Mapping metabolic changes associated with early Radiation Induced Lung Injury post conformal radiotherapy using hyperpolarized ¹³C-pyruvate Magnetic Resonance Spectroscopic Imaging.

PURPOSE: Radiation Pneumonitis (RP) limits radiotherapy. Detection of early metabolic changes in the lungs associated with RP may provide an opportunity to adjust treatment before substantial toxicities occur. In this work, regional lactate-to-pyruvate signal ratio (lac/pyr) was quantified in rat lungs and heart following administration of hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) at day 5, 10, 15 and 25-post conformal radiotherapy. These results were also compared to histology and blood analyses. METHODS: The lower right lungs of 12 Sprague Dawley rats were irradiated in 2 fractions with a total dose of 18.5 Gy using a modified micro-CT system. Regional lactate and pyruvate data were acquired from three irradiated and three age-matched healthy rats at each time point on days 5, 10, 15 and 25-post radiotherapy. Arterial blood was collected from each animal prior to the (13)C-pyruvate injection and was analyzed for blood lactate concentration and arterial oxygen concentration (paO2). Macrophage count was computed from the histology of all rat lungs. RESULTS: A significant increase in lac/pyr was observed in both right and left lungs of the irradiated cohort compared to the healthy cohort for all time points. No increase in lac/pyr was observed in the hearts of the irradiated cohort compared to the hearts of the healthy cohorts. Blood lactate concentration and paO2 did not show a significant change between the irradiated and the healthy cohorts. Macrophage count in both right and left lungs was elevated for the irradiated cohort compared to the healthy cohort. CONCLUSIONS: Metabolic changes associated with RP may be mapped as early as five days post conformal radiotherapy. Over the small sample size in each cohort, elevated macrophage count, consistent with early phase of inflammation was highly correlated to increases in lac/pyr in both the irradiated and unirradiated lungs. Further experiments with larger sample size may improve the confidence of this finding.

Genistein can mitigate the effect of radiation on rat lung tissue.

We investigated whether genistein could protect the lung from radiation-induced injury. We hypothesized that genistein would reduce the levels of inflammatory cytokines and ROS after irradiation and therefore lead to reduced DNA damage and functional deficits. Whole lungs of Sprague-Dawley rats were irradiated with 18 Gy at approximately 0.5 Gy/min. At 28 weeks a micronucleus assay was used to examine DNA damage and, using immunohistochemical analysis, expression of IL-1alpha, IL-1beta, IL-6, TNF-alpha and TGF-beta, macrophage activation, oxidative stress (8-OHdG) and collagen levels were measured. A TBARS assay was used to measure the level of malondialdehyde. Functional damage was assessed by measuring the breathing rate of the rats over the course of the experiment. The increase in breathing rate after irradiation was damped in rats receiving genistein during the phase of pneumonitis (6-10 weeks), and there was a 50-80-day delay in lethality in this group. Genistein treatment also decreased the levels of the inflammatory cytokines TNF-alpha, IL-1beta and TGF-beta and led to a reduction in collagen content, a reduction in 8-OHdG levels, and complete protection against DNA damage measured in surviving rats at 28 weeks after irradiation. These results demonstrates that genistein treatment can provide partial protection against the early (pneumonitis) effects of lung irradiation and reduce the extent of fibrosis, although not sufficiently to prevent lethality at the radiation dose used in this study.

The effects of field-of-view and patient size on CT numbers from cone-beam computed tomography.

Cone-beam computed tomography (CBCT) is used for patient alignment before treatment and is ideal for use in adaptive radiotherapy to account for tumor shrinkage, organ deformation and weight loss. However, CBCT images are prone to artifacts such as streaking and cupping effects, reducing image quality and CT number accuracy. Our goal was to determine the optimum combination of cone-beam imaging options to increase the accuracy of image CT numbers. Several phantoms with and without inserts of known relative electron densities were imaged using the Varian on-board imaging system. It was found that CT numbers are most influenced by the selection of field-of-view and are dependent on object size and filter type. Image acquisition in half-fan mode consistently produced more accurate CT numbers, regardless of phantom size. Values measured using full-fan mode can differ by up to 7% from planning CT values. No differences were found between CT numbers of all phantom images with low and standard dose modes.

Variations of lung density and geometry on inhomogeneity correction algorithms: a Monte Carlo dosimetric evaluation.

This work contributed the following new information to the study of inhomogeneity correction algorithm: (1) Evaluation of lung dose calculation methods as a function of lung relative electron density (rhoe,lung) and treatment geometry and (2) comparison of doses calculated using the collapsed cone convolution (CCC) and adaptive convolution (AC) in lung using the Monte Carlo (MC) simulation with the EGSnrc-based code. The variations of rhoe,lung and geometry such as the position and dimension of the lung were studied with different photon beam energies and field sizes. Three groups of inhomogeneous lung phantoms, namely, "slab," "column," and "cube," with different positions, volumes, and shapes of lung in water as well as clinical computed tomography lung images were used. The rhoe,lung in each group of phantoms vary from 0.05 to 0.7. 6 and 18 MV photon beams with small (4 x 4 cm2) and medium (10 x 10 cm2) field sizes produced by a Varian 21 EX linear accelerator were used. This study reveals that doses in the inhomogeneous lung calculated by the CCC match well with those by AC within +/- 1%, indicating that the AC, with an advantage of shorter computing times (three to four times shorter than CCC), is a good substitute for CCC. Comparing the CCC and AC to MC in general, significant dose deviations are found when the rhoe,lung is < or =0.3. The degree of deviation depends on the photon beam energy and field size and is relatively large when high-energy photon beams with small fields are used. For penumbra widths (20%-80%), the CCC and AC agree well with MC for the slab and cube phantoms with the lung volumes at the central beam axis (CAX). However, deviations (>2 mm) occur in the column phantoms, with two lung volumes separated by a unit density column along the CAX in the middle using the 18 MV beam with 4 x 4 cm2 field for rhoe,lung < or =0.1. This study provides new dosimetric data to evaluate the impact of the variations of rhoe,lung and geometry on dose calculations in inhomogeneous media using CCC and AC.

Adaptive radiation therapy for localized mesothelioma with mediastinal metastasis using helical tomotherapy.

The purpose of this study was to compare 2 adaptive radiotherapy strategies with helical tomotherapy. A patient having mesothelioma with mediastinal nodes was treated using helical tomotherapy with pretreatment megavoltage CT (MVCT) imaging. Gross tumor volumes (GTVs) were outlined on every MVCT study. Two alternatives for adapting the treatment were investigated: (1) keeping the prescribed dose to the targets while reducing the dose to the OARs and (2) escalating the target dose while maintaining the original level of healthy tissue sparing. Intensity modulated radiotherapy (step-and-shoot IMRT) and 3D conformal radiotherapy (3DCRT) plans for the patient were generated and compared. The primary lesion and nodal mass regressed by 16.2% and 32.5%, respectively. Adapted GTVs and reduced planning target volume (PTV) margins of 4 mm after 22 fractions decrease the planned mean lung dose by 19.4%. For dose escalation, the planned prescribed doses may be increased from 50.0 to 58.7 Gy in PTV(1) and from 60.0 to 70.5 Gy in PTV(2). The step-and-shoot IMRT plan was better in sparing healthy tissue but did not provide target coverage as well as the helical tomotherapy plan. The 3DCRT plan resulted in a prohibitively high planned dose to the spinal cord. MVCT studies provide information both for setup correction and plan adaptation. Improved healthy tissue sparing and/or dose escalation can be achieved by adaptive planning.

Successful treatment of primary renal lymphoma using image guided helical tomotherapy.

PURPOSE: To describe a clinical pilot case of renal lymphoma successfully treated using helical tomotherapy, and to evaluate alternative hypofractionated treatment schedules and their potential applicability to future cases of renal cell carcinoma (RCC). PATIENTS AND METHODS: An 82-year-old female patient with a large right perinephric mass encircling the lower pole of the right kidney was treated on the Hi-ART unit (TomoTherapy Inc. Madison, WI, USA) with daily pretreatment megavoltage CT imaging. Gross tumor volumes (GTVs) were outlined on every MVCT study. The Planned Adaptive software was used for calculation of dosimetric parameters for both the target and organs at risk (OARs). In response to observed GTV regression, a hypothetical anatomy changes adjusted plan was generated and analyzed. Six alternative treatment schedules were investigated: 48 Gy in 4 and 3 fractions, and 60 Gy in 30, 5, 4 and 3 fractions, as possible clinical scenarios for RCC. Normal tissue complication probability (NTCP) and tumor control probability (TCP) values were estimated for each scenario in the study. RESULTS: During 30 days, the GTV was reduced by 50.6%. The smaller GTV and the reduced planning target volume (PTV) margins from 15 mm to 10 mm after 12 fractions would allow for a decrease of the planned mean liver and spinal cord dose by 3.8 Gy and 4 Gy, respectively. Improvements to portions of the colon include a 3.3 Gy and 9.2 Gy reduction in planned mean dose to the descending and ascending colons, respectively. NTCP and TCP estimates have shown that hypofractionated treatment schedules provide a much higher probability of local control, but the risk of tissue complication rises simultaneously. For this particular case, hypofractionation would not be suitable due to the potential adverse affects brought on to the liver. CONCLUSIONS: Caution should be observed in high dose hypofractionated radiotherapy in right sided, whole kidney carcinoma due to increased risk of liver complication. The accelerated treatment may however be justified by the significantly higher TCP rates for left sided kidney cases. Further investigation of small renal tumors is needed to evaluate control rates, vasculopathy, and residual normal function.

Effects of genistein following fractionated lung irradiation in mice.

BACKGROUND AND PURPOSE: This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response. MATERIAL AND METHODS: C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet ( approximately 10mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of small lung nodules (KHT fibrosarcoma). RESULTS: Genistein caused about a 50% reduction in the MN damage observed during the fractionated radiation treatment and this damage continued to decrease at later times to background levels by 16 weeks. In mice not receiving Genistein MN levels remained well above background out to 28 weeks after irradiation. Genistein reduced macrophage accumulation by 22% and reduced collagen deposition by 28%. There was minimal protection against increases in breathing rate or severe morbidity during pneumonitis. No tumor protection by genistein treatment was observed. CONCLUSIONS: Genistein at the dose levels used in this study partially reduced the extent of fibrosis developing in mouse lung caused by irradiation but gave minimal protection against pneumonitis. There was no evidence that genistein caused protection of small tumors growing in the lung.

A fully automated non-external marker 4D-CT sorting algorithm using a serial cine scanning protocol.

Current 4D-CT methods require external marker data to retrospectively sort image data and generate CT volumes. In this work we develop an automated 4D-CT sorting algorithm that performs without the aid of data collected from an external respiratory surrogate. The sorting algorithm requires an overlapping cine scan protocol. The overlapping protocol provides a spatial link between couch positions. Beginning with a starting scan position, images from the adjacent scan position (which spatial match the starting scan position) are selected by maximizing the normalized cross correlation (NCC) of the images at the overlapping slice position. The process was continued by 'daisy chaining' all couch positions using the selected images until an entire 3D volume was produced. The algorithm produced 16 phase volumes to complete a 4D-CT dataset. Additional 4D-CT datasets were also produced using external marker amplitude and phase angle sorting methods. The image quality of the volumes produced by the different methods was quantified by calculating the mean difference of the sorted overlapping slices from adjacent couch positions. The NCC sorted images showed a significant decrease in the mean difference (p < 0.01) for the five patients.

The use of CT density changes at internal tissue interfaces to correlate internal organ motion with an external surrogate.

The purpose of this paper is to describe a non-invasive method to monitor the motion of internal organs affected by respiration without using external markers or spirometry, to test the correlation with external markers, and to calculate any time shift between the datasets. Ten lung cancer patients were CT scanned with a GE LightSpeed Plus 4-Slice CT scanner operating in a ciné mode. We retrospectively reconstructed the raw CT data to obtain consecutive 0.5 s reconstructions at 0.1 s intervals to increase image sampling. We defined regions of interest containing tissue interfaces, including tumour/lung interfaces that move due to breathing on multiple axial slices and measured the mean CT number versus respiratory phase. Tumour motion was directly correlated with external marker motion, acquired simultaneously, using the sample coefficient of determination, r(2). Only three of the ten patients showed correlation higher than r(2) = 0.80 between tumour motion and external marker position. However, after taking into account time shifts (ranging between 0 s and 0.4 s) between the two data sets, all ten patients showed correlation better than r(2) = 0.8. This non-invasive method for monitoring the motion of internal organs is an effective tool that can assess the use of external markers for 4D-CT imaging and respiratory-gated radiotherapy on a patient-specific basis.

Image registration of a moving target phantom with helical tomotherapy: effect of the CT acquisition technique and action level proposal.

This study aims to quantify the effects of target motion and resultant motion artifacts in planning and megavoltage CT (MVCT) studies on the automatic registration processes of helical tomotherapy. Clinical and experimental data were used to derive an action level for patient repositioning on helical tomotherapy. Planning CT studies of a respiratory motion phantom were acquired using conventional and four-dimensional CT (4D CT) techniques. MVCT studies were acquired on helical tomotherapy in the presence and absence of target motion and were registered with different planning CT studies. The residual errors of the registration process were calculated from the registration values to quantify the ability of the process to detect 5 or 10 mm translations of the phantom in two directions. Twenty-seven registration combinations of MVCT inter-slice spacing, technique and resolution were investigated. The residual errors were used as an estimate of the localization error of the registration process, and the accuracy of couch repositioning was determined from couch position measurements during 866 treatment fractions. These two parameters were used to calculate the action level for patient repositioning on helical tomotherapy. Automatic registration of an MVCT study with 0% breathing phase, average intensity and maximum intensity 4D CT projections did not differ from that of an MVCT study with a conventional planning CT. Motion artifacts in the MVCT or planning CT studies changed the accuracy of the automatic registration process by less than 2.0%. The action level for patient repositioning using MVCT studies of 6 mm inter-slice spacing was determined to be 0.7, 1.1 and 0.6 mm in the x-, y- and z-directions, respectively. These action levels have the greatest effect on treatments for disease sites in the brain.

Experience-driven dose-volume histogram maps of NTCP risk as an aid for radiation treatment plan selection and optimization.

Commonly, the quality of treatment plans is judged by a dose-volume histogram (DVH) in regards to satisfying a series of dose-volume constraints. This paper presents a novel technique for mapping normal tissue complication probabilities (NTCP) onto regions of dose-volume space with statistical considerations of risk. Mapping is done for DVHs specific to one treatment technique for one disease site. In this study, the method is illustrated for simplified intensity modulated arc therapy of the prostate, and the resulting NTCP values apply to complications in the rectum. The method consists of implementing a Monte Carlo algorithm that creates a large set of DVH curves by simulating random walks through dose-volume space. The walks are guided by a base set of clinical DVHs. Grid points in the dose-volume space have an associated NTCP spectrum for curves passing above right of the grid point of interest. After a DVH is simulated and the NTCP estimate calculated using the Lyman model, dose-volume points located to the bottom left of the curve are scored with this NTCP value and contributed to the spectrum of each point. A NTCP tolerance value is then selected and the risk of violating this tolerance is identified by a gray-scale map in regions of dose-volume space. The generated maps distinguish technique-specific, high-risk regions, a feature which is advantageous over fixed single-point dose-volume constraints commonly used. The maps also provide a visualization tool to help select safe and robust treatment plans and open the possibility for improving the efficiency of biologically based plan optimization by focusing on the more critical sections of DVH curves.

Adaptive radiotherapy planning on decreasing gross tumor volumes as seen on megavoltage computed tomography images.

PURPOSE: To evaluate gross tumor volume (GTV) changes for patients with non-small-cell lung cancer by using daily megavoltage (MV) computed tomography (CT) studies acquired before each treatment fraction on helical tomotherapy and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV. METHODS AND MATERIALS: Seventeen patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for non-small-cell lung cancer at London Regional Cancer Program from Dec 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kilovoltage CT image sets to investigate the advantages of replanning for patients with differing GTV regression characteristics. RESULTS: Average GTV change observed over 30 fractions was -38%, ranging from -12 to -87%. No significant correlation was observed between GTV change and patient's physical or tumor features. Patterns of GTV changes in the 17 patients could be divided broadly into three groups with distinctive potential for benefit from adaptive planning. CONCLUSIONS: Changes in GTV are difficult to predict quantitatively based on patient or tumor characteristics. If changes occur, there are points in time during the treatment course when it may be appropriate to adapt the plan to improve sparing of normal tissues. If GTV decreases by greater than 30% at any point in the first 20 fractions of treatment, adaptive planning is appropriate to further improve the therapeutic ratio.

Optimization of megavoltage CT scan registration settings for thoracic cases on helical tomotherapy.

This study aims to investigate the settings that provide optimum registration accuracy when registering megavoltage CT (MVCT) studies acquired on tomotherapy with planning kilovoltage CT (kVCT) studies of patients with lung cancer. For each experiment, the systematic difference between the actual and planned positions of the thorax phantom was determined by setting the phantom up at the planning isocenter, generating and registering an MVCT study. The phantom was translated by 5 or 10 mm, MVCT scanned, and registration was performed again. A root-mean-square equation that calculated the residual error of the registration based on the known shift and systematic difference was used to assess the accuracy of the registration process. The phantom study results for 18 combinations of different MVCT/kVCT registration options are presented and compared to clinical registration data from 17 lung cancer patients. MVCT studies acquired with coarse (6 mm), normal (4 mm) and fine (2 mm) slice spacings could all be registered with similar residual errors. No specific combination of resolution and fusion selection technique resulted in a lower residual error. A scan length of 6 cm with any slice spacing registered with the full image fusion selection technique and fine resolution will result in a low residual error most of the time. On average, large corrections made manually by clinicians to the automatic registration values are infrequent. Small manual corrections within the residual error averages of the registration process occur, but their impact on the average patient position is small. Registrations using the full image fusion selection technique and fine resolution of 6 cm MVCT scans with coarse slices have a low residual error, and this strategy can be clinically used for lung cancer patients treated on tomotherapy. Automatic registration values are accurate on average, and a quick verification on a sagittal MVCT slice should be enough to detect registration outliers.

Optimization of megavoltage CT scan registration settings for brain cancer treatments on tomotherapy.

This study aims to determine the settings that provide the optimal clinical accuracy and consistency for the registration of megavoltage CT (MVCT) with planning kilovoltage CT image sets on the Hi-ART tomotherapy system. The systematic offset between the MVCT and the planning kVCT was determined by registration of multiple MVCT scans of a head phantom aligned with the planning isocentre. Residual error vector lengths and components were used to quantify the alignment quality for the phantom shifted by 5 mm in different directions obtained by all 27 possible combinations of MVCT inter-slice spacing, registration techniques and resolution. MVCT scans with normal slices are superior to coarse slices for registration of shifts in the superior-inferior, lateral and anterior-posterior directions. Decreasing the scan length has no detrimental effect on registration accuracy as long as the scan lengths are larger than 24 mm. In the case of bone technique and fine resolution, normal and fine MVCT scan slice spacing options give similar accuracy, so normal mode is preferable due to shorter procedure and less delivered dose required for patient set-up. A superior-inferior field length of 24-30 mm, normal slice spacing, bone technique, and fine resolution is the optimum set of registration settings for MVCT scans of a Rando head phantom acquired with the Hi-ART tomotherapy system, provided the registration shifts are less than 5 mm.

Dosimetric evaluation of daily rigid and nonrigid geometric correction strategies during on-line image-guided radiation therapy (IGRT) of prostate cancer.

The purpose of this study is to evaluate a geometric image guidance strategy that simultaneously correct for various inter-fractional rigid and nonrigid geometric uncertainties in an on-line environment, using field shape corrections (called the "MU-MLC" technique). The effectiveness of this strategy was compared with two other simpler on-line image guidance strategies that are more commonly used in the clinic. To this end, five prostate cancer patients, with at least 15 treatment CT studies each, were analyzed. The prescription dose was set to the maximum dose that did not violate the rectum and bladder dose-volume constraints, and hence, was unique to each patient. Deformable image registration and dose-tracking was performed on each CT image to obtain the cumulative treatment dose distributions. From this, maximum, minimum, and mean dose, as well as generalized equivalent uniform dose (gEUD) were calculated for each image guidance strategy. As expected, some dosimetric differences in the clinical target volume (CTV) were observed between the three image guidance strategies investigated. For example, up to +/-2% discrepancy in prostate minimum dose were observed among the techniques. Of them, only the "MU -MLC" technique did not reduce the prostate minimum dose for all patients (i.e., > or = 100%). However, the differences were clinically not significant to indicate the preference of one strategy over another, when using a uniform 5 mm margin size. For the organ-at-risks (OARs), the large rectum sparing effect (< or =5.7 Gy, gEUD) and bladder overdosing effect (< or = 16 Gy, gEUD) were observed. This was likely due to the use of bladder contrast during CT simulation studies which was not done during the treatment CT studies. Therefore, ultimately, strategies to maintain relatively constant rectum and bladder volumes, throughout the treatment course, are required to minimize this effect. In conclusion, the results here suggest that simple translational corrections based on three-dimensional (3D) images is adequate to maintain target coverage, for margin sizes at least as large as 5 mm. In addition, due to large fluctuations in OAR volumes, innovative image guidance strategies are needed to minimize dose and maintain consistent sparing during the whole course of radiation therapy.

A prospective evaluation of helical tomotherapy.

PURPOSE: To report results from two clinical trials evaluating helical tomotherapy (HT). METHODS AND MATERIALS: Patients were enrolled in one of two prospective trials of HT (one for palliative and one for radical treatment). Both an HT plan and a companion three-dimensional conformal radiotherapy (3D-CRT) plan were generated. Pretreatment megavoltage computed tomography was used for daily image guidance. RESULTS: From September 2004 to January 2006, a total of 61 sites in 60 patients were treated. In all but one case, a clinically acceptable tomotherapy plan for treatment was generated. Helical tomotherapy plans were subjectively equivalent or superior to 3D-CRT in 95% of plans. Helical tomotherapy was deemed equivalent or superior in two thirds of dose-volume point comparisons. In cases of inferiority, differences were either clinically insignificant and/or reflected deliberate tradeoffs to optimize the HT plan. Overall imaging and treatment time (median) was 27 min (range, 16-91 min). According to a patient questionnaire, 78% of patients were satisfied to very satisfied with the treatment process. CONCLUSIONS: Helical tomotherapy demonstrated clear advantages over conventional 3D-CRT in this diverse patient group. The prospective trials were helpful in deploying this technology in a busy clinical setting.

A treatment planning study comparing whole breast radiation therapy against conformal, IMRT and tomotherapy for accelerated partial breast irradiation.

PURPOSE AND BACKGROUND: Conventional early breast cancer treatment consists of a lumpectomy followed by whole breast radiation therapy. Accelerated partial breast irradiation (APBI) is an investigational approach to post-lumpectomy radiation for early breast cancer. The purpose of this study is to compare four external beam APBI techniques, including tomotherapy, with conventional whole breast irradiation for their radiation conformity index, dose homogeneity index, and dose to organs at risk. METHODS AND MATERIALS: Small-field tangents, three-dimensional conformal radiation therapy, intensity-modulated radiation therapy and helical tomotherapy were compared for each of 15 patients (7 right, 8 left). One radiation conformity and two dose homogeneity indices were used to evaluate the dose to the target. The mean dose to organs at risk was also evaluated. RESULTS: All proposed APBI techniques improved the conformity index significantly over whole breast tangents while maintaining dose homogeneity and without a significant increase in dose to organs at risk. CONCLUSION: The four-field IMRT plan produced the best dosimetric results; however this technique would require appropriate respiratory motion management. An alternative would be to use a four-field conformal technique that is less sensitive to the effects of respiratory motion.

Prostate contouring uncertainty in megavoltage computed tomography images acquired with a helical tomotherapy unit during image-guided radiation therapy.

PURPOSE: To evaluate the image-guidance capabilities of megavoltage computed tomography (MVCT), this article compares the interobserver and intraobserver contouring uncertainty in kilovoltage computed tomography (KVCT) used for radiotherapy planning with MVCT acquired with helical tomotherapy. METHODS AND MATERIALS: Five prostate-cancer patients were evaluated. Each patient underwent a KVCT and an MVCT study, a total of 10 CT studies. For interobserver variability analysis, four radiation oncologists, one physicist, and two radiation therapists (seven observers in total) contoured the prostate and seminal vesicles (SV) in the 10 studies. The intraobserver variability was assessed by asking all observers to repeat the contouring of 1 patient's KVCT and MVCT studies. Quantitative analysis of contour variations was performed by use of volumes and radial distances. RESULTS: The interobserver and intraobserver contouring uncertainty was larger in MVCT compared with KVCT. Observers consistently segmented larger volumes on MVCT where the ratio of average prostate and SV volumes was 1.1 and 1.2, respectively. On average (interobserver and intraobserver), the local delineation variability, in terms of standard deviations [Deltasigma = radical(sigma2MVCT-sigma2KVCT)], increased by 0.32 cm from KVCT to MVCT. CONCLUSIONS: Although MVCT was inferior to KVCT for prostate delineation, the application of MVCT in prostate radiotherapy remains useful.

Partial volume rat lung irradiation: the protective/mitigating effects of Eukarion-189, a superoxide dismutase-catalase mimetic.

BACKGROUND AND PURPOSE: The purpose of the current study was to elucidate the protective/mitigating effects of a SOD-catalase mimetic, Eukarion-189 (EUK-189), on DNA damage in rat lung following irradiation. The particular focus of these studies was the efficacy of EUK-189 when given after irradiation (mitigation). PATIENTS AND METHODS: We exposed whole or lower lungs of female Sprague-Dawley rats to doses ranging from 10 to 20.5 Gray (Gy) of (60)Co gamma rays. Animals in the EUK-189 treated groups received 2 or 30 mg/kg intraperitoneally (i.p.) at various times postirradiation (PI). A micronucleus assay was used to examine DNA damage at various times up to 16 weeks PI. RESULTS: Our results indicated that EUK-189 administration after irradiation is effective at reducing micronucleus formation in lung fibroblasts at various times following radiation exposure. Treatment with EUK-189 in the first 3 days after thoracic irradiation did not, however, modify the dose required to cause severe morbidity at 2-3 months after irradiation. CONCLUSIONS: The protection produced when Eukarion-189 was given shortly after irradiation suggests that DNA damage observed in the lung may be caused by chronic production of ROS induced by a chronic inflammatory response initiated by the radiation treatment. We speculate that our failure to observe protection against severe morbidity at 2-3 months may be because our treatment regime only blocked the initial wave of ROS production and that treatment needs to be more prolonged to suppress the effects of a chronic inflammatory response.