A Generalized Linear-Quadratic Model for Radiosurgery, Stereotactic Body Radiation Therapy, and High–Dose Rate Brachytherapy
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A generalized mathematical model for the relation between radiation dose and tumor cell death enables better treatment planning and dose schedule designs for current targeted high-dose radiation therapies in cancer.Keywords:
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Stereotactic radiosurgery (SRS) is a precise focusing of radiation to a targeted point or larger area of tissue. With advances in technology, the radiobiological understanding of this modality has trailed behind. Although found effective in both short- and long-term follow-up, there are ongoing evolution and controversial topics such as dosing pattern, dose per fraction in hypo-fractionnated regimens, inter-fraction interval, and so on. Radiobiology of radiosurgery is not a mere extension of conventional fractionation radiotherapy, but it demands further evaluation of the dose calculation on the linear linear-quadratic model, which has also its limits, biologically effective dose, and radiosensitivity of the normal and target tissue. Further research is undergoing to understand this somewhat controversial topic of radiosurgery better.
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Chapter 7 discusses the use of brachytherapy for prostate cancer, and covers both permanent low dose rate (LDR) and temporary high dose rate (HDR) brachytherapy, which both use a similar template-based transrectal ultrasound-guided transperineal technique and therefore represent similar technical challenges.
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Applied Radiobiology: Continuous Irradiation and Brachytherapy Wigg David R. with CD of interactive graphs. Applied Radiobiology: Continuous Irradiation and Brachytherapy Wigg David R. Medical Physics Publishing, Madison, WI, 2008. Hardcover 288 pp. Price: $140.00. ISBN: 9781930524392 (book), 9781930524453 (interactive CD)
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IMPROVEMENT in results of cancer radiotherapy during recent years is due more to the fact that patients now seek treatment at an earlier stage of the disease than to true progress in treatment. Megavoltage therapy has, of course, meant indubitable progress—and the results in some tumor groups have improved because of it—but the better results depend on physical benefits and bigger dose. The essential problems of radiotherapy, on the other hand, are of a biological nature. The most important of these are the tumor characteristics and the proper utilization of the biological effects of irradiation. The recent advances in radiobiological research have greatly stimulated clinical radiotherapy. The aim of radiotherapy is practical; its achievement requires observation in the field of basic research, and, on the other hand, clinical therapy repeatedly poses new problems for radiobiology. Testing the validity of the observations and hypotheses of experimental radiobiology in clinical work is a task for radiotherapists. Fractionation is an important problem to both biologist and therapist, and splitcourse radiotherapy represents one form of the newer fractionation regimes. Here the treatment is divided into two or perhaps more phases separated by a rest interval. The theoretical basis of this therapy is the difference in cell proliferation between normal and tumor cells (23). During the rest interval, normal tissue proliferates as a result of cell loss stimulating the homeostatic feedback, inducing rapid proliferation. In malignant cells stimulation like this fails, and there is very little regrowth during a rest interval of two to three weeks. This method has been used by Sambrook in England and by Scanlon in the United States for many years. We have employed it increasingly in Helsinki since 1963. As early as 1935 Coutard (5) discussed the value of repeated short series of radiotherapy. Zuppinger (34, 35) was the first to use radiotherapy in two phases in treating patients with advanced cancer of the hypopharynx. Planned splitting of the radiotherapy course was reported by Sambrook in 1959 (21). A retrospective study of the effect of unplanned interruption of radiotherapy was reported in 1959 by Scanlon (25) and in 1964 by Holsti and Taskinen (14). In both studies it was concluded that interrupted treatment might be more favorable than continuous daily irradiation. Afterward, prospective clinical experiences confirmed the preliminary results of retrospective studies (9–12, 15, 22, 24, 26–32). Dutreix et al. (7) presented a modification of the treatment, in which the first part of the split-course therapy is given in two large fractions and the second part is fractionated as daily treatment or three times weekly. Both phases of the treatment have been given as a few large fractions by Levitt et al. (18).
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Brachythrapy is a technique to implant radioactive isotype into or near tumors. The obvious properties of brachytherapy are a very high dose distribution of center, and rapid dose attenuation with the increasing of distance. Brachytherapy generally includes three major categories: low dose rate, high dose rate and pulse dose rate. The most significant clinical value of brachytherapy is that it could create dose distribution to tumor tissues, but decreased radiation injury of normal tissues close to tumor. The development of the clinical brachytherapy technique is always involved in the radiobiological characteristics. The basic concepts involving clinical brachytherapy radiobiology mainly includes: dose-rate effect, repair of radiation injury, re-oxygenation, cell cycle redistribution and repopulation. An amount of translational medical approach is needed to guide the application of clinical brachytherapy by exploring the interaction between brachytherapy radiobiology and clinical brachytherapy effect, as well as taking advantage of brachytherapy radiobiological characteristics. The ultimate goal is to improve tumor local control rate, reduce the occurrence of adverse reactions, and improve patients′ overall survival.
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Brachytherapy; Clinical treatment; Radiobiology
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LARS LEKSELL BEGAN radiobiological investigations to study the effect of high-dose focused radiation on the central nervous system more than 5 decades ago. Although the effects of radiosurgery on the brain tumor microenvironment are still under investigation, radiosurgery has become a preferred management modality for many intracranial tumors and vascular malformations. The effects and the pathogenesis of biological effects after radiosurgery may be unique. The need for basic research concerning the radiobiological effects of high-dose, single-fraction, ionizing radiation on nervous system tissue is crucial. Information from those studies would be useful in devising strategies to avoid, prevent, or ameliorate damage to normal tissue without compromising treatment efficacy. The development of future applications of radiosurgery will depend on an increase in our understanding of the radiobiology of radiosurgery, which in turn will affect the efficacy of treatment. This article analyzes the current state of radiosurgery research with regard to the nature of central nervous system effects, the techniques developed to increase therapeutic efficacy, investigations into the use of radiosurgery for functional disorders, radiosurgery as a tool for investigations into basic central nervous system biology, and the additional areas that require further investigation.
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The unique geometrical features of brachytherapy, together with the wide variety of temporal patterns of dose delivery, result in important interactions between physics and radiobiology. These interactions exert a major influence on the way in which brachytherapy treatments should be evaluated, both in absolute and comparative terms. This article reviews the main physical and radiobiological aspects of brachytherapy and considers examples of their influence on specific types of treatment. The issues relating to the optimization of high dose rate brachytherapy are presented, together with the implications of multiphasic repair kinetics for low dose-rate and pulsed high dose rate brachytherapy. The opportunities for application of radiobiological principles to improve various brachytherapy techniques, together with the integration of brachytherapy with teletherapy, are also outlined. Equations for the numerical evaluation of brachytherapy treatments are presented in the Appendices.
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Introduction - the significance of radiobiology for radiotherapy the growth of tumours cell proliferation in tumours proliferative and cellular organization of normal tumours radiation response and tolerance of normal tissues clonogenic cells and the concept of cell survival models of radiation cell killing DNA damage and cell killing genetic control for the cellular response to ionizing radiation dose-response relationships in radiotherapy clinical manifestations of normal-tissue damage time-dose relationships in radiotherapy the linear-quadratic approach to fractionation and calculation of isoeffect relationships hyperfractionation and accelerated radiotherapy the oxygen effect overcoming hypoxic radioresistance the radiobiology of tumours the dose-rate effect - brachytherapy particle beams in radiotherapy combination of radiotherapy and chemotherapy - principles combination of radiotherapy and chemotherapy - clinical application and evaluation re-treatment tolerance of normal tissues hyperthermia targeted radiotherapy individualization of radiotherapy.
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Abstract Brachytherapy is a form of radiotherapy whereby a radioactive source is used inside or at short distance from the tumor. There are three different forms of brachytherapy: interstitial, intracavitary, and skin therapy. In interstitial brachytherapy, the radioactive sources are implanted inside and throughout the tumor volume; in intracavitary brachytherapy the sources are placed in the body cavities very close to the tumor; while in skin therapy the sources are placed on the skin surface. Conventionally, brachytherapy implants have delivered the radiation at a low dose rate (dose rates of <1 Gy/h). Low dose‐rate (LDR) interstitial implants can be temporary (meaning that the radioactive sources are left in place for a period of time, usually a few days, and then removed) or permanent (left in place without removal), while intracavitary implants are temporary. The advent of methods to deliver the dose at a much higher dose rates, in the range of 1–5 Gy/min, brought an increase in the use of brachytherapy. All high dose‐rate (HDR) brachytherapy treatments are temporary and treatments are administered using discrete fractions.
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