3D dosimetry study of 188Re liquid balloon for intravascular brachytherapy using bang polymer gel dosemeters.

It has been suggested that the combination of intravascular brachytherapy and coronary stent implantation may result in further reduction of restenosis after percutaneous balloon angioplasty. The use of an angioplasty balloon filled with a 188Re liquid beta source for intravascular brachytherapy provides the advantages of accurate source positioning and uniform dose distribution to the coronary vessel wall. The effect of source edge and stent on the dose distribution of the target tissue may be clinically important. In BANG gels, the absorbed radiation produces free-radical chain polymerisation of acrylic monomers that are initially dissolved in the gel. The number of polymer particles is proportional to the absorbed dose. In this study, 3D dose distributions are presented for 188Re balloons, with and without stents, using a prototype He-Ne laser CT scanner and the proprietary BANG polymer gel dosemeters.

Spectrum-analysis and neural networks for imaging to detect and treat prostate cancer.

Conventional B-mode ultrasound currently is the standard means of imaging the prostate for guiding prostate biopsies and planning brachytherapy to treat prostate cancer. Yet B-mode images do not adequately display cancerous lesions of the prostate. Ultrasonic tissue-type imaging based on spectrum analysis of radiofrequency (rf) echo signals has shown promise for overcoming the limitations of B-mode imaging for visualizing prostate tumors. This method of tissue-type imaging utilizes nonlinear classifiers, such as neural networks, to classify tissue based on values of spectral parameter and clinical variables. Two- and three-dimensional images based on these methods demonstrate potential for guiding prostate biopsies and targeting radiotherapy of prostate cancer. Two-dimensional images are being generated in real time in ultrasound scanners used for real-time biopsy guidance and have been incorporated into commercial dosimetry software used for brachytherapy planning. Three-dimensional renderings show promise for depicting locations and volumes of cancer foci for disease evaluation to assist staging and treatment planning, and potentially for registration or fusion with CT images for targeting external-beam radiotherapy.

Factors predicting for postimplantation urinary retention after permanent prostate brachytherapy.

PURPOSE: Urinary retention requiring catheterization is a known complication among prostate cancer patients treated with permanent interstitial radioactive seed implantation. However, the factors associated with this complication are not well known. This study was conducted to determine these factors. METHODS AND MATERIALS: Ninety-one consecutive prostate cancer patients treated with permanent interstitial implantation at our institution from 1996 to 1999 were evaluated. All patients underwent pre-implant ultrasound and postimplant CT volume studies. Isotopes used were (125)I (54 patients) or (103)Pd (37 patients). Twenty-three patients were treated with a combination of 45 Gy of external beam radiation therapy as well as seed implantation, of which only 3 patients were treated with (125)I. Mean pretreatment prostate ultrasound volume was 35.4 cc (range, 10.0-70.2 cc). The mean planning ultrasound target volume (PUTV) was 39.6 cc (range, 16.1-74.5 cc), whereas the mean posttreatment CT target volume was 55.0 cc (range, 20.2-116 cc). Patient records were reviewed to determine which patients required urinary catheterization for relief of urinary obstruction. The following factors were analyzed as predictors for urinary retention: clinical stage; Gleason score; prostate-specific antigen; external beam radiation therapy; hormone therapy; pre-implant urinary symptoms (asymptomatic/nocturia x 1 vs. more significant urinary symptoms); pretreatment ultrasound prostate volume; PUTV; PUTV within the 125%, 150%, 200%, 250%, 300% isodose lines; postimplant CT volume within the 125%, 150%, 200%, 250%, 300% isodose lines; D90; D80; D50; ratio of post-CT volume to the PUTV; the absolute change in volume between the CT volume and PUTV; number of needles used; activity per seed; and the total activity of the implant. Statistical analyses using logistic regression and chi2 were performed. RESULTS: Eleven of 91 (12%) became obstructed. Significant factors predicting for urinary retention were the total number of needles used (p < 0.038); the pretreatment ultrasound prostate volume (p < 0.048); the PUTV (p < 0.02); and the posttreatment CT volume (p < 0.021). Two of 51 patients (3.9%) requiring 33 or fewer needles (median) experienced obstruction vs. 9 of 40 (22.5%) requiring more than 33 (p < 0.007). If the pretreatment ultrasound prostate volume was 35 cc or less (median), 3 of 43 (7%) vs. 8 of 36 (22%) with a volume greater than 35 cc experienced obstruction (p < 0.051). CONCLUSION: The number of needles required (perhaps related to trauma to the prostate) and the prostate volumes were significant factors predicting for urinary retention after permanent prostate seed implantation.

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.

Potential decreased morbidity of interstitial brachytherapy for gynecologic malignancies using laparoscopy: A pilot study.

OBJECTIVES: This pilot study was designed to prospectively assess whether the addition of laparoscopy at the time of interstitial brachytherapy is safe, provides verification and/or guidance of needle placement, and results in a reduction of treatment-related morbidity. METHODS: Between 7/93 and 2/97 15 consecutive eligible patients were entered into this study. All patients received external pelvic radiation to a dose range between 45 and 61.20 Gy using 1.8-Gy fractions. In each patient the minimum prescribed dose for the brachytherapy portion was 20 Gy. Minimum cumulative doses to sites of gross disease ranged from 71.8 to 115.3 Gy. A Syed-Neblett afterloading perineal template was used in all the procedures. Laparoscopy using established guidelines was performed during placement of interstitial needles. During template placement, verification of interstitial needles on laparoscopy and any subsequent changes or needle rearrangement were noted. RESULTS: No acute radiation toxicity greater than Grade 2 was noted during the external beam portion of treatment, and no perioperative complications were encountered. These needles were withdrawn under laparoscopic guidance to just below the peritoneal reflection, avoiding proximity to the bowel and improving tumor coverage. Median follow-up time was 26 months. No late radiation morbidity greater than Grade 2 nor any laparoscopic-related complications were noted. To date, one patient has died of disease; six are alive with disease; and eight are alive free of disease with a mean disease-free survival of 17.3 months. CONCLUSION: Laparoscopy at the time of interstitial brachytherapy appears to be safe. No radiation toxicity greater than Grade 2 has developed. No perioperative complications were seen with the addition of laparoscopy. The addition of laparoscopy to the placement of transperineal interstitial implants impacted needle arrangement and/or loading of sources in 50% of patients.

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.

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.

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.

The combined effects of sublethal damage repair, cellular repopulation and redistribution in the mitotic cycle. I. Survival probabilities after exposure to radiation.

An analytical model is presented that describes radiation-induced cellular inactivation in the presence of sublethal damage repair, cellular repopulation and redistribution in the mitotic cycle (the 3 Rs). The parameters of the model are measurable experimentally. Also taken into account are the initial age distribution of the cell population, the fact that subgroups of cells progress through the cycle at different speeds, the effects of a dose of radiation on the duration of the four phases of the cycle (G1, S, G2, M), the possibility that a certain fraction of the cells are quiescent, and cell loss and/or cell removal from the proliferating population. Survival probabilities are expressed as linear-quadratic functions of dose where the coefficient alpha and beta as well as the recovery constant (t0) are taken to depend on the position of the cell in the mitotic cycle. Explicit analytical expressions for inactivation probability are given for clonogenic cells exposed to continuous or fractionated radiation. Two model calculations are used to illustrate the formalism: in one, the redistribution of cells during fractionated therapy is examined. In the other calculation, it is shown that it is sufficient to take into account differences in proliferation rates and the change in the ratio alpha/beta within the generation cycle for cells that may have otherwise equal response to acute exposures to explain that in a fractionated treatment protocol late-responding cells are more sensitive to the dose per fraction than early-responding cells. It is not necessary to invoke differences in radiosensitivity between these two classes of cells.

Application of the HSEF to assessing radiation risks in the practice of radiation protection.

The primary risk coefficients upon which exposure limits for radiation protection purposes are currently based are derived almost exclusively from cancer-induction data obtained from human populations exposed to radiations of low linear energy transfer. The question of higher linear energy transfer radiations is handled by means of quality factors derived from values for relative biological effectiveness obtained from animal data. However, the advent of microdosimetry has made it possible to establish hit size effectiveness functions from single-cell systems, both in vitro and in vivo. This type of function can substitute completely for the concept of relative biological effectiveness, Q and equivalent dose. A common basis for risk coefficients and the hit size effectiveness function lies in the fact that human cancers are monoclonal and thus single cell in origin. The present communication utilizes this common base as a means of extending the present low-linear energy transfer based risk coefficients to include carcinogenic responses from exposure in radiation fields of any one or mixed qualities, extending from the smallest to the largest linear energy transfers of practical consequence. In doing so, risks from ionizing radiations of any linear energy transfer may be predicted more accurately than at present.

The effects of sublethal damage recovery and cell cycle progression on the survival probability of cells exposed to radioactive sources.

Cell progression through the mitotic cycle during low dose rate irradiation may alter notably the survival probability, particularly when a fraction of the dose is delivered during a sensitive phase of the cycle. In this paper we indicate that the consequences of this phenomenon, commonly believed to lead to an "inverse dose rate effect", may be significantly modulated (and even cancelled) as a result of (a) interactions among sublethal lesions produced in different phases of the mitotic cycle, and (b) variations in these lesions' production rates and repair ability from one phase of the cycle to another. The mathematical model presented (and accompanying numerical examples) takes into account the possibility of changes (e.g. radioactive decay) in the dose rate during exposure.

Rapid dose calculations for stereotactic radiosurgery.

A three-dimensional dose calculation algorithm is described for stereotactic radiosurgery using multiple noncoplanar beam arcs. Precalculated dose libraries of 20-deg arc segments, or mini arcs, are stored in computer memory which permits rapid calculation of complete, high resolution, three-dimensional isodose distributions and dose volume histograms. Three-dimensional patient contours and target volumes are obtained from CT scans and angiographic x rays. Rapid dose calculations are made possible by the use of arc libraries and an improved algorithm for mapping beam doses to the dose calculation grid. This permits more flexibility in designing optimum treatment plans, as five-six complete plans can be generated in less than 1 h. Thus many possible treatment options can be tested in the 3-4-h time period typically available in stereotactic procedures between CT scanning and treatment.

Microdosimetry for boron neutron capture therapy.

Preclinical studies for boron neutron capture therapy (BNCT) using epithermal neutrons are ongoing at several laboratories. The absorbed dose in tumor cells is a function of the thermal neutron flux at depth, the microscopic boron concentration, and the size of the cell. Dosimetry is therefore complicated by the admixture of thermal, epithermal, and fast neutrons, plus gamma rays, and the array of secondary high-linear-energy-transfer particles produced within the patient from neutron interactions. Microdosimetry can be a viable technique for determining absorbed dose and radiation quality. A 2.5-cm-diameter tissue-equivalent gas proportional counter has been built with 50 parts per million (ppm) 10B incorporated into the walls and counting gas to simulate the boron uptake anticipated in tumors. Measurements of lineal energy (y) spectra for BNCT in simulated volumes of 1-10 microns diameter show a dose enhancement factor of 4.3 for 30 ppm boron, and a "y" of 250 keV/microns for the boron capture process. Chamber design plus details of experimental and calculated linear energy spectra will be presented.

Determination of the kerma factors in tissue-equivalent plastic, C, Mg, and Fe for 14.7-MeV neutrons.

Microdosimetric measurements were made with tissue-equivalent plastic (TEP), C-, Mg-, and Fe-walled proportional counters filled with propane-based tissue equivalent (TE) gas and Ar gas and irradiated with 14.7-MeV neutrons. A theoretical model was used for the analysis of energy deposition in spherical detectors. An effective average mass stopping-power ratio and a W correction were calculated to convert the gas ionization to the kerma in the wall material. The neutron fluence at the position of microdosimetric measurements was determined with an associated particle chamber mounted with surface barrier detectors. The experimental measurements along with the calculated correction factors yielded kerma factors of 0.660 X 10(-8) cGy cm2 for TEP, 0.219 X 10(-8) cGy cm2 for C, 0.122 X 10(-8) cGy cm2 for Mg, and 0.479 X 10(-9) cGy cm2 for Fe. The estimated uncertainties are 8.0% for TEP, 10.5% for C, and 9.3% for Mg and Fe.

The direct determination of dose-to-water using a water calorimeter.

A flexible, temperature-regulated, water calorimeter has been constructed which consists of three nested cylinders. The innermost "core" is a 10 X 10 cm right cylinder made of glass, the contents of which are isolated from the environment. It has two Teflon-washered glass valves for filling, and two thermistors are supported at the center by glass capillary tubes. Surrounding the core is a "jacket" that provides approximately 2 cm of air insulation between the core and the "shield." The shield surrounds the jacket with a 2.5-cm layer of temperature-regulated water flowing at 51/min. The core is filled with highly purified water the gas content of which is established prior to filling. Convection currents, which may be induced by dose gradients or thermistor power dissipation, are eliminated by operating the calorimeter at 4 degrees C. Depending upon the power level of the thermistors, 15-200 microW, and the insulation provided by the glass capillary tubing, the temperature of the thermistors is higher than that of the surrounding water. To minimize potential errors caused by differences between calibration curves obtained at finite power levels, the zero-power-level calibration curve obtained by extrapolation is employed. Also the calorimeter response is corrected for the change in power level, and therefore thermistor temperature, that follows the resistance change caused by irradiation. The response of the calorimeter to 4-MV x rays has been compared to that of an ionization chamber irradiated in an identical geometry.(ABSTRACT TRUNCATED AT 250 WORDS)