Improving IMRT-plan quality with MLC leaf position refinement post plan optimization.

PURPOSE: In intensity-modulated radiation therapy (IMRT) planning, reducing the pencil-beam size may lead to a significant improvement in dose conformity, but also increase the time needed for the dose calculation and plan optimization. The authors develop and evaluate a postoptimization refinement (POpR) method, which makes fine adjustments to the multileaf collimator (MLC) leaf positions after plan optimization, enhancing the spatial precision and improving the plan quality without a significant impact on the computational burden. METHODS: The authors' POpR method is implemented using a commercial treatment planning system based on direct aperture optimization. After an IMRT plan is optimized using pencil beams with regular pencil-beam step size, a greedy search is conducted by looping through all of the involved MLC leaves to see if moving the MLC leaf in or out by half of a pencil-beam step size will improve the objective function value. The half-sized pencil beams, which are used for updating dose distribution in the greedy search, are derived from the existing full-sized pencil beams without need for further pencil-beam dose calculations. A benchmark phantom case and a head-and-neck (HN) case are studied for testing the authors' POpR method. RESULTS: Using a benchmark phantom and a HN case, the authors have verified that their POpR method can be an efficient technique in the IMRT planning process. Effectiveness of POpR is confirmed by noting significant improvements in objective function values. Dosimetric benefits of POpR are comparable to those of using a finer pencil-beam size from the optimization start, but with far less computation and time. CONCLUSIONS: The POpR is a feasible and practical method to significantly improve IMRT-plan quality without compromising the planning efficiency.

Verification of MLC based real-time tumor tracking using an electronic portal imaging device.

PURPOSE: The authors have developed a novel technique using an electronic portal imaging device (EPID) to verify the geometrical accuracy of delivery of dose-rate-regulated tracking (DRRT). This technique, called verification of real-time tracking with EPID (VORTE), can potentially be used for both on-line and off-line quality assurance (QA) of MLC-based dynamic tumor tracking. METHODS: The shape and position of target as a function of time, which is assumed to be known, is projected onto the EPID plane. This projected sequence of apertures as a function of time (target motion) is then used as the reference. The accuracy of dynamic MLC tracking can then be assessed by how well the delivered beam follows this projected target motion without the use of a physical moving phantom. The beam apertures controlled by DRRT (aperture motion) is detected by the EPID as a function of time. The aperture motion is compared to the target motion to evaluate tracking error introduced by DRRT. The accuracy of VORTE was measured using film measurements of ten static fields. The VORTE for dynamic tumor tracking was tested with several target motions, including (1) rigid-body two-dimensional (2-D) cyclic motion in the superior-inferior direction with various period and amplitude; (2) the above 2-D cyclic motion plus cyclic deformation; and (3) 2-D cyclic motion with both deformation and rotation. For each target motion, the controlled aperture motion resulting from DRRT was acquired at approximately 8 Hz using EPID in the continuous-acquisition mode. Leaf positions in all captured frames were measured from the EPID and compared to their expected positions. The passing rate of 2 mm criteria for all leaves from all frames was calculated for each of the four patterns of tumor motion. Additionally, the root-mean-square (RMS) deviations of the centroid of the apertures between the designed and delivered beams were calculated for all three cases. RESULTS: The accuracy of MLC-leaf position determination by VORTE is 0.5 mm (1 standard deviation) by comparison to film measurements. With DRRT, the passing rates using the 2 mm criteria for all acquired frames are 100% for the 2-D displacement, 99% for the 2-D displacement with deformation, and 88% for the 2-D displacement combined with both deformation and rotation. The RMS deviations are 0.6 mm for the 2-D displacement, 1.0 mm for the 2-D displacement with deformation, and 1.1 mm for the 2-D displacement combined with both deformation and rotation. CONCLUSIONS: The VORTE can measure the accuracy of MLC-based tumor tracking without the necessity of employing a moving phantom. Moreover, it can be used for complex target motion (i.e., 2-D displacement combined with deformation and rotation) that is difficult to create with physical moving phantoms. Therefore, the VORTE and the novel QA process illustrated by this study have a great potential for verifying real-time tumor tracking.

Usefulness of guided breathing for dose rate-regulated tracking.

PURPOSE: To evaluate the usefulness of guided breathing for dose rate-regulated tracking (DRRT), a new technique to compensate for intrafraction tumor motion. METHODS AND MATERIALS: DRRT uses a preprogrammed multileaf collimator sequence that tracks the tumor motion derived from four-dimensional computed tomography and the corresponding breathing signals measured before treatment. Because the multileaf collimator speed can be controlled by adjusting the dose rate, the multileaf collimator positions are adjusted in real time during treatment by dose rate regulation, thereby maintaining synchrony with the tumor motion. DRRT treatment was simulated with free, audio-guided, and audiovisual-guided breathing signals acquired from 23 lung cancer patients. The tracking error and duty cycle for each patient were determined as a function of the system time delay (range, 0-1.0 s). RESULTS: The tracking error and duty cycle averaged for all 23 patients was 1.9 +/- 0.8 mm and 92% +/- 5%, 1.9 +/- 1.0 mm and 93% +/- 6%, and 1.8 +/- 0.7 mm and 92% +/- 6% for the free, audio-guided, and audiovisual-guided breathing, respectively, for a time delay of 0.35 s. The small differences in both the tracking error and the duty cycle with guided breathing were not statistically significant. CONCLUSION: DRRT by its nature adapts well to variations in breathing frequency, which is also the motivation for guided-breathing techniques. Because of this redundancy, guided breathing does not result in significant improvements for either the tracking error or the duty cycle when DRRT is used for real-time tumor tracking.

Real-time tumor tracking with preprogrammed dynamic multileaf-collimator motion and adaptive dose-rate regulation.

The authors have developed a new method for real-time tumor tracking with dynamic multileaf-collimator (MLC) motion under condition of free breathing. Unlike other previously proposed tumor-tracking methods, their new method uses a preprogrammed dynamic MLC sequence in combination with real-time dose-rate control. This new scheme circumvents the technical challenge in MLC-based tumor tracking of having to control the MLC motion in real time, based on real-time detected tumor motion. With their new method, the movement of the tumor, as a function of breathing phase, amplitude, or tidal volume, is reflected in the preprogrammed MLC sequence. The irregularity of breathing during treatment is handled by real-time regulation of the machine dose rate, which effectively speeds up or slows down the delivery of radiation as needed. This method is based on the fact that all of the parameters in dynamic radiation delivery, including MLC motion, are enslaved to the cumulative dose, which, in turn, can be accelerated or decelerated by varying the dose rate. Because commercially available MLC systems do not allow the MLC delivery sequence to be modified in real time based on the patient's breathing signal, previously proposed tumor-tracking techniques using a MLC cannot be readily implemented in the clinic today. By using a preprogrammed MLC sequence to handle the required motion, the task for real-time control is greatly simplified. With their new scheme, which they call dose-rate-regulated tracking (DRRT), it is possible to use existing linear accelerators that have dynamic MLC capability to achieve real-time tumor tracking, provided that the beam dose rate can be controlled externally. Tracking-error evaluation for 13 patients out of 14 resulted in a tracking error of less than 1 mm (1 sigma), if the effect of the response time of the treatment machine on the dose-rate modulation can be neglected. Film measurements on a moving phantom with variable breathing patterns and DRRT delivery showed that 97% of the measurement points have gamma values less than 1 (for 3% and 2-mm criteria), while non-DRRT delivery showed only 87%. This study shows that real-time tracking is feasible with DRRT even when the patient breathing frequency is irregular. Effects of the variation of breathing amplitude and of base line drift on the tracking error with DRRT are discussed; pending further study, a criterion is suggested for patient selection in the application of this new technique in the clinic.

Spatial distribution of radiation-induced double-strand breaks in plasmid DNA as resolved by atomic force microscopy.

Atomic force microscopy (AFM) has been used to directly visualize, size and compare the DNA fragments resulting from exposure to low- and high-LET radiation. Double-stranded pUC-19 plasmid ("naked") DNA samples were irradiated by electron-beam or reactor neutron fluxes with doses ranging from 0.9 to 10 kGy. AFM scanning in the tapping mode was used to image and measure the DNA fragment lengths (ranging from a few bp up to 2864 bp long). Double-strand break (DSB) distributions resulting from high-LET neutron and lower-LET electron irradiation revealed a distinct difference between the effects of these two types of radiation: Low-LET radiation-induced DSBs are distributed more uniformly along the DNA, whereas a much larger proportion of neutron-induced DSBs are distributed locally and densely. Furthermore, comparisons with predictions of a random DSB model of radiation damage show that neutron-induced DSBs deviate more from the model than do electron-induced DSBs. In summary, our high-resolution AFM measurements of radiation-induced DNA fragment-length distributions reveal an increased number of very short fragments and hence clustering of DSBs induced by the high-LET neutron radiation compared with low-LET electron radiation and a random DSB model prediction.