Dose Delivery Efficiency Research Articles

SU-GG-T-233: An Integration Calculation Method for Dose Verification of Arc-Based Radiotherapy

Purpose: Arc techniques can improve dose delivery efficiency and isodose distributions but can also introduce uncertainties in dose calculation particularly for tissue heterogeneity and irregular external contours within an arc. Available QA programs have failed to produce accurate MU calculation. Thus, we introduce a new QA algorithm for arc radiotherapy. Method and Materials: Modified power law (MPL) and equivalent path-length (EPL) with/without modified Clarkson integration (MCI) were used for MU verification in arc therapy for 21 patients with small lung tumors or brain lesions. Instead of treating each arc as multiple beams with 5-degree gantry angle interval, we averaged the CT density over the arc with a given radius and then integrated over the radii to determine the effective density and the true heterogeneity-corrected path-length (TPL). Planned CT and arc data in DICOMRT format were parsed into a custom program and geometry between the dose point and a moving ray with fixed angle relative to the dose point in the beam-eye-view (BEV) were converted to a fixed beamlet relative to the point having its own effective density distribution along the path-length. Then, concepts of MCI were used. Results: In cases with arc MU deviation of 5 to 18% using existing algorithms, application of the proposed algorithm of the true arc integration had significantly reduced the dose deviation to < 6% because the TPL corrected the EPL by up to 17 mm. The equivalent square of the field improved correction by another 2 to 5%. Conclusion: A novel arc integration algorithm has been tested successfully for quantification of effects of tissue heterogeneity, irregular surface, and position devices in arcs. The arc-integration and the concepts for converting arcs to fix beams provide a new dose calculation and QA tool for emerging arc techniques.

Methodology to Incorporate Biologically Effective Dose and Equivalent Uniform Dose in Patient-Specific 3-Dimensional Dosimetry for Non-Hodgkin Lymphoma Patients Targeted with 131I-Tositumomab Therapy

A 3-dimensional (3D) imaging-based patient-specific dosimetry methodology incorporating antitumor biologic effects using biologically effective dose (BED) and equivalent uniform dose (EUD) was developed in this study. The methodology was applied to the dosimetry analysis of 6 non-Hodgkin lymphoma patients with a total of 10 tumors. Six registered SPECT/CT scans were obtained for each patient treated with (131)I-labeled antibody. Three scans were obtained after tracer administration and 3 after therapy administration. The SPECT/CT scans were used to generate 3D images of cumulated activity. The cumulated activity images and corresponding CT scans were used as input to Monte Carlo dose-rate calculations. The dose-rate distributions were integrated over time to obtain 3D absorbed dose distributions. The time-dependent 3D cumulative dose distributions were used to generate 3D BED distributions. Techniques to incorporate the effect of unlabeled antibody (cold protein) in the BED analysis were explored. Finally, BED distributions were used to estimate an EUD for each tumor volume. Model parameters were determined from optimal fits to tumor regression data. The efficiency of dose delivery to tumors--the ratio of EUD to cumulative dose--was extracted for each tumor and correlated with patient response parameters. The model developed in this study was validated for dosimetry of non-Hodgkin lymphoma patients treated with (131)I-labeled antibody. Correlations between therapy efficiency generated from the model and tumor response were observed using averaged model parameters. Model parameter determination favored a threshold for the cold effect and typical magnitude for tumor radiosensitivity parameters. The inclusion of radiobiologic effects in the dosimetry modeling of internal emitter therapy provides a powerful platform to investigate correlations of patient outcome with planned therapy.

SU‐FF‐T‐455: Methodology to Incorporate the BED and EUD in Patient‐Specific 3‐Dimensional Dosimetry for Non‐Hodgkin's Lymphoma Patients Targeted with 131I Tositumomab Therapy

Purpose: The efficacy of targeted radionuclide therapy depends on the uniformity of radionuclide distribution within the target volume as well as on the radiosensitivity of the tissue. The inclusion of dose non uniformity and biologic effects in the dosimetry of radionuclide may help in correlating dose with patient outcome. Our goal is to develop a methodology incorporating the biologic equivalent dose (BED) and the equivalent uniform dose (EUD) formalism for radionuclide dosimetry. Materials and Methods: A 3D imaging‐based patient‐specific dosimetry methodology was applied to six non‐Hodgkin's lymphoma (NHL) patients treated with I‐131 labeled tositumomab for model evaluation purposes. Six registered SPECT/CT scans were obtained for each patient and used to generate 3D dose rate distributions using a Monte Carlo code. The dose rate distributions were integrated over time to obtain 3D time‐dependent absorbed dose distributions using fitted activity curves. Radial deformation model was used to account for tumor regression during therapy relative to initial volume. 3D time‐dependent biological equivalent dose (BED) distributions were calculated and used to estimate a single equivalent uniform dose (EUD) for each tumor volume. Results: The methodology developed in this work allows for the adjustment of model parameters such as radiosensitivity, proliferation, unlabeled protein effect, and clearance time based on patient data. Model outputs are being validated against tumor regression. The EUD values for the tumors included in this study show a reduction between 11% −23% in the efficiency of dose delivery and appear to correlate with tumor regression better than total tumor dose. Conclusions: The methodology developed in this work allows for the inclusion of various effects that influence the effectiveness of targeted radionuclide therapy of NHL. Model parameters could be adjusted to aid in improving predictions of patient outcome.

SU-FF-T-608: Planning Comparison Between IMRT and RapidArc in CGMH Experience

Purpose: To evaluate the dose performance and delivery efficiency for RapidArc plan. Material and methods: Fixed‐beam IMRT can deliver prescribed dose to target and spare dose to OAR. Because it had an ineffective beam on time, some patients would lie on treatment couch for a long time. A new technique‐ RapidArc‐ was developed for shortening treatment time to compare with fixed‐beam IMRT. A selected NPC case was involved in this study, and treatment plans were created with IMRT and RapidArc technique for evaluating dose performance and delivery efficiency. In this case, the prescribed dose of CTV was 46Gy in the first phase. Fixed‐beam IMRT plan with 7 fields was used and RapidArc plan was performed using two arcs with total 718 rotation angle. Both plans executed on Eclipse ver 8.6 planning system. CTV coverage and avoidance structures sparing are two major indexes to compare through DVH. Results: Compared DVH showed 46Gy covering 96% and 95% volume of CTV for fixed‐beam IMRT and RapidArc respectively. High dose did not exceed 110.5% of prescribed dose in both. RapidArc can have heterogeneity dose in CTV as IMRT. With more than received dose 23Gy in parotid glands, the former had 30%∼31% volume and the later had 40.5%∼42% volume. Other avoidance structures showed the former had lower mean dose than the later. The total MU was 627 MU and delivery time was 3.5 min. in RapidArc. But, IMRT had 1195 MU and around 10 min. treatment time. Conclusions: In this study, RapidArc provided better plan quality than fixed‐beam IMRT. The features of lower MU and lower delivery time are the clinical advantage in RapidArc.

SU-FF-T-203: Evaluation of a New Metric for Assessing IMRT Modulation Complexity and Plan Deliverability

Purpose: A single metric, the modulation complexity score (MCS), has been developed to quantitatively define the segmentation complexity in IMRT treatment plans. The goal of this study is to evaluate the utility of the MCS in the quality assurance (QA) process, via dosimetric measurements. Method and Materials: The MCS, and associated metrics, have been tabulated for 38 clinical IMRT lung plans. Ten of these plans were selected for dosimetric analysis, representing a range of plan complexities, as assessed by typical qualitative surrogates for plan complexity such as number of beams, segments and monitor units (MU). The MCS, which is calculated based on segment shape, segment area and segment weight, was calculated for each beam using a QA tool. Dose measurements were acquired using a 2D diode-array (MapCheck, Sun Nuclear, Melbourne, FL)) and compared to the dose calculated by the treatment planning system (Pinnacle3, Phillips, Madison, WI). The MCS and simple beam characteristics were compared with the dose measurement results using multiple percentage dose difference and distance to agreement criteria. Results: On average, 98.9% of the diodes met the 3%/3mm criterion for comparison between planned and measured dose. The average difference in maximum dose was 0.8 cGy. No clear relationship was evident between treatment beam parameters and deliverability. However, MCS scores in the top 20% of plans correlated with more accurate dose delivery. These plans maintained a high pass rate (>84%) even under stringent evaluation criteria (2%/0mm), thus providing a link between complexity and robust delivery. Conclusions: The MCS allows for simple, quantitative assessment of beam complexity, and is applicable to all treatment sites. Scores can be used to assess the degree of complexity and its potential impact on accurate, robust and efficient dose delivery. This tool can be incorporated into various stages of the treatment planning and QA process.

Integration of Real-Time Internal Electromagnetic Position Monitoring Coupled With Dynamic Multileaf Collimator Tracking: An Intensity-Modulated Radiation Therapy Feasibility Study

Continuous tumor position measurement coupled with a tumor tracking system would result in a highly accurate radiation therapy system. Previous internal position monitoring systems have been limited by fluoroscopic radiation dose and low delivery efficiency. We aimed to incorporate a continuous, electromagnetic, three-dimensional position tracking system (Calypso 4D Localization System) with a dynamic multileaf collimator (DMLC)-based dose delivery system. A research version of the Calypso System provided real-time position of three Beacon transponders. These real-time three-dimensional positions were sent to research MLC controller with a motion-tracking algorithm that changed the planned leaf sequence. Electromagnetic transponders were embedded in a solid water film phantom that moved with patient lung trajectories while being irradiated with two different plans: a step-and-shoot intensity-modulated radiation therapy (S-IMRT) field and a dynamic IMRT (D-IMRT) field. Dosimetric results were recorded under three conditions: no intervention, DMLC tracking, and a spatial gating system. Dosimetric accuracy was comparable for gating and DMLC tracking. Failure rates for gating/DMLC tracking are as follows: +/-3 cGy 10.9/ 7.5% for S-IMRT, 3.3/7.2% for D-IMRT; gamma (3mm/3%) 0.2/1.2% for S-IMRT, 0.2/0.2% for D-IMRT. DMLC tracking proved to be as efficient as standard delivery, with a two- to fivefold efficiency increase over gating. Real-time target position information was successfully integrated into a DMLC effector system to modify dose delivery. Experimental results show both comparable dosimetric accuracy as well as improved efficiency compared with spatial gating.

Dosimetric verification of modulated electron radiotherapy delivered using a photon multileaf collimator for intact breasts

Modulated electron radiotherapy (MERT) may potentially be an effective modality for the treatment of shallow tumors, but dose calculation accuracy and delivery efficiency challenges remain. The purpose of this work is to investigate the dose accuracy of MERT delivery using a photon multileaf collimator (pMLC) on a Siemens Primus accelerator. A Monte Carlo (MC)-based inverse treatment planning system was developed for the 3D treatment planning process. Phase space data of 6, 9, 12 and 15 MeV electron beams were commissioned and used as the input source for MC dose calculations. A treatment plan was performed based on the 3D CT data of a heterogeneous ‘breast phantom’ that mimics a breast cancer patient, and delivered with 22 segments, each associated with a particular energy and Monitor Unit value. Film and ion chamber dosimetry was carefully performed for the conversion from measurement reading to dose, and the results were employed for plan verification using the heterogeneous breast phantom and a solid water phantom. Dose comparisons between measurements and calculations showed agreement within 2% or 1 mm. We conclude that our in-house MC treatment planning system is capable of performing treatment planning and accurate dose calculations for MERT using the pMLC to deliver radiation therapy to the intact breast.

Commissioning and Quality Assurance of RapidArc Radiotherapy Delivery System

The Varian RapidArc is a system for intensity-modulated radiotherapy (IMRT) treatment planning and delivery. RapidArc incorporates capabilities such as variable dose-rate, variable gantry speed, and accurate and fast dynamic multileaf collimators (DMLC), to optimize dose conformality, delivery efficiency, accuracy and reliability. We developed RapidArc system commissioning and quality assurance (QA) procedures. Tests have been designed that evaluate RapidArc performance in a stepwise manner. First, the accuracy of DMLC position during gantry rotation is examined. Second, the ability to vary and control the dose-rate and gantry speed is evaluated. Third, the combined use of variable DMLC speed and dose-rate is studied. Adapting the picket fence test for RapidArc, we compared the patterns obtained with stationary gantry and in RapidArc mode, and showed that the effect of gantry rotation on leaf accuracy was minimal (< or =0.2 mm). We then combine different dose-rates (111-600 MU/min), gantry speeds (5.5-4.3 degrees /s), and gantry range (Deltatheta = 90-12.9 degrees ) to give the same dose to seven parts of a film. When normalized to a corresponding open field (to account for flatness and asymmetry), the dose of the seven portions show good agreement, with a mean deviation of 0.7%. In assessing DMLC speed (0.46, 0.92, 1.84, and 2.76 cm/s) during RapidArc, the analysis of designed radiation pattern indicates good agreement, with a mean deviation of 0.4%. The results of these tests provide strong evidence that DMLC movement, variable dose-rates and gantry speeds can be precisely controlled during RapidArc.

SU-GG-T-83: A Scanning Photon Pencil Beam for Temporally Precise IMRT

Purpose: We present an early feasibility analysis of a scanning photon pencil beam (SPPB) system capable of producing temporally optimized IMRT fields for real-time motion tracking. A high energy electron beam will be electromagnetically scanned with dwell times corresponding to beam weights, and impinge upon a target. A dual focused collimator (DFC) will transmit only pencil beams whose divergence matches the incoming electron beam angle. Method and Materials: The EGSnrc, BEAMnrc and DOSxyz Monte Carlo simulation codes were used to model relevant system characteristics including forward bremsstrahlung efficiency, focal spot size, and DFC transmission efficiency. Monte Carlo modeling of a potential DFC was used to assess whether the proposed system is capable of producing a sharply focused pencil beam, and both uniform and modulated treatment fields. We simulated an 18 MeV electron beam, 5 mm thick tungsten target and an 8 cm thick tungsten DFC containing 200 hexagonal channels, each with a 0.5 mm radius and wall thickness. The dose to water at 2 cm following a 20 cm air gap was simulated for a single pencil beam. A pencil beam summation script was used to assess the system's ability to produce uniform and modulated fields. Results: The efficiency of dose delivery to a very small forward-directed cross section increases by an order of magnitude between energies of 6 MeV and 50 MeV. The focal spot size produced using a tungsten target is approximately 4 times smaller than that produced using a Be target. Our simulated system produced a pencil beam with FWHM of 6mm. The uniformly irradiated field possessed local uniformity to within +/−1%, verifying that septa-induced dead spots are compensated by phantom scatter. Conclusion: These early results support the feasibility of producing a DFC-based SPPB system. This work was supported by Varian Medical Systems.

SU-FF-T-302: Monte Carlo Dose Verification and Application of Complex IOHDR Geometries

Purpose: Dose computation algorithm may lead to serious dose errors in intra-operative high dose rate (IOHDR) brachytherapy due to the lack of scatter from one side of the applicator and/or complex geometries of treated areas. Our group has reported the inaccuracy in clinical dose delivery for general cases through several experimental approaches. However, more accurate Monte Carlo calculations are needed to quantify dose errors in IOHDR delivered with more complex geometries and scattering environment. Method and Materials: Dose calculations were done using the EGSnrc Monte Carlo code system and the setup geometry including source structure was designed with the geometry package using EGSnrc C++ library class. User-code was developed from an existing EGSnrc user-code CAVRZnrc. To benchmark the code, a few steps were carried out to ensure that the accuracy of the cavity dose for a given simple geometry option and the ratio of cavity doses with the varying distance from the source to the center of cavity for different geometries. Based on accurate results of benchmarking geometries, test input files were developed to verify the accuracy of delivered doses for the measured known results that we had already reported the with linear array ion-chamber. Results: For the 1.0 cm prescription distance, Monte Carlo results showed about 14 % higher for added tissue equivalent materials of 15 cm. Also, calculated doses were 1.5 to 2 % higher than measured doses for added materials of above 5 cm. However, Monte Carlo showed an excellent agreement for 1.5 cm prescription distance and simulated uncertainties of 0.01 % to 0.1 %. Conclusion: Computed doses obtained using EGSnrc system for known geometries validate the results of ion-chamber measurement. This Monte Carlo calculation will improve the approach of dose calculations for complex geometries and the efficiency of dose delivery in clinical cases.

TH‐D‐M100F‐06: Surface Smoothing of a Tubular Structure Using a Non‐Shrinking Algorithm

Purpose: The modeling of a 3D structure by interpolating a stack of 2D contours may result in an unrealistic faceted shape, even though each contour is smooth. A difficulty with geometric smoothing is that the surface can shrink after a number of iterations. This work investigates the use of a non‐shrinking smoothing algorithm in structure delineation for radiotherapy treatment planning. Materials and methods: The surface of a tubular structure is parameterized by an interpolating function using original contour data points in cylindrical coordinates. The center of the polar coordinates for each axial contour is placed on a smooth fitting function while the contour is still a single‐valued function. By interpolation the surface is re‐sampled into a set of evenly spaced vertices. In an iterative process each vertex is shifted by an average displacement vector from its neighbor vertices and scaled by a factor. Each step of iteration involves two shifts for every vertex with the scaling factor in opposite signs, in order to avoid shrinkage. The iterative process stops after a desired smoothness is achieved with all average displacement vectors smaller than a specified tolerance. This method is tested on five prostate IMRT cases. The axial contours of smoothed structure are displayed with the original contours for validation by three physicians. Results: The resulting surface appeared smooth in all projections. The physician approved the new contours for all five patients. The volume change for each structure was less than 2%. Treatment planning using smoothed CTVs and PTVs reduced the numbers of MU and MLC segments by 8 – 11%. Conclusions: A technique was developed for smoothing a structure surface constructed using 2D contours. The calculation was fast for 3D contouring. Our planning results suggested that unrealistically irregular target shapes can have adverse effects on dose conformity and delivery efficiency.

TU-FF-A3-04: Empirical Investigation of 3D Intrafraction Motion Management Using a Generalized Methodology for Tracking Translating, Rotating and Deforming Targets

Purpose: Real‐time tracking of tumor motion is a highly promising approach for intrafraction motion management in thoracic and abdominal cancerradiotherapy. We investigate the geometric and dosimetric impact of a generalized methodology for conformal and IMRT‐based radiation delivery to translating, rotating and deforming targets. Materials and Methods: The methodology is based on the concept of “relocation vectors”, which correlate instantaneous target position to each point on the treatment aperture(s), throughout the entire respiratory cycle. These vectors are determined during 4D treatment planning by combining instantaneous target position information, obtained from a real‐time position‐monitoring (RPM) system, with concurrently acquired 4DCT. The resulting plan comprises multiple “control points”. For each point, a set of MLC leaf positions is defined so as to conform to the instantaneous shape of the target and deliver the desired fluence. The methodology is, therefore, independent of the nature of target motion. During dose delivery, real‐time RPM data are used to update the relocation vectors so as to dynamically account for changes target shape/position relative to the shape/position observed in the planning stage. Initial studies were performed to demonstrate tracking of linear and elliptical motion. A laboratory system was designed and optical measurements of tracking accuracy and system latency were obtained. The methodology was subsequently tested on a moving lung phantom placed under a clinical linac, and dosimetric measurements were performed using a 2D ion‐chamber array. Results: Tracking accuracy (without using any predictive algorithm) was observed to be ∼1.25 mm for motion parallel to MLC leaf travel. For motion perpendicular to leaf travel, accuracy was significantly lower. Dosimetric measurements indicate that tracking achieves efficient dose delivery to the target and, simultaneously, significant dose reduction in surrounding regions. Conclusions: We have developed a robust, universal tracking methodology to manage 3D intrafraction motion. This work was partially supported by Varian.

Adequacy of quotidian hemodialysis

Background: Several methods exist to quantitate small-solute clearance by daily hemodialysis (HD) regimens, but these have not been empirically applied or compared. Methods: In the London Daily/Nocturnal Hemodialysis Study, dosing and adequacy of quotidian HD regimens, both short daily HD (n = 11) and long nocturnal HD (n = 12), were compared with conventional thrice-weekly HD (n = 22) using several models. Urea clearance was computed by percentage of reduction in urea, kinetic modeling (single-pool Kt/V [spKt/V]), Daugirdas rate equation (equilibrated Kt/V [eKt/V]), and Gotch standardized Kt/V (stdKt/V). Results: Nocturnal HD patients maintained a mean single-session spKt/V of 1.64 throughout the study, similar to that of conventional HD patients (1.73), whereas daily HD patients showed a significant decrease in mean single-session spKt/V (0.93) compared with baseline (t 0) values. Mean weekly spKt/V values increased from t 0 for both quotidian HD groups (9.08 for nocturnal HD, 5.55 for daily HD) and were higher in both quotidian HD groups compared with conventional HD patients. Weekly eKt/V, stdKt/V, and normalized protein equivalent of nitrogen appearance values showed similar trends. Comparison of the 3 different adequacy models showed an increase in weekly HD doses for both quotidian HD regimens compared with conventional HD; however, percentages of increases from t 0 to follow-up differed according to the model used. The calculated efficiency of dose delivery at the 10-month follow-up comparing daily HD with conventional HD was 257 ± 26 minutes versus 306 ± 17 stdKt/V unit delivered, respectively, amounting to almost 1 dialysis-hour saved per stdKt/V unit delivered for daily HD. Conclusion: These results show that both quotidian HD regimens are more effective than conventional HD in improving weekly urea clearance measured by spKt/V, stdKt/V, and eKt/V.

Evaluation of nose-only aerosol inhalation chamber and comparison of experimental results with mathematical simulation of aerosol deposition in mouse lungs

In vivo small rodent efficacy testing of new synthetic and biological molecules for the pulmonary route requires an efficient delivery device. For this purpose, a nose-only inhalation chamber was used to deliver aerosolized aqueous compounds to the respiratory tract of mice. The aim of the study was to determine the efficiency of dose delivery and deposition in the lungs of the mice using this chamber. A secondary goal was to compare the experimental lung deposition results with values predicted from mathematical simulation. Experimental tests were conducted by generating aerosols of a radiolabeled formulation of human serum albumin (HSA) with a mass median aerodynamic diameter (MMAD) of 3.9±0.5 μm and a geometric standard deviation (GSD) of 1.43±0.05 using PARI LC STAR jet nebulizers. Based on the total activity placed in the nebulizer, the chamber delivered 0.108±0.027% to the mice and 0.0087±0.0021% to the lungs of the mice. In vivo lung deposition was found to be 8.19±3.56% of total activity deposited in the mouse. Mathematical simulation predictions ranged between 5.89 and 4.40% for various breathing patterns, and did not differ significantly from the in vivo results (p>0.10). These results provide important quantitative information relevant to aerosol delivery experiments in mouse models. Our results also suggest that the nose-only inhalation chamber would benefit from significant changes to increase the efficiency of deposition in mice such that it can be used for nebulization of expensive therapeutic drugs.

Lung trajectory mapping

Purpose: Breathing motion has limited the use of intensity modulated radiation therapy (IMRT) for lung cancer treatments. We propose a method for directly measuring the complex three-dimensional motion of the entire lung during breathing (lung trajectory) for the purpose of optimizing IMRT treatment plans and improving the spatial resolution and small-lesion detectability of nuclear medicine imaging, principally positron emission tomography (PET). For IMRT, patient-specific knowledge of lung motion will enable the study of the compromise between dose distribution conformality (associated with fluence modulation complexity and margin size), dose delivery accuracy, and dose delivery efficiency (gating). We propose to measure patient-specific lung trajectory maps by combining gated CT images with automated deformable image registration techniques. This study investigates the feasibility and utility of this technique.

Conformal intensity-modulated radiotherapy (IMRT) deliveredby robotic linac - conformality versus efficiency of dose delivery

Intensity-modulated radiotherapy (IMRT) may be delivered with ahigh-energy-photon linac mounted on a robotic gantry and executing a complextrajectory. In a previous paper an inverse-planning technique was developedfor such an application. Here the work is extended to demonstrate thedependence of conformality on the size of the elemental pencil beam, on thecomplexity of the trajectory and on the sampling of azimuth and elevation ofthe collimated source. The improved conformality of complex trajectories isdemonstrated and benchmarked relative to simpler trajectories, morerepresentative of existing non-robotic IMRT techniques. Specifically, bychoosing a very fine pencil beam, exquisitely conformal dose distributionshave been obtained. Important sampling considerations have been determined.Expressions have been derived for the dosimetry and monitor-unit efficiency ofrobotic IMRT. Equivalent trajectories were computed for executing the complexrobotic trajectories instead by using a conventional linac. The workbenchmarks an ideal in IMRT against which more practical and more commontechniques may be measured.

Drug delivery characteristics of Bricanyl Turbohaler TM dry powder inhalers

The Turbohaler TM is the one multidose reservoir type dry powder inhaler (DPI) with significant clinical usage but there is little information on the precision of its single dose delivery characteristics. The single dose delivery efficiency of terbutaline sulphate (nominally 500 μg) from two batches of Bricanyl Turbohalers TM (11 and 59 devices) has therefore been studied at air flow rates of 28–30 and 60 1 min −1 which are clinically relevant test conditions for this DPI. At 60 1 min −1 statistically significant differences both within and between batches were obtained for emitted dose (± SD, n = 110, 130), 421 ± 73, 387 ± 58μg and fine particle dose (0.5–6.4 μm MMAD), 249 ± 41, 214 ± 44μg. These data imply an emitted dose range of ± 50% and a fine particle dose range of ± 70% from this DPI system. Through-life total dose emission in terms of the average values remain consistent. Reducing air flow rates to approx. 30 1 min −1 lowered the mean emitted dose by about one third with the clinically important fine particle dose being reduced 3-fold to 59 ± 25 μg; this underlines the likely sensitivity of effective delivery, to patients' lung function. These results reinforce the need to provide single dose data at clinically relevant flow rates in the assessment of DPI performance. Expressing data as mean performance for a cumulative series of dose units smooths down this single dose variability by a factor of two.