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Biomedical subjects

R Allen White

Publications and source records attributed to R Allen White.

15 recordsLinked to original sources

Quantification of bleomycin-induced murine lung damage in vivo with micro-computed tomography.

RATIONALE AND OBJECTIVES: We explored noninvasive, in vivo cone-beam microcomputed tomography (micro-CT) to visualize and quantify fibrotic and inflammatory damage over the entire lung volume of mice. MATERIALS AND METHODS: We used bleomycin to induce pulmonary damage in vivo and compared the results from micro-CT with histologic measurements. Ten C57BL/6 mice were given 5 U/kg bleomycin intratracheally. Seven surviving mice were scanned with micro-CT before administration of bleomycin, and again before sacrifice. The resulting images were analyzed for lung volume measurements. After the final scan, all lungs were examined histologically and pulmonary damage was quantified. Damaged lung tissue regions were matched between micro-CT images and histologic sections for each mouse. RESULTS: The percent lung damage calculated from micro-CT and histology were correlated (r(2) = 0.49, r = 0.64 with P = 0.12), and the means of their respective distributions were not different (P > 0.05). CONCLUSION: This study shows that micro-CT is a promising alternative to predicting lung damage caused by bleomycin. CT image volumes of the thorax allow for global tissue sampling, which may be useful when following nonuniform lung damage that can occur from intratracheal administration of bleomycin.

Animals↗

A Monte Carlo model for calculating out-of-field dose from a varian 6 MV beam.

Dose to the patient outside of the treatment field is important when evaluating the outcome of radiotherapy treatments. However, determining out-of-field doses for any particular treatment plan currently requires either time-consuming measurements or calculated estimations that may be highly uncertain. A Monte Carlo model may allow these doses to be determined quickly, accurately, and with a great degree of flexibility. MCNPX was used to create a Monte Carlo model of a Varian Clinac 2100 accelerator head operated at 6 MV. Simulations of the dose out-of-field were made and measurements were taken with thermoluminescent dosimeters in an acrylic phantom and with an ion chamber in a water tank to validate the Monte Carlo model. Although local differences between the out-of-field doses calculated by the model and those measured did exceed 50% at some points far from the treatment field, the average local difference was only 16%. This included a range of doses as low as 0.01% of the central axis dose, and at distances in excess of 50 cm from the central axis of the treatment field. The out-of-field dose was found to vary with field size and distance from the central axis, but was almost independent of the depth in the phantom except where the dose increased substantially at depths less than dmax. The relationship between dose and kerma was also investigated, and kerma was found to be a good estimate of dose (within 3% on average) except near the surface and in the field penumbra. Our Monte Carlo model was found to well represent typical Varian 2100 accelerators operated at 6 MV.

Computer Simulation↗

Out-of-field photon and neutron dose equivalents from step-and-shoot intensity-modulated radiation therapy.

PURPOSE: To measure the photon and neutron out-of-treatment-field dose equivalents to various organs from different treatment strategies (conventional vs. intensity-modulated radiation therapy [IMRT]) at different treatment energies and delivered by different accelerators. METHODS AND MATERIALS: Independent measurements were made of the photon and neutron out-of-field dose equivalents resulting from one conventional and six IMRT treatments for prostate cancer. The conventional treatment used an 18-MV beam from a Clinac 2100; the IMRT treatments used 6-MV, 10-MV, 15-MV, and 18-MV beams from a Varian Clinac 2100 accelerator and 6-MV and 15-MV beams from a Siemens Primus accelerator. Photon doses were measured with thermoluminescent dosimeters in a Rando phantom, and neutron fluence was measured with gold foils. Dose equivalents to the colon, liver, stomach, lung, esophagus, thyroid, and active bone marrow were determined for each treatment approach. RESULTS: For each treatment approach, the relationship between dose equivalent per MU, distance from the treatment field, and depth in the patient was examined. Photon dose equivalents decreased approximately exponentially with distance from the treatment field. Neutron dose equivalents were independent of distance from the treatment field and decreased with increasing tissue depth. Neutrons were a significant contributor to the out-of field dose equivalent for beam energies > or =15 MV. CONCLUSIONS: Out-of-field photon and neutron dose equivalents can be estimated to any point in a patient undergoing a similar treatment approach from the distance of that point to the central axis and from the tissue depth. This information is useful in determining the dose to critical structures and in evaluating the risk of associated carcinogenesis.

Algorithms↗

The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy.

PURPOSE: Out-of-field radiation doses to normal tissues may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Step-and-shoot intensity-modulated radiation therapy (IMRT), an increasingly popular treatment modality, yields higher out-of-field doses than do conventional treatments, because of an increase in required monitor units (beam-on time). METHODS: We used published risk coefficients (NRCP Report 116) and out-of-field dose equivalents to multiple organ sites to estimate a conservative maximal risk of fatal secondary malignancy associated with 6 IMRT approaches and 1 conventional external-beam approach for prostate cancer. RESULTS: Depending on treatment energy, the IMRT treatments required 3.5-4.9 times as many monitor units to deliver as did the conventional treatment. The conservative maximum risk of fatal second malignancy was 1.7% for conventional radiation, 2.1% for IMRT using 10-MV X-rays, and 5.1% for IMRT using 18-MV X-rays. Intermediate risks were associated with IMRT using 6-MV X-rays: 2.9% for treatment with the Varian accelerator and 3.7% for treatment with the Siemens accelerator, as well as using 15-MV X-rays: 3.4% (Varian) and 4.0% (Siemens). CONCLUSION: The risk of fatal secondary malignancy differed substantially between IMRT and conventional radiation therapy for prostate cancer, as well as between different IMRT approaches. Perhaps this risk should be considered when choosing the optimal treatment technique and delivery system for patients who will undergo prostate radiation.

Dose-Response Relationship, Radiation↗

Estimating cell death in G(2)M using bivariate BrdUrd/DNA flow cytometry.

BACKGROUND: In an accompanying paper (Asmuth et al.) it was found necessary to include cell death explicitly to estimate parameters of cell proliferation. The use of bivariate flow cytometry to estimate the phase durations and the doubling times of cells labeled with thymidine analogues is well established. However, these methods of analysis do not consider the possibility of cell death. This report demonstrates that estimating cell death in G(2)/M is possible. METHODS: Mathematical models for the experimental quantities, the fraction of labeled undivided cells, the fraction of labeled divided cells, and the relative movement were developed. These models include the possibility that, of the cells with G(2)/M DNA content, only a certain fraction will divide, with the remainder dying after some time T(R). Simulation studies were conducted to test the possibility of using simple methods to estimate phase durations and cell death rates. RESULTS: Cell death alters the estimates of phase transit times in a rather complex manner that depends on the lifetime of the doomed cells. However, it is still possible to obtain estimates of the phase durations of cells in S and G(2)/M and the death rates of cells in G(2)/M. CONCLUSIONS: The methods presented herein provide a new way to characterize cell populations that includes cell death rates and common measurements of cell proliferation.

Animals↗

Cell cycle kinetic dysregulation in HIV-infected normal lymphocytes.

BACKGROUND: Viruses alter cellular gene transcription and protein binding at many steps critical for cell cycle regulation to optimize the milieu for productive infection. Reasoning that virus-host cell interactions would result in perturbations of cell cycle kinetics, measurement of the duration of the phases of the cell cycle in normal T lymphocytes infected with human immunodeficiency virus (HIV) was undertaken. METHODS: Flow cytometric measurement of bromodeoxyuridine-labeled and DNA content-stained cells at multiple points through the cell cycle allowed estimation of the fraction of cells in each phase, the potential doubling-time, and the durations of S and G(2)/M phases. Separate analysis of the HIV(+) and HIV(-) populations within the infected cultures was performed based on intracellular, anti-HIV core p24 antibody labeling. A novel mathematical model, which accounted for cell loss, was developed to estimate cell cycle phases. RESULTS: (a) S phase was prolonged in the HIV-1(SF2)-infected cells compared with control. (b) This delay in S phase was due to delay in the population of cells not expressing HIV-1 antigens (p24 negative). (c) Accumulation of cells in G(2)/M phase was confirmed in HIV-1-infected cultures and was proportional to the level of infection as measured by p24 fluorescent intensity. However, all mock and HIV-1-infected populations predicted to proceed through cell division demonstrated similar G(2)/M-phase durations. (c) Potential doubling times were longer in the infected cultures; in contrast, the p24(+) subpopulations accounted for this delay. This suggests an isolated delay in the G(0)/G(1) phase for that population of cells. CONCLUSIONS: Multiple phases of host cell cycle durations were affected by HIV-1(SF2) infection in this in vitro model, suggesting novel HIV-1 pathogenesis mechanisms. Prolonged S-phase durations in HIV-1 infected/p24(-) and G(0)/G(1)-phase durations in HIV-1 infected/p24(+) subpopulations require further study to identify mechanistic pathways.

Bromodeoxyuridine↗

Input parameter sensitivity analysis and comparison of quantification models for continuous arterial spin labeling.

The regional cerebral blood flow (rCBF) values determined using continuous arterial spin labeling (CASL) are subject to several sources of variability, including natural physiologic variations, sensitivity to the input parameters, and the use of different quantification models. To date, a thorough analysis of the impact of input parameters and the choice of quantification model has not been performed. These sources of variability were investigated through computer simulations using bootstrap techniques on actual CASL data. Coefficients of variation for representative single voxels were 6.7% for gray matter and 29% for white matter, and for eight-voxel regions of interest they were 4.5% for gray matter and 23% for white matter. Comparison of nine CASL quantification models showed differences in gray matter rCBF values of up to 42%. An analysis of the sensitivity of the rCBF to input parameters for each of the nine quantification models demonstrated that accurate quantification of the inversion efficiency, tissue and arterial blood longitudinal relaxation times, and transit times were critical in calculating precise rCBF values. The large potential variations in rCBF and the effect of the choice of quantification model suggest that interpreting absolute rCBF values in CASL studies can be challenging and requires great care.

Adult↗

Detection of IMRT delivery errors using a quantitative 2D dosimetric verification system.

We investigated the feasibility of detecting intensity modulated radiotherapy delivery errors automatically using a scalar evaluation of two-dimensional (2D) transverse dose measurement of the complete treatment delivery. Techniques using the gamma index and the normalized agreement test (NAT) index were used to parametrize the agreement between measured and computed dose distributions to seven different scalar metrics. Simulated verifications with delivery errors calculated using a commercially available treatment planning system for 9 prostate and 7 paranasal sinus cases were compared to 433 clinical verifications. The NAT index with 5% and 3 mm criteria that included cold areas outside the planning target volume detected the largest percent of delivery errors. Assuming a false positive rate of 5%, it was able to detect 88% of beam energy changes, 94% of a different patient's plan being delivered, 25% of plans with one beam's collimator rotated by 90 degrees, 81% of rotating one beam's gantry angle by 10 degrees, and 100% of omitting the delivery of one beam. However, no instances of changing one beam's monitor unit setting by 10% or shifting the isocenter by 5 mm were detected. Although the phantom shift could not be detected by the small change it made in the dose distribution, our autopositioning algorithm clearly identified the spatial anomaly. Using tighter 3 %/2 mm criteria or combining dose and distance disagreements in an either/or fashion resulted in poorer delivery error detection. The mean value of the 2D gamma index distribution was less sensitive to delivery errors than the other scalar metrics studied. Although we found that scalar metrics do not have sufficient delivery error detection rates to be used as the sole clinical analysis technique, manually examining 2D dose comparison images would result in a near 100% detection rate while performing an ion chamber measurement alone would only detect 54% of these errors.

Algorithms↗

Dosimetric accuracy of Kodak EDR2 film for IMRT verifications.

Patient-specific intensity-modulated radiotherapy (IMRT) verifications require an accurate two-dimensional dosimeter that is not labor-intensive. We assessed the precision and reproducibility of film calibrations over time, measured the elemental composition of the film, measured the intermittency effect, and measured the dosimetric accuracy and reproducibility of calibrated Kodak EDR2 film for single-beam verifications in a solid water phantom and for full-plan verifications in a Rexolite phantom. Repeated measurements of the film sensitometric curve in a single experiment yielded overall uncertainties in dose of 2.1% local and 0.8% relative to 300 cGy. 547 film calibrations over an 18-month period, exposed to a range of doses from 0 to a maximum of 240 MU or 360 MU and using 6 MV or 18 MV energies, had optical density (OD) standard deviations that were 7%-15% of their average values. This indicates that daily film calibrations are essential when EDR2 film is used to obtain absolute dose results. An elemental analysis of EDR2 film revealed that it contains 60% as much silver and 20% as much bromine as Kodak XV2 film. EDR2 film also has an unusual 1.69:1 silver:halide molar ratio, compared with the XV2 film's 1.02:1 ratio, which may affect its chemical reactions. To test EDR2's intermittency effect, the OD generated by a single 300 MU exposure was compared to the ODs generated by exposing the film 1 MU, 2 MU, and 4 MU at a time to a total of 300 MU. An ion chamber recorded the relative dose of all intermittency measurements to account for machine output variations. Using small MU bursts to expose the film resulted in delivery times of 4 to 14 minutes and lowered the film's OD by approximately 2% for both 6 and 18 MV beams. This effect may result in EDR2 film underestimating absolute doses for patient verifications that require long delivery times. After using a calibration to convert EDR2 film's OD to dose values, film measurements agreed within 2% relative difference and 2 mm criteria to ion chamber measurements for both sliding window and step-and-shoot fluence map verifications. Calibrated film results agreed with ion chamber measurements to within 5 % /2 mm criteria for transverse-plane full-plan verifications, but were consistently low. When properly calibrated, EDR2 film can be an adequate two-dimensional dosimeter for IMRT verifications, although it may underestimate doses in regions with long exposure times.

Dose-Response Relationship, Radiation↗

Retrospective analysis of 2D patient-specific IMRT verifications.

We performed 858 two-dimensional (2D) patient-specific intensity modulated radiotherapy verifications over a period of 18 months. Multifield, composite treatment plans were measured in phantom using calibrated Kodak EDR2 film and compared with the calculated dose extracted from two treatment planning systems. This research summarizes our findings using the normalized agreement test (NAT) index and the percent of pixels failing the gamma index as metrics to represent the agreement between measured and computed dose distributions. An in-house dose comparison software package was used to register and compare all verifications. We found it was important to use an automatic positioning algorithm to achieve maximum registration accuracy, and that our automatic algorithm agreed well with anticipated results from known phantom geometries. We also measured absolute dose for each case using an ion chamber. Because the computed distributions agreed with ion chamber measurements better than the EDR2 film doses, we normalized EDR2 data to the computed distributions. The distributions of both the NAT indices and the percentage of pixels failing the gamma index were found to be exponential distributions. We continue to use both the NAT index and percent of pixels failing gamma with 5%/3 mm criteria to evaluate future verifications, as these two metrics were found to be complementary. Our data showed that using 2%/2 mm or 3%/3 mm criteria produces results similar to those using 5%/3 mm criteria. Normalized comparisons that have a NAT index greater than 45 and/or more than 20% of the pixels failing gamma for 5%/3 mm criteria represent outliers from our clinical data set and require further analysis. Because our QA verification results were exponentially distributed, rather than a tight grouping of similar results, we continue to perform patient-specific QA in order to identify and correct outliers in our verifications. The data from this work could be useful as a reference for other clinics to indicate anticipated trends in 2D verifications under various conditions.

Algorithms↗

Improving conformational searches by geometric screening.

MOTIVATION: Conformational searches in molecular docking are a time-consuming process with wide range of applications. Favorable conformations of the ligands that successfully bind with receptors are sought to form stable ligand-receptor complexes. Usually a large number of conformations are generated and their binding energies are examined. We propose adding a geometric screening phase before an energy minimization procedure so that only conformations that geometrically fit in the binding site will be prompted for energy calculation. RESULTS: Geometric screening can drastically reduce the number of conformations to be examined from millions (or higher) to thousands (or lower). The method can also handle cases when there are more variables than geometric constraints. An early-stage implementation is able to finish the geometric filtering of conformations for molecules with up to nine variables in 1 min. To the best of our knowledge, this is the first time such results are reported deterministically. CONTACT: mzhang@mdanderson.org.

Algorithms↗

Evaluation of a contour-alignment technique for CT-guided prostate radiotherapy: an intra- and interobserver study.

PURPOSE: The recent introduction of integrated CT/linear accelerator systems may mean that daily CT localization can become a reality in the clinic, possibly allowing further dose escalation to the prostate while limiting unwanted doses to the rectum and bladder. However, the implementation of CT localization is currently impeded by the lack of precise and robust techniques to align the treatment plan with the daily CT images. The purpose of this study was to evaluate a manual alignment technique, in which the gross target volume contours are overlaid on the daily CT images and then shifted to match the structures visible in the images. METHODS AND MATERIALS: A total of 28 CT image sets were taken before the standard delivery of intensity-modulated radiotherapy for prostate cancer for 2 patients. Seven observers (four radiation oncologists and three medical physicists) manually shifted the gross target volume contours from the treatment plan to best match the daily CT images. One observer repeated the process 1 week later to evaluate intraobserver variations. The experiment was then repeated, but the CT images from the original treatment plan were used as a reference to reduce interobserver uncertainty when aligning the contours. The shifts in prostate position found by different observers, both with and without reference data, were evaluated using a factorial analysis of variance to determine the standard errors of measurement for the intra- and interobserver uncertainty (SEM(intra) and SEM(inter), respectively). The differences in the SEM for the two groups of observers (radiation oncologists and medical physicists), the two alignment techniques (with and without reference information), and the two patients were evaluated using the t test at 90% confidence levels. RESULTS: With no reference information, the SEM(inter) using one patient data set (Patient 1) was 0.8 mm, 2.0 mm, and 2.2 mm in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The use of the treatment plan as a reference reduced the SEM(inter) to 0.7 mm, 1.0 mm, and 1.6 mm in the RL, AP, and SI directions, respectively. In Patient 2, localization of the prostate was more difficult; the best SEM(inter) achieved with this patient was 0.8 mm, 1.9 mm, and 2.0 mm in the RL, AP, and SI directions, respectively. The SEM(intra) values with Patient 1 were also slightly better than with Patient 2. When reference data were used, the SEM(intra) value was 0.5 mm, 0.7 mm, and 0.5 mm for Patient 1 and 0.6 mm, 1.0 mm, and 0.7 mm for Patient 2 in the RL, AP, and SI directions, respectively. Despite the larger than expected interobserver variation reported here, the SEM(inter) was smaller than the typical day-to-day variation in prostate position. The contour alignment technique may still be useful to aid daily prostate localization or in a correction scheme to minimize the effect of target positional error. CONCLUSION: The interobserver uncertainties associated with aligning the gross target volume contours with daily CT images were sufficiently small that this method may be used for daily CT localization of the prostate. The use of a reference image is important to improve the consistency among different users in this technique.

Analysis of Variance↗

Cellular kinetics of murine lung: model system to determine basis for radioprotection with keratinocyte growth factor.

PURPOSE: Normal tissue toxicity remains a dose limitation for cancer radiotherapy and chemoradiotherapy. Growth factors offer a novel means of mitigating normal tissue radiotoxicity. In particular, keratinocyte growth factor (rHuKGF), whose proliferative activity is restricted to epithelial cells, holds promise on the basis of the findings of preclinical models of epithelial cytoprotection and the clinical developments to date. We report the radioprotection of murine lung by an increase in tissue cellularity after rHuKGF-induced proliferation. METHODS AND MATERIALS: Flow cytometric and image analysis techniques after bromodeoxyuridine labeling were used to estimate proliferative parameters. Our specialized analytical methods measure not only labeling indexes, but also the durations of S and G(2)+M phases, potential doubling times, and the net cell production rate. Image analysis techniques were used to identify the specific cell types that were proliferating (type II pneumocytes). RESULTS: Lung labeling index control values (0.5%) rose to a maximum (5.5%) at 3 days after intratracheal rHuKGF, returning to normal by Day 7. The potential doubling time fell from 66 days to 4.4 days. The net cell production rate rose from a control value of 1%/d to >15%/d by Day 3. This resulted in a nearly twofold increase in alveolar epithelial cellularity, which remained significantly elevated on Day 7. Saline-treated control animals exhibited no significant changes in the proliferative parameter values or cellularity. On the basis of these data, mice were irradiated, solely to the thorax, with ranges of single doses of 250 kVp X-rays 7 days after either intratracheal administration of 5 mg/kg rHuKGF or phospate-buffered saline. This interval was chosen because the proliferative response of the type II cells was finished but the cellularity of the lung remained increased. Pretreatment with rHuKGF extended the latent period before onset of pneumonitis after all radiation doses. rHuKGF treatment 7 days before thoracic irradiation significantly protected against pneumonitis (median effective dose 13.7 Gy, 95% confidence limit 13.4-14.0) compared with the control pretreatment with phosphate-buffered saline (median effective dose 12.8 Gy, 95% confidence limit 12.6-13.1). CONCLUSION: The data showed that an increase in tissue cellularity, caused by rHuKGF treatment before irradiation, protected the lung from damage due to pneumonitis.

Algorithms↗

The use of an extra-focal electron source to model collimator-scattered electrons using the pencil-beam redefinition algorithm.

Currently, the pencil-beam redefinition algorithm (PBRA) utilizes a single electron source to model clinical electron beams. In the single-source model, the electrons appear to originate from a virtual source located near the scattering foils. Although this approach may be acceptable for most treatment machines, previous studies have shown dose differences as high as 8% relative to the given dose for small fields for some machines such as the Varian Clinac 1800. In such machines collimation-scattered electrons originating from the photon jaws and the applicator give rise to extra-focal electron sources. In this study, we examined the impact of modeling an additional electron source to better account for the collimator-scattered electrons. The desired dose calculation accuracy in water throughout the dose distribution is 3% or better relative to the given dose. We present here a methodology for determining the electron-source parameters for the dual-source model using a minimal set of data, that is, two central-axis depth-dose curves and two off-axis profiles. A Varian Clinac 1800 accelerator was modeled for beam energies of 20 and 9 MeV and applicator sizes of 15 x 15 and 6 x 6 cm2. The improvement in the accuracy of PBRA-calculated dose, evaluated using measured two-dimensional dose distributions in water, was characterized using the figure of merit, FA3%, which represents the fractional area containing dose differences greater than 3%. For the 15 x 15 cm2 field the evaluation was restricted to the penumbral region, and for the 6 x 6 cm2 field the central region of the beam was included as it was impacted by the penumbra. The greatest improvement in dose accuracy was for the 6 x 6 cm2 applicator. At 9 MeV, FA3% decreased from 15% to 0% at 100 cm SSD and from 34% to 4% at 110 cm SSD. At 20 MeV, FA3% decreased from 17% to 2% at 100 cm SSD and from 41% to 10% at 110 cm SSD. In the penumbra of the 15 x 15 cm2 applicator, the improvement was less, but still significant. At 9 MeV, FA3% changed from 11% to 1% at 100 cm SSD and from 10% to 12% at 110 cm SSD. At 20 MeV, FA3% decreased from 12% to 8% at 100 cm SSD and from 14% to 5% at 110 cm SSD. Results demonstrate that use of a dual-source beam model can provide significantly improved accuracy in the PBRA-calculated dose distribution that was not achievable with a single-source beam model when modeling the Varian Clinac 1800 electron beams. Time of PBRA dose calculation was approximately doubled; however, dual-source beam modeling of newer accelerators (e.g., the Varian Clinac 2100) may not be necessary because of less impact of collimator-scattered electrons on dosimetry.

Algorithms↗

PTV margin determination in conformal SRT of intracranial lesions.

The planning target volume (PTV) includes the clinical target volume (CTV) to be irradiated and a margin to account for uncertainties in the treatment process. Uncertainties in miniature multileaf collimator (mMLC) leaf positioning, CT scanner spatial localization, CT-MRI image fusion spatial localization, and Gill-Thomas-Cosman (GTC) relocatable head frame repositioning were quantified for the purpose of determining a minimum PTV margin that still delivers a satisfactory CTV dose. The measured uncertainties were then incorporated into a simple Monte Carlo calculation for evaluation of various margin and fraction combinations. Satisfactory CTV dosimetric criteria were selected to be a minimum CTV dose of 95% of the PTV dose and at least 95% of the CTV receiving 100% of the PTV dose. The measured uncertainties were assumed to be Gaussian distributions. Systematic errors were added linearly and random errors were added in quadrature assuming no correlation to arrive at the total combined error. The Monte Carlo simulation written for this work examined the distribution of cumulative dose volume histograms for a large patient population using various margin and fraction combinations to determine the smallest margin required to meet the established criteria. The program examined 5 and 30 fraction treatments, since those are the only fractionation schemes currently used at our institution. The fractionation schemes were evaluated using no margin, a margin of just the systematic component of the total uncertainty, and a margin of the systematic component plus one standard deviation of the total uncertainty. It was concluded that (i) a margin of the systematic error plus one standard deviation of the total uncertainty is the smallest PTV margin necessary to achieve the established CTV dose criteria, and (ii) it is necessary to determine the uncertainties introduced by the specific equipment and procedures used at each institution since the uncertainties may vary among locations.

Brain Neoplasms↗