Uncertainty in dose estimation for gynecological implants.

One source of uncertainty in doses computed for intracavitary gynecological applications is the imprecision inherent in localizing the sources and the points of interest on radiographs of the implant and in transferring that data into the treatment planning computer. To quantify the effect of these activities on the accuracy of computed doses, five physicists and two dosimetrists performed computerized dose calculations on five applications chosen randomly from our patient files. For each of these applications, doses were computed at the traditional points A and B and at points in the bladder and rectum. Using identical sets of films, each planner located both the radioactive sources and points of interest, or only the sources, or only the points of interest. Another set of films was used to measure the accuracy of digitizing alone. Planners received no instructions on either the definition or the placement of the points of interest. Overall uncertainties in computed doses to points A and B and bladder were found to be about 7%. Uncertainty in dose to the rectum was on the order of 50%. Analysis of the results showed that about 1% of the error was due to digitization and about 2% to identification of source locations. Among the individual planners, almost all of the dose variation was from differences in placement of the points of interest on the implant radiographs. The results demonstrate the need for standard definitions and locations for points of calculation so that meaningful comparisons can be made among institutions.

Very fast simulated reannealing in radiation therapy treatment plan optimization.

PURPOSE: Very Fast Simulated Reannealing is a relatively new (1989) and sophisticated algorithm for simulated annealing applications. It offers the advantages of annealing methods while requiring shorter execution times. The purpose of this investigation was to adapt Very Fast Simulated Reannealing to conformal treatment planning optimization. METHODS AND MATERIALS: We used Very Fast Simulated Reannealing to optimize treatments for three clinical cases with two different cost functions. The first cost function was linear (minimum target dose) with nonlinear dose-volume normal tissue constraints. The second cost function (probability of uncomplicated local control) was a weighted product of normal tissue complication probabilities and the tumor control probability. RESULTS: For the cost functions used in this study, the Very Fast Simulated Reannealing algorithm achieved results within 5-10% of the final solution (100,000 iterations) after 1000 iterations and within 3-5% of the final solution after 5000-10000 iterations. These solutions were superior to those produced by a conventional treatment plan based on an analysis of the resulting dose-volume histograms. However, this technique is a stochastic method and results vary in a statistical manner. Successive solutions may differ by up to 10%. CONCLUSION: Very Fast Simulated Reannealing, with modifications, is suitable for radiation therapy treatment planning optimization. It produced results within 3-10% of the optimal solution, produced using another optimization algorithm (Mixed Integer Programming), in clinically useful execution times.

Custom beam profiles in computer-controlled radiation therapy.

A computer-controlled radiation therapy technique is demonstrated which uses multiple concurrent boost fields to modify the beam profile of a conventional treatment beam. A principal field, identical to that of a corresponding conventional treatment plan, delivers the major component of the prescribed dose. Dose increments given from boost fields placed within this principal field compensate for variations in patient anatomy, for variations in target volume shape, and/or for imperfect beam characteristics, such as excessive off-axis dose or inadequate beam wedge angle. This concurrent boost field technique is demonstrated for several treatment sites. It produces significant improvement in uniformity of dose delivered to the target compared to conventional treatment. Implementation of these treatments requires a computer-controlled linear accelerator with independently-movable collimator jaws, an automatic beam set-up procedure, and a patient prescription database. Since all fields are delivered under computer control, concurrent boost technique treatment times are not much longer than those of conventional treatments.

Tissue heterogeneity effects in treatment plan optimization.

PURPOSE: There is general agreement that tissue density correction factors improve the accuracy of dose calculations. However, there is disagreement over the proper heterogeneity correction algorithm and a lack of clinical experience in using them. Therefore, there has not been widespread implementation of density correction factors into clinical practice. Furthermore, the introduction of optimized conformal therapy leads to new and radically different treatment techniques outside the clinical experience of the physician. It is essential that the effects of tissue density corrections are understood so that these types of treatments can be safely delivered. METHODS AND MATERIALS: In this paper, we investigate the effect of tissue density corrections on optimized conformal type treatment planning in the thorax region. Specifically, we study the effects on treatment plans optimized without type treatment planning in the thorax region. Specifically, we study the effects on treatment plans optimized without tissue density corrections, when those corrections are applied to the resulting dose distributions. These effects are compared for two different conformal techniques. RESULTS: This study indicates that failure to include tissue density correction factors results in an increased dose of approximately 5-15%. This is consistent with published studies using conventional treatment techniques. Additionally, the high-dose region of the dose distribution expands laterally into the uninvolved lung and other normal structures. The use of dose-volume histograms to compare these distributions demonstrates that treatment plans optimized without tissue density corrections lead to an increased dose to uninvolved normal structures. This increase in dose often violates the constraints used to determine the optimal solution. CONCLUSIONS: The neglect of tissue density correction factors can result in a 5-15% increase in the delivered dose. In addition, suboptimal dose distributions are produced. To benefit from the advantages of optimized conformal therapy in the thorax, tissue density correction factors should be used.

The influence of dose constraint point placement on optimized radiation therapy treatment planning.

To efficiently use linear and quadratic programming for treatment planning optimization on a routine basis, automated methods are needed for placing dose constraint points. We have investigated, for linear programming optimization, the minimum number of constraint points needed to achieve an acceptable approximation to the desired (ideal) solution. Seven different constraint point placement algorithms were evaluated for a given objective function. One of these algorithms was chosen for routine clinical use at our institution. This algorithm places constraint points on the perimeter of the target volume and on the perimeter and in the interior of each normal structure. Additional points are placed on the perimeter of a constant thickness buffer region surrounding the target volume. Excellent optimization results are obtained with 40-70 constraint points per treatment planning slice.

Improved dose homogeneity in the head and neck using computer controlled radiation therapy.

Computer-controlled radiation therapy techniques are demonstrated which improve dose homogeneity throughout the nasopharynx when compared to conventional treatment techniques. The typical approach using a heavily weighted anterior field and opposed wedged lateral fields results in a dose gradient from 95% to 110% or greater. All three of the computer-controlled techniques investigated improved the dose uniformity to a range from 95% to 105% or less. Multiple overlapping fields are used to compensate for patient anatomy and treatment beam characteristics. Treatment planning and monitor unit calculations are quite time-consuming at this stage of development. Actual treatment time is not unreasonably long and can be improved in future releases of the therapy machine control software.

Comparison of simulated annealing algorithms for conformal therapy treatment planning.

PURPOSE: The efficiency of four fast simulated annealing algorithms for optimizing conformal radiation therapy treatment plans was studied and the resulting plans were compared with each other and to optimized conventional plans. METHODS AND MATERIALS: Four algorithms were selected on the basis of their reported successes in solving other minimization problems: fast simulated annealing with a Cauchy generating function, fast simulated annealing with a Lorentzian generating function, variable step size generalized simulated annealing (VSGSA), and very fast simulated reannealing (VFSR). They were tested on six clinical cases using a multiple beam coplanar conformal treatment technique. Relative beam weights were computed that maximized the minimum tumor dose subject to dose-volume constraints on normal organ doses. Following some initial tuning of the annealing parameters, each algorithm was applied identically to each test case. Optimization tests were run using different random number sequences and different numbers of iterations. RESULTS: The VSGSA algorithm consistently produced the best results. Using long run times, it generated plans with the highest minimum tumor dose in five of the six cases. For the short run times, the VSGSA solutions averaged larger minimum tumor doses than those of the other algorithms for all six patients, with increases ranging from 0.4 to 5.9 Gy. For three of the patients, the conformal plan gave a clinically significant increase in the minimum tumor dose over the conventional plan, ranging from 8.2 to 13.0 Gy. In two other cases, there was little difference between the two treatment approaches. For one case, the optimized conventional plan was much better than the conformal plan because the conventional beam arrangement included wedges, which offset the multiple beam advantage of the conformal plans. CONCLUSIONS: For equal computing times of both long and short duration, the VSGSA algorithm consistently produced conformal plans that were superior to those produced by the other algorithms. The simple conformal technique used in this study showed a significant potential advantage in the treatment of abdominal tumors. In three of the cases, the conformal plans showed clinically important increases in tumor dose over optimized conventional plans.

Fraction size, dose and time dependence of X ray induced late renal injury.

Histologic quantitation of renal radiation injury based on an intact mouse model correlates well with loss of renal mass, as measured by the ratio of right to left renal weight, radiation dose, and time after irradiation. Use of the radiation dose at which 50% of animals show renal tubular changes of a specified grade (ED50), allows comparison of 1, 5 and 15 fraction exposures. The X-ray dose necessary to effect significant injury (Grade 3 change) by six months after irradiation (ED50) was 11.6, 25.7, and 44.0 Gy for single, 5, and 15 fractions, respectively. Isoeffect plots of total radiation dose as a function of fraction number are linear on logarithmic coordinates, indicating that this relationship followed a power function. When plotted as inverse total dose versus dose per fraction, the six month post-irradiation data were linear, but the 12 month data were not. Lack of linearity is not in agreement with the multi-fraction isoeffect linear quadratic model.

Biomarker monitoring of a population residing near uranium mining activities.

We investigated whether residents residing near uranium mining operations (target population), who are potentially exposed to toxicants from mining waste, have increased genotoxic effects compared with people residing elsewhere (reference population). Population surveys were conducted, and 24 target and 24 reference residents were selected. The selected subjects and controls were matched on age and gender and they were nonsmokers. Blood samples were collected for laboratory studies. The standard cytogenetic assay was used to determine chromosome aberration frequencies, and the challenge assay was used to investigate DNA repair responses. We found that individuals who resided near uranium mining operations had a higher mean frequency of cells with chromosome aberrations and higher deletion frequency but lower dicentric frequency than the reference group, although the difference was not statistically significant. After cells were challenged by exposure to gamma-rays, the target population had a significantly higher frequency of cells with chromosome aberrations and deletion frequency than the reference group. The latter observation is indicative of abnormal DNA repair response in the target population.

Assessment of a linear accelerator for segmented conformal radiation therapy.

Segmented conformal radiation therapy is a new computer-controlled treatment technique under investigation in which the target volume is subdivided into thick transverse segments each of which is then treated individually by rectangular transverse abutting fields. In order to obtain uniform dose at abutments, the machine isocenter remains fixed in the patient and field edges are defined by independently moving focused collimator jaws to give matching geometric divergence. Mechanical variation in jaw and gantry positioning will create some dose variation at field abutments. Film dosimetry was used to study the radiation field positioning accuracy and precision of a commercial linear accelerator. A method of field position calibration was developed using multiple nonabutting fields exposed on the same radiograph. Verification of collimator jaw calibration measurements was performed using multiple abutting fields exposed on a single radiograph. Measurements taken over 5 months of clinical accelerator operation studied the effects of simple jaw motion, simple gantry motion, and combined jaw/gantry motion on jaw position precision and accuracy. The inherent precision and accuracy of radiation field positioning was found to be better than +/- 0.3 mm for both jaws with all types of motions except for the Y2 jaw under combined jaw/gantry motion. When the ability to deliver abutting beams was verified in clinical mode, the average dose variation at abutments was less than 6% at all gantry angles except for one. However, due to accelerator software limitations in clinical mode, the settings for collimator positions could not take advantage of the maximum accuracy of which the hardware is capable.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimized dynamic rotation with wedges.

Dynamic rotation is a computer-controlled therapy technique utilizing an automated multileaf collimator in which the radiation beam shape changes dynamically as the treatment machine rotates about the patient so that at each instant the beam shape matches the projected shape of the target volume. In simple dynamic rotation, the dose rate remains constant during rotation. For optimized dynamic rotation, the dose rate is varied as a function of gantry angle. Optimum dose rate at each gantry angle is computed by linear programming. Wedges can be included in the optimized dynamic rotation therapy by using additional rotations. Simple and optimized dynamic rotation treatment plans, with and without wedges, for a pancreatic tumor have been compared using optimization cost function values, normal tissue complication probabilities, and positive difference statistic values. For planning purposes, a continuous rotation is approximated by static beams at a number of gantry angles equally spaced about the patient. In theory, the quality of optimized treatment planning solutions should improve as the number of static beams increases. The addition of wedges should further improve dose distributions. For the case studied, no significant improvements were seen for more than 36 beam angles. Open and wedged optimized dynamic rotations were better than simple dynamic rotation, but wedged optimized dynamic rotation showed no definitive improvement over open beam optimized dynamic rotation.

An equivalent squares template.

A template for calculating equivalent squares of irregularly shaped fields is described. Calculations using the template are essentially scatter summations. Comparisons with a computer program showed good agreement in equivalent squares and tumor doses (within 0.8%). Comparisons with area-perimeter ratio methods of computing equivalent squares showed consistently better accuracy using the template. For highly irregular fields, the template calculation required 3-10 min for central axis computation, comparable to that required by the other manual methods.

Accuracy of a two-sensor sonic digitizer.

Digitizing devices are typically used in radiotherapy computer treatment planning for entering patient anatomy, the locations of internal radioactive source, and the outlines of irregularly shaped external beams. The errors encountered in the use of a large-area two-sensor sonic digitizer for computer input have been studied. Conversion of data from triangular to Cartesian coordinates makes the precision of the digitizer nonuniform over the sensitive area. The response of each senor has been measured and found to be a nonlinear function of distance. The assumption of linearity in computing the triangular distances from the sensor readings produces errors in the computed distances of up to 0.8%. An alternative method of computing the distances using a fitted cubic function reduces the errors to less than 0.1%. For a test pattern, the maximum position error was reduced from 0.5 to 0.1 cm.

Collimator scatter in modeling radiation beam profiles.

In computer dose calculations using scatter-air ratio sector summation algorithms, the primary dose from the target to points away from the central axis of a beam is computed using an exponential intensity model of the source and a transmission parameter for the collimator. This model works well inside the beam and near edges but is inaccurate outside the beam at distances of more than 1-2 cm from beam edges. We have modified the standard beam profile model to include a dose contribution representing photon radiation scattered from the collimators. Collimator edges are treated mathematically as line sources and an adjustable parameter is introduced which represents the activity per unit length of the collimator edges. Dose from the collimator edges is assumed to decrease purely geometrically as the inverse of the square of the distance and no modification is made for tissue attenuation. With these assumptions, the total collimator scatter dose to a point is most accurately computed by a line integral over the edges of the beam outline. This modification fits naturally into the standard scatter-air ratio sector summation computer algorithm but adds significantly to dose computation time. Some approximations eliminate the line integration and lead to a collimator scatter term which is proportional to field perimeter and independent of off-axis distance. The modified dose model was tested by comparing measured dose profiles with computed ones using x-ray beams from Philips (6 and 15 MV) and Varian (4 and 6 MV) accelerators. There was significant improvement in fit compared to the standard beam model for points outside the radiation beam.

Satellite digital display for the Clinac-18.

A satellite digital display of the gantry and collimator positions has been mounted on the Clinac-18 console. This module provides simultaneous digital readout of the gantry angle, collimator rotation angle, upper-jaw position, and lower-jaw position. Continuous display of these parameters during the treatment is important in minimizing patient treatment errors.

Treatment plan optimization using linear programming.

Linear programming is a versatile mathematical tool for optimizing radiation therapy treatment plans. For planning purposes, dose constraint points, possible treatment beams, and an objective function are defined. Dose constraint points are specified in and about the target volume and normal structures with minimum and maximum dose values assigned to each point. A linear objective function is designed that defines the goal of optimization. A list of potential treatment beams is defined by energy, angle, and wedge selection. Then, linear programming calculates the relative weights of all the potential beams such that the objective function is optimized and doses to all constraint points are within the prescribed limits. Historically, linear programming has been used to improve conventional treatment techniques. It can also be used to create sophisticated, complex treatment plans suitable for delivery by computer-controlled therapy techniques.

Long term variation in beam symmetry as a function of gantry angle for a computer-controlled linear accelerator.

Testing computer-controlled linear accelerators for patient safety and proper patient dose delivery requires that certain beam characteristics be monitored over an extended period of time. Computer-controlled conformal radiation therapy using asymmetric collimator jaw settings necessitates stable symmetric treatment beams. Long term beam symmetry measurements have been performed on a Philips SL20 dual energy computer-controlled linear accelerator. Symmetry in both the radial and transverse axis of each x-ray beam was monitored for eight gantry positions. These measurements were undertaken to determine the effectiveness of the SL20 beam steering system during dose delivery of 50 monitor units (MU) per field. Evaluation of the data shows that careful beam steering setup procedures result in x-ray beams in which fluctuations in symmetry as a function of gantry angle are within +/- 1.5%. Day to day instabilities produce a total overall variation in beam symmetry on the order of +/- 2.0%. Results suggest the measurement of symmetry as a function of gantry position become a routine quality assurance procedure for this accelerator.

The effect of geometric errors in the reconstruction of iridium-192 seed implants.

In the treatment of tumors using interstitial implants of radioactive seeds, the accuracy of computed dose distributions depends upon the accuracy with which the three-dimensional source geometries are reconstructed from radiographs of the implants. The effect of geometric reconstruction errors in iridium-192 seed implants were studied, using tumor dose as the measure. Tumor dose was defined as the average dose around the periphery of the treatment volume. Three ideal mathematical implants and five actual patient implants were used. The implants were distorted by randomly moving a specified number of seeds a specified distance. Tumor doses were directly calculated for the ideal implants. For the actual implants, isodose distributions were plotted and were read by a radiotherapist. For both types of implants, percentage errors in the tumor doses were calculated for the distorted reconstructions relative to the correct reconstructions. It was found that the tumor dose was accurate to within 5% if all the seeds were reconstructed to within 0.5 cm of their actual positions. Furthermore, up to 5% of the seeds could be mismatched between films, or otherwise incorrectly reconstructed, with position errors as large as 20 cm, and not change the tumor dose by more than 5%.

Computer interface for a linear accelerator.

A computer interface for the Clinac-18 linear accelerator has been developed, using a standard CAMAC interface plus buffer amplifiers to isolate the CAMAC from the accelerator electronics. Buffer amplifiers are employed because direct connection of the CAMAC system to the accelerator was found to affect accelerator operation. The total interface accommodates the four gantry position analog signals and thirteen digital signals describing all available treatment options. The interface also allows the computer to inhibit beam operation.

Dose-volume considerations with linear programming optimization.

A method of incorporating dose-volume considerations within the framework of conventional linear programming is presented. This method is suitable for the optimization of beam weights and angles using a conformal treatment philosophy (i.e., tailoring the high-dose region to the target volume only). Dose-volume constraints are introduced using the concept that volumes of normal tissue nearer the target volume will be allowed higher dose constraints than volumes of normal tissue distal to the target volume. Each involved normal structure is divided into high-dose and low-dose volumes. These two volume partitions are represented by constraint points with either high-dose or low-dose constraints, respectively. Optimized treatment plans for three clinical sites demonstrate that this technique meets or surpasses the original dose-volume constraints for a conformal-type treatment plan using straightforward linear programming in a time frame that is comparable to other linear programming problems.