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Irradiation therapy for lung cancer is mostly restricted to conventional methods. To improve therapeutic ratio, we have combined a treatment planning and a gene therapy approach. Three-dimensional conformal radiotherapy is described as carried out by methods of gene therapy for radiation protection using the manganese-superoxide-dismutase transgene delivered by inhalation gene transfer. These methods may improve therapeutic outcomes in lung cancer.

The Presbyterian-University Hospital of Pittsburgh installed the first clinically designated Leksell gamma knife in the U.S. in August 1987. Gamma knife radiosurgery involves stereotactic target localization with the Leksell frame and subsequent closed-skull single-treatment session irradiation of a lesion with multiple highly focused gamma ray beams produced from 60Co sources. The hemispherical array of sources, the large number of small-diameter beams, and the steep dose gradients surrounding a targeted lesion make physical characterization of the radiation field complex. This paper describes the physical features and the operation of the gamma knife as well as the calibration procedures of the very small, well-collimated beams. The results of studies using in-phantom ion chamber, diode, film, and lithium fluoride thermoluminescent dosimetry were all in close agreement. Both single-beam and multiple-beam dose profiles were measured and reported for the interchangeable helmets, which have 4-, 8-, 14-, and 18-mm-diameter collimators. We also describe the dose calculation and treatment planning algorithm in the treatment planning system. Measurements of the accuracy of mechanical and radiation alignment are also performed and discussed.

Purpose/Objective: In IMRT of tumors abutting critical structures, the PTV substantially overlaps with normal tissue volumes (NTV). Standard IMRT optimization techniques impose constraints only on the PTV and NTV and thus fail to modulate predictably the dose gradient in these overlapping regions. The purpose of this paper is to present the Transitional Boolean Dose Constraints Conjugation, or the TBDCC, optimization technique. This IMRT optimization technique uses constraints conjugation to achieve predictable IMRT dose gradients across overlapping tissue volumes. We report on the TBDCC technique and its effectiveness in more than 150 IMRT patients’ plans otherwise difficult to optimize by standard techniques. Patients presented include post-prostatectomy with iliac nodes, cervix with para-aortic nodes, large meningioma abutting optic nerves and chiasm, and mesothelioma invading the heart and lung pleura. Their comparative IMRT plans, with and without constraints conjugation, are presented.

We propose a mathematical model with the potential capability of predicting the probability of cure and of normal tissue damage in a cancer patient treated with radiation. The basic assumption of the model is that complications occur when small volumes of tissue are totally depleted of the stem cells that are necessary for the repair of radiation damage. We apply this model to the specific problem of radiation injury to the spinal cord (radiation myelitis) and derive a relation between the probability of this complication and the survival probability of individual stem cells. We will perform computer calculations of the complication probability as a function of the dose, fraction size and other parameters of the model and show that good agreement with experimental animal data for this complication can be obtained. Our main objective is to develop mathematical models that would predict the dependence of the probability of cure and of complications on the parameters of the radiation therapy treatment. Such models, together with modern computerized treatment planning techniques could aid the radiotherapist in choosing the optimum treatment strategy. Our approach is a generalization of the model of Munro and Gilbert (Munro, 1961) relating the probability of tumor control to the survival probability of individual tumor cells. We assume that complications arise from the local depletion of clonogenic stem cells and are thus able to relate the complication probability directly to the cell survival probability.

The Leksell gamma unit at the University of Pittsburgh uses 201 highly focused 60Co beams arranged in a hemispherical array. Selective beam blocking can be used to modify the treatment volume into ellipsoid shapes oriented in different directions to match better the shape of the target volume. Dose distributions for different blocking patterns were calculated using specially developed computerized 3-D treatment planning software. The changes in dose distribution with different blocking patterns predicted by computer were verified by film densitometry. Techniques for using selective beam blocking to match more closely the treatment volume to the intended target volume have the potential of reducing the likelihood of complications for radiosurgery with the Leksell gamma unit and need to be further developed.