically, the sources are implanted in the target tissue directly (interstitial brachytherapy) or are placed at distances of the order of a few millimeters from the target tissue, in body cavities such as the uterus, mouth, etc. (intracavitary brachytherapy), or externally on structures such as the eye, skin, etc., (surface plaques or molds). Brachytherapy generates highly conformal dose distributions in a target volume because radioactive seeds are implanted directly within or in the vicinity of the target tissue. For example, in a typical interstitial brachytherapy implant, 50 to 100 radioactive seeds, each about the size of a rice grain, are implanted in the tumor using image-guided implantation techniques such as ultrasound, computed tomography (CT), or fluoroscopy, which allow the physician to place radioactive seeds precisely at desired locations with minimal invasiveness. For these applications, low-energy, photon-emitting radionuclides such as 125I (27 keV) and 103Pd (21 keV) are preferred because these sources provide adequate coverage of tumor when used in a grid of about 1 cm spacing and produce minimal exposures to distant organs in the patient, to the hospital personnel performing the procedure, and to the family members and friends of the patient after he/she is released from the hospital with the radioactive seeds in place. Most brachytherapy procedures today are performed in one-day surgery suites without the need for hospitalization. These factors and the depth dose characteristics make brachytherapy a very cost effective and patient friendly procedure compared to 3-D conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT), which also produce highly conformal dose distributions. A key advantage of 3DCRT or IMRT over brachytherapy is that it is noninvasive. However, both 3DCRT and IMRT are very sensitive to patient localization and setup errors because of high dose gradients at the periphery of the target volume. Therefore, the target must be placed at the right position with a precision of about a millimeter relative to the linear accelerator (linac) daily over a course of 5 to 6 weeks of 3DCRT and IMRT, and the clinical target volume

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expanded by 5 to 10 mm for intrafraction movement. In contrast, brachytherapy requires a single visit to a one-day surgery clinic or 3 to 5 visits in an outpatient clinic for high dose-rate (HDR) intracavitary brachytherapy. Unlike 3DCRT and IMRT, brachytherapy is far more forgiving of localization and target motion errors because the implanted sources of radiation in an interstitial implant move with the target. Thus, brachytherapy solves a critical problem of 3DCRT and IMRT, which is that they have a potential to miss the target very precisely unless they are implemented with extreme precision. This high-precision requirement makes 3DCRT and IMRT very expensive, labor intensive, and technically complex. For these practical reasons and other important radiobiological reasons related to continuous low doserate (LDR) irradiation, brachytherapy remains a valuable treatment modality for selected cancers despite the current trend of widespread adoption of 3DCRT and IMRT in radiotherapy. In this chapter, an overview of the rich spectrum of various brachytherapy procedures is presented so that the students have an appreciation of the overall field. Most brachytherapy uses gamma-emitting radionuclides. Many use radionuclides such as 137Cs and 192 Ir, which emit high-energy gammas, that penetrate deeply and also require heavy shielding for radiation protection of the personnel and the patients family. Whenever possible, brachytherapy with low-energy gamma emitters, like 125I and 103Pd is preferred because it requires minimal shielding for radiation protection. On the other hand, beta-emitting sources are commonly used as unsealed sources for systemic brachytherapy similar to nuclear medicine diagnostic procedures. Beta particles are absorbed within a few millimeters in tissues. Hence, beta emitters require minimal radiation shielding unless there is spillage of radioactive material in a liquid form and subsequent contamination of work surfaces. Beta emitters commonly used for brachytherapy include 32P, 106Ru, 90Sr, and 90Y. In the last decade, the betaemitting sources also generated a great deal of interest in intravascular brachytherapy for prevention of restenosis after angioplasty because the distances of interest for treatment are about 2 mm, typical wall thickness of a coronary blood vessel. In this application, the sealed sources of 32P and 90Sr were widely used and 90Sr is still being used today. The only neutron emitter, which has been used clinically, is 252Cf. The advantage of neutron emitters is that their interactions with tissues produce heavy charged particles that have much higher linear energy transfer (LET) than the secondary electrons produced by gammas or betas and because of the higher LET, neutrons are theoretically more effective against hypoxic tumors. Neutrons are, however, notoriously difficult to shield and present a far greater challenge in reducing the radiation hazards to personnel. For these reasons, neutrons are rarely used except in a few major medical research centers.

Different Types of Brachytherapy Intracavitary Brachytherapy

Intracavitary techniques involve placing radioactive sources into custom-designed applicators, which are placed in body cavities. This is commonly used for the treatment of gynecological tumors where the radioactive material can be placed in the uterine cavity and vagina. This is also the most common brachytherapy procedure done worldwide.

Interstitial Brachytherapy
Interstitial brachytherapy involves placing the sealed radioactive sources within tissues. Thus, most nongynecological implants are performed using interstitial techniques. This is the most common brachytherapy procedure performed in the United States. The most common application is permanent implantation for treatment of prostate cancer. Less common are interstitial implants such as the Syed implants for gynecological tumors, which are more challenging to execute because large variations in

1Overview of Brachytherapy Physics

size, shape, and location prevent them from being visualized and implanted with a uniformly applicable algorithm, like prostates.

Intraluminal Brachytherapy
This is really a subclass of intracavitary brachytherapy in which the radioactive sources are inserted in the lumen of a vessel such as the blood vessel, bronchus, esophagus, or bile duct.

Surface Molds and Plaques for Brachytherapy

In this technique, the radioactive sources are placed in custom-designed molds or plaques, which are then placed on the surface of the target tissue rather than being placed inside the target tissue. These techniques are not very commonly used.

Different Types of Brachytherapy Loading Systems

Over the years, many techniques have been developed for handling and loading radioactive materials in order to reduce the radiation exposure of the personnel. These techniques are based upon the three cardinal principles of radiation protection, reducing time of exposure, increasing the distance from the radioactive material, and inserting shielding between the user and the radioactive material. Most of these techniques fall in one of the following categories.

Manual Hot Loading Techniques

When brachytherapy was first introduced over a century ago, the radiotherapy sources were manually introduced into the tumor, hence subjecting the physicians and other operating room personnel to unwanted radiation exposure and the subsequent adverse effects of radiation. Direct hot loading is almost never used today because of its associated radiation hazards that can now be reduced by the adoption of alternative techniques.

Manual Afterloading Techniques

Since 1950s or so, most brachytherapy procedures have been performed using afterloading techniques whereby hollow needles, catheters, or applicators are first inserted into the target volume. The applicators are usually inserted in the operating room. Once the position of the applicators is confirmed, the radioactive material is introduced manually into the applicator. This procedure is usually performed in the patients room rather than the operating room. This afterloading procedure improves placement accuracy because the clinicians can take their time in optimizing the positioning of the applicator without incurring excessive radiation exposure.

Remote Afterloading Techniques

Although the manual afterloading techniques mentioned above reduce radiation exposure for the physician and the operating room staff, the nursing staff and other caregivers as well as visitors continue to be exposed to a small amount of radiation exposure. Even this small exposure can be virtually eliminated by the use of remote-controlled afterloading, in which the radioactive material is loaded into and out of the applicator by microprocessor controls positioned and operated remotely by the caregivers in an adja-

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cent room. Advances in the developments of remote afterloading techniques, especially remote HDR brachytherapy, have changed profoundly the clinical practice of brachytherapy, so that HDR has become a very popular form of brachytherapy, especially in developed countries.

Image-Guided Techniques
Before the use of computerized treatment planning systems became popular, clinicians relied on generalized systems of rules (i.e., the Paterson-Parker System, the Quimby system, the Memorial system, the Paris system, the Manchester system, etc.) for pre-implant or intraoperative planning. All of these early systems depended on tables and nomograms to select number, location, and activities of radioactive sources in an implant to achieve desired dose coverage of an estimated target volume. While traditional systems are the culmination of years of clinical experience and still provide a good point of comparison with modern computerized treatment planning, the description in traditional systems of the actual dose distribution and the underlying anatomy is at best approximate and qualitative. In the last decade, two major advances have been made in brachytherapy treatment planning. One is the increased use of imagebased treatment planning and dose evaluation and the other is the development of computer-assisted dose optimization algorithms for brachytherapy. Developments in three-dimensional tomographic image-based source localization techniques have made it possible to calculate and display dose distributions directly on top of the tomographic images of involved anatomy. This enables clinical decisions to be made based on the visualization of dose distributions with respect to patient anatomy instead of dose tables. It has almost become routine in the last several years that the target volume and normal organs be localized from CT, magnetic resonance imaging (MRI), or ultrasound (US) images. Pre-implant planning can now be carried out by inspecting the instantaneous dose distribution changes resulting from different source placements. In addition, some modern analytic tools including dose volume histograms, normal tissue complication probabilities, and tumor control probabilities can be used to estimate the quality of an implant more quantitatively.

Different Types of Brachytherapy Based on Dose Rate and Duration of Brachytherapy Different Durations of Brachytherapy Typically Used
Permanent Implants In a permanent implant, the radioactive sources are permanently implanted into the tumor, the patient is released from the hospital with radioactive material in him or her, and radioactivity is allowed to decay within the patient. Hence, the dose, dose rate, or the dose distribution cannot be changed after the initial insertion. Many of these procedures are relatively simple, and can be performed in an outpatient clinic and one-day surgery units. Other clinical advantages of the permanent implant are that, in deep-seated tumors, it may be safer because of the lower risk of infection and that a second operation for its removal is not required. Permanent implants are performed with relatively short half-life radioisotopes like 125I, 103 Pd, or 198Au so that the radioactivity decays to a safe level within a few weeks or months and does not present the risk of radiation-induced carcinogenesis due to long-term chronic radiation exposure. Temporary Implants In a removable implant, the radioactive material is temporarily implanted into or close to the tumor and is removed once the desired radiation dose has been delivered. When the treatment time is short (less than 20 minutes), there is better control of the total dose and the dose distribution. Removable implants with

1Overview of Brachytherapy Physics

short treatment times require more precision compared to permanent implants. On the other hand, lower precision and accuracy can be tolerated in LDR temporary implants, because in such implants dwell locations and times may be adjusted to correct for poor needle placement. In intracavitary implants, if the dosimetry is inadequate, the dose for that fraction may be reduced and positioning or packing adjusted for subsequent fractions. If radiobiologically equivalent doses for each modality have been adopted, the decision to use either temporary or permanent implantation depends upon the judgment of the radiation oncologist and his skill and experience with a given system.

Dose Rates Used in Brachytherapy

Brachytherapy can be delivered at enormously different dose rates over a very wide range of treatment times varying from minutes to months. Brachytherapy dose rates have been divided into low, medium, and high dose rates by International Commission for Radiation Units and Measurements (ICRU) Report No. 38 as follows: 1. Low Dose Rate (LDR): 0.4 to 2.0 Gy per Hour This is the traditional dose rate for permanent and manually afterloaded brachytherapy. Temporary implant LDR techniques result in typical treatment times of 3 to 5 days. This requires hospitalization of the patient. These implants are generally manually afterloaded, although LDR remote afterloaders are also available, but not commonly used. Most of the long-term clinical experience with brachytherapy is with LDR. Many of the advantages of brachytherapy are attributed to the radiobiology of continuous LDR irradiation in LDR brachytherapy. 2. Medium Dose Rate (MDR): 2 to 12 Gy per Hour This dose rate, also called intermediate dose rate, is rarely used since it gives excessive exposure if such an implant is manually loaded, and this dose rate does not have the advantages of outpatient brachytherapy afforded by the HDR technique. Pulsed dose rate (PDR) brachytherapy afterloaders were developed in this dose rate realm to replicate the LDR experience in terms of total treatment duration but with the source exposed in pulses for only 5 to 10 minutes per hour. 3. High-Dose-Rate (HDR): More than 12 Gy per Hour HDR brachytherapy utilizes very high activity sources, typically a 10 Ci 192Ir source, which produces a very intense radiation field around the source. Since HDR brachytherapy is associated with high radiation exposure rates, it is only used in well-shielded bunkers. Depending on distance and usage factors, 1 to 2 feet of concrete shielding or its equivalent in other materials is required. Treatment is delivered by remote-control techniques rather than manual loading. The usual dose rate in the commercially available HDR brachytherapy systems is about 100 to 300 Gy per hour, allowing the treatments to be given in only a few minutes on an outpatient basis. The introduction of HDR remote brachytherapy, with its advantages of thorough radiation protection and outpatient treatments, has led to a resurgence of interest in brachytherapy.