Semi-Supervised Segmentation of Radiation-Induced Pulmonary Fibrosis From Lung CT Scans With Multi-Scale Guided Dense Attention.

Computed Tomography (CT) plays an important role in monitoring radiation-induced Pulmonary Fibrosis (PF), where accurate segmentation of the PF lesions is highly desired for diagnosis and treatment follow-up. However, the task is challenged by ambiguous boundary, irregular shape, various position and size of the lesions, as well as the difficulty in acquiring a large set of annotated volumetric images for training. To overcome these problems, we propose a novel convolutional neural network called PF-Net and incorporate it into a semi-supervised learning framework based on Iterative Confidence-based Refinement And Weighting of pseudo Labels (I-CRAWL). Our PF-Net combines 2D and 3D convolutions to deal with CT volumes with large inter-slice spacing, and uses multi-scale guided dense attention to segment complex PF lesions. For semi-supervised learning, our I-CRAWL employs pixel-level uncertainty-based confidence-aware refinement to improve the accuracy of pseudo labels of unannotated images, and uses image-level uncertainty for confidence-based image weighting to suppress low-quality pseudo labels in an iterative training process. Extensive experiments with CT scans of Rhesus Macaques with radiation-induced PF showed that: 1) PF-Net achieved higher segmentation accuracy than existing 2D, 3D and 2.5D neural networks, and 2) I-CRAWL outperformed state-of-the-art semi-supervised learning methods for the PF lesion segmentation task. Our method has a potential to improve the diagnosis of PF and clinical assessment of side effects of radiotherapy for lung cancers.

Dosimetric effects of the kV based image-guided radiation therapy of prone breast external beam radiation: Towards the optimized imaging frequency.

PURPOSE: For prone breast treatment, daily image-guided radiation therapy (IGRT) allows couch shifting to correct breast position relative to the treatment field. This work investigates the dosimetric effect of reducing kV imaging frequencies and the feasibility of optimizing the frequency using patient anatomy or their first 3-day shifts. METHOD: Thirty-seven prone breast patients who had been treated with skin marker alignment followed by daily kV were retrospectively analyzed. Three IGRT schemes (daily-kV, weekly-kV, no-kV) were simulated, assuming that fractions with kV imaging deliver a dose distribution equivalent to that in computed tomography (CT) planning, whereas other fractions yield a dose distribution as recreated by shifting the CT plan isocenter back to its position before the couch shift was applied. Treatment dose to targets (breast and lumpectomy cavity [LPC]) and organs at risks (OAR)s (heart, ipsilateral lung) in different schemes were calculated. Patient anatomy information on CT plans and first 3-day couch shift data were analyzed to investigate whether these factors could guide imaging scheme optimization. RESULTS: When kV imaging frequency was reduced, the percentage dose changes (δD) for breast and LPC objectives (average <1%) were smaller than those for heart and lung (average 28%-31% for Dmean ). In general, the δD of no-kV imaging was approximately that of weekly kV imaging × a factor of 1.2-1.4. Although most dose objectives were not affected, the potential higher heart dose may be of concern. No strong correlation was found between δD for different kV frequencies and patient anatomy size/distance or the first 3-day couch shift data. CONCLUSIONS: Despite resulting in lower imaging dose, time, cost, and similar target coverage, a reduction in kV imaging frequency may introduce higher heart complication risk. Daily kVs are needed more in left-sided breast patients. A less frequent imaging schedule, if considered, cannot be individually optimized using CT anatomic features or early shift data.

Correlation of radiation dose and activity with clinical outcomes in metastatic colorectal cancer after selective internal radiation therapy using yttrium-90 resin microspheres.

PURPOSE: Yttrium-90 (Y)-resin microspheres are prescribed using activity. We evaluated overall survival (OS) and radiographic tumor response after selective internal radiation therapy (SIRT) with resin microspheres in patients with liver metastases from colorectal cancer. PATIENTS AND METHODS: We retrospectively reviewed 60 metastatic colorectal cancer patients treated at our institution with SIRT using Y-resin microspheres. Each patient underwent pre-SIRT MRI or computed tomography imaging of the liver with intravenous contrast. Patients underwent post-treatment imaging at 2-3-month intervals with response assessed according to unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) criteria as well as published three-dimensional volumetric criteria. We then related the prescribed activity established by the body surface area method and the corresponding prescribed dose to radiographic treatment response and OS. RESULTS: The median follow-up after the first SIRT treatment was 8.9 months. The mean prescribed activity and the prescribed dose were 26.6 mCi and 52.8 Gy, respectively. OS was not significantly associated with either prescribed activity or prescribed dose. Prescribed dose was also not related to response. However, a significant relationship was found between a higher prescribed activity and an improved radiographic response by RECIST (P=0.04) at the second follow-up. CONCLUSION: The prescribed activity of Y-resin microspheres may be correlated with radiographic response by RECIST criteria at 4-6 months post-treatment. For a more accurate prediction of response, a valid dose calculation model based on post-Y PET dosimetry is likely needed given the heterogeneous dose delivery seen in SIRT.

Feasibility of CBCT-based dose with a patient-specific stepwise HU-to-density curve to determine time of replanning.

PURPOSE: (a) To investigate the accuracy of cone-beam computed tomography (CBCT)-derived dose distributions relative to fanbeam-based simulation CT-derived dose distributions; and (b) to study the feasibility of CBCT dosimetry for guiding the appropriateness of replanning. METHODS AND MATERIALS: Image data corresponding to 40 patients (10 head and neck [HN], 10 lung, 10 pancreas, 10 pelvis) who underwent radiation therapy were randomly selected. Each patient had both intensity-modulated radiation therapy and volumetric-modulated arc therapy plans; these 80 plans were subsequently recomputed on the CBCT images using a patient-specific stepwise curve (Hounsfield units-to-density). Planning target volumes (PTVs; D98%, D95%, D2%), mean dose, and V95% were compared between simulation-CT-derived treatment plans and CBCT-based plans. Gamma analyses were performed using criterion of 3%/3 mm for three dose zones (>90%, 70%~90%, and 30%~70% of maximum dose). CBCT-derived doses were then used to evaluate the appropriateness of replanning decisions in 12 additional HN patients whose plans were previously revised during radiation therapy because of anatomic changes; replanning in these cases was guided by the conventional observed source-to-skin-distance change-derived approach. RESULTS: For all disease sites, the difference in PTV mean dose was 0.1% ± 1.1%, D2% was 0.7% ± 0.1%, D95% was 0.2% ± 1.1%, D98% was 0.2% ± 1.0%, and V95% was 0.3% ± 0.8%; For 3D dose comparison, 99.0% ± 1.9%, 97.6% ± 4.4%, and 95.3% ± 6.0% of points passed the 3%/3 mm criterion of gamma analysis in high-, medium-, and low-dose zones, respectively. The CBCT images achieved comparable dose distributions. In the 12 previously replanned 12 HN patients, CBCT-based dose predicted well changes in PTV D2% (Pearson linear correlation coefficient = 0.93; P < 0.001). If 3% of change is used as the replanning criteria, 7/12 patients could avoid replanning. CONCLUSIONS: CBCT-based dose calculations produced accuracy comparable to that of simulation CT. CBCT-based dosimetry can guide the decision to replan during the course of treatment.

Four-dimensional dose reconstruction through in vivo phase matching of cine images of electronic portal imaging device.

PURPOSE: A method is proposed to reconstruct a four-dimensional (4D) dose distribution using phase matching of measured cine images to precalculated images of electronic portal imaging device (EPID). METHODS: (1) A phantom, designed to simulate a tumor in lung (a polystyrene block with a 3 cm diameter embedded in cork), was placed on a sinusoidally moving platform with an amplitude of 1 cm and a period of 4 s. Ten-phase 4D computed tomography (CT) images of the phantom were acquired. A planning target volume (PTV) was created by adding a margin of 1 cm around the internal target volume of the tumor. (2) Three beams were designed, which included a static beam, a theoretical dynamic beam, and a planning-optimized dynamic beam (PODB). While the theoretical beam was made by manually programming a simplistic sliding leaf motion, the planning-optimized beam was obtained from treatment planning. From the three beams, three-dimensional (3D) doses on the phantom were calculated; 4D dose was calculated by means of the ten phase images (integrated over phases afterward); serving as "reference" images, phase-specific EPID dose images under the lung phantom were also calculated for each of the ten phases. (3) Cine EPID images were acquired while the beams were irradiated to the moving phantom. (4) Each cine image was phase-matched to a phase-specific CT image at which common irradiation occurred by intercomparing the cine image with the reference images. (5) Each cine image was used to reconstruct dose in the phase-matched CT image, and the reconstructed doses were summed over all phases. (6) The summation was compared with forwardly calculated 4D and 3D dose distributions. Accounting for realistic situations, intratreatment breathing irregularity was simulated by assuming an amplitude of 0.5 cm for the phantom during a portion of breathing trace in which the phase matching could not be performed. Intertreatment breathing irregularity between the time of treatment and the time of planning CT was considered by utilizing the same reduced amplitude when the phantom was irradiated. To examine the phase matching in a humanoid environment, the matching was also performed in a digital phantom (4D XCAT phantom). RESULTS: For the static, the theoretical, and the planning-optimized dynamic beams, the 4D reconstructed doses showed agreement with the forwardly calculated 4D doses within the gamma pass rates of 92.7%, 100%, and 98.1%, respectively, at the isocenter plane given by 3%/3 mm criteria. Excellent agreement in dose volume histogram of PTV and lung-PTV was also found between the two 4D doses, while substantial differences were found between the 3D and the 4D doses. The significant breathing irregularities modeled in this study were found not to be noticeably affecting the reconstructed dose. The phase matching was performed equally well in a digital phantom. CONCLUSIONS: The method of retrospective phase determination of a moving object under irradiation provided successful 4D dose reconstruction. This method will provide accurate quality assurance and facilitate adaptive therapy when distinguishable objects such as well-defined tumors, diaphragm, and organs with markers (pancreas and liver) are covered by treatment beam apertures.

Optimizing the MLC model parameters for IMRT in the RayStation treatment planning system.

Unlike other commercial treatment planning systems (TPS) which model the rounded leaf end differently (such as the MLC dosimetric leaf gap (DLG) or rounded leaf-tip radius), the RayStation TPS (RaySearch Laboratories, Stockholm, Sweden) models transmission through the rounded leaf end of the MLC with a step function, in which the radiation transmission through the leaf end is the square root of the average MLC transmission factor. We report on the optimization of MLC model parameters for the RayStation planning system. This (TPS) models the rounded leaf end of the MLC with the following parameters: eaf-tip offset, leaf-tip width, average transmission factor, and tongue and groove. We optimized the MLC model parameters for IMRT in the RayStation v. 4.0 planning system and for a Varian C-series linac with a 120-leaf Millennium MLC, and validated the model using measured data. The leaf-tip offset is the geometric offset due to the rounded leaf-end design and resulting divergence of the light/radiation field. The offset value is a function of the leaf-tip position, and tabulated data are available from the vendor. The leaf-tip width was iteratively evaluated by comparing computed and measured transverse dose profiles of MLC defined fields at dmax in water. In-water profile comparisons were also used to verify the MLC leaf position (leaf-tip offset). The average transmission factor and leaf tongue-and-groove width were derived iteratively by maximizing the agreement between measurements and RayStation TPS calculations for five clinical IMRT QA plans. Plan verifications were performed by comparing MapCHECK2 measurements and Monte Carlo calculations. The MLC model was validated using five test IMRT cases from the AAPM Task Group 119 report. Absolute gamma analyses (3 mm/3% and 2 mm/2%) were applied. In addition, computed output factors for MLC-defined small fields (2 × 2, 3 × 3, 4 × 4, 6× 6cm2) of both 6 MV and 18 MV photons were compared to those independently measured by the Imaging and Radiation Oncology Core (IROC), Houston, TX. 6MV and 18 MV models were both determined to have the same MLC parameters: leaf-tip offset = 0.3 cm, 2.5% transmission, and leaf tongue-and-groove width = 0.05 cm. IMRT QA analysis for five test cases in TG-119 resulted in a 100% passing rate with 3 mm/3% gamma analysis for 6 MV, and > 97.5% for 18 MV. The passing rate was > 94.6% for 6 MV and > 90.9% for 18 MV when the 2 mm/2% gamma analysis criteria was applied. These results compared favorably with those published in AAPM Task Group 119. The reported MLC model parameters serve as a reference for other users.

An analytical formalism to calculate phantom scatter factors for flattening filter free (FFF) mode photon beams.

Phantom Scatter Factors, Sp in the Khan formalism (Khan et al 1980 J. Radiat. Oncol. Biol. Phys. 6 745-51) describe medium-induced changes in photon-beam intensity as a function of size of the beam. According to the British Journal of Radiology, Supplement 25, megavoltage phantom scatter factors are invariant as a function of photon-beam energy. However, during the commissioning of an accelerator with flattening filter free (FFF) photon beams (Varian TrueBeam(TM) 6-MV FFF and 10-MV FFF), differences were noted in phantom scatter between the filtered beams and FFF-mode beams. The purpose of this work was to evaluate this difference and provide an analytical formalism to explain the phantom scatter differences between FFF-mode and the filtered mode. An analytical formalism was devised to demonstrate the source of phantom scatter differences between the filtered and the FFF-mode beams. The reason for the differences in the phantom scatter factors between the filtered and the FFF-mode beams is hypothesized to be the non-uniform beam profiles of the FFF-mode beams. The analytical formalism proposed here is based on this idea, taking the product of the filtered phantom scatter factors and the ratio of the off-axis ratio between the FFF-mode and the filtered beams. All measurements were performed using a Varian TrueBeam(TM) linear accelerator with photon energies of 6-MV and 10-MV in both filtered and FFF-modes. For all measurements, a PTW Farmer type chamber and a Scanditronix CC04 cylindrical ionization were used. The in-water measurements were made at depth dose maximum and 100 cm source-to-axis distance. The in-air measurements were done at 100 cm source-to-axis distance with appropriate build-up cap. From these measurements, the phantom scatter factors were derived for the filtered beams and the FFF-mode beams for both energies to be evaluated against the phantoms scatter factors calculated using the proposed algorithm. For 6-MV, the difference between the measured and the calculated FFF-mode phantom scatter factors ranged from -0.34% to 0.73%. The average per cent difference was -0.17% (1σ = 0.25%). For 10-MV, the difference ranged from -0.19% to 0.24%. The average per cent difference was -0.17% (1σ = 0.13%). An analytical formalism was presented to calculate the phantom scatter factors for FFF-mode beams using filtered phantom scatter factors as a basis. The overall differences between measurements and calculations were within ± 0.5% for 6-MV and ± 0.25% for 10-MV.

Conditions for reliable time-resolved dosimetry of electronic portal imaging devices for fixed-gantry IMRT and VMAT.

PURPOSE: The continuous scanning mode of electronic portal imaging devices (EPID) that offers time-resolved information has been newly explored for verifying dynamic radiation deliveries. This study seeks to determine operating conditions (dose rate stability and time resolution) under which that mode can be used accurately for the time-resolved dosimetry of intensity-modulated radiation therapy (IMRT) beams. METHODS: The authors have designed the following test beams with variable beam holdoffs and dose rate regulations: a 10 × 10 cm open beam to serve as a reference beam; a sliding window (SW) beam utilizing the motion of a pair of multileaf collimator (MLC) leaves outside the 10 × 10 cm jaw; a step and shoot (SS) beam to move the pair in step; a volumetric modulated arc therapy (VMAT) beam. The beams were designed in such a way that they all produce the same open beam output of 10 × 10 cm. Time-resolved ion chamber measurements at isocenter and time-resolved and integrating EPID measurements were performed for all beams. The time-resolved EPID measurements were evaluated through comparison with the ion chamber and integrating EPID measurements, as the latter are accepted procedures. For two-dimensional, time-resolved evaluation, a VMAT beam with an infield MLC travel was designed. Time-resolved EPID measurements and Monte Carlo calculations of such EPID dose images for this beam were performed and intercompared. RESULTS: For IMRT beams (SW and SS), the authors found disagreement greater than 2%, caused by frame missing of the time-resolved mode. However, frame missing disappeared, yielding agreement better than 2%, when the dose rate of irradiation (and thus the frame acquisition rates) reached a stable and planned rate as the dose of irradiation was raised past certain thresholds (a minimum 12 s of irradiation per shoot used for SS IMRT). For VMAT, the authors found that dose rate does not affect the frame acquisition rate, thereby causing no frame missing. However, serious inplanar nonuniformities were found. This could be overcome by sacrificing temporal resolution (10 frames or 0.95 s/image): the continuous images agreed with ion chamber responses at the center of EPID and the calculation two-dimensionally in a time-resolved manner. CONCLUSIONS: The authors have determined conditions under which the continuous mode can be used for time-resolved dosimetry of fixed-gantry IMRT and VMAT and demonstrated it for VMAT.

Feasibility study on inverse four-dimensional dose reconstruction using the continuous dose-image of EPID.

PURPOSE: When an intensity-modulated radiation beam is delivered to a moving target, the interplay effect between dynamic beam delivery and the target motion due to miss-synchronization can cause unpredictable dose delivery. The portal dose image in electronic portal imaging device (EPID) represents radiation attenuated and scattered through target media. Thus, it may possess information about delivered radiation to the target. Using a continuous scan (cine) mode of EPID, which provides temporal dose images related to target and beam movements, the authors' goal is to perform four-dimensional (4D) dose reconstruction. METHODS: To evaluate this hypothesis, first, the authors have derived and subsequently validated a fast method of dose reconstruction based on virtual beamlet calculations of dose responses using a test intensity-modulated beam. This method was necessary for processing a large number of EPID images pertinent for four-dimensional reconstruction. Second, cine mode acquisition after summation over all images was validated through comparison with integration mode acquisition on EPID (IAS3 and aS1000) for the test beam. This was to confirm the agreement of the cine mode with the integrated mode, specifically for the test beam, which is an accepted mode of image acquisition for dosimetry with EPID. Third, in-phantom film and exit EPID dosimetry was performed on a moving platform using the same beam. Heterogeneous as well as homogeneous phantoms were used. The cine images were temporally sorted at 10% interval. The authors have performed dose reconstruction to the in-phantom plane from the sorted cine images using the above validated method of dose reconstruction. The reconstructed dose from each cine image was summed to compose a total reconstructed dose from the test beam delivery, and was compared with film measurements. RESULTS: The new method of dose reconstruction was validated showing greater than 95.3% pass rates of the gamma test with the criteria of dose difference of 3% and distance to agreement of 3 mm. The dose comparison of the reconstructed dose with the measured dose for the two phantoms showed pass rates higher than 96.4% given the same criteria. CONCLUSIONS: Feasibility of 4D dose reconstruction was successfully demonstrated in this study. The 4D dose reconstruction demonstrated in this study can be a promising dose validation method for radiation delivery on moving organs.

Dosimetric and geometric evaluation of a novel stereotactic radiotherapy device for breast cancer: the GammaPod™.

PURPOSE: A dedicated stereotactic gamma irradiation device, the GammaPod™ from Xcision Medical Systems, was developed specifically to treat small breast cancers. This study presents the first evaluation of dosimetric and geometric characteristics from the initial prototype installed at University of Maryland Radiation Oncology Department. METHODS: The GammaPod™ stereotactic radiotherapy device is an assembly of a hemi-spherical source carrier containing 36 (60)Co sources, a tungsten collimator, a dynamically controlled patient support table, and the breast immobilization system which also functions as a stereotactic frame. The source carrier contains the sources in six columns spaced longitudinally at 60° intervals and it rotates together with the variable-size collimator to form 36 noncoplanar, concentric arcs focused at the isocenter. The patient support table enables motion in three dimensions to position the patient tumor at the focal point of the irradiation. The table moves continuously in three cardinal dimensions during treatment to provide dynamic shaping of the dose distribution. The breast is immobilized using a breast cup applying a small negative pressure, where the immobilization cup is embedded with fiducials also functioning as the stereotactic frame for the breast. Geometric and dosimetric evaluations of the system as well as a protocol for absorbed dose calibration are provided. Dosimetric verifications of dynamically delivered patient plans are performed for seven patients using radiochromic films in hypothetical preop, postop, and target-in-target treatment scenarios. RESULTS: Loaded with 36 (60)Co sources with cumulative activity of 4320 Ci, the prototype GammaPod™ unit delivers 5.31 Gy/min at the isocenter using the largest 2.5 cm diameter collimator. Due to the noncoplanar beam arrangement and dynamic dose shaping features, the GammaPod™ device is found to deliver uniform doses to targets with good conformity. The spatial accuracy of the device to locate the radiation isocenter is determined to be less than 1 mm. Single shot profiles with 2.5 cm collimator are measured with radiochromic film and found to be in good agreement with respect to the Monte Carlo based calculations (congruence of FWHM less than 1 mm). Dosimetric verifications corresponding to all hypothetical treatment plans corresponding to three target scenarios for each of the seven patients demonstrated good agreement with gamma index pass rates of better than 97% (99.0% ± 0.7%). CONCLUSIONS: Dosimetric evaluation of the first GammaPod™ stereotactic breast radiotherapy unit was performed and the dosimetric and spatial accuracy of this novel technology is found to be feasible with respect to clinical radiotherapy standards. The observed level of agreement between the treatment planning system calculations and dosimetric measurements has confirmed that the system can deliver highly complex treatment plans with remarkable geometric and dosimetric accuracy.

Is RapidArc more susceptible to delivery uncertainties than dynamic IMRT?

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

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

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

Protons offer reduced normal-tissue exposure for patients receiving postoperative radiotherapy for resected pancreatic head cancer.

PURPOSE: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. METHODS AND MATERIALS: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. RESULTS: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). CONCLUSIONS: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

Development of a one-stop beam verification system using electronic portal imaging devices for routine quality assurance.

In this study, a computer-based system for routine quality assurance (QA) of a linear accelerator (linac) was developed by using the dosimetric properties of an amorphous silicon electronic portal imaging device (EPID). An acrylic template phantom was designed such that it could be placed on the EPID and be aligned with the light field of the collimator. After irradiation, portal images obtained from the EPID were transferred in DICOM format to a computer and analyzed using a program we developed. The symmetry, flatness, field size, and congruence of the light and radiation fields of the photon beams from the linac were verified simultaneously. To validate the QA system, the ion chamber and film (X-Omat V2; Kodak, New York, NY) measurements were compared with the EPID measurements obtained in this study. The EPID measurements agreed with the film measurements. Parameters for beams with energies of 6 MV and 15 MV were obtained daily for 1 month using this system. It was found that our QA tool using EPID could substitute for the film test, which is a time-consuming method for routine QA assessment.

Verification of MLC based real-time tumor tracking using an electronic portal imaging device.

PURPOSE: The authors have developed a novel technique using an electronic portal imaging device (EPID) to verify the geometrical accuracy of delivery of dose-rate-regulated tracking (DRRT). This technique, called verification of real-time tracking with EPID (VORTE), can potentially be used for both on-line and off-line quality assurance (QA) of MLC-based dynamic tumor tracking. METHODS: The shape and position of target as a function of time, which is assumed to be known, is projected onto the EPID plane. This projected sequence of apertures as a function of time (target motion) is then used as the reference. The accuracy of dynamic MLC tracking can then be assessed by how well the delivered beam follows this projected target motion without the use of a physical moving phantom. The beam apertures controlled by DRRT (aperture motion) is detected by the EPID as a function of time. The aperture motion is compared to the target motion to evaluate tracking error introduced by DRRT. The accuracy of VORTE was measured using film measurements of ten static fields. The VORTE for dynamic tumor tracking was tested with several target motions, including (1) rigid-body two-dimensional (2-D) cyclic motion in the superior-inferior direction with various period and amplitude; (2) the above 2-D cyclic motion plus cyclic deformation; and (3) 2-D cyclic motion with both deformation and rotation. For each target motion, the controlled aperture motion resulting from DRRT was acquired at approximately 8 Hz using EPID in the continuous-acquisition mode. Leaf positions in all captured frames were measured from the EPID and compared to their expected positions. The passing rate of 2 mm criteria for all leaves from all frames was calculated for each of the four patterns of tumor motion. Additionally, the root-mean-square (RMS) deviations of the centroid of the apertures between the designed and delivered beams were calculated for all three cases. RESULTS: The accuracy of MLC-leaf position determination by VORTE is 0.5 mm (1 standard deviation) by comparison to film measurements. With DRRT, the passing rates using the 2 mm criteria for all acquired frames are 100% for the 2-D displacement, 99% for the 2-D displacement with deformation, and 88% for the 2-D displacement combined with both deformation and rotation. The RMS deviations are 0.6 mm for the 2-D displacement, 1.0 mm for the 2-D displacement with deformation, and 1.1 mm for the 2-D displacement combined with both deformation and rotation. CONCLUSIONS: The VORTE can measure the accuracy of MLC-based tumor tracking without the necessity of employing a moving phantom. Moreover, it can be used for complex target motion (i.e., 2-D displacement combined with deformation and rotation) that is difficult to create with physical moving phantoms. Therefore, the VORTE and the novel QA process illustrated by this study have a great potential for verifying real-time tumor tracking.

Optimal beam arrangement for stereotactic body radiation therapy delivery in lung tumors.

PURPOSE: To compare the different beam arrangement and delivery techniques for stereotactic body radiation therapy (SBRT) of lung lesions using the criteria of Radiation Therapy Oncology Group (RTOG) 0236 protocol. MATERIAL AND METHODS: Thirty-seven medically inoperable lung cancers were evaluated with various planning techniques including multiple coplanar multiple static beams, multiple non-coplanar static beams and arc delivery. Twelve plans were evaluated for each case, including five plans using coplanar fixed beams, six plans using non-coplanar fixed beams and one plan using arc therapy. These plans were compared using the target prescription isodose coverage, high and low dose volumes, and critical organ dose-volume limits. RESULTS: The prescription isodose coverage, high dose evaluation criteria and dose to critical organs were similar among treatment delivery techniques. However, there were differences in low dose criteria, especially in the ratio of the volume of 50% isodose of the prescription dose to the volume of planning treatment volume (R(50%)). The R(50%) in plans using non-coplanar static beams was lower than other plans in 30 of 37 cases (81%). CONCLUSION: Based on the dosimetric criteria outlined in RTOG 0236, the treatment technique using non-coplanar static beams showed the most preferable results for SBRT of lung lesions.

Usefulness of guided breathing for dose rate-regulated tracking.

PURPOSE: To evaluate the usefulness of guided breathing for dose rate-regulated tracking (DRRT), a new technique to compensate for intrafraction tumor motion. METHODS AND MATERIALS: DRRT uses a preprogrammed multileaf collimator sequence that tracks the tumor motion derived from four-dimensional computed tomography and the corresponding breathing signals measured before treatment. Because the multileaf collimator speed can be controlled by adjusting the dose rate, the multileaf collimator positions are adjusted in real time during treatment by dose rate regulation, thereby maintaining synchrony with the tumor motion. DRRT treatment was simulated with free, audio-guided, and audiovisual-guided breathing signals acquired from 23 lung cancer patients. The tracking error and duty cycle for each patient were determined as a function of the system time delay (range, 0-1.0 s). RESULTS: The tracking error and duty cycle averaged for all 23 patients was 1.9 +/- 0.8 mm and 92% +/- 5%, 1.9 +/- 1.0 mm and 93% +/- 6%, and 1.8 +/- 0.7 mm and 92% +/- 6% for the free, audio-guided, and audiovisual-guided breathing, respectively, for a time delay of 0.35 s. The small differences in both the tracking error and the duty cycle with guided breathing were not statistically significant. CONCLUSION: DRRT by its nature adapts well to variations in breathing frequency, which is also the motivation for guided-breathing techniques. Because of this redundancy, guided breathing does not result in significant improvements for either the tracking error or the duty cycle when DRRT is used for real-time tumor tracking.

Real-time tumor tracking with preprogrammed dynamic multileaf-collimator motion and adaptive dose-rate regulation.

The authors have developed a new method for real-time tumor tracking with dynamic multileaf-collimator (MLC) motion under condition of free breathing. Unlike other previously proposed tumor-tracking methods, their new method uses a preprogrammed dynamic MLC sequence in combination with real-time dose-rate control. This new scheme circumvents the technical challenge in MLC-based tumor tracking of having to control the MLC motion in real time, based on real-time detected tumor motion. With their new method, the movement of the tumor, as a function of breathing phase, amplitude, or tidal volume, is reflected in the preprogrammed MLC sequence. The irregularity of breathing during treatment is handled by real-time regulation of the machine dose rate, which effectively speeds up or slows down the delivery of radiation as needed. This method is based on the fact that all of the parameters in dynamic radiation delivery, including MLC motion, are enslaved to the cumulative dose, which, in turn, can be accelerated or decelerated by varying the dose rate. Because commercially available MLC systems do not allow the MLC delivery sequence to be modified in real time based on the patient's breathing signal, previously proposed tumor-tracking techniques using a MLC cannot be readily implemented in the clinic today. By using a preprogrammed MLC sequence to handle the required motion, the task for real-time control is greatly simplified. With their new scheme, which they call dose-rate-regulated tracking (DRRT), it is possible to use existing linear accelerators that have dynamic MLC capability to achieve real-time tumor tracking, provided that the beam dose rate can be controlled externally. Tracking-error evaluation for 13 patients out of 14 resulted in a tracking error of less than 1 mm (1 sigma), if the effect of the response time of the treatment machine on the dose-rate modulation can be neglected. Film measurements on a moving phantom with variable breathing patterns and DRRT delivery showed that 97% of the measurement points have gamma values less than 1 (for 3% and 2-mm criteria), while non-DRRT delivery showed only 87%. This study shows that real-time tracking is feasible with DRRT even when the patient breathing frequency is irregular. Effects of the variation of breathing amplitude and of base line drift on the tracking error with DRRT are discussed; pending further study, a criterion is suggested for patient selection in the application of this new technique in the clinic.

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

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

Dosimetric effects of the prone and supine positions on image guided localized prostate cancer radiotherapy.

PURPOSE: To compare target coverage and doses to rectum and bladder in IMRT of localized prostate cancer in the supine versus prone position, with the inclusion of image guidance. MATERIALS AND METHODS: Twenty patients with early stage localized prostate carcinoma who received external beam radiotherapy in the supine and prone positions underwent approximately 10 serial CT examinations in their respective treatment position in non-consecutive days, except for one patient who was treated prone but serially imaged supine. The prostate, bladder and rectum were contoured on all CT scans. A PTV was generated on the first scan of each patient's CT series by expanding the prostate with a 5mm margin and an IMRT plan was created. The resultant IMRT plan was then applied to that patient's remaining serial CT scans by aligning the initial CT image set with the subsequent serial CT image sets using (1) skin marks, (2) bony anatomy and (3) center of mass of the prostate. The dosimetric results from these three alignments were compared between the supine and prone groups. To account for the uncertainties associated with prostate delineation and intra-fractional geometric changes, a fictional "daily PTV" was generated by expanding the prostate with a 3mm margin on each serial CT scan. Thus, a more realistic target coverage index, V95, was quantified as the fraction of the daily PTV receiving at least 95% of the prescription dose. Dose-volume measures of the organs at risk were also compared. The fraction of the daily PTV contained by the initial PTV after each alignment method was quantified on each patient's serial CT scan, and is defined as PTV overlap index. RESULTS: As expected, alignment based on skin marks yielded unacceptable dose coverage for both groups of patients. Under bony alignment, the target coverage index, V95, was 97.3% and 93.6% for prone and supine patients (p<0.0001), respectively. The mean PTV overlap indices were 90.7% and 84.7% for prone and supine patients (p<0.0002), respectively. In the supine position 36% of cases showed a V95<95% after bony alignment, while only 12.5% of prone patients with V95<95% following bony alignment. Under soft-tissue alignment matching the center of mass of the prostate, the mean V95 was 99.3% and 98.6% (p<0.03) and the PTV overlap index was 97.7% and 94.8% (p<0.0002) for prone and supine groups, respectively. CONCLUSIONS: Soft-tissue alignment combined with 5mm planning margins is appropriate in minimizing treatment planning and delivery uncertainties in both the supine and prone positions. Alignment based on bony structures showed improved results over the use of skin marks for both supine and prone setups. Under bony alignment, the dose coverage and PTV overlap index for prone setup were statistically better than for supine setup, illustrating a more consistent geometric relationship between the prostate and the pelvic bony structures when patients were treated in the prone position.