Is RapidArc more susceptible to delivery uncertainties than dynamic IMRT?

PURPOSE: Rotational IMRT has been adopted by many clinics for its promise to deliver treatments in a shorter amount of time than other conventional IMRT techniques. In this paper, the authors investigate whether RapidArc is more susceptible to delivery uncertainties than dynamic IMRT using fixed fields. METHODS: Dosimetric effects of delivery uncertainties in dose rate, gantry angle, and MLC leaf positions were evaluated by incorporating these uncertainties into RapidArc and sliding window IMRT (SW IMRT) treatment plans for five head-and-neck and five prostate cases. Dose distributions and dose-volume histograms of original and modified plans were recalculated and compared using Gamma analysis and dose indices of planned treatment volumes (PTV) and organs at risk (OAR). Results of Gamma analyses using passing criteria ranging from 1%-1 mm up to 5%-3 mm were reported. RESULTS: Systematic shifts in MLC leaf bank positions of SW-IMRT cases resulted in 2-4 times higher average percent differences than RapidArc cases. Uniformly distributed random variations of 2 mm for active MLC leaves had a negligible effect on all dose distributions. Sliding window cases were much more sensitive to systematic shifts in gantry angle. Dose rate variations during RapidArc must be much larger than typical machine tolerances to affect dose distributions significantly; dynamic IMRT is inherently not susceptible to such variations. CONCLUSIONS: RapidArc deliveries were found to be more tolerant to variations in gantry position and MLC leaf position than SW IMRT. This may be attributed to the fact that the average segmental field size or MLC leaf opening is much larger for RapidArc. Clinically acceptable treatments may be delivered successfully using RapidArc despite large fluctuations in dose rate and gantry position.

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.

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: constant dose rate vs dose rate regulation.

PURPOSE: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. METHODS: Step-and-shoot IMRT plans optimized at a reference phase were extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. RESULTS: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10% faster or slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing period irregularities. When ±20% variation of target motion amplitude was present as breathing irregularity, the two delivery methods show compatible plan quality if the dose distribution of CDRT delivery is renormalized. CONCLUSIONS: Delivery of 4D-IMRT treatment plans, stemmed from 3D step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate regulation. Comparison of cumulative dose distribution indicates that the preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT strategy, as it compensates the interplay between patient breathing irregularity and tracking delivery without compromising the segment-weight modulation.

GPU-accelerated Monte Carlo convolution/superposition implementation for dose calculation.

PURPOSE: Dose calculation is a key component in radiation treatment planning systems. Its performance and accuracy are crucial to the quality of treatment plans as emerging advanced radiation therapy technologies are exerting ever tighter constraints on dose calculation. A common practice is to choose either a deterministic method such as the convolution/superposition (CS) method for speed or a Monte Carlo (MC) method for accuracy. The goal of this work is to boost the performance of a hybrid Monte Carlo convolution/superposition (MCCS) method by devising a graphics processing unit (GPU) implementation so as to make the method practical for day-to-day usage. METHODS: Although the MCCS algorithm combines the merits of MC fluence generation and CS fluence transport, it is still not fast enough to be used as a day-to-day planning tool. To alleviate the speed issue of MC algorithms, the authors adopted MCCS as their target method and implemented a GPU-based version. In order to fully utilize the GPU computing power, the MCCS algorithm is modified to match the GPU hardware architecture. The performance of the authors' GPU-based implementation on an Nvidia GTX260 card is compared to a multithreaded software implementation on a quad-core system. RESULTS: A speedup in the range of 6.7-11.4x is observed for the clinical cases used. The less than 2% statistical fluctuation also indicates that the accuracy of the authors' GPU-based implementation is in good agreement with the results from the quad-core CPU implementation. CONCLUSIONS: This work shows that GPU is a feasible and cost-efficient solution compared to other alternatives such as using cluster machines or field-programmable gate arrays for satisfying the increasing demands on computation speed and accuracy of dose calculation. But there are also inherent limitations of using GPU for accelerating MC-type applications, which are also analyzed in detail in this article.

Planning and delivery of intensity-modulated radiation therapy.

Intensity modulated radiation therapy (IMRT) is an advanced form of external beam radiation therapy. IMRT offers an additional dimension of freedom as compared with field shaping in three-dimensional conformal radiation therapy because the radiation intensities within a radiation field can be varied according to the preferences of locations within a given beam direction from which the radiation is directed to the tumor. This added freedom allows the treatment planning system to better shape the radiation doses to conform to the target volume while sparing surrounding normal structures. The resulting dosimetric advantage has shown to translate into clinical advantages of improving local and regional tumor control. It also offers a valuable mechanism for dose escalation to tumors while simultaneously reducing radiation toxicities to the surrounding normal tissue and sensitive structures. In less than a decade, IMRT has become common practice in radiation oncology. Looking forward, the authors wonder if IMRT has matured to such a point that the room for further improvement has diminished and so it is pertinent to ask what the future will hold for IMRT. This article attempts to look from the perspective of the current state of the technology to predict the immediate trends and the future directions. This article will (1) review the clinical experience of IMRT; (2) review what we learned in IMRT planning; (3) review different treatment delivery techniques; and finally, (4) predict the areas of advancements in the years to come.

Leaf-sequencing for intensity-modulated arc therapy using graph algorithms.

Intensity-modulated arc therapy (IMAT) is a rotational IMRT technique. It uses a set of overlapping or nonoverlapping arcs to create a prescribed dose distribution. Despite its numerous advantages, IMAT has not gained widespread clinical applications. This is mainly due to the lack of an effective IMAT leaf-sequencing algorithm that can convert the optimized intensity patterns for all beam directions into IMAT treatment arcs. To address this problem, we have developed an IMAT leaf-sequencing algorithm and software using graph algorithms in computer science. The input to our leaf-sequencing software includes (1) a set of (continuous) intensity patterns optimized by a treatment planning system at a sequence of equally spaced beam angles (typically 10 degrees apart), (2) a maximum leaf motion constraint, and (3) the number of desired arcs, k. The output is a set of treatment arcs that best approximates the set of optimized intensity patterns at all beam angles with guaranteed smooth delivery without violating the maximum leaf motion constraint. The new algorithm consists of the following key steps. First, the optimized intensity patterns are segmented into intensity profiles that are aligned with individual MLC leaf pairs. Then each intensity profile is segmented into k MLC leaf openings using a k-link shortest path algorithm. The leaf openings for all beam angles are subsequently connected together to form 1D IMAT arcs under the maximum leaf motion constraint using a shortest path algorithm. Finally, the 1D IMAT arcs are combined to form IMAT treatment arcs of MLC apertures. The performance of the implemented leaf-sequencing software has been tested for four treatment sites (prostate, breast, head and neck, and lung). In all cases, our leaf-sequencing algorithm produces efficient and highly conformal IMAT plans that rival their counterpart, the tomotherapy plans, and significantly improve the IMRT plans. Algorithm execution times ranging from a few seconds to 2 min are observed on a laptop computer equipped with a 2.0 GHz Pentium M processor.

On the sources of drift in a turbine-based spirometer.

A systematic study on the sources of drift in a turbine-based spirometer (VMM-400) is presented. The study utilized an air-tight cylinder to pump air through the spirometer in a precise and programmable manner. Factors contributing to the drift were isolated and quantified. The drift due to imbalance in the electronics and the mechanical blade increased from 1% per breathing cycle to as much as 10% when the flow rate decreased from 0.24 to 0.08 l s(-1). A temperature difference of 16 degrees between the ambient and the air in the cylinder contributed about 3.5%. Most significantly, a difference in the breathing between inhalation and exhalation could produce a drift of 40% per breathing cycle, or even higher, depending on the extent of the breathing asymmetry. The origin of this drift was found to be rooted in the differential response of the spirometer to the different flow rate. Some ideas and suggestions for a correction strategy are provided for future work. The present work provides an important first step for eventual utilization of a spirometer as a stand-alone breathing surrogate for gating or tracking radiation therapy.

Arc-modulated radiation therapy (AMRT): a single-arc form of intensity-modulated arc therapy.

Arc-modulated radiation therapy (AMRT) is a novel rotational intensity-modulated radiation therapy (IMRT) technique developed for a clinical linear accelerator that aims to deliver highly conformal radiation treatment using just one arc of gantry rotation. Compared to fixed-gantry IMRT and the multiple-arc intensity-modulated arc therapy (IMAT) techniques, AMRT promises the same treatment quality with a single-arc delivery. In this paper, we present a treatment planning scheme for AMRT, which addresses the challenges in inverse planning, leaf sequencing and dose calculation. The feasibility and performance of this AMRT treatment planning scheme have been verified with multiple clinical cases of various sites on Varian linear accelerators.

Stochastic versus deterministic kernel-based superposition approaches for dose calculation of intensity-modulated arcs.

Dose calculations for radiation arc therapy are traditionally performed by approximating continuous delivery arcs with multiple static beams. For 3D conformal arc treatments, the shape and weight variation per degree is usually small enough to allow arcs to be approximated by static beams separated by 5 degrees -10 degrees . But with intensity-modulated arc therapy (IMAT), the variation in shape and dose per degree can be large enough to require a finer angular spacing. With the increase in the number of beams, a deterministic dose calculation method, such as collapsed-cone convolution/superposition, will require proportionally longer computational times, which may not be practical clinically. We propose to use a homegrown Monte Carlo kernel-superposition technique (MCKS) to compute doses for rotational delivery. The IMAT plans were generated with 36 static beams, which were subsequently interpolated into finer angular intervals for dose calculation to mimic the continuous arc delivery. Since MCKS uses random sampling of photons, the dose computation time only increased insignificantly for the interpolated-static-beam plans that may involve up to 720 beams. Ten past IMRT cases were selected for this study. Each case took approximately 15-30 min to compute on a single CPU running Mac OS X using the MCKS method. The need for a finer beam spacing is dictated by how fast the beam weights and aperture shapes change between the adjacent static planning beam angles. MCKS, however, obviates the concern by allowing hundreds of beams to be calculated in practically the same time as for a few beams. For more than 43 beams, MCKS usually takes less CPU time than the collapsed-cone algorithm used by the Pinnacle(3) planning system.

The use of gated and 4D CT imaging in planning for stereotactic body radiation therapy.

The localization of treatment targets is of utmost importance for patients receiving stereotactic body radiation therapy (SBRT), where the dose per fraction is large. While both setup or respiration-induced motion components affect the localization of the treatment volume, the purpose of this work is to describe our management of the intrafraction localization uncertainty induced by normal respiration. At our institution, we have implemented gated computed tomography (CT) acquisition with an active breathing control system (ABC), and 4-dimensional (4D) CT using a skin-based marker and retrospective respiration phase-based image sorting. During gated simulation, 3D CT images were acquired corresponding to end-inhalation and end-exhalation. For 4D CT imaging, 3D CT images were acquired corresponding to 8 phases of the respiratory cycle. In addition to gated or 4D CT images, we acquired a conventional free-breathing CT (FB). For both gated and 4D CT images, the target contours were registered to the FB scan in the planning system. These contours were then combined in the FB image set to form the internal target volume (ITV). Dynamic conformal arc treatment plans were generated for the ITV using the FB scan and the gated or 4D scans with an additional 7-mm margin for patient setup uncertainty. We have described our results for a pancreas and a lung tumor case. Plans were normalized so that the PTV received 95% of the prescription dose. The dose distribution for all the critical structures in the pancreas and lung tumor cases resulted in increased sparing when the ITV was defined using gated or 4D CT images than when the FB scan was used. Our results show that patient-specific target definition using gated or 4D CT scans lead to improved normal tissue sparing.

Planning 4D intensity-modulated arc therapy for tumor tracking with a multileaf collimator.

This study introduces a practical four-dimensional (4D) planning scheme of IMAT using 4D computed tomography (4D CT) for planning tumor tracking with dynamic multileaf beam collimation. We assume that patients can breathe regularly, i.e. the same way as during 4D CT with an unchanged period and amplitude, and that the start of 4D-IMAT delivery can be synchronized with a designated respiratory phase. Each control point of the IMAT-delivery process can be associated with an image set of 4D CT at a specified respiratory phase. Target is contoured at each respiratory phase without a motion-induced margin. A 3D-IMAT plan is first optimized on a reference-phase image set of 4D CT. Then, based on the projections of the planning target volume in the beam's eye view at different respiratory phases, a 4D-IMAT plan is generated by transforming the segments of the optimized 3D plan by using a direct aperture deformation method. Compensation for both translational and deformable tumor motion is accomplished, and the smooth delivery of the transformed plan is ensured by forcing connectivity between adjacent angles (control points). It is envisioned that the resultant plans can be delivered accurately using the dose rate regulated tracking method which handles breathing irregularities (Yi et al 2008 Med. Phys. 35 3955-62).This planning process is straightforward and only adds a small step to current clinical 3D planning practice. Our 4D planning scheme was tested on three cases to evaluate dosimetric benefits. The created 4D-IMAT plans showed similar dose distributions as compared with the 3D-IMAT plans on a single static phase, indicating that our method is capable of eliminating the dosimetric effects of breathing induced target motion. Compared to the 3D-IMAT plans with large treatment margins encompassing respiratory motion, our 4D-IMAT plans reduced radiation doses to surrounding normal organs and tissues.

Feasibility of delivering grid therapy using a multileaf collimator.

The feasibility of using a multileaf collimator (MLC) for grid therapy is demonstrated in this study. Grids with the projected field openings of 10 mm x 10 mm and 5 mm x 5 mm were created using multiple MLC-shaped fields. The deposited doses were measured with films at different depths in a solid water phantom and compared to those of Cerrobend grid collimators of similar hole sizes and hole separations. At the depth of maximum dose (dmax), the valley-to-peak dose ratios of the MLC grids were found to be about 11% and 19% for the respective 10 mm x 10 mm and 5 mm X 5 mm grid openings, and those of the corresponding grid blocks were about 15% and 20%. To quantify the dose contributed by transmission in the blocked areas due to the limited leaf thickness, Monte Carlo simulations (based on convolution/superposition method) were performed to calculate the doses in the solid water phantom using an ideal MLC with no leakage and perfect divergence in both the leaf end and side. About 7% reduction in the valley-to-peak dose ratio was found for both grid sizes at dmax. The results clearly showed that MLCs can be used to provide grid treatments with at least as good dosimetric properties as those of the Cerrobend grid blocks, though the former would in general require a longer delivery time.

An improved MLC segmentation algorithm and software for step-and-shoot IMRT delivery without tongue-and-groove error.

We present an improved multileaf collimator (MLC) segmentation algorithm, denoted by SLS(NOTG) (static leaf sequencing with no tongue-and-groove error), for step-and-shoot intensity-modulated radiation therapy (IMRT) delivery. SLS(NOTG) is an improvement over the MLC segmentation algorithm called SLS that was developed by Luan et al. [Med. Phys. 31(4), 695-707 (2004)], which did not consider tongue-and-groove error corrections. The aims of SLS(NOTG) are (1) shortening the treatment times of IMRT plans by minimizing their numbers of segments and (2) minimizing the tongue-and-groove errors of the computed IMRT plans. The input to SLS(NOTG) is intensity maps (IMs) produced by current planning systems, and its output is (modified) optimized leaf sequences without tongue-and-groove error. Like the previous SLS algorithm [Luan et al., Med. Phys. 31(4), 695-707 (2004)], SLS(NOTG) is also based on graph algorithmic techniques in computer science. It models the MLC segmentation problem as a weighted minimum-cost path problem, where the weight of the path is the number of segments and the cost of the path is the amount of tongue-and-groove error. Our comparisons of SLS(NOTG) with CORVUS indicated that for the same intensity maps, the numbers of segments computed by SLS(NOTG) are up to 50% less than those by CORVUS 5.0 on the Elekta LINAC system. Our clinical verifications have shown that the dose distributions of the SLS(NOTG) plans do not have tongue-and-groove error and match those of the corresponding CORVUS plans, thus confirming the correctness of SLS(NOTG). Comparing with existing segmentation methods, SLS(NOTG) also has two additional advantages: (1) SLS(NOTG) can compute leaf sequences whose tongue-and-groove error is minimized subject to a constraint on the maximum allowed number of segments, which may be desirable in clinical situations where a treatment with the complete correction of tongue-and-groove error takes too much time, and (2) SLS(NOTG) can be used to minimize a more general type of error called the tongue-or-groove error.

Gated CT imaging using a free-breathing respiration signal from flow-volume spirometry.

Respiration-induced tumor motion is known to cause artifacts on free-breathing spiral CT images used in treatment planning. This leads to inaccurate delineation of target volumes on planning CT images. Flow-volume spirometry has been used previously for breath-holds during CT scans and radiation treatments using the active breathing control (ABC) system. We have developed a prototype by extending the flow-volume spirometer device to obtain gated CT scans using a PQ 5000 single-slice CT scanner. To test our prototype, we designed motion phantoms to compare image quality obtained with and without gated CT scan acquisition. Spiral and axial (nongated and gated) CT scans were obtained of phantoms with motion periods of 3-5 s and amplitudes of 0.5-2 cm. Errors observed in the volume estimate of these structures were as much as 30% with moving phantoms during CT simulation. Application of motion-gated CT with active breathing control reduced these errors to within 5%. Motion-gated CT was then implemented in patients and the results are presented for two clinical cases: lung and abdomen. In each case, gated scans were acquired at end-inhalation, end-exhalation in addition to a conventional free-breathing (nongated) scan. The gated CT scans revealed reduced artifacts compared with the conventional free-breathing scan. Differences of up to 20% in the volume of the structures were observed between gated and free-breathing scans. A comparison of the overlap of structures between the gated and free-breathing scans revealed misalignment of the structures. These results demonstrate the ability of flow-volume spirometry to reduce errors in target volumes via gating during CT imaging.

Real-time intra-fraction-motion tracking using the treatment couch: a feasibility study.

Significant differences between planned and delivered treatments may occur due to respiration-induced tumour motion, leading to underdosing of parts of the tumour and overdosing of parts of the surrounding critical structures. Existing methods proposed to counter tumour motion include breath-holds, gating and MLC-based tracking. Breath-holds and gating techniques increase treatment time considerably, whereas MLC-based tracking is limited to two dimensions. We present an alternative solution in which a robotic couch moves in real time in response to organ motion. To demonstrate proof-of-principle, we constructed a miniature adaptive couch model consisting of two movable platforms that simulate tumour motion and couch motion, respectively. These platforms were connected via an electronic feedback loop so that the bottom platform responded to the motion of the top platform. We tested our model with a seven-field step-and-shoot delivery case in which we performed three film-based experiments: (1) static geometry, (2) phantom-only motion and (3) phantom motion with simulated couch motion. Our measurements demonstrate that the miniature couch was able to compensate for phantom motion to the extent that the dose distributions were practically indistinguishable from those in static geometry. Motivated by this initial success, we investigated a real-time couch compensation system consisting of a stereoscopic infra-red camera system interfaced to a robotic couch known as the Hexapod, which responds in real time to any change in position detected by the cameras. Optical reflectors placed on a solid water phantom were used as surrogates for motion. We tested the effectiveness of couch-based motion compensation for fixed fields and a dynamic arc delivery cases. Due to hardware limitations, we performed film-based experiments (1), (2) and (3), with the robotic couch at a phantom motion period and dose rate of 16 s and 100 MU min(-1), respectively. Analysis of film measurements showed near-equivalent dose distributions (

Deformable image registration for the use of magnetic resonance spectroscopy in prostate treatment planning.

PURPOSE: There is now convincing evidence that prostate cancer cells lack the ability to produce and accumulate citrate. Using magnetic resonance spectroscopy imaging (MRSI), regions of absent or low citrate concentration in the prostate can be visualized at a resolution of a few mm. This new advancement provides not only a tool for early diagnosis and screening but also the opportunity for preferential targeting of radiation to regions of high tumor burden in the prostate. The differences in the shape and location of the prostate between MRSI imaging and treatment have been the major obstacle in integrating MRSI in radiation therapy treatment planning. The purpose of this study is to develop a reliable method for deforming the prostate and surrounding regions from the geometry of MRSI imaging to the geometry of treatment planning, so that the regions of high tumor burden identified by the MRSI study can be faithfully transferred to the images used for treatment planning. METHODS AND MATERIALS: Magnetic resonance spectroscopy imaging studies have been performed on 2 prostate cancer patients using a commercial MRSI system with an endorectal coil and coupling balloon. At the end of each study, we also acquired the MRI of the pelvic region at both the deformed state where the prostate is distorted by the endorectal balloon and the resting state with the endorectal balloon deflated and removed. The task is to find a three-dimensional matrix of transformation vectors for all volume elements that links the two image sets. We have implemented an optimization method to iteratively optimize the transformation vectors using a Newton-Ralphson algorithm. The objective function is based on the mutual information. The distorted images using the transformation vectors are compared with the images acquired at the resting conditions. RESULTS AND DISCUSSION: The algorithm is capable of performing the registration automatically without the need for intervention. It does not require manual contouring of the organs. By applying the algorithm to multiple image sets of different patients, we found a good agreement between the images transformed from those acquired at the deformed state and those acquired at resting conditions. The computation time required for achieving the registration is in the range of a half-hour (for image size: 256 pixels x 256 pixels x 25 slices). However, the space of registration can be restricted to speed up the process. CONCLUSION: In this article, we described a three-dimensional deformable image registration method to automatically transform images from the deformed imaging state to resting state. Our examples show that this method is feasible and useful to the treatment planning system.

The low alpha/beta ratio for prostate cancer: what does the clinical outcome of HDR brachytherapy tell us?

PURPOSE: Accumulating evidence demonstrates that prostate cancer has a low alpha/beta ratio. However, several challenging issues have been raised from previous studies, including the biologic equivalence between external beam radiotherapy (EBRT) and brachytherapy, the effect of relative biologic effectiveness (RBE) for permanent implantation, and the systematic uncertainties of multi-institutional and multi-modality clinical data. The purpose of this study is to address these issues by reexamining a reported clinical outcome of high-dose-rate (HDR) brachytherapy and to confirm the low alpha/beta ratio for prostate cancer. METHODS AND MATERIALS: The generalized linear-quadratic (LQ) model with considerations of sublethal damage repair and clonogen repopulation was used to calculate the cell-killing efficiency of radiotherapy treatments for prostate cancer. Standard models of tumor cure based on Poisson statistics were used to bridge cell killing to treatment outcome. The data collected in a clinical trial using EBRT plus HDR brachytherapy boost for prostate cancer at William Beaumont Hospital (WBH) were reanalyzed. A 4-year post-treatment time endpoint was chosen as compared to the 3-year endpoint used in the previous study because of better maturity and stability of the data. The least chi-square method was employed to fit the clinical data to estimate the LQ parameters as well as their confidence intervals. The number of clonogens for prostate tumors derived in a separate study was used as a constraint for the data modeling to improve the confidence level. RESULTS: Our analysis demonstrates that only relationships among the LQ parameters, not their definitive and unique values, can be derived from the WBH data set alone. This is due to the large statistical uncertainties, i.e., the small numbers of sampled patients. By combining with the results obtained with the clinical data from Memorial Sloan-Kettering Cancer Center (MSKCC), a new set of LQ parameters (alpha = 0.14 +/- 0.05 Gy(-1), alpha/beta = 3.1(-1.6)(+2.6) Gy) was obtained from the current analysis of the WBH data without dealing with data from permanent implants. The results are consistent with a previous study based on the biologic equivalence between EBRT and permanent implants with a consideration of tumor repopulation. This set of LQ parameters provides a consistent interpretation of clinical data currently available for prostate cancer. CONCLUSIONS: This study provides further evidence to support that prostate cancer has a low alpha/beta ratio of about 3.1 Gy. This study shows that the RBE effect in permanent implantation may not be clinically significant for prostate cancer. The consistency found between this analysis and the previous reported study supports the general biologic equivalence between EBRT and brachytherapy treatments for prostate cancer. The low alpha/beta ratio opens the door to search for more effective radiotherapeutic approaches for prostate cancer, e.g., hypofractionation radiotherapy.

Clinical implementation of intensity-modulated arc therapy.

PURPOSE: Intensity-modulated arc therapy (IMAT) is a method for delivering intensity-modulated radiation therapy (IMRT) using rotational beams. During delivery, the field shape, formed by a multileaf collimator (MLC), changes constantly. The objectives of this study were to (1) clinically implement the IMAT technique, and (2) evaluate the dosimetry in comparison with conventional three-dimensional (3D) conformal techniques. METHODS AND MATERIALS: Forward planning with a commercial system (RenderPlan 3D, Precision Therapy International, Inc., Norcross, GA) was used for IMAT planning. Arcs were approximated as multiple shaped fields spaced every 5-10 degrees around the patient. The number and ranges of the arcs were chosen manually. Multiple coplanar, superimposing arcs or noncoplanar arcs with or without a wedge were allowed. For comparison, conventional 3D conformal treatment plans were generated with the same commercial forward planning system as for IMAT. Intensity-modulated treatment plans were also created with a commercial inverse planning system (CORVUS, Nomos Corporation). A leaf-sequencing program was developed to generate the dynamic MLC prescriptions. IMAT treatment delivery was accomplished by programming the linear accelerator (linac) to deliver an arc and the MLC to step through a sequence of fields. Both gantry rotation and leaf motion were enslaved to the delivered MUs. Dosimetric accuracy of the entire process was verified with phantoms before IMAT was used clinically. For each IMAT treatment, a dry run was performed to assess the geometric and dosimetric accuracy. Both the central axis dose and dose distributions were measured and compared with predictions by the planning system. RESULTS: By the end of May 2001, 50 patients had completed their treatments with the IMAT technique. Two to five arcs were needed to achieve highly conformal dose distributions. The IMAT plans provided better dose uniformity in the target and lower doses to normal structures than 3D conformal plans. The results varied when the comparison was made with fixed gantry IMRT. In general, IMAT plans provided more uniform dose distributions in the target, whereas the inverse-planned fixed gantry treatments had greater flexibility in controlling dose to the critical structures. Because the field sizes and shapes used in the IMAT were similar to those used in conventional treatments, the dosimetric uncertainty was very small. Of the first 32 patients treated, the average difference between the measured and predicted doses was -0.54 +/- 1.72% at isocenter. The 80%-95% isodose contours measured with film dosimetry matched those predicted by the planning system to within 2 mm. The planning time for IMAT was slightly longer than for generating conventional 3D conformal plans. However, because of the need to create phantom plans for the dry run, the overall planning time was doubled. The average time a patient spent on the table for IMAT treatment was similar to conventional treatments. CONCLUSION: Initial results demonstrated the feasibility and accuracy of IMAT for achieving highly conformal dose distributions for different sites. If treatment plans can be optimized for IMAT cone beam delivery, we expect IMAT to achieve dose distributions that rival both slice-based and fixed-field IMRT techniques. The efficient delivery with existing linac and MLC makes IMAT a practical choice.

A dose delivery verification method for conventional and intensity-modulated radiation therapy using measured field fluence distributions.

Treatment verification has been a weak link in external beam radiation therapy. As new and more complicated treatment techniques, such as intensity-modulated radiation therapy (IMRT), are implemented into clinical practice, verifying the accuracy of treatment delivery becomes increasingly important. Existing methods for treatment verification are highly labor intensive. We have developed a method for verifying the delivery of external beam radiotherapy and implemented the methodology into a system consisting of both hardware and software components. The system uses grayscale images acquired on the treatment machine from the planned treatment beams. From these images, the photon fluence distribution of each beam is derived. These measured photon fluence maps are then used as input to a separate dose calculation engine to compute the delivered absolute dose and the dose distribution in the same patient, assuming that the patient is set up as required by the treatment plan. The dose distribution generated from the measured fluence maps can then be compared to that of the treatment plan. Software tools, such as overlaying isodose curves generated with this method on those imported from the plan, dose difference maps, dose difference volume histograms, and three-dimensional perspective views of the dose differences, have also been developed. The system thus provides a means to verify the dose, the dose prescription, and the monitor units applied. The potential exists with a suitable electronic portal imaging system to reduce the quality assurance efforts, especially for IMRT.

Radiation absorbed dose distribution in a patient treated with yttrium-90 microspheres for hepatocellular carcinoma.

We have implemented a three-dimensional dose calculation technique accounting for dose inhomogeneity within the liver and tumor of a patient treated with 90Y microspheres. Single-photon emission computed tomography (SPECT) images were used to derive the activity distribution within liver. A Monte Carlo calculation was performed to create a voxel dose kernel for the 90Y source. The activity distribution was convolved with the voxel dose kernel to obtain the three-dimensional (3D) radiation absorbed dose distribution. An automated technique was developed to accurately register the computed tomography (CT) and SPECT scans in order to display the 3D dose distribution on the CT scans. In addition, dose-volume histograms were generated to fully analyze the tumor and liver doses. The calculated dose-volume histogram indicated that although the patient was treated to the nominal whole liver dose of 110 Gy, only 16% of the liver and 83% of the tumor received a dose higher than 110 Gy. The mean tumor and liver doses were 163 and 58 Gy, respectively.