One health in regenerative medicine: report on the second Havemeyer symposium on regenerative medicine in horses.

Regenerative medicine is commonly used in human and equine athletes. Potential therapies include culture expanded stem cells, stromal vascular fraction of adipose tissue, platelet-rich plasma, bone marrow concentrate, or autologous conditioned serum. The purpose of this manuscript is to disseminate findings from a workshop on the development of translational regenerative medicine in the equine field. Five themes emerged: stem cell characterization and tenogenic differentiation; interactions between mesenchymal stem cells, other cells and the environment; scaffolds and cell packaging; blood- and bone marrow-based regenerative medicines; clinical use of regenerative therapies. Evidence gained through the use of regenerative medicine applications in the horse should continue to translate to the human patient, bringing novel regenerative therapies to both humans and horses.

Biological Effects of Bone Marrow Concentrate in Knee Pathologies.

With our aging population desiring to remain active, the incidence and costs associated with managing knee pain from both acute injury and symptomatic knee osteoarthritis continue to dramatically increase. Current treatment methods fall short with respect to their ability to improve the intra-articular environment and restore normal joint homeostasis. With increasing basic science and clinical evidence showing efficacy, cell-based therapies such as bone marrow concentrate (BMC) hold promise as a nonsurgical joint preserving treatment approach. BMC has inherent advantages over other treatments commonly used for various knee pathologies because it is a point-of-care orthobiologic product that uniquely and simultaneously delivers growth factors, anti-inflammatory proteins, and mesenchymal stem cells. There is increasing evidence for the use of BMC for repair of focal cartilage defects and for the treatment of generalized knee pain. However, continued high-quality studies are necessary for the clinical utility of BMC to be critically assessed with particular attention paid to appropriate patient selection, standardized aspiration, and processing and reporting of both functional and imaging-based outcomes.

Does gated beam delivery impact delivery accuracy on an Elekta linac?

In this study, we evaluated the performance of an Elekta linac in the delivery of gated radiotherapy. Delivery accuracy was examined with an emphasis on the impact of using short gating windows (low monitor unit beam-on segments) or long beam hold times. The performance was assessed using a 20cm by 20cm open field with the radiation delivered using a range of beam-on and beam-off time periods. Gated delivery measurements were also performed for two SBRT plans delivered using volumetric modulated arc therapy (VMAT). Tests included both free-breathing based gating (covering a variety of gating windows) and simulated breath-hold based gating. An IBA MatriXX 2D ion chamber array was used for data collection, and the gating accuracy at low MU was evaluated using gamma passing rates. For the 20 cm by 20 cm open field, the measurements generally showed close agreement between the gated and non-gated beam deliveries. Discrepancies, however, began to appear with a 5-to-1 ratio of the beam-off to beam-on times. The discrepancies observed for these tight gating windows can be attributed to the small number of monitor units delivered during each beam-on segment. Dose distribution analysis from the delivery of the two SBRT plans showed gamma passing rates (± 1%, 2%/1 mm) in the range of 95% to 100% for gating windows of 25%, 38%, 50%, 63%, 75%, and 83%. Using a simulated sinusoidal breathing signal with a 4 second period, the gamma passing rate of free-breathing gating and breath-hold gating deliveries were measured in the range of 95.7% to 100%. In conclusion, the results demonstrate that Elekta linacs can accurately deliver respiratory gated treatments for both free-breathing and breath-hold patients. Some caution should be exercised with the use of very tight gating windows.

Delivery efficiency of an Elekta linac under gated operation.

In this study, we have characterized the efficiency of an Elekta linac in the delivery of gated radiotherapy. We have explored techniques to reduce the beam-on delay and to improve the delivery efficiency, and have investigated the impact of frequent beam interruptions on the dosimetric accuracy of gated deliveries. A newly available gating interface was installed on an Elekta Synergy. Gating signals were generated using a surface mapping system in conjunction with a respiratory motion phantom. A series of gated deliveries were performed using volumetric modulated arc therapy (VMAT) treatment plans previously generated for lung cancer patients treated with stereotactic body radiotherapy. Baseline values were determined for the delivery times. The machine was then tuned in an effort to minimize beam-on delays and improve delivery efficiency. After that process was completed, the dosimetric accuracy of the gated deliveries was evaluated by comparing the measured and the planned coronal dose distributions using gamma index analyses. Comparison of the gated and the non-gated deliveries were also performed. The results demonstrated that, with the optimal machine settings, the average beam-on delay was reduced to less than 0.22 s. High dosimetric accuracy was demonstrated with gamma index passing rates no lower than 99.0% for all tests (3%/3 mm criteria). Consequently, Elekta linacs can provide a practical solution for gated VMAT treatments with high dosimetric accuracy and only a moderate increase in the overall delivery time.

Dosimetric impact of breathing motion in lung stereotactic body radiotherapy treatment using intensity modulated radiotherapy and volumetric modulated arc therapy [corrected].

PURPOSE: The objective of this study was to investigate the influence of tumor motion on dose delivery in stereotactic body radiotherapy (SBRT) for lung cancer, using fixed field intensity- modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: For each of 10 patients with stage I/II non-small-cell pulmonary tumors, a respiration-correlated four-dimensional computed tomography (4DCT) study was carried out. The internal target volume was delineated on the maximum intensity projection CT, which was reconstructed from the 4DCT dataset. A 5-mm margin was used for generation of the planning target volume. VMAT and five-field IMRT plans were generated using Pinnacle(3) SmartArc and direct machine parameter optimization, respectively. All plans were generated for an Elekta Synergy linear accelerator using 6-MV photons. Simulation was performed to study the interplay between multileaf collimator (MLC) sequences and target movement during the delivery of VMAT and IMRT. For each plan, 4D dose was calculated using deformable image registration of the 4DCT images. Target volume coverage and doses to critical structures calculated using 4D methodology were compared with those calculated using 3D methodology. RESULTS: For all patients included in this study, the interplay effect was found to present limited impact (less than 1% of prescription) on the target dose distribution, especially for SBRT, in which fewer fractions (three fractions) are delivered. Dose to the gross tumor volume (GTV) was, on average, slightly decreased (1% of prescription) in the 4D calculation compared with the 3D calculation. The motion impact on target dose homogeneity was patient-dependent and relatively small. CONCLUSIONS: Both VMAT and IMRT plans experienced negligible interplay effects between MLC sequence and tumor motion. For the most part, the 3D doses to the GTV and critical structures provided good approximations of the 4D dose calculations.

Impact of leaf motion constraints on IMAT plan quality, deliver accuracy, and efficiency.

PURPOSE: Intensity modulated arc therapy (IMAT) is a radiation therapy delivery technique that combines the efficiency of arc based delivery with the dose painting capabilities of intensity modulated radiation therapy (IMRT). A key challenge in developing robust inverse planning solutions for IMAT is the need to account for the connectivity of the beam shapes as the gantry rotates from one beam angle to the next. To overcome this challenge, inverse planning solutions typically impose a leaf motion constraint that defines the maximum distance a multileaf collimator (MLC) leaf can travel between adjacent control points. The leaf motion constraint ensures the deliverability of the optimized plan, but it also impacts the plan quality, the delivery accuracy, and the delivery efficiency. In this work, the authors have studied leaf motion constraints in detail and have developed recommendations for optimizing the balance between plan quality and delivery efficiency. METHODS: Two steps were used to generate optimized IMAT treatment plans. The first was the direct machine parameter optimization (DMPO) inverse planning module in the Pinnacle(3) planning system. Then, a home-grown arc sequencer was applied to convert the optimized intensity maps into deliverable IMAT arcs. IMAT leaf motion constraints were imposed using limits of between 1 and 30 mm∕deg. Dose distributions were calculated using the convolution∕superposition algorithm in the Pinnacle(3) planning system. The IMAT plan dose calculation accuracy was examined using a finer sampling calculation and the quality assurance verification. All plans were delivered on an Elekta Synergy with an 80-leaf MLC and were verified using an IBA MatriXX 2D ion chamber array inserted in a MultiCube solid water phantom. RESULTS: The use of a more restrictive leaf motion constraint (less than 1-2 mm∕deg) results in inferior plan quality. A less restrictive leaf motion constraint (greater than 5 mm∕deg) results in improved plan quality but can lead to less accurate dose distribution as evidenced by increasing discrepancies between the planned and the delivered doses. For example, the results from our patient-specific quality assurance measurements demonstrated that the average gamma analysis passing rate decreased from 98% to 80% when the allowable leaf motion increased from 3 to 20 mm∕deg. Larger leaf motion constraints also led to longer treatment delivery times (2 to 4 folds) due to the additional MLC leaf motion. CONCLUSIONS: Leaf motion constraints significantly impact IMAT plans in terms of plan quality, delivery accuracy, and delivery efficiency with the impact magnified for more complex cases. Our studies indicate that a leaf motion constraint of 2 to 3 mm∕deg of gantry rotation can provide an optimal balance between plan quality, delivery accuracy, and efficiency.

Clinical implementation of intensity-modulated arc therapy.

Intensity-modulated arc therapy (IMAT) is a rotational approach to radiation therapy delivered on a conventional linear accelerator using a conventional multileaf collimator. There are 2 key advantages of IMAT. First, the rotational nature of the delivery provides great flexibility in shaping each dose distribution. As a result, IMAT can provide dosimetric advantages relative to fixed-field intensity-modulated radiation therapy (IMRT). The second advantage is the highly efficient nature of the delivery. For centers with an active IMRT program, the clinical implementation of IMAT should be relatively straightforward. For clinical implementation of IMAT, it is important to fully characterize the accuracy of the dose model used, and the performance of the quality assurance equipment.

Comparison of anatomy-based, fluence-based and aperture-based treatment planning approaches for VMAT.

Volumetric modulated arc therapy (VMAT) has the potential to reduce treatment times while producing comparable or improved dose distributions relative to fixed-field intensity-modulated radiation therapy. In order to take full advantage of the VMAT delivery technique, one must select a robust inverse planning tool. The purpose of this study was to evaluate the effectiveness and efficiency of VMAT planning techniques of three categories: anatomy-based, fluence-based and aperture-based inverse planning. We have compared these techniques in terms of the plan quality, planning efficiency and delivery efficiency. Fourteen patients were selected for this study including six head-and-neck (HN) cases, and two cases each of prostate, pancreas, lung and partial brain. For each case, three VMAT plans were created. The first VMAT plan was generated based on the anatomical geometry. In the Elekta ERGO++ treatment planning system (TPS), segments were generated based on the beam's eye view (BEV) of the target and the organs at risk. The segment shapes were then exported to Pinnacle TPS followed by segment weight optimization and final dose calculation. The second VMAT plan was generated by converting optimized fluence maps (calculated by the Pinnacle TPS) into deliverable arcs using an in-house arc sequencer. The third VMAT plan was generated using the Pinnacle SmartArc IMRT module which is an aperture-based optimization method. All VMAT plans were delivered using an Elekta Synergy linear accelerator and the plan comparisons were made in terms of plan quality and delivery efficiency. The results show that for cases of little or modest complexity such as prostate, pancreas, lung and brain, the anatomy-based approach provides similar target coverage and critical structure sparing, but less conformal dose distributions as compared to the other two approaches. For more complex HN cases, the anatomy-based approach is not able to provide clinically acceptable VMAT plans while highly conformal dose distributions were obtained using both aperture-based and fluence-based inverse planning techniques. The aperture-based approach provides improved dose conformity than the fluence-based technique in complex cases.

Comparison of Elekta VMAT with helical tomotherapy and fixed field IMRT: plan quality, delivery efficiency and accuracy.

PURPOSE: Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are arc-based approaches to IMRT delivery. The objective of this study is to compare VMAT to both HT and fixed field IMRT in terms of plan quality, delivery efficiency, and accuracy. METHODS: Eighteen cases including six prostate, six head-and-neck, and six lung cases were selected for this study. IMRT plans were developed using direct machine parameter optimization in the Pinnacle3 treatment planning system. HT plans were developed using a Hi-Art II planning station. VMAT plans were generated using both the Pinnacle3 SmartArc IMRT module and a home-grown arc sequencing algorithm. VMAT and HT plans were delivered using Elekta's PreciseBeam VMAT linac control system (Elekta AB, Stockholm, Sweden) and a TomoTherapy Hi-Art II system (TomoTherapy Inc., Madison, WI), respectively. Treatment plan quality assurance (QA) for VMAT was performed using the IBA MatriXX system while an ion chamber and films were used for HT plan QA. RESULTS: The results demonstrate that both VMAT and HT are capable of providing more uniform target doses and improved normal tissue sparing as compared with fixed field IMRT. In terms of delivery efficiency, VMAT plan deliveries on average took 2.2 min for prostate and lung cases and 4.6 min for head-and-neck cases. These values increased to 4.7 and 7.0 min for HT plans. CONCLUSIONS: Both VMAT and HT plans can be delivered accurately based on their own QA standards. Overall, VMAT was able to provide approximately a 40% reduction in treatment time while maintaining comparable plan quality to that of HT.

A generalized inverse planning tool for volumetric-modulated arc therapy.

The recent development in linear accelerator control systems, named volumetric-modulated arc therapy (VMAT), has generated significant interest in arc-based intensity-modulated radiation therapy (IMRT). The VMAT delivery technique features simultaneous changes in dose rate, gantry angle and gantry rotation speed as well as multi-leaf collimator (MLC) leaf positions while radiation is on. In this paper, we describe a generalized VMAT planning tool that is designed to take full advantage of the capabilities of the new linac control systems. The algorithm incorporates all of the MLC delivery constraints such as restrictions on MLC leaf interdigitation and the MLC leaf velocity constraints. A key feature of the algorithm is that it is able to plan for both single- and multiple-arc deliveries. Compared to conventional step-and-shoot IMRT plans, our VMAT plans created using this tool can achieve similar or better plan quality with less MU and better delivery efficiency. The accuracy of the obtained VMAT plans is also demonstrated through plan verifications performed on an Elekta Synergy linear accelerator equipped with a conventional MLC of 1 cm leaf width using a PreciseBeam VMAT linac control system.

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.

Comparison of plan quality provided by intensity-modulated arc therapy and helical tomotherapy.

PURPOSE: Intensity-modulated arc therapy (IMAT) is an arc-based approach to intensity-modulated radiotherapy (IMRT) that can be delivered on a conventional linear accelerator using a conventional multileaf collimator. In a previous work, we demonstrated that our arc-sequencing algorithm can produce highly conformal IMAT plans. Through plan comparisons, we explored the ability of IMAT to serve as an alternative to helical tomotherapy. METHODS AND MATERIALS: The IMAT plans were created for 10 patients previously treated with helical tomotherapy. Treatment plan comparisons, according to the target dose coverage and critical structure sparing, were performed to determine whether similar plan quality could be achieved using IMAT. RESULTS: In 8 of 10 patient cases, IMAT was able to provide plan quality comparable to that of helical tomotherapy. In 2 of these 8 cases, the use of non-axial coplanar or non-coplanar arcs in IMAT planning led to significant improvements in normal tissue sparing. The remaining 2 cases posed particular dosimetric challenges. In 1 case, the target was immediately adjacent to a spinal cord that had received previous irradiation. The second case involved multiple target volumes and multiple prescription levels. Both IMAT and tomotherapy were able to produce clinically acceptable plans. Tomotherapy, however, provided a more uniform target dose and improved critical structure sparing. CONCLUSIONS: For most cases, IMAT can provide plan qualities comparable to that of helical tomotherapy. For some intracranial tumors, IMAT's ability to deliver non-coplanar arcs led to significant dosimetric improvements. Helical tomotherapy, however, can provide improved dosimetric results in the most complex cases.

Efficacy and quality of life outcomes in patients with atypical trigeminal neuralgia treated with gamma-knife radiosurgery.

PURPOSE: To assess efficacy and quality of life (QOL) outcomes associated with gamma-knife radiosurgery (GK-RS) in treating atypical trigeminal neuralgia (ATN) compared with classic trigeminal neuralgia (CTN). METHODS AND MATERIALS: Between September 1996 and September 2004, 35 cases of ATN were treated with GK-RS. Patients were categorized into two groups: Group I comprised patients presenting with ATN (57%); Group II consisted of patients presenting with CTN then progressing to ATN (43%). Median prescription dose 75 Gy (range, 70-80 Gy) was delivered to trigeminal nerve root entry zone. Treatment efficacy and QOL improvements were assessed with a standardized questionnaire. RESULTS: With median follow-up of 29 months (range, 3-74 months), 72% reported excellent/good outcomes, with mean time to relief of 5.8 weeks (range, 0-24 weeks) and mean duration of relief of 62 weeks (range, 1-163 weeks). This rate of pain relief is similar to rate achieved in our previously reported experience treating CTN with GK-RS (p = 0.36). There was a trend toward longer time to relief (p = 0.059), and shorter duration of relief (p = 0.067) in patients with ATN. There was no difference in rate of, time to, or duration of pain relief between Groups I and II. Of the patients with ATN, 88% discontinued or decreased the use of pain medications. Among the patients with sustained pain relief, QOL improved an average of 85%. CONCLUSION: This is the largest reported GK-RS experience for the treatment of ATN. Patients with ATN can achieve rates of pain relief similar to those in patients with CTN. Further follow-up is necessary to assess adequately the durability of response.

Direct aperture optimization of breast IMRT and the dosimetric impact of respiration motion.

We have studied the application of direct aperture optimization (DAO) as an inverse planning tool for breast IMRT. Additionally, we have analysed the impact of respiratory motion on the quality of the delivered dose distribution. From this analysis, we have developed guidelines for balancing the desire for a high-quality optimized plan with the need to create a plan that will not degrade significantly in the presence of respiratory motion. For a DAO optimized breast IMRT plan, the tangential fields incorporate a flash field to cover the range of respiratory motion. The inverse planning algorithm then optimizes the shapes and weights of additional segments that are delivered in combination with the open fields. IMRT plans were generated using DAO with the relative weights of the open segments varied from 0% to 95%. To assess the impact of breathing motion, the dose distribution for the optimized IMRT plan was recalculated with the isocentre sampled from a predefined distribution in a Monte Carlo convolution/superposition dose engine with the breast simulated as a rigid object. The motion amplitudes applied in this study ranged from 0.5 to 2.0 cm. For a range of weighting levels assigned to the open field, comparisons were made between the static plans and the plans recalculated with motion. For the static plans, we found that uniform dose distributions could be generated with relative weights for the open segments equal to and below 80% and unacceptable levels of underdosage were observed with the weights larger than 80%. When simulated breathing motion was incorporated into the dose calculation, we observed a loss in dose uniformity as the weight of the open field was decreased to below 65%. More quantitatively, for each 1% decrease in the weight, the per cent volume of the target covered by at least 95% of the prescribed dose decreased by approximately 0.10% and 0.16% for motion amplitudes equal to 1.5 cm and 2.0 cm, respectively. When taking into account the motion effects, the most uniform and conformal dose distributions were achieved when the open segment weights were in the range of 65-80%. Within this range, high-quality IMRT plans were produced for each case. The study demonstrates that DAO with tangential fields provides a robust and efficient technique for breast IMRT planning and delivery when the open segment weight is selected between 65% and 80%.

New developments in intensity modulated radiation therapy.

As intensity modulated radiation therapy (IMRT) becomes routine clinical practice, its advantages and limitations are better understood. With these new understandings, some new developments have emerged in an effort to alleviate the limitations of the current IMRT practice. This article describes a few of these efforts made at the University of Maryland, including: i) improving IMRT efficiency with direct aperture optimization; ii) broadening the scope of optimization to include the mode of delivery and beam angles; and iii) new planning methods for intensity modulated arc therapy (IMAT).

Continuous intensity map optimization (CIMO): a novel approach to leaf sequencing in step and shoot IMRT.

A new leaf-sequencing approach has been developed that is designed to reduce the number of required beam segments for step-and-shoot intensity modulated radiation therapy (IMRT). This approach to leaf sequencing is called continuous-intensity-map-optimization (CIMO). Using a simulated annealing algorithm, CIMO seeks to minimize differences between the optimized and sequenced intensity maps. Two distinguishing features of the CIMO algorithm are (1) CIMO does not require that each optimized intensity map be clustered into discrete levels and (2) CIMO is not rule-based but rather simultaneously optimizes both the aperture shapes and weights. To test the CIMO algorithm, ten IMRT patient cases were selected (four head-and-neck, two pancreas, two prostate, one brain, and one pelvis). For each case, the optimized intensity maps were extracted from the Pinnacle3 treatment planning system. The CIMO algorithm was applied, and the optimized aperture shapes and weights were loaded back into Pinnacle. A final dose calculation was performed using Pinnacle's convolution/superposition based dose calculation. On average, the CIMO algorithm provided a 54% reduction in the number of beam segments as compared with Pinnacle's leaf sequencer. The plans sequenced using the CIMO algorithm also provided improved target dose uniformity and a reduced discrepancy between the optimized and sequenced intensity maps. For ten clinical intensity maps, comparisons were performed between the CIMO algorithm and the power-of-two reduction algorithm of Xia and Verhey [Med. Phys. 25(8), 1424-1434 (1998)]. When the constraints of a Varian Millennium multileaf collimator were applied, the CIMO algorithm resulted in a 26% reduction in the number of segments. For an Elekta multileaf collimator, the CIMO algorithm resulted in a 67% reduction in the number of segments. An average leaf sequencing time of less than one minute per beam was observed.

Effect of beamlet step-size on IMRT plan quality.

We have studied the degree to which beamlet step-size impacts the quality of intensity modulated radiation therapy (IMRT) treatment plans. Treatment planning for IMRT begins with the application of a grid that divides each beam's-eye-view of the target into a number of smaller beamlets (pencil beams) of radiation. The total dose is computed as a weighted sum of the dose delivered by the individual beamlets. The width of each beamlet is set to match the width of the corresponding leaf of the multileaf collimator (MLC). The length of each beamlet (beamlet step-size) is parallel to the direction of leaf travel. The beamlet step-size represents the minimum stepping distance of the leaves of the MLC and is typically predetermined by the treatment planning system. This selection imposes an artificial constraint because the leaves of the MLC and the jaws can both move continuously. Removing the constraint can potentially improve the IMRT plan quality. In this study, the optimized results were achieved using an aperture-based inverse planning technique called direct aperture optimization (DAO). We have tested the relationship between pencil beam step-size and plan quality using the American College of Radiology's IMRT test case. For this case, a series of IMRT treatment plans were produced using beamlet step-sizes of 1, 2, 5, and 10 mm. Continuous improvements were seen with each reduction in beamlet step size. The maximum dose to the planning target volume (PTV) was reduced from 134.7% to 121.5% and the mean dose to the organ at risk (OAR) was reduced from 38.5% to 28.2% as the beamlet step-size was reduced from 10 to 1 mm. The smaller pencil beam sizes also led to steeper dose gradients at the junction between the target and the critical structure with gradients of 6.0, 7.6, 8.7, and 9.1 dose%/mm achieved for beamlet step sizes of 10, 5, 2, and 1 mm, respectively.

Racial differences in the use of aspirin: an important tool for preventing heart disease and stroke.

BACKGROUND: Regular aspirin use, particularly as secondary prevention, reduces morbidity from heart disease and stroke. Few studies have examined racial/ethnic differences in aspirin use for the prevention of cardiovascular disease (CVD). METHODS: Data from the 2001 Behavioral Risk Factor Surveillance System (n=2,514 African Americans; n=865 Hispanics; n=28,038 Whites) were used to assess racial/ethnic differences in aspirin use. Multivariable logistic regression was used to examine whether the likelihood of aspirin use differs by race/ethnicity after accounting for sociodemographic and CVD risk factors. RESULTS: Regular aspirin use was associated with increasing age, male gender, lower educational attainment, hypertension, diabetes, overweight, and histories of myocardial infarction, coronary heart disease, and stroke. Aspirin use was lower among African Americans and Hispanics than Whites (28.6% and 28.7% vs 37.1%, respectively). After adjustment for sociodemographic and CVD risk factors, African Americans and Hispanics were 30%-40% less likely than Whites (OR=0.6, 95% C1=0.5, 0.7, African Americans; OR=0.7, 95% CI=0.5, 1.0, Hispanics) to take aspirin. Although aspirin use was higher among those with CVD (73.6% African Americans, 73.6% Hispanics, and 82.7% Whites), after multivariable adjustment, African Americans and Hispanics with CVD remained 30% to 50% less likely to use aspirin than Whites (OR=0.7, 95% CI=0.4, 1.2, African Americans; OR=0.5, 95% CI=0.2, 1.1, Hispanics). CONCLUSIONS: African Americans and Hispanics are less likely to take aspirin than their White counterparts. Differences in sociodemographic characteristics and CVD risk factors do not account for lower aspirin use among racial/ethnic minorities. Additional studies should examine methods to increase aspirin use in these populations.

Convolution/superposition using the Monte Carlo method.

The convolution/superposition calculations for radiotherapy dose distributions are traditionally performed by convolving polyenergetic energy deposition kernels with TERMA (total energy released per unit mass) precomputed in each voxel of the irradiated phantom. We propose an alternative method in which the TERMA calculation is replaced by random sampling of photon energy, direction and interaction point. Then, a direction is randomly sampled from the angular distribution of the monoenergetic kernel corresponding to the photon energy. The kernel ray is propagated across the phantom, and energy is deposited in each voxel traversed. An important advantage of the explicit sampling of energy is that spectral changes with depth are automatically accounted for. No spectral or kernel hardening corrections are needed. Furthermore, the continuous sampling of photon direction allows us to model sharp changes in fluence, such as those due to collimator tongue-and-groove. The use of explicit photon direction also facilitates modelling of situations where a given voxel is traversed by photons from many directions. Extra-focal radiation, for instance, can therefore be modelled accurately. Our method also allows efficient calculation of a multi-segment/multi-beam IMRT plan by sampling of beam angles and field segments according to their relative weights. For instance, an IMRT plan consisting of seven 14 x 12 cm2 beams with a total of 300 field segments can be computed in 15 min on a single CPU, with 2% statistical fluctuations at the isocentre of the patient's CT phantom divided into 4 x 4 x 4 mm3 voxels. The calculation contains all aperture-specific effects, such as tongue and groove, leaf curvature and head scatter. This contrasts with deterministic methods in which each segment is given equal importance, and the time taken scales with the number of segments. Thus, the Monte Carlo superposition provides a simple, accurate and efficient method for complex radiotherapy dose calculations.