Search PubMed⌕ Search

Biomedical subjects

M Zaider

Publications and source records attributed to M Zaider.

At least 37 records · Page 2Linked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

Dosimetric considerations for catheter-based beta and gamma emitters in the therapy of neointimal hyperplasia in human coronary arteries.

PURPOSE: Recent data indicate that intraluminal irradiation of coronary arteries following balloon angioplasty reduces proliferation of smooth muscle cells, neointima formation, and restenosis. We present calculations for various isotopes and geometries in an attempt to identify suitable source designs for such treatments. METHODS AND MATERIALS: Analytical calculations of dose distributions and dose rates are presented for 192Ir, 125I, 103Pd, 32P, and 90Sr for use in intracoronary irradiation. The effects of source geometry and positioning accuracy are studied. RESULTS: Accurate source centering, high dose rate, well-defined treatment volume, and radiation safety are all of concern; 15-20 Gy are required to a length of 2-3 cm of vessel wall (2-4 mm diameter). Dose must be confined to the region of the angioplasty, with reduced doses to normal tissues. Beta emitters have radiation safety advantages, but may not have suitable ranges for treating large diameter vessels. Gamma emitters deliver larger doses to normal tissues and to staff. Low energy x-ray emitters such as 125I and 103Pd reduce these risks but are not available at high enough activities. The feasibility of injecting a radioactive liquid directly into the angioplasty balloon is also explored. CONCLUSIONS: Accurate source centering is found to be of great importance. If this can be accomplished, then high energy beta emitters such as 90Sr would be ideal sources. Otherwise, gamma emitters such as 192Ir may be optimal. A liquid beta source would have optimal geometry and dose distribution, but available sources, such as 32P are unsafe for use with available balloon catheters.

Brachytherapy↗
PubMed1996

Microdosimetric evaluation of relative biological effectiveness for 103Pd, 125I, 241Am, and 192Ir brachytherapy sources.

PURPOSE: To determine the microdosimetric-derived relative biological effectiveness (RBE) of 103Pd, 125I, 241Am, and 192Ir brachytherapy sources at low doses and/or low dose rates. METHODS AND MATERIALS: The Theory of Dual Radiation Action can be used to predict expected RBE values based on the spatial distribution of energy deposition at microscopic levels from these sources. Single-event lineal energy spectra for these isotopes have been obtained both experimentally and theoretically. A grid-defined wall-less proportional counter was used to measure the lineal energy distributions. Unlike conventional Rossi proportional counters, the counter used in these measurements has a conducting nylon fiber as the central collecting anode and has no metal parts. Thus, the Z-dependence of the photoelectric effect is eliminated as a source of measurement error. Single-event spectra for these brachytherapy sources have been also calculated by: (a) the Monte Carlo code MCNP to generate the electron slowing down spectrum, (b) transport of monoenergetic electron tracks, event by event, with our Monte Carlo code DELTA, (c) using the concept of associated volume to obtain the lineal energy distribution f(y) for each monoenergetic electron, and (d) obtaining the composite lineal energy spectrum for a given brachytherapy source based on the electron spectrum calculated at step (a). RESULTS: Relative to 60Co, the RBE values obtained from this study are: 2.3 for 103Pd, 2.1 for 125I, 2.1 for 241Am, and 1.3 for 192Ir. CONCLUSIONS: These values are consistent with available data from in vitro cell survival experiments. We suggest that, at least for these brachytherapy sources, microdosimetry may be used as a credible alternative to time-consuming (and often uncertain) radiobiological experiments to obtain information on radiation quality and make reliable predictions of RBE in low dose rate brachytherapy.

Americium↗