Advanced automated treatment planning for total body irradiation: Implementation and effects on standardization.

PURPOSE: This work describes the automation of our volumetric modulated arc therapy (VMAT) total body irradiation (TBI) treatment planning. It also aims to determine if plan standardization is impacted by automation. METHODS: We introduced automated beam placement for TBI in March 2021. For manual beam placement pre-2021, Python-modified DICOM files were imported to pre-set cumulative meterset weights, with other parameters selected by dosimetrists. Our automated planning script automates these processes and sets gantry stop angles and isocentre placement. To determine the impact of automation on plan standardization, we performed a retrospective review of a matched cohort of 168 patients. Plan parameters were compared with an external standard, and passing rates compared between patient cohorts. The dosimetric impact was investigated by comparing a Body-5 mm homogeneity index (HI = D2%/D98%) and mean lung dose (MLD) between cohorts. RESULTS: Results are listed for manual and automated groups respectively. Median (range) passing rates were 97.7% (96.1-100) and 99.2% (98.3-100). Automated plans had a significantly higher passing rate (p â‰ª 0.05) and smaller variance (p = 0.001). Most failures were attributed to human error. Automated plans also had more consistent parameter identifiers. After considering dimensional outliers, median (range) Body-5 mm HI were 1.18 (1.14-1.23) and 1.18 (1.15-1.26), and mean ± standard deviation MLD were 103.8 ± 1.3% and 104.1 ± 0.9%. Variances were not significantly different between Body-5 mm HI (p = 0.092) but were for MLD (p = 0.013). CONCLUSIONS: Implementation of automated planning in TBI resulted in significantly improved plan standardization. The decrease in variance of the MLD for the automated planning group points towards a potential dosimetric benefit of automation.

A high-throughput alpha particle irradiation system for monitoring DNA damage repair, genome instability and screening in human cell and yeast model systems.

Ionizing radiation (IR) is environmentally prevalent and, depending on dose and linear energy transfer (LET), can elicit serious health effects by damaging DNA. Relative to low LET photon radiation (X-rays, gamma rays), higher LET particle radiation produces more disease causing, complex DNA damage that is substantially more challenging to resolve quickly or accurately. Despite the majority of human lifetime IR exposure involving long-term, repetitive, low doses of high LET alpha particles (e.g. radon gas inhalation), technological limitations to deliver alpha particles in the laboratory conveniently, repeatedly, over a prolonged period, in low doses and in an affordable, high-throughput manner have constrained DNA damage and repair research on this topic. To resolve this, we developed an inexpensive, high capacity, 96-well plate-compatible alpha particle irradiator capable of delivering adjustable, low mGy/s particle radiation doses in multiple model systems and on the benchtop of a standard laboratory. The system enables monitoring alpha particle effects on DNA damage repair and signalling, genome stability pathways, oxidative stress, cell cycle phase distribution, cell viability and clonogenic survival using numerous microscopy-based and physical techniques. Most importantly, this method is foundational for high-throughput genetic screening and small molecule testing in mammalian and yeast cells.

Standardized flattening filter free volumetric modulated arc therapy plans based on anteroposterior width for total body irradiation.

In this work, the feasibility of using flattening filter free (FFF) beams in volumetric modulated arc therapy (VMAT) total body irradiation (TBI) treatment planning to decrease protracted beam-on times for these treatments was investigated. In addition, a methodology was developed to generate standardized VMAT TBI treatment plans based on patient physical dimensions to eliminate plan optimization time. A planning study cohort of 47 TBI patients previously treated with optimized VMAT ARC 6 MV beams was retrospectively examined. These patients were sorted into six categories depending on height and anteroposterior (AP) width at the umbilicus. Using Varian Eclipse, clinical 40 cm × 10 cm open field arcs were substituted with 6 MV FFF. Mid-plane lateral dose profiles in conjunction with relative arc output factors (RAOF) yielded how far a given multileaf collimator (MLC) leaf must move in order to achieve a mid-plane 100% isodose for a specific control point. Linear interpolation gave the dynamic MLC aperture for the entire arc for each patient AP width category, which was subsequently applied through Python scripting. All FFF VMAT TBI plans were then evaluated by two radiation oncologists and deemed clinically acceptable. The FFF and clinical VMAT TBI plans had similar Body-5 mm D98% distributions, but overall the FFF plans had statistically significantly increased or broader Body-5 mm D2% and mean lung dose distributions. These differences are not considered clinically significant. Median beam-on times for the FFF and clinical VMAT TBI plans were 11.07 and 18.06 min, respectively, and planning time for the FFF VMAT TBI plans was reduced by 34.1 min. In conclusion, use of FFF beams in VMAT TBI treatment planning resulted in dose homogeneity similar to our current VMAT TBI technique. Clinical dosimetric criteria were achieved for a majority of patients while planning and calculated beam-on times were reduced, offering the possibility of improved patient experience.

Extended SSD VMAT treatment for total body irradiation.

In this work, we develop a total body irradiation technique that utilizes arc delivery, a buildup spoiler, and inverse optimized multileaf collimator (MLC) motion to shield organs at risk. The current treatment beam model is verified to confirm its applicability at extended source-to-surface distance (SSD). The delivery involves 7-8 volumetric modulated arc therapy arcs delivered to the patient in the supine and prone positions. The patient is positioned at a 90° couch angle on a custom bed with a 1 cm acrylic spoiler to increase surface dose. Single-step optimization using a patient CT scan provides enhanced dose homogeneity and limits organ at risk dose. Dosimetric data of 109 TBI patients treated with this technique is presented along with the clinical workflow. Treatment planning system (TPS) verification measurements were performed at an extended SSD of 175 cm. Measurements included: a 4-point absolute depth-dose curve, profiles at 1.5, 5, and 10 cm depth, absolute point-dose measurements of an treatment field, 2D Gafchromic® films at four locations, and measurements of surface dose at multiple locations of a Alderson phantom. The results of the patient DVH parameters were: Body-5 mm D98 95.3 ± 1.5%, Body-5 mm D2 114.0 ± 3.6%, MLD 102.8 ± 2.1%. Differences between measured and calculated absolute depth-dose values were all <2%. Profiles at extended SSD had a maximum point difference of 1.3%. Gamma pass rates of 2D films were greater than 90% at 5%/1 mm. Surface dose measurements with film confirmed surface dose values of >90% of the prescription dose. In conclusion, the inverse optimized delivery method presented in the paper has been used to deliver homogenous dose to over 100 patients. The method provides superior patient comfort utilizing a commercial TPS. In addition, the ability to easily shield organs at risk is available through the use of MLCs.

The influence of plan modulation on the interplay effect in VMAT liver SBRT treatments.

Volumetric modulated arc therapy (VMAT) uses multileaf collimator (MLC) leaves, gantry speed, and dose rate to modulate beam fluence, producing the highly conformal doses required for liver radiotherapy. When targets that move with respiration are treated with a dynamic fluence, there exists the possibility for interplay between the target and leaf motions. This study employs a novel motion simulation technique to determine if VMAT liver SBRT plans with an increase in MLC leaf modulation are more susceptible to dosimetric differences in the GTV due to interplay effects. For ten liver SBRT patients, two VMAT plans with different amounts of MLC leaf modulation were created. Motion was simulated using a random starting point in the respiratory cycle for each fraction. To isolate the interplay effect, motion was also simulated using four specific starting points in the respiratory cycle. The dosimetric differences caused by different starting points were examined by subtracting resultant dose distributions from each other. When motion was simulated using random starting points for each fraction, or with specific starting points, there were significantly more dose differences in the GTV (maximum 100cGy) for more highly modulated plans, but the overall plan quality was not adversely affected. Plans with more MLC leaf modulation are more susceptible to interplay effects, but dose differences in the GTV are clinically negligible in magnitude.

Technical Note: A novel quality assurance test to identify gantry angle inaccuracies in respiratory-gated VMAT treatments.

PURPOSE: During respiratory-gated volumetric-modulated arc therapy (VMAT), the radiation beam is turned off each time the target exits the gating window. At the same time, the gantry slows, stops, and rewinds before the beam is turned back on. A quality assurance (QA) test was developed to detect inaccuracies in the gantry angle position between beam-off and beam-on events during respiratory-gated VMAT. METHODS: Strips of Gafchromic™ EBT3 film were taped to the surface of a Capthan® 504 phantom mounted at isocenter. A homogeneous dose was delivered to the films through a 2 cm × 10 cm slit in the jaws using a respiratory-gated VMAT arc without the multileaf collimator. A periodic breathing cycle was used. Errors in gated delivery ranging from 0.5 to 5° were simulated by delivering nongated arcs with the same field size with over- and underlapping sections of 0.5-5°. The simulated errors were used to define QA levels to analyze the gated delivery. RESULTS: The QA test was capable of detecting errors as small as 0.5°. The test was delivered to three Varian TrueBeam™ linacs, and no gantry angle inaccuracies greater than or equal to 0.5° were detected on any of the films. CONCLUSIONS: A QA test capable of detecting gantry angle inaccuracies at beam-off and subsequent beam-on as small as 0.5° was developed and implemented for Varian TrueBeam™ linacs.

Applying an animal model to quantify the uncertainties of an image-based 4D-CT algorithm.

The purpose of this paper is to use an animal model to quantify the spatial displacement uncertainties and test the fundamental assumptions of an image-based 4D-CT algorithm in vivo. Six female Landrace cross pigs were ventilated and imaged using a 64-slice CT scanner (GE Healthcare) operating in axial cine mode. The breathing amplitude pattern of the pigs was varied by periodically crimping the ventilator gas return tube during the image acquisition. The image data were used to determine the displacement uncertainties that result from matching CT images at the same respiratory phase using normalized cross correlation (NCC) as the matching criteria. Additionally, the ability to match the respiratory phase of a 4.0 cm subvolume of the thorax to a reference subvolume using only a single overlapping 2D slice from the two subvolumes was tested by varying the location of the overlapping matching image within the subvolume and examining the effect this had on the displacement relative to the reference volume. The displacement uncertainty resulting from matching two respiratory images using NCC ranged from 0.54 ± 0.10 mm per match to 0.32 ± 0.16 mm per match in the lung of the animal. The uncertainty was found to propagate in quadrature, increasing with number of NCC matches performed. In comparison, the minimum displacement achievable if two respiratory images were matched perfectly in phase ranged from 0.77 ± 0.06 to 0.93 ± 0.06 mm in the lung. The assumption that subvolumes from separate cine scan could be matched by matching a single overlapping 2D image between to subvolumes was validated. An in vivo animal model was developed to test an image-based 4D-CT algorithm. The uncertainties associated with using NCC to match the respiratory phase of two images were quantified and the assumption that a 4.0 cm 3D subvolume can by matched in respiratory phase by matching a single 2D image from the 3D subvolume was validated. The work in this paper shows the image-based 4D-CT algorithm to be a promising method for producing 4D-CT images for radiotherapy.

CT image construction of a totally deflated lung using deformable model extrapolation.

PURPOSE: A novel technique is proposed to construct CT image of a totally deflated lung from a free-breathing 4D-CT image sequence acquired preoperatively. Such a constructed CT image is very useful in performing tumor ablative procedures such as lung brachytherapy. Tumor ablative procedures are frequently performed while the lung is totally deflated. Deflating the lung during such procedures renders preoperative images ineffective for targeting the tumor. Furthermore, the problem cannot be solved using intraoperative ultrasound (U.S.) images because U.S. images are very sensitive to small residual amount of air remaining in the deflated lung. One possible solution to address these issues is to register high quality preoperative CT images of the deflated lung with their corresponding low quality intraoperative U.S. images. However, given that such preoperative images correspond to an inflated lung, such CT images need to be processed to construct CT images pertaining to the lung's deflated state. METHODS: To obtain the CT images of deflated lung, we present a novel image construction technique using extrapolated deformable registration to predict the deformation the lung undergoes during full deflation. The proposed construction technique involves estimating the lung's air volume in each preoperative image automatically in order to track the respiration phase of each 4D-CT image throughout a respiratory cycle; i.e., the technique does not need any external marker to form a respiratory signal in the process of curve fitting and extrapolation. The extrapolated deformation field is then applied on a preoperative reference image in order to construct the totally deflated lung's CT image. The technique was evaluated experimentally using ex vivo porcine lung. RESULTS: The ex vivo lung experiments led to very encouraging results. In comparison with the CT image of the deflated lung we acquired for the purpose of validation, the constructed CT image was very similar. The intensity mean absolute difference between these two images was calculated to be at 1%. Tumor center as well as a number of anatomical fiducial markers were traced in different corresponding slices of the two images. The average misalignment obtained for the constructed CT image was (0.64, 0.39, 0.11) mm, which indicates a very desirable accuracy for lung brachytherapy applications. CONCLUSIONS: The image construction accuracy obtained in this research is suitable for intraoperative tasks; e.g., tumor localization and fusing with real time navigation data in lung brachytherapy. These applications involve image registration with intraoperative U.S. images in order to enhance their poor quality. The proposed technique is also useful for preoperative tasks such as planning of lung brachytherapy treatment.

The effect of an inconsistent breathing amplitude on the relationship between an external marker and internal lung deformation in a porcine model.

PURPOSE: Investigate the relationship between the motion of the Varian Real-time Position Management (RPM) device and the internal motion of a pig during induced inconsistencies in the amplitude of breathing. METHODS: Twelve studies were performed on four ventilated female Landrace cross pigs using a GE Healthcare, Discovery CT 750 HD scanner. In each study, a 4.0 cm section (64 slices) of the pig's lungs was repeatedly scanned 20 times using cine mode, each time lasting more than one breathing cycle. During these cine scans, a Varian RPM device was used to collect respiratory amplitudes and the ventilator air return tube was periodically crimped to induce inconsistent breathing amplitudes. Each breathing cycle and its associated cine scan were categorized as either consistent or inconsistent, based on thresholds of the minimum expiration and maximum inspiration amplitudes. From the group of consistent amplitude cine scans in a study, a reference scan was chosen. The effect of inconsistent breathing amplitudes on the relationship between the motion of the RPM marker and the motion within three regions of interest (in each lung and the chest wall) was investigated with two methods: (1) A 4D-CT sorting algorithm based on RPM amplitude was used to sort volumes into 4D-CT phase bins. Within each phase bin, the nonlinear deformation of volumes collected during consistent and inconsistent breathing amplitude was calculated with respect to the reference volume. The magnitude of the deformations (in mm) were compared to determine if inconsistent breathing amplitude caused greater deformations. (2) Nonlinear deformations between each CT volume from a cine scan and the maximum expiration volume of the reference scan were calculated. Regression analyses between the nonlinear deformations within three regions of interest (in each lung and the chest wall) and the RPM amplitudes were performed to test the effect of inconsistent breathing amplitudes on the linearity of the relationship between the 3D motion of internal anatomy and the 1D motion of the RPM external marker. RESULTS: (1) Inconsistent versus consistent breathing amplitudes caused a significant increase in deformation relative to the reference scan within the left lung (1.40 +/- 0.42 versus 1.29 +/- 0.36 mm, p < 0.05). (2) One-to-one correspondences between motions of internal anatomies and motion of the RPM external marker did not exist. The regression lines between the two types of motions did not yield an identity relationship (unity slope and zero intercept). Inconsistent breathing produced significantly different regression lines than consistent breathing in ten of the 12 studies within a left lung region of interest. CONCLUSIONS: The results of these two studies indicate that inconsistency in the amplitude of breathing disrupted the correspondence between the motion of the external marker and internal anatomies. As a consequence, radiation therapy of tumors embedded in lung tissue may be prone to significant errors if inconsistent breathing amplitudes occur during treatment.