Radiation oncology consists of two primary treatment modalities: external beam radiation therapy (EBRT) and brachytherapy. Brachytherapy entails placement of sealed radioactive sources, natural or manufactured radioactive isotopes or radionuclides, very close to, or in contact with, target tissues. The absorbed doses diminish rapidly with increased distance from the radioactive sources, thereby enabling the safe delivery of high radiation doses to a localized target region over short periods of time. Brachytherapy techniques are classified according to surgical approach to target volume (i.e., interstitial, intracavitary, transluminal, or surface molds); methods for controlling dose rates (i.e., temporary or permanent implants); source-loading technology (i.e., preloaded, manually afterloaded, remotely afterloaded); and dose rate (i.e., low, medium, or high).
Brachytherapy may be performed concomitantly with surgical resection or in conjunction with procedures that may be required to achieve access to the disease site, such as endoscopy or angioplasty. There are two distinct phases of the brachytherapy process: the insertion of nonradioactive applicators or conduits (e.g., needle, balloon catheter) that receive or transmit the radioactive material into the body, and the loading of the radioactive material (e.g., seeds, wires, liquid colloid isotopes) into the conduits or directly into the tissue. Brachytherapy may be used alone or as an adjunctive treatment in combination with EBRT to increase the total radiation dose directed at a specific target.
Low-dose rate (LDR) and high-dose rate (HDR) brachytherapy deliver intensive radiation therapy to a well-defined local site (treatment volume). LDR and HDR brachytherapy may be used to cure, palliate, or obtain local control of a neoplasm, while sparing sensitive, healthy tissues that may be nearby. Treatment may be given in conjunction with a course of EBRT, or as a single modality.
LDR brachytherapy implants deliver doses at rates generally ranging from 40 to 200 cGy/hr (0.2Gy to 2 Gy/hr), requiring treatment times of 24 to 144 hours, during which time the patient is normally confined to an inpatient treatment room. However, LDR may also be performed as an ambulatory or inpatient procedure in which permanently implanted source(s) deliver radiation as the isotope decays. Permanent interstitial LDR implants that remain in place indefinitely deliver an ultra-low-dose range, generally of 0.01 to 0.3 Gy/hr. The source strength of these permanent implants is chosen so that the prescribed dose is fully delivered when the implanted radioactive source has decayed to a negligible level.
HDR brachytherapy can deliver dose rates in excess of 0.2 Gy/minute (12 Gy/hr). The application of remote afterloading in heavily shielded vaults, instantaneous rates as high as 0.12 Gy/sec (430 Gy/hr) at distances of 1 cm. These HDR brachytherapy applications allow the dose to be delivered in minutes and usually on an outpatient basis; it is often given in a series of multiple fractions.
Generally, cancers with clinically and radiologically well-defined margins that have a low potential for regional and metastatic spread are the most applicable applications for brachytherapy as a single treatment modality. Increasingly, brachytherapy is being utilized in conjunction with EBRT to give a highly localized boost. Combination treatment regimens utilize EBRT as a method to sterilize a larger area of possible microscopic or nodal disease spread, with brachytherapy used in the treatment of areas with gross macroscopic or microscopic residual disease. The combination of these techniques ensures the delivery of high doses of radiation within tumors while normal surrounding tissue is not taken beyond recognized organ tolerance levels, and has the potential for conformal localized dose escalation to areas at high risk for tumor reoccurrence.
Several breast lumpectomy bed brachytherapy devices (e.g., MammoSite®) use a specialized procedure to treat early-stage breast cancer. It is typically performed during initial lumpectomy, but it can also be done as a separate procedure. The MammoSite® catheter, for example, which has a balloon at the tip, is temporarily implanted into the breast zone where the tumor was removed. Once inserted, the balloon is expanded. A radioactive source is then inserted through the catheter directly to the tumor site to allow for treatment of the tumor bed and the surrounding tissue that may contain residual microscopic tumor cells. In this way, side effects such as irradiation of healthy tissue (which is commonly seen with EBRT) are avoided, and treatment can be completed in four to five days (outpatient) compared with seven weeks for traditional EBRT.
Accuboost® (also called noninvasive breast brachytherapy) is breast-conservation therapy that delivers a targeted dose of radiation directly to the tissue surrounding the tumor bed. The Accuboost® system provides image-guided radiotherapy, usually in combination with surgical lumpectomy and other forms of radiation therapy, to treat any remaining pre-cancerous cells around the surgical excision site that, if left untreated, may grow into a new tumor. The breast is placed between X-ray imaging mammography paddles, where images are taken and radiation is delivered to create a focused radiation field pointed directly at the lumpectomy site. A proposed benefit of this therapy is that it reduces radiation exposure to adjacent tissues, including the heart and lung, since the radiation can be delivered from one side of the breast to the other, or from the top of the breast to the bottom. However, no long-term studies are available to confirm this. There is only one comparative study evaluating Accuboost® for this use. In a matched retrospective study, subjects received the boost dose using Accuboost® (n=47) or electron beams (a type of EBRT; n=93). Accuboost® subjects were compared with two electron beam controls matched on age, stage, chemotherapy use, fractionation, and when possible, breast size, comorbidities, and smoking status. Main differences between the two treatment groups were in radiation dose received and timing of radiotherapy administration. With a median follow-up period of 13.6 months, skin/subcutaneous tissue toxicity occurred less often among patients treated with Accuboost® than among those treated with electron beam (p=0.046). Study limitations included the between-group differences in whole-breast radiation dose and timing of boost, as well as selection bias and the study’s retrospective design.
The Xoft® Axxent® Electronic Brachytherapy System (Fremont, CA) is a proprietary platform designed to deliver nonradioactive, isotope-free, ionizing radiation therapy. Although the FDA has given this system a 510(k) approval, there is a paucity of literature available and only a few clinical studies have been conducted on this method of brachytherapy. Therefore, the safety and/or efficacy of this service cannot be established by review of the available published literature.
The Esteya® Electronic Brachytherapy System is designed for High Dose Rate (HDR) brachytherapy, treatment of skin surface lesions. The system utilizes a mobile treatment unit that focuses the treatment dose directly to the skin lesion with the aid of a shielded surface applicator. Typical applications include treatment for Basal Bell Carcinoma, Squamous Cell Carcinoma, Kaposi's Sarcoma, Merkel Cell Carcinoma, Lentigo Maligna, Lentigo Maligna Melanoma, Keloids, and Cutaneous Lymphomas (B and T cell).
Ocular brachytherapy using the Epi-Rad90™ Ophthalmic System (NeoVista, Inc., Fremont, CA) is aimed at providing a therapeutic option for the treatment of subfoveal choroidal neovascularization (CNV) associated with wet, age-related macular degeneration (AMD), a leading cause of vision loss. The Epi-Rad90™ Ophthalmic System treats neovascularization of retinal tissue by means of a focal, directional delivery of radiation to the target tissues in the retina. This device was given an investigational device exemption (IDE) in order to begin clinical trials; recruiting for the Phase III CABERNET (CNV secondary to AMD treated with BEta RadiatioN Epiretinal Therapy) clinical trial started in April 2007, and the study was to conclude in April 2011. The experimental arm of the study used the Epi-Rad90™ Ophthalmic System plus two injections of an antiangiogenic drug, Lucentis® (Genentech, South San Francisco, CA), administered one month apart. The comparator arm used Lucentis® injections administered monthly for the first three injections followed by quarterly injections. At this time, the safety and efficacy of the Epi-Rad90™ Ophthalmic System cannot be established because there is limited available published literature. Also, the device has not yet received US Food and Drug Administration (FDA) approval.