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Treatment of recurrent malignant gliomas with stereotactic intensity modulated radiation therapy.

Malignant gliomas are usually refractory to aggressive combined-modality therapy, and the incidence of recurrence and death after treatment is very high. State-of-the-art techniques such as stereotactic intensity-modulated radiation therapy (IMRT) are now available to deliver a high dose of radiation to the tumor with relative preservation of surrounding tissues to achieve optimal tumor coverage with minimal toxicity. We report 10 patients (median age 48 years) with recurrent malignant gliomas that were treated with stereotactic directed IMRT. Initial tumor histologies included one low grade glioma (upgraded to anaplastic astrocytoma at recurrence), four anaplastic astrocytomas, and four glioblastomas multiforme. One patient was originally presumed to have a brain metastasis secondary to renal cell carcinoma but was pathologically confirmed as having glioblastoma multiforme at the time of recurrence. Before recurrence, all patients had been treated with external beam radiation therapy (median 59.7 Gy). All recurrences were confirmed by a subtotal resection (5/10) or by imaging (5/10). The median Karnofsky performance score at the time of IMRT was 80. The median tumor volume was 34.69 cm. Treatment was delivered on a 10-MV linear accelerator with a mini-multileaf collimator, MIMiC, and planned with Peacock/Corvus software. Radiation was delivered in daily fractions of 5 Gy, to a total median dose of 30 Gy at the 71% to 93% median isodose line. Median overall survival time was 10.1 months from the date of stereotactic treatment, with 1- and 2-year survival rates of 50% and 33.3%, respectively. Fractionated stereotactic intensity modulated radiation therapy is a novel technique used in the treatment of recurrent malignant gliomas, which produces results comparable to other currently used stereotactic techniques.

Adult↗

Dependence of linac output on the switch rate of an intensity-modulated tomotherapy collimator.

The electro-mechanical, multivane intensity modulated collimator ("MIMiC") slit collimator with 40 vanes has been applied in the delivery of inversely planned sequential tomotherapy to over 4,000 patients. The collimator is binary in that each vane switches between fully open or closed status. Resulting beamlet patterns provide the intensity distributions imparting dose to the patient. The bouncing and damping of vanes at the two ends of their travel cause transient dose perturbations near and at the borders of the treatment field. These perturbations are not explicitly modeled by the planning system. Clinical beamlet profiles and output factors may then differ from those in the planning system and as a function of the vane switch period. A mechanical model of vane switching was developed to describe this dependency. Dose output and distribution of seven simple vane patterns with different switch times were measured with ionization chambers and radiographic films in polystyrene and anthropomorphic phantoms. Linac output dependence on switch time relative to vane open time was determined for four intensity modulated radiotherapy (IMRT) patients from measurements of an ionization chamber embedded in a cylindrical polystyrene phantom. Results demonstrate output dependence on switch time and, accordingly, on the servo mechanism for monitor units, arc length, dose rate, and gantry speed. In conclusion, the output dependence borders on clinical significance-improvements to collimator, dose calculation, commissioning, and quality assurance (QA) are suggested.

Humans↗

Implementing multiple static field delivery for intensity modulated beams.

A clinically oriented two-dimensional intensity-modulated beam delivery method is implemented using multiple static segmented fields, i.e., the "step-and-shoot" approach. Starting with a desired al" intensity distribution, it creates a multiple-level intensity approximation, and then constructs a sequence of segmented fields to deliver the multiple-level intensities using multileaf collimator (MLC) and independent backup jaws. The approach starts with a simple grouping of all the nonzero intensity values into a minimum number of clusters for a user specified deviation tolerance for the ideal plan. The k-means clustering algorithm is then employed to find the optimal levels of intensity that minimize the discrepancies between the ideal and the approximated intensities, without violating the user specified deviation tolerance. The multiple-level intensities are then decomposed into a sequence of machine deliverable segments. Apart from the first segment for each gantry angle, all the other segments are arranged to minimize the total travel distance of the leaves. The first segment covers the entire irradiated area and is used for treatment verification by electronic portal imaging. The implementation issues due to the physical constraints of the MLCs are also addressed.

Algorithms↗

Minimizing the number of segments in a delivery sequence for intensity-modulated radiation therapy with a multileaf collimator.

This paper proposes a sequencing algorithm for intensity-modulated radiation therapy with a multileaf collimator in the static mode. The algorithm aims to minimize the number of segments in a delivery sequence. For a machine with a long verification and recording overhead time (e.g., 15 s per segment), minimizing the number of segments is equivalent to minimizing the delivery time. The proposed new algorithm is based on checking numerous candidates for a segment and selecting the candidate that results in a residual intensity matrix with the least complexity. When there is more than one candidate resulting in the same complexity, the candidate with the largest size is selected. The complexity of an intensity matrix is measured in the new algorithm in terms of the number of segments in the delivery sequence obtained by using a published algorithm. The beam delivery efficiency of the proposed algorithm and the influence of different published algorithms used to calculate the complexity of an intensity matrix were tested with clinical intensity-modulated beams. The results show that no matter which published algorithm is used to calculate the complexity of an intensity matrix, the sequence generated by the algorithm proposed here is always more efficient than that generated by the published algorithm itself. The results also show that the algorithm used to calculate the complexity of an intensity matrix affects the efficiency of beam delivery. The delivery sequences are frequently most efficient when the algorithm of Bortfeld et al. is used to calculate the complexity of an intensity matrix. Because no single variation is most efficient for all beams tested, we suggest implementing multiple variations of our algorithm.

Algorithms↗

Smoothing intensity-modulated beam profiles to improve the efficiency of delivery.

Intensity-modulated beam profiles are generated by an inverse planning or optimization algorithm, a process that, being computationally complex and intensive, is inherently susceptible to noise and numerical artifacts. These artifacts make delivery of the beams more difficult, oftentimes for little, if any, observable improvement in the dose distributions. In this work we examine two approaches for smoothing the beam profiles. The first approach is to smooth the beam profiles subsequent to each iteration in the optimization process (method A). The second approach is to include a term within the objective function that specifies the smoothness of the profiles as an optimization criterion (method B). The two methods were applied to a phantom study as well as three clinical sites: paraspinal, nasopharynx, and prostate. For the paraspinal and nasopharynx cases, which have critical organs with low tolerance doses in close proximity, method B produced sharper dose gradients, better target dose homogeneity, and more critical organ sparing. In the less demanding prostate case, the two methods give similar results. In addition, method B is more efficient during optimization, requiring fewer iterations, but less efficient during DMLC delivery, requiring a longer beam-on time.

Algorithms↗

Verification of dynamic intensity-modulated beam deliveries in canine subjects.

Our objective in this work was to assess the precision and degree of accuracy with which intensity modulated radiation therapy (IMRT) can deliver highly localized dose distributions to tumors near critical structures using the dynamic sliding window technique. Measurements of dose distribution were performed both in vivo and in vitro using a combination of dosimeters [thermoluminescent dosimeters (TLD's), films, and diodes]. In vivo measurements were performed in two groups of purpose-bred dogs: one receiving four-field three-dimensional (3D) conformal treatment and the other receiving IMRT. The algorithms used in the inverse planning process included the Macro Pencil Beam (MPB) model and Projections onto Convex Sets (POCS). Single beam measurements were performed in phantoms to verify the accuracy of monitor unit settings required for delivering the desired doses. The composite doses from the delivery of the seven beam intensity modulated plans were measured in phantoms and cadavers, Biological end points (spinal cord toxicity and neurologic deficits due to irradiation) were evaluated at the end of one year to determine the spatial accuracy of the IMRT treatments over a fractionated course in live subjects. Results in single beam measurements were used at first to improve the dose calculation and translation algorithms. Results of the measurements for the delivery of all seven beams in phantoms confirmed that the system was capable of accurate spatial and dosimetric IMRT delivery. The in vivo results showed dramatic differences between control and IMRT-treated dogs, with the IMRT group showing no adverse effects and the control animals showing severe spinal cord injuries due to irradiation. The measurements presented in this paper have helped to verify the successful and accurate delivery of IMRT in a clinically related model using the University of Washington Medical Center (UWMC) system.

Algorithms↗

Delivery of intensity-modulated radiation therapy with a conventional multileaf collimator: comparison of dynamic and segmental methods.

Intensity-modulated radiation therapy (IMRT) can be delivered with a conventional multileaf collimator (MLC), either in dynamic mode (DMLC) or in segmental mode (SMLC, also known as "step-and-shoot"). The advantage of DMLC is its ability to deliver the desired intensity profile produced by inverse planning with a high degree of fidelity. The SMLC method, on the other hand, resembles treatment with multiple static fields, and can be more easily verified. However, the use of SMLC requires that the desired profile be approximated by discrete levels of intensity, which may lead to degradation in the delivered dose distribution. Clearly, the results of SMLC delivery depend on the number of levels and the spatial resolution of the intensity distribution. In this work, we compare the DMLC method and the SMLC method employing different numbers of levels and different spatial resolutions. Three disease sites were studied: prostate, nasopharynx, and breast, with three cases for each. In general, a 5- to 10-level SMLC plan produced results comparable to that from a DMLC plan. The target coverage is improved by increasing the number of levels while critical organs are better protected with finer spatial resolutions. The beam-on-time (MUs) requirement for SMLC was approximately 20% less than DMLC, but the delivery time (in minutes) was about twice as long. Thus, the choice depends on many factors including machine capability, quality assurance, target coverage, critical organ protection, beam-on-time, delivery time, and other clinical considerations.

Breast Neoplasms↗

Incorporation of realistic delivery limitations into dynamic MLC treatment delivery.

The clinical implementation of IMRT involves the use of a number of complex software-based systems, typically including an inverse planning system, a leaf sequencer, and a computer-controlled treatment delivery system. The inverse planning system determines the desired fluence patterns, the leaf sequencer translates those fluence maps into leaf trajectories, and the control system delivers those trajectories. While verification of intensity-modulated treatment fields has focused primarily on the dosimetric aspects of delivery, accurate delivery of the intended fluence distribution is dependent upon both the leaf sequencer and delivery control systems. Leaf sequencing algorithms typically do not incorporate many control system limitations, and this can lead to discrepancies between planned and delivered sequences. In this work, simple and complex fields were sequenced for the dynamic sliding window technique using different leaf speeds and tolerance settings to identify various limitations of the accelerator control system. This work was conducted on a Varian 2100 EX equipped with a Millennium 120 leaf MLC. The identified limitations were then incorporated into the sequencing algorithm using a limiting leaf velocity (less than the maximum leaf velocity), the leaf position tolerance, and the communications delay in the control system. Collision avoidance in leaf pairs was found to depend on a control system-enforced minimum gap between leaves and led to acceleration effects. By incorporating these effects into the leaf sequencing algorithm, dynamic sliding-window leaf sequences were produced which did not require beam interruptions or dose rate modulations for the parameter values used in calculating the sequence (dose rate, tolerance, leaf speed, and total monitor units). Incorporation of control system limitations into the leaf sequencing algorithm results in IMRT fields that are delivered with the prescribed constant dose rate, require less time to deliver, and have well-defined, calculable transmission dose characteristics.

Acceleration↗

Multiple local minima in IMRT optimization based on dose-volume criteria.

Multiple local minima traps are known to exist in dose-volume and dose-response objective functions. Nevertheless, their presence and consequences are not considered impediments in finding satisfactory solutions in routine optimization of IMRT plans using gradient methods. However, there is often a concern that a significantly superior solution may exist unbeknownst to the planner and that the optimization process may not be able to reach it. We have investigated the soundness of the assumption that the presence of multiple minima traps can be ignored. To find local minima, we start the optimization process a large number of times with random initial intensities. We investigated whether the occurrence of local minima depends upon the choice of the objective function parameters and the number of variables and whether their existence is an impediment in finding a satisfactory solution. To learn about the behavior of multiple minima, we first used a symmetric cubic phantom containing a cubic target and an organ-at-risk surrounding it to optimize the beam weights of two pairs of parallel-opposed beams using a gradient technique. The phantom studies also served to test our software. Objective function parameters were chosen to ensure that multiple minima would exist. Data for 500 plans, optimized with random initial beam weights, were analyzed. The search process did succeed in finding the local minima and showed that the number of minima depends on the parameters of the objective functions. It was also found that the consequences of local minima depended on the number of beams. We further searched for the multiple minima in intensity-modulated treatment plans for a head-and-neck case and a lung case. In addition to the treatment plan scores and the dose-volume histograms, we examined the dose distributions and intensity patterns. We did not find any evidence that multiple local minima affect the outcome of optimization using gradient techniques in any clinically significant way. Our study supports the notion that multiple minima should not be an impediment to finding a good solution when gradient-based optimization techniques are employed. Changing the parameters for the objective function had no observable effect on our findings.

Dose-Response Relationship, Radiation↗

Dosimetric performance of an enhanced dose range radiographic film for intensity-modulated radiation therapy quality assurance.

Film-based quality assurance (QA) is an important element of any intensity modulated radiation therapy (IMRT) program. XV2 film is often used for IMRT QA, however, it has saturation and energy response limitations which hinder accurate film dosimetry. A new commercially released ready-pack film has been introduced that has an extended dose range (EDR2), reportedly allowing measured doses above 600 cGy without saturation. Also, this film may have less energy dependence due to its composition. The purpose of this paper is to study and compare the two types of film with respect to absolute dose accuracy for IMRT plans, percent depth dose accuracy for square fields between 2 and 20 cm, ability to measure composite plan isodoses and single beam fluence maps for IMRT cases, and sensitivity to processor variations over time. In 19 IMRT patient QA tests, the EDR2 film was able to achieve an absolute dose accuracy of better than 2% vs over 4% for XV2 film. The EDR2 film was able to reproduce ionization chamber and diode-measured percent depth doses to 20 cm depth generally to within 1% over the range of field sizes tested compared to about 10% for the XV2 film. When compared to calculations, EDR2 film agreed better than XV2 film for both composite plan isodoses and single beam fluence intensity maps. The EDR2 film was somewhat more resistant to processor changes over time than the XV2 film, with a standard deviation of dose reproducibility of less than 2% compared to 6%, respectively.

Equipment Failure Analysis↗

Smoothing intensity-modulated treatment delivery under hardware constraints.

A method is developed to smooth intensity-modulated beam delivery while considering hardware constraints. The method uses matrix algebra to model MLC leaf motion and hardware constraints such as interleaf digitization, synchronization requirements, and intersegment field abutment to deliver intensity modulated beam sequences. It was implemented and demonstrated for simulated and clinical intensity modulated cases. The simulated cases included intensity distributions from 3 x 3 to 30 x 30 in dimension with 1,000 intensity levels. The clinical examples included four treatments sites: prostate, head and neck, lung, and esophagus cancers. In particular, we studied the relationships between the intensity levels, segment numbers and their influence on the dose-volume histograms of the inversely optimized IMRT treatment plans. It was found that a significant reduction in the leaf segment numbers was achieved by applying the smoothing approach. The effects were found to be more significant for the unconstrained delivery than for the constrained delivery. The effects were also found to be more sensitive for the complex intensity distributions such as the head-and-neck cases than for the less complex ones such as the prostate cases. These results demonstrated the feasibility of maintaining inversely optimized treatment plans under acceptable tolerance levels while smoothing IMRT treatments with hardware constraints.

Algorithms↗

Validation of dynamic MLC-controller log files using a two-dimensional diode array.

Intensity-modulated radiation therapy (IMRT) delivered with multi-leaf collimator (MLC) in the step-and-shoot mode uses multiple static MLC segments to achieve intensity modulation. For typical IMRT treatment plans, significant numbers of segments are delivered with monitor units (MUs) of much less than 10. Verification of the ability of the linear accelerator (linac) to deliver small MU segments accurately is an important step in the IMRT commissioning and quality assurance (QA) process. Recent studies have reported large discrepancies between the intended and delivered segment MUs. These discrepancies could potentially cause large errors in the delivered patient dose. We have undertaken a systematic study to evaluate the accuracy of the dynamic MLC log files, which are created automatically by our commercial MLC workstation after each delivery, in recording the fractional MU delivered in the step-and-shoot mode. Two linac models were evaluated with simple-geometry leaf sequences and delivered with different total MUs and different nominal dose rates. A commercial two-dimensional diode array was used for the measurement. Large discrepancies between the intended and delivered segment MUs were found. The discrepancies were larger for small MU segments at higher dose rate, with some small MU segments completely undelivered. The recorded fractional MUs in the log files were found to agree with what was delivered within the limits of our experimental uncertainty. Our results indicate that it is important to verify the delivery accuracy of small MU segments that could potentially occur in a patient treatment and that the log files are useful in checking the integrity of the linac delivery once validated. Thus validated log files can be used as a QA tool for general IMRT delivery and patient-specific plan verification.

Documentation↗

MAGIC-type polymer gel for three-dimensional dosimetry: intensity-modulated radiation therapy verification.

A new type of polymer gel dosimeter, which responds well to absorbed dose even when manufactured in the presence of normal levels of oxygen, was recently described by Fong et al. [Phys. Med. Biol. 46, 3105-3113 (2001)] and referred to by the acronym MAGIC. The aim of this study was to investigate the feasibility of using this new type of gel for intensity-modulated radiation therapy (IMRT) verification. Gel manufacturing was carried out in room atmosphere under normal levels of oxygen. IMRT inverse treatment planning was performed using the Helios software. The gel was irradiated using a linear accelerator equipped with a dynamic multileaf collimator, and intensity modulation was achieved using sliding window technique. The response to absorbed dose was evaluated using magnetic resonance imaging. Measured and calculated dose distributions were compared with regard to in-plane isodoses and dose volume histograms. In addition, the spatial and dosimetric accuracy was evaluated using the gamma formalism. Good agreement between calculated and measured data was obtained. In the isocenter plane, the 70% and 90% isodoses acquired using the different methods are mostly within 2 mm, with up to 3 mm disagreement at isolated points. For the planning target volume (PTV), the calculated mean relative dose was 96.8 +/- 2.5% (1 SD) and the measured relative mean dose was 98.6 +/- 2.2%. Corresponding data for an organ at risk was 34.4 +/- 0.9% and 32.7 +/- 0.7%, respectively. The gamma criterion (3 mm spatial/3% dose deviation) was fulfilled for 94% of the pixels in the target region. Discrepancies were found in hot spots the upper and lower parts of the PTV, where the measured dose was up to 11% higher than calculated. This was attributed to sub optimal scatter kernels used in the treatment planning system dose calculations. Our results indicate great potential for IMRT verification using MAGIC-type polymer gel.

Ascorbic Acid↗

Guidance document on delivery, treatment planning, and clinical implementation of IMRT: report of the IMRT Subcommittee of the AAPM Radiation Therapy Committee.

Intensity-modulated radiation therapy (IMRT) represents one of the most significant technical advances in radiation therapy since the advent of the medical linear accelerator. It allows the clinical implementation of highly conformal nonconvex dose distributions. This complex but promising treatment modality is rapidly proliferating in both academic and community practice settings. However, these advances do not come without a risk. IMRT is not just an add-on to the current radiation therapy process; it represents a new paradigm that requires the knowledge of multimodality imaging, setup uncertainties and internal organ motion, tumor control probabilities, normal tissue complication probabilities, three-dimensional (3-D) dose calculation and optimization, and dynamic beam delivery of nonuniform beam intensities. Therefore, the purpose of this report is to guide and assist the clinical medical physicist in developing and implementing a viable and safe IMRT program. The scope of the IMRT program is quite broad, encompassing multileaf-collimator-based IMRT delivery systems, goal-based inverse treatment planning, and clinical implementation of IMRT with patient-specific quality assurance. This report, while not prescribing specific procedures, provides the framework and guidance to allow clinical radiation oncology physicists to make judicious decisions in implementing a safe and efficient IMRT program in their clinics.

Algorithms↗

Fuzzy logic guided inverse treatment planning.

A fuzzy logic technique was applied to optimize the weighting factors in the objective function of an inverse treatment planning system for intensity-modulated radiation therapy (IMRT). Based on this technique, the optimization of weighting factors is guided by the fuzzy rules while the intensity spectrum is optimized by a fast-monotonic-descent method. The resultant fuzzy logic guided inverse planning system is capable of finding the optimal combination of weighting factors for different anatomical structures involved in treatment planning. This system was tested using one simulated (but clinically relevant) case and one clinical case. The results indicate that the optimal balance between the target dose and the critical organ dose is achieved by a refined combination of weighting factors. With the help of fuzzy inference, the efficiency and effectiveness of inverse planning for IMRT are substantially improved.

Algorithms↗

Beam orientation optimization for IMRT by a hybrid method of the genetic algorithm and the simulated dynamics.

We have developed a new method for beam orientation optimization in intensity-modulated radiation therapy (IMRT). The problem of beam orientation optimization in IMRT is solved by a decoupled two-step iterative process: (1) optimization of the intensity profiles for given beam configurations; (2) selection of optimal beam configurations based on the ranking by an objective function score for the results of the intensity profile optimization. The simulated dynamics algorithm is used for the intensity profile optimization. This algorithm enforces both the hard constraints and dose-volume constraints. A genetic algorithm is used to select beam orientation configurations. The method has been tested for both a simulated and clinical case, and the results show that beam orientation optimization significantly improved IMRT plans within a time period that is clinically acceptable. The results also show the dependence of the optimal orientation configurations on the prescribed constraints. In addition, beam orientation optimization by the method described here can provide multiple plans with similar dose distributions. This degeneracy characteristic can be exploited to our advantage in introducing additional planning objectives, e.g., the smoothness of intensity profiles, for the selection of the optimal plan among the degenerate configurations for treatment delivery.

Algorithms↗

The optimum intensities for multiple static multileaf collimator field compensation.

A method of determining the optimum beam intensities for compensation using multiple static multileaf collimator fields is presented. In this method a histogram of the number of beam pixels against beam intensity is generated for the intensity-modulated beam (IMB). The intensity of each beam to be used is chosen to minimize the mean square deviation between each bin in the histogram and the closest beam intensity. This method has been applied to sample IMBs possessing one maximum and two maxima. For both cases, the use of uniform beam intensity increments is shown to be close to optimal. In the case with two maxima, the efficacy of irradiating both peaks simultaneously, rather than separately, has been studied and shown to be of potential benefit. The optimum intensities for an IMB for breast radiotherapy are also presented.

Humans↗

Beam orientation optimization in intensity-modulated radiation treatment planning.

Beam direction optimization is an important problem in radiation therapy. In intensity modulated radiation therapy (IMRT), the difficulty for computer optimization of the beam directions arises from the fact that they are coupled with the intensity profiles of the incident beams. In order to obtain the optimal incident beam directions using iterative or stochastic methods, the beam profiles ought to be optimized after every change of beam configuration. In this paper we report an effective algorithm to optimize gantry angles for IMRT. In our calculation the gantry angles and the beam profiles (beamlet weights) were treated as two separate groups of variables. The gantry angles were sampled according to a simulated annealing algorithm. For each sampled beam configuration, beam profile calculation was done using a fast filtered backprojection (FBP) method. Simulated annealing was also used for beam profile optimization to examine the performance of the FBP for beam orientation optimization. Relative importance factors were incorporated into the objective function to control the relative importance of the target and the sensitive structures. Minimization of the objective function resulted in the best possible beam orientations and beam profiles judged by the given objective function. The algorithm was applied to several model problems and the results showed that the approach has potential for IMRT applications.

Algorithms↗