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Biomedical subjects

M Zaider

Publications and source records attributed to M Zaider.

At least 37 records · Page 2Linked to original sources

Dosimetric and volumetric criteria for selecting a source activity and a source type ((125)I or (103)Pd) in the presence of irregular seed placement in permanent prostate implants.

PURPOSE: The dosimetric merit of a permanent prostate implant relies on two factors: the quality of the plan itself, and the fidelity of its implementation. The former factor depends on source type and on source strength, while the latter is a combination of skill and experience. The purpose of this study is to offer criteria by which to select a source type ((125)I or (103)Pd) and activity. METHODS AND MATERIALS: Given a prescription dose and potential seed positions along needles, treatment plans were designed for a number of seed types and activities, specifically for (125)I with activities ranging from 0.3 to 0.7 mCi, and for (103)Pd with activities in the range of 0.8 to 1.6 mCi. To avoid human planner bias, an automated computerized planning system based on integer programming was used to obtain optimal seed configurations for each seed type and activity. To simulate the effect of seed-placement inaccuracies, random seed-displacement "errors" were generated for all plans. The displacement errors were assumed to be uniformly distributed within a cube with side equal to 2sigma. The resulting treatment plans were assessed using two volumetric and two dosimetric indices. RESULTS: For (125)I implants a coverage index (CI) of 98.5% or higher can be achieved for all activities (CI is the fraction of the target volume receiving the prescribed or larger dose). The external volume index (EI) (i.e., the amount of healthy tissue, as percentage of the target volume, receiving the prescribed or larger dose) increases from 13.9% to 20% as the activity increases from 0.3 to 0.7 mCi. For implants using (103)Pd, the external volume index increases from 10. 2% to 13.9% whenever CI exceeds 98.5%. Volumetric and dosimetric indices (coverage index, external volume index, D90, and D80) are all sensitive to seed displacement, although the activity dependence of these indices is more pronounced for (125)I than for (103)Pd implants. CONCLUSIONS: For both isotopes, the lower activities studied systematically result in lower EIs. If seeds can be placed within approximately 0.5 cm of their intended position (103)Pd should be preferred because its EI is lower than that of (125)I. For all activities the coverage indices and D90 are within the required range. If seed placement uncertainties are larger than 0.5 cm, (125)I provides slightly better target coverage; however, in terms of external volume (healthy tissue) covered, (103)Pd is superior to (125)I.

Brachytherapy↗

Tumour control probability: a formulation applicable to any temporal protocol of dose delivery.

An analytic expression for the tumour control probability (TCP), valid for any temporal distribution of dose, is discussed. The TCP model, derived using the theory of birth-and-death stochastic processes, generalizes several results previously obtained. The TCP equation is [equation: see text] where S(t) is the survival probability at time t of the n clonogenic tumour cells initially present (at t = 0), and b and d are, respectively, the birth and death rates of these cells. Equivalently, b = 0.693/Tpot and d/b is the cell loss factor of the tumour. In this expression t refers to any time during or after the treatment; typically, one would take for t the end of the treatment period or the expected remaining life span of the patient. This model, which provides a comprehensive framework for predicting TCP, can be used predictively, or--when clinical data are available for one particular treatment modality (e.g. fractionated radiotherapy)--to obtain TCP-equivalent regimens for other modalities (e.g. low dose-rate treatments).

Brachytherapy↗

Accuracy in catheter reconstruction in computed tomography planning of high dose rate prostate brachytherapy.

In high dose rate prostate brachytherapy, inadequate reconstruction of catheter geometry in treatment planning may result in erroneous dose delivery. Catheters may be digitized with: (1) Parallel reconstruction: digitized at only one point and assumed parallel and horizontal: (2) Straight reconstruction: digitized at both ends and assumed straight while at an angle: (3) Slice-by-slice reconstruction: digitized on all slices to obtain exact geometry. Our results show that individual catheters are often not parallel to each other, but fairly straight. Parallel reconstruction is the least accurate for dosimetric planning, while slice-by-slice reconstruction is time-consuming. Straight (two-point) reconstruction represents a balance between accuracy and efficiency.

Brachytherapy↗

Practical considerations in using calculated healthy-tissue complication probabilities for treatment-plan optimization.

PURPOSE: Healthy and neoplastic tissues are generally exposed nonuniformly to ionizing radiation. It is thus useful to develop algorithms that predict the probability of tumor control or normal tissue complication probability (NTCP) for any given spatial pattern of dose delivery. The questions addressed here concern: (a) the sensitivity of the NTCP predictions to the actual model used for extrapolation from uniform irradiation (where some clinical data exist) to nonuniform exposures, (b) its dependence on tissue type, and (c) consequences for treatment-plan optimization. METHODS AND MATERIALS: Two (of several possible) NTCP formulations are used here: the Lyman model and a binomial equation. The effective volume-reduction scheme of Kutcher and Burman is used to obtain the NTCP for an arbitrary distribution of dose. NTCP was calculated for seven organs by postulating a dose distribution of maximum nonuniformity. RESULTS: Both models fit available NTCP data well, but have very different extrapolations for exposures of small tissue volumes and very low values of NTCP (e.g., < 5%) where no data exist. Organs with pronounced volume effects (lung, kidneys) show substantial NTCP differences between the two models. Even in organs where the volume effect is small (e.g., spinal cord, brain), differences in NTCP due to the model selected may still have serious clinical consequences, as an actual example (for the spinal cord) indicates. CONCLUSIONS: NTCP calculations based on extrapolations to volume fractions and/or NTCP levels for which reliable data do not exist depend on the model used to fit the data and the degree of dose nonuniformity. If NTCP is to be used in treatment-plan optimization, the prudent approach is to design plans that reproduce the conditions under which available dose-volume data were taken (e. g., uniform dose distributions).

Algorithms↗

Treatment planning for brachytherapy: an integer programming model, two computational approaches and experiments with permanent prostate implant planning.

An integer linear programming model is proposed as a framework for optimizing seed placement and dose distribution in brachytherapy treatment planning. The basic model involves using 0/1 indicator variables to describe the placement or non-placement of seeds in a prespecified three-dimensional grid of potential locations. The dose delivered to each point in a discretized representation of the diseased organ and neighbouring healthy tissue can then be modelled as a linear combination of the indicator variables. A system of linear constraints is imposed to attempt to keep the dose level at each point to within specified target bounds. Since it is physically impossible to satisfy all constraints simultaneously, each constraint uses a variable to either record when the target dose level is achieved, or to record the deviation from the desired level. These additional variables are embedded into an objective function to be optimized. Variations on this model are discussed and two computational approaches--a branch-and-bound algorithm and a genetic algorithm--for finding 'optimal' seed placements are described. Results of computational experiments on a collection of prostate cancer cases are reported. The results indicate that both optimization algorithms are capable of producing good solutions within 5 to 15 min, and that small variations in model parameters can have a measurable effect on the dose distribution of the resulting plans.

Algorithms↗

A little to a lot or a lot to a little: is NTCP always minimized in multiport therapy?

PURPOSE: We address the question of whether or not, for the same average (or integral) dose, a smaller uniform dose to an entire normal tissue structure always results in a lower normal tissue complication probability (NTCP) than does a proportionally larger dose to a partial volume of the same structure. METHODS AND MATERIALS: A recent compilation of NTCP data and two theoretical formulations of the dependence of NTCP on dose and partial volume irradiated-the Lyman probit equation and the binomial model-are used to examine this question. Both models fit equally well available NTCP data. RESULTS: Empirical data indicate that for lung, kidney, and possibly liver (but not for esophagus, brain, or heart), given a fixed tumor dose and fixed integral dose, NTCP can be minimized by irradiating a partial volume fraction rather than the entire normal organ. The binomial model supports this interpretation, whereas the probit model predicts that for all organs uniform irradiation of the whole organ always results in the lowest possible NTCP. CONCLUSIONS: In contrast to what is commonly believed, this study suggests that for at least two normal tissues, namely lung and kidney, there may be situations where "a lot to a little" (i.e., fewer treatment ports) will result in higher tumor control probability and better treatment plan than "a little to a lot" (i.e., multifield treatment). This finding, which is independent of the binomial or probit models used here, depends only on the accuracy of the empirical NTCP data. It is also interesting to note that: a) lung and kidney are commonly classified as parallel tissues, while the others have more of a serial architecture; and b) the choice of the NTCP model can have a profound impact on treatment planning decisions.

Models, Theoretical↗

Definitions of physical and biological low dose.

The concept of 'low dose' may be understood to refer to an average frequency of microdosimetric events (charged-particle traversals) that is substantially less than unity in cells or their nuclei. An important consequence is that in this case the probability of any effect on autonomous cells must be proportional to the absorbed dose and independent of dose rate. However, this definition may be unnecessarily restrictive because--especially in the case of low-LET radiation--only a small fraction of events may cause the effects under consideration (e.g. cell lethality). This results in larger 'biological' rather than 'physical' 'small doses'. From a pragmatic viewpoint, one may consider the fact that in the linear-quadratic model deviations from proportionality between effect probability and absorbed dose are attributed to a term that depends on the square of the absorbed dose. This permits the selection of a criterion which establishes as 'small doses' those in which such deviations are less than a chosen value which in the examples given here is 10%. Different applications of this criterion to the inactivation of V 79 hamster cells are considered.

Animals↗

A calculation of the relative biological effectiveness of 125I and 103Pd brachytherapy sources using the concept of proximity function.

The clinical application of encapsulated radioactive sources in brachytherapy plays an important role in the treatment of malignancy. 125I and 103Pd sources have been widely used in the permanent implant of prostate cancer. An important consideration for the choice of brachytherapy sources is their relative biological effectiveness (RBE). Previous calculations of this quantity have used the dose-averaged lineal energy, yD, as a measure of biological effectiveness. In this approach, however, the selection of a relevant site size remains an open question. Here we avoid this problem by using the generalized theory of dual radiation action to calculate the initial slope, alpha, of the dose-effect curves using the proximity function, t(x), and the biological response function, gamma(x). At low doses and/or low dose rates (e.g., prostate implants) the parameter alpha determines the RBE. Proximity function, t(x), is the probability distribution function of distances between pairs of sublesions; and the biological function, gamma(x), is the probability that two sublesions at a distance x apart results in a lesion. Functions t(x) have been calculated for each source using the Monte Carlo transport codes PHOEL and PROTON5. The function gamma(x) has been taken from a published analysis. The RBE values thus obtained are: 1.5 for 125I and 1.6 for 103Pd. The question of whether an "effective" site size exists where yD approximates best the variation of alpha with radiation quality is also addressed.

Brachytherapy↗

Ab initio electronic structure calculation of a new gene system using the negative factor counting method.

We report a calculation of the electronic structure (density of states and molecular orbitals) of a new gene system-the plasmid shuttle vector pCRR1-performed at the ab initio Hartree-Fock level. To deal with the aperiodicity of the biopolymer, a vectorized version of a negative factor counting (NFC) program has been implemented. With this efficient tool, DNA molecules of up to 100 deoxynucleotides (approximately 10,000 basis functions at the ab initio level) can be calculated routinely. In our calculation the base sequence of the plasmid is explicitly taken into account and a standard helical structure is assumed. Minimum as well as 6-31G basis sets are used in the calculation, and solvation effects are explicitly included. The calculation shows that solvation does not have a significant effect on the electronic structure of the biopolymer. It is found that the frontier orbitals (HOMO and LUMO) are highly localized on the bases. The interpretation of this result in terms of the frontier molecular orbital theory is that the attack of radiation-induced radicals is mainly on the base moieties.

Models, Genetic↗

Physician/patient-driven risk assignment in radiation oncology: reality or fancy?

PURPOSE: Treatment plan optimization in radiation oncology entails designing multiple x-ray beams to irradiate a tumor to a dose that will achieve locoregional control while minimizing normal tissue complications. For some anatomical sites, it is possible to estimate tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) as a function of radiation dose. Thus, treatment plan optimization can be based on biologic end points rather than on dose calculations alone. Given multiple plans with different NTCPs and TCPs, a tradeoff must be made between maximizing TCP and maintaining an acceptable NTCP. How do physicians reach these decisions? Can the process be quantified? Should patients participate in the process? METHODS AND MATERIALS: Physicians and patients were asked to rank a series of treatment plans having different combinations of TCP and NTCP. Responses were parametrized into a figure of merit (FM) equation which quantifies predilections of TCP and NTCP. RESULTS: Physician-based FM equations are site- and patient-specific. Variations exist among physicians, but treatment plan selection is often conservative in accordance with the primum non nocere dictum. FM equations generated from the responses of patients suggest that some patients may be willing to accept higher treatment toxicity in exchange for increased TCP. CONCLUSION: The term "optimized treatment plan" contains inherently subjective criteria which reflect one's willingness to accept treatment morbidity in exchange for probability of cure. These criteria may differ among patients and/or physicians. A quantifiable FM may permit the design of custom-made treatment plans that include physician and patient input.

Decision Making↗

Astigmatism and visual recovery after 'large incision' extracapsular cataract surgery and 'small' incisions for phakoemulsification.

PURPOSE: This study compares the change over time of the astigmatism caused by "large" incision extracapsular cataract extraction (ECCE) and three smaller incisions for phakoemulsification. Based on this data, a mathematical model that predicts the course of astigmatism after a superior incision of length 3 to 12 mm has been developed. The relationship of axial length and preoperative astigmatism to induced post-operative astigmatism, the recovery of visual acuity, and the rate of YAG laser capsulotomy after each procedure also are documented. METHODS: Induced astigmatic change was calculated using a simple method of vector analysis. The change in induced astigmatism was calculated for 8 years after ECCE (n = 144), for 3 years after 6 mm superior incisions (6SUP) (n = 93), for 2 years after 3 mm superior incisions (3SUP) (n = 120), and for 18 months after 3 mm temporal incisions (3Temp) (n = 65). Plotted semi-logarithmically, the astigmatic change in each group may be represented mathematically. RESULTS: Two weeks after ECCE the mean induced cylinder was +3.47 D, which decayed to about -1.25 D after 6 months. Induced cylinder increased gradually to about -1.6 D after 8 years, although this further change was not significantly different than that at 6 months after surgery. For the phako groups, the net induced cylinder on the first post-operative day was: +1.23 D (6SUP), +0.49 D (3Sup), and -0.19 D (3Temp). After 6Sup the wound was astigmatically stable after approximately 3 months, and 3 years after surgery net induced cylinder was -0.66 D. After 3Sup the wound was astigmatically stable after about 6 weeks, and after 18 months net induced cylinder was -0.35 D. No significant change in astigmatism was detected at any time after 3Temp. Maximum visual acuity was reached after a mean of approximately 6 weeks after ECCE, 2 weeks after 6Sup, and between 1 day and 1 week after 3Sup and 3Temp. The rate of YAG laser capsulotomy was higher after ECCE than after any of the phakoemulsification procedures. No relationship of axial length or preoperative astigmatism to astigmatic change was detected. CONCLUSIONS: Incision size and location affect post-operative astigmatism. Induced astigmatism decreases with wound size, and only the 3 mm temporal incision is astigmatically neutral. The time for visual recovery increases with wound size. There appears to be less need for laser capsulotomy after phakoemulsification with capsulorrhexis than after ECCE. Axial length does not affect induced astigmatism after any of the 4 incisions, and preoperative astigmatism does not affect astigmatic change after ECCE and 6Sup.

Aged↗