Practical considerations for maximizing heat production in a novel thermobrachytherapy seed prototype.

PURPOSE: A combination of hyperthermia and radiation in the treatment of cancer has been proven to provide better tumor control than radiation administered as a monomodality, without an increase in complications or serious toxicities. Moreover, concurrent administration of hyperthermia and radiation displays synergistic enhancement, resulting in greater tumor cell killing than hyperthermia and radiation delivered separately. The authors have designed a new thermobrachytherapy (TB) seed, which serves as a source of both radiation and heat for concurrent brachytherapy and hyperthermia treatments when implanted in solid tumors. This innovative seed, similar in size and geometry to conventional seeds, will have self-regulating thermal properties. METHODS: The new seed's geometry is based on the standard BEST Model 2301(125)I seed, resulting in very similar dosimetric properties. The TB seed generates heat when placed in an oscillating magnetic field via induction heating of a ferromagnetic Ni-Cu alloy core that replaces the tungsten radiographic marker of the standard Model 2301. The alloy composition is selected to undergo a Curie transition near 50 °C, drastically decreasing power production at higher temperatures and providing for temperature self-regulation. Here, the authors present experimental studies of the magnetic properties of Ni-Cu alloy material, the visibility of TB seeds in radiographic imaging, and the ability of seed prototypes to uniformly heat tissue to a desirable temperature. Moreover, analyses are presented of magnetic shielding and thermal expansion of the TB seed, as well as matching of radiation dose to temperature distributions for a short interseed distance in a given treatment volume. RESULTS: Annealing the Ni-Cu alloy has a significant effect on its magnetization properties, increasing the sharpness of the Curie transition. The TB seed preserves the radiographic properties of the BEST 2301 seed in both plain x rays and CT images, and a preliminary experiment demonstrates thermal self-regulation and adequate heating of a tissue-mimicking phantom by seed prototypes. The effect of self-shielding of the seed against the external magnetic field is small, and only minor thermal stress is induced in heating of the seeds from room temperature to well above the seed operating temperature. With proper selection of magnetic field parameters, the thermal dose distribution of an arrangement of TB and hyperthermia-only seeds may be made to match with its radiation dose distribution. CONCLUSIONS: The presented analyses address several practical considerations for manufacturing of the proposed TB seeds and identify critical issues for the prototype implementation. The authors' preliminary experiments demonstrate close agreement with the modeling results, confirming the feasibility of combining sources of heat and radiation into a single thermobrachytherapy seed.

Dosimetric and thermal properties of a newly developed thermobrachytherapy seed with ferromagnetic core for treatment of solid tumors.

PURPOSE: Studies of the curative effects of hyperthermia and radiation therapy on treatment of cancer show a strong evidence of a synergistic enhancement when both radiation and hyperthermia modalities are applied simultaneously. Varieties of tissue heating approaches developed up to date still fail to overcome such essential limitations as an inadequate temperature control, temperature nonuniformity, and prolonged time delay between hyperthermia and radiation treatments. The authors propose a new self-regulating thermobrachytherapy seed, which serves as a source of both radiation and heat for concurrent administration of brachytherapy and hyperthermia. METHODS: The proposed seed is based on the BEST Medical, Inc., Seed Model 2301-I(125), where tungsten marker core and the air gap are replaced with a ferromagnetic material. The ferromagnetic core produces heat when subjected to alternating electromagnetic (EM) field and effectively shuts off after reaching the Curie temperature (T(C)) of the ferromagnetic material thus realizing the temperature self-regulation. The authors present a Monte Carlo study of the dose rate constant and other TG-43 factors for the proposed seed. For the thermal characteristics, the authors studied a model consisting of 16 seeds placed in the central region of a cylindrical water phantom using a finite-element partial differential equation solver package "COMSOL Multiphysics." RESULTS: The modification of the internal structure of the seed slightly changes dose rate and other TG-43 factors characterizing radiation distribution. The thermal modeling results show that the temperature of the thermoseed surface rises rapidly and stays constant around T(C) of the ferromagnetic material. The amount of heat produced by the ferromagnetic core is sufficient to raise the temperature of the surrounding phantom to the therapeutic range. The phantom volume reaching the therapeutic temperature range increases with increase in frequency or magnetic field strength. CONCLUSIONS: An isothermal distribution matching with the radiation isodose distribution can be achieved within a target volume by tuning frequency and intensity of the alternating magnetic field. The proposed combination seed model has a potential for implementation of concurrent brachytherapy and hyperthermia.

Off-label use of medical products in radiation therapy: summary of the report of AAPM Task Group No. 121.

Medical products (devices, drugs, or biologics) contain information in their labeling regarding the manner in which the manufacturer has determined that the products can be used in a safe and effective manner. The Food and Drug Administration (FDA) approves medical products for use for these specific indications which are part of the medical product's labeling. When medical products are used in a manner not specified in the labeling, it is commonly referred to as off-label use. The practice of medicine allows for this off-label use to treat individual patients, but the ethical and legal implications for such unapproved use can be confusing. Although the responsibility and, ultimately, the liability for off-label use often rests with the prescribing physician, medical physicists and others are also responsible for the safe and proper use of the medical products. When these products are used for purposes other than which they were approved, it is important for medical physicists to understand their responsibilities. In the United States, medical products can only be marketed if officially cleared, approved, or licensed by the FDA; they can be used if they are not subject to or specifically exempt from FDA regulations, or if they are being used in research with the appropriate regulatory safeguards. Medical devices are either cleared or approved by FDA's Center for Devices and Radiological Health. Drugs are approved by FDA's Center for Drug Evaluation and Research, and biological products such as vaccines or blood are licensed under a biologics license agreement by FDA's Center for Biologics Evaluation and Research. For the purpose of this report, the process by which the FDA eventually clears, approves, or licenses such products for marketing in the United States will be referred to as approval. This report summarizes the various ways medical products, primarily medical devices, can legally be brought to market in the United States, and includes a discussion of the approval process, along with manufacturers' responsibilities, labeling, marketing and promotion, and off-label use. This is an educational and descriptive report and does not contain prescriptive recommendations. This report addresses the role of the medical physicist in clinical situations involving off-label use. Case studies in radiation therapy are presented. Any mention of commercial products is for identification only; it does not imply recommendations or endorsements of any of the authors or the AAPM. The full report, containing extensive background on off-label use with several appendices, is available on the AAPM website (http://www.aapm.org/pubs/reports/).

Interstitial gene delivery in human xenograft prostate tumors using titanium metal seeds.

Gene therapy is a promising approach for the treatment of cancers. Strategies for gene vector delivery include systemic and local-regional approaches. Intratumoral delivery of vectors has generally employed direct injections into single or multiple locations throughout the tumor volume. However, this approach leads to nonuniform distributions of reagents within tumors and becomes cumbersome as the required number of injections is increased. We have investigated the effectiveness of an interstitial plasmid gene delivery based on using tiny metallic seeds (GeneSeeds) analogous to technology used for brachytherapy. Feasibility for interstitial use of GeneSeeds was demonstrated expressing reporter plasmids (green fluorescence protein or beta-galactosidase) in human xenograft prostate tumors. Immunohistochemical analysis confirmed effective interstitial delivery, vector expression, and distributions of reporter genes within tumors. Applicability of GeneSeeds for delivery of radiosensitizing cytokines was examined by generating a cytokine [tumor necrosis factor-alpha (TNF-alpha)] expressing vector under the cytomegaloviral promoter and interstitially implanting GeneSeeds with this vector into prostate cancer tumors. TNF-alpha protein expression was observed around the ends of seeds and decreasing in an exponential gradient as a function of distance. The expression of TNF-alpha resulted in tumor growth delay of a human prostate cancer xenograft. These results demonstrate the feasibility of applying interstitial delivery of gene expressing vectors for the treatment of human cancers.