Automation framework for online review of daily dose distributions using CT on Rails in proton therapy.

PURPOSE: To demonstrate a framework for calculating daily dose distributions for proton therapy in a timeframe amenable to online evaluation using CT-on-Rails. METHODS: Tasks associated with calculation of daily dose are fully automated. A rigid registration between daily and planning images is used to propagate beams and targets for calculation of daily dose; additionally, risk structures are propagated using deformable registration to facilitate online evaluation. An end-to-end constancy test was carried out using a pelvis phantom containing a simulated target and bladder contour. 97 Daily fan-beam CT data sets associated with 10 clinical patients were processed to demonstrate feasibility and utility of online evaluation. Computing times and dosimetric differences are reported. RESULTS: The phantom constancy test took 62 s to complete with no notable discrepancies in the registrations or calculated dose. Max doses were identical for target and bladder contours on initial and repeat scans (359 and 310 cGy (RBE) respectively). Total processing time for 97 daily patient images averaged 154.6 s (73.0 - 222.0 s; SD = 31.8 s). On average, dose calculation accounted for 35 % of total processing time. Average differences in D95 for target contours was 1.5 % (SD = 1.6 %) with a max decrease of 5.9 % on a single daily image. CONCLUSION: Daily dose can be automatically calculated in a timeframe amenable to online evaluation using scanner utilities in conjunction with the scripting API of a commercial treatment planning system. Online evaluation of dose in proton therapy is useful to detect clinically relevant changes, guide setup, and facilitate treatment or replanning decisions.

Image-guided preplanning workflow for high-dose-rate interstitial brachytherapy for gynecological malignancies.

PURPOSE: To demonstrate image-guided preplan workflows for high-dose-rate (HDR) brachytherapy for advanced gynecological malignancies. METHODS AND MATERIALS: Two different preplanning scenarios are presented: (1) CT- or MRI-based preplan with partial applicator in place; (2) Preplans generated from prior fractions. The first scenario can be applied to Syed-Neblett template-based implants or hybrid brachytherapy applicators, while the second scenario applies to hybrid applicators. Both scenarios use MRI or CT images acquired with the applicator in place to demonstrate tumor and applicator relative locations and therefore, provide the ability to show optimized suggested needle positions including the implant depths before the actual insertion. RESULTS: The preplanning techniques have demonstrated feasibility and shown five areas of potential improvement: (1) shorter procedure time, (2) decreased number of total needles inserted, (3) shorter physician tumor contour time, (4) shorter planning time, and (5) evaluation of appropriateness for brachytherapy. CONCLUSIONS: The use of image-guided brachytherapy preplanning improves clinical efficiency and is recommended for consideration for adaptation into clinical workflows for HDR interstitial and hybrid brachytherapy.

Characterization of an Onboard Transmission Detector for Efficient Linear Accelerator Output Quality Assurance.

Purpose To investigate the potential to perform linear accelerator output quality assurance (QA) with the ScandiDos Delta4 Discover (Discover) onboard transmission detector. Materials and methods Using the ScandiDos Delta4 software (version 8), a conversion factor from raw signal to output was obtained via cross-calibration with an accredited dosimetry calibration laboratory (ADCL) calibrated ionization chamber for each photon energy, including flattening-filter-free (FFF) energies. With the calibration factor for 6 MV (6x) photon energy, output measurements were taken with both the Delta4 Discover and ion chamber and compared for output as a function of gantry angle and dose-rate dependence. Monitor unit (MU) linearity for 6x was measured and compared with ion chamber measurements. Additionally, the Discover was used to take output measurements, for 6x, approximately every hour throughout the course of a treatment day, and compared with ion chamber output measurements at the beginning and end of the treatment day. Results Output measurements for each photon energy were comparable with a maximum difference of -0.57% for flattened beams (6x) and 0.21% for FFF beams (10FFF). Output measurements using the Discover matched ion chamber output measurements at every dose rate within 2%, and within 1% for output as a function of gantry angle. MU linearity test agreed with ion chamber measurements with a maximum difference of 0.41%. Output measurements using the Discover showed a daily drift in output throughout the course of a treatment day of around 2% and correlated very well with ion chamber outputs measured at the beginning and end of the treatment day (within 0.2%). Conclusions The ScandiDos Delta4 Discover onboard transmission detector is able to accurately measure linear accelerator output comparable to ion chamber measurements.

Adipose Tissue Distribution and Body Mass Index (BMI) Correlation With Daily Image-Guided Radiotherapy (IGRT) Shifts of Abdominal Radiation Therapy Patients.

Purpose There are several studies suggesting a correlation between image-guided radiotherapy (IGRT) setup errors and body mass index (BMI). However, abdominal fat content has visceral and subcutaneous components, which may affect setup errors differently. This study aims to analyze a potential workflow for characterizing adipose content and distribution in the region of the target that would allow a quickly calculated metric of abdominal fat content to stratify these patients. Methods IGRT shift data was retrospectively tabulated from daily fan-beam CT-on-rails pre-treatment alignment for 50 abdominal radiation therapy (RT) patients, and systematic and random errors in the daily setup were characterized by tabulating average and standard deviations of shift data for each patient and looking at differences for different distributions of adipose content. Visceral and subcutaneous fat content were defined by visceral fat area (VFA) and subcutaneous fat area (SFA) using a region-growing algorithm to contour adipose tissue on CT simulation scans. All contours were created for a single slice at the treatment isocenter, on which the VFA and SFA were calculated. A log-rank test was used to test trends in shifts over quartiles of adiposity. Results VFA ranged from 1.9-342.8c m2, and SFA from 11.8-756.0 cm2. The standard definition (SD) of random error (σ) in the lateral axis for Q1 vs. Q4 VFA was 0.10cm vs. 0.29cm, 0.12cm vs. 0.28cm for SFA, and 0.12cm vs. 0.31cm for BMI. The percentage of longitudinal shifts greater than 10mm for Q1 vs. Q4 VFA was 0% vs. 9%, 2% vs. 19% for SFA, and 0% vs. 20% for BMI. Statistically significant trends in shifts vs. the BMI quartile were seen for both pitch and the longitudinal direction, as well as for pitch corrections vs. the VFA quartile. Conclusion Within this dataset, abdominal cancer patients showed statistically significant trends in shift probability vs. BMI and VFA. Also, patients in the upper quartiles of all adiposity metrics showed an increased SD of σ in the lateral direction and increased shifts over 10 mm in the longitudinal direction. However, despite these relationships, neither VFA nor SFA offered discernible advantages in their relationship to shift uncertainty relative to BMI.

Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A Comprehensive PENTEC Genitourinary Review.

PURPOSE: Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. METHODS AND MATERIALS: We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. RESULTS: The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and <3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a <5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. CONCLUSIONS: In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure.

An evaluation of the use of DirectSPR images for proton planning in the RayStation treatment planning software.

An important source of uncertainty in proton therapy treatment planning is the assignment of stopping-power ratio (SPR) from CT data. A commercial product is now available that creates an SPR map directly from dual-energy CT (DECT). This paper investigates the use of this new product in proton treatment planning and compares the results to the current method of assigning SPR based on a single-energy CT (SECT). Two tissue surrogate phantoms were CT scanned using both techniques. The SPRs derived from single-energy CT and by DirectSPR™ were compared to measured values. SECT-based values agreed with measurements within 4% except for low density lung and high density bone, which differed by 13% and 8%, respectively. DirectSPR™ values were within 2% of measured values for all tissues studied. Both methods were also applied to scanned containers of three types of animal tissue, and the expected range of protons of two different energies was calculated in the treatment planning system and compared to the range measured using a multi-layer ion chamber. The average difference between range measurements and calculations based on SPR maps from dual- and single-energy CT, respectively, was 0.1 mm (0.07%) versus 2.2 mm (1.5%). Finally, a phantom was created using a layer of various tissue surrogate plugs on top of a 2D ion chamber array. Dose measurements on this array were compared to predictions using both single- and dual-energy CTs and SPR maps. While standard gamma pass rates for predictions based on DECT-derived SPR maps were slightly higher than those based on single-energy CT, the differences were generally modest for this measurement setup. This study showed that SPR maps created by the commercial product from dual-energy CT can successfully be used in RayStation to generate proton dose distributions and that these predictions agree well with measurements.

Technical note: A method for generating lesion-specific nonuniform rotational margins for targets remote from isocenter.

PURPOSE: To present a novel method for generating nonuniform lesion-specific rotational margins for targets remote from isocenter, as encountered in single isocenter multiple metastasis radiotherapy. METHODS: Target contours are rotated using a large series of 3D rotations, corresponding to a given range of rotational uncertainty, and combined to create a rotational envelope that encompasses potential motion. A set of artificial spherical targets ranging from 0.5 to 2.0 cm in diameter, and residing a distance of 1 - 15 cm from isocenter, is used to generate rotational envelopes assuming uncertainties of 0.5-3.0°. Computing time and number of samples are reported for simulated scenarios. Hausdorff distances (HD) between rotational envelopes and original target structures are calculated to represent the magnitude of uniform expansion required to encompass potential rotation. Volume differences between uniform expansions (based on HD) and rotational envelopes are reported to articulate potential advantages. RESULTS: Median time to generate rotational envelopes was 60 s (31-974 s). Median required samples was 86 (61-851). Maximum HD for all targets located 10 cm from isocenter was 1.5 mm, 3.0 mm, 5.8 mm, and 8.6 mm assuming 0.5°, 1.0°, 2.0°, and 3.0° of rotational uncertainty, respectively. At 5 cm from isocenter and assuming 0.5° of rotational uncertainty, volumes were decreased by 0.07 cc (60%), 0.24 cc (39%), and 1.08 cc (19%) for 5 mm, 10 mm, and 20 mm targets respectively. At 10 cm from isocenter and 1.0° of uncertainty, volumes decreased by 0.42 cc (58%), 2.0 cc (40%), and 2.5 cc (27%). On average target volumes decreased 45% (SD = 17%) when compared with uniform expansions based on HD. CONCLUSION: Rotational margins may be generated by sampling a set of 3D rotations. Resulting margins explicitly account for target shape, distance from isocenter, and magnitude of rotational uncertainty, while reducing treated volumes when compared with uniform expansions.

Feasibility and Clinical Utility of a Workflow Interfacing Radiation Oncology Lung Stereotactic Body Radiation Therapy Treatment Planning and Diagnostic Radiology.

Stereotactic body radiation therapy (SBRT) is commonly used to treat early-stage non-small cell lung cancer. Beam arrangements for SBRT include multiple entry and exit pathways resulting in irregular low-dose distributions within normal lung parenchyma. An improved understanding of posttreatment radiographic changes may improve the ability to predict clinical complications including radiation pneumonitis as well as assist in early detection of local failures. Radiation treatment planning is conducted using software systems separate from diagnostic radiology, often not accessible to the diagnostic radiologist. We developed a workflow for interfacing radiation dose information from lung SBRT treatments with a diagnostic radiology picture archiving and communication system (PACS). In an anonymized PACS study folder, SBRT dose maps depicting high-dose, low-dose, and nonirradiated lung volumes were viewable side by side with pretreatment and follow-up diagnostic computed tomography scans. Clinical utility was evaluated by 2 thoracic diagnostic radiologists reviewing posttreatment diagnostic follow-up scans in the PACS both with and without radiation dose maps available. The addition of the biologically effective dose map did not significantly change identification rates of radiation induced lung injury) (92% vs 95%; P = .32) but did significantly decrease radiologic suspicion for local recurrence (22% vs 8%; P = .003). The addition of biologically effective dose maps significantly increased confidence in identifying radiation induced lung injury (7.75 vs 8.82; P = .004) and local recurrence (5.5 vs 6.6; P = .005). The recommendation for additional workup was not significantly different (10% vs 7%; P = .41). We demonstrated the feasibility and clinical utility of a workflow generating simplified radiation dose maps that are viewable within a PACS for diagnostic radiology review.

Impact of detector selection on commissioning of Leipzig surface applicators with improving immobilization in high-dose-rate brachytherapy.

PURPOSE: Commission and treatment setup of Leipzig surface applicators, because of the steep dose gradient and lack of robust immobilization, is challenging. We aim to improve commissioning reliability by investigating the impact of detector choice on percentage depth dose (PDD) verifications, and to enhance accuracy and reproducibility in calibration/treatment setup through a simple and novel immobilization device. METHODS AND MATERIALS: PDD distributions were measured with radiochromic films, optically stimulated luminescent dosimeters (OSLDs), a diode detector, and both cylindrical and parallel plate ionization chambers. The films were aligned to the applicators in parallel and transverse orientations. PDD data from a benchmarking Monte Carlo (MC) study were compared with the measured results, where surface doses were acquired from extrapolation. To improve setup accuracy and reproducibility, a custom-designed immobilization prototype device was made with cost-effective materials using a 3D printer. RESULTS: The measured PDD data with different detectors had an overall good agreement (<±10%). The parallel plate ionization chamber reported unreliable doses for the smallest applicator. There was no remarkable dose difference between the two film setups. The two-in-one prototype device provided a rigid immobilization and a flexible positioning of the applicator. It enhanced accuracy and reproducibility in calibration and treatment setup. CONCLUSION: We recommend using radiochromic films in the transverse orientation for a reliable and efficient PDD verification. The applicator's clinical applicability has been limited by a lack of robust immobilization. We expect this economical, easy-to-use prototype device can promote the use of Leipzig applicators in surface brachytherapy.

FMEA occurrence values for four failure modes occurring using look-up tables for dose calculations.

PURPOSE: For a number of different treatment types [such as Total Body Irradiation (TBI), etc.] most institutions utilize tables from commissioned databooks to perform the dose calculations. Each time one manually looks up data from a large table and then copies the numbers for a manual calculation, there is potential for errors. While a second check effectively mitigates the potential error from such calculations, information regarding the frequency and nature of such mistakes is important to develop protocols and workflows that avoid related errors. METHODS: Five years' worth of TBI calculations were reviewed. Each calculation was re-performed and evaluated against the original calculation and original second check. Any discrepancies were noted and those discrepancies were checked to see if the number was the result of misreading from the look-up table, a typo, copying/skipping partially redundant steps, or rounding/avoiding interpolation. The number of calculations that contained these various types of discrepancies was tallied and percentages representing the frequency of said discrepancies were derived. RESULTS: All of the discrepancies only resulted in a monitor unit (MU) calculation difference of <1.7%. Typos, looking up wrong values from tables, rounding/avoiding interpolation, and skipping steps occurred in 10.4% ( ± 3.1%), 6.3% ( ± 2.5%), 53.1% ( ± 5.1%), and 4.2% ( ± 2.0%) of MU calculations, respectively. CONCLUSIONS: While all of the discrepancies only resulted in a monitor unit (MU) calculation difference of <1.7%, this review shows how frequently various discrepancies can occur. Typos and rounding/avoiding interpolation are the steps most likely to potentially cause a miscalculation of MU. To avoid direct human interaction on such a large repetitive scale, creating forms that calculate MU automatically from initial measurement data would reduce the incidences that numbers are written/transcribed and eliminate the need to look up data in a table, thus reducing the chance for error.

Evaluation of the effects of implementing a diode transmission device into the clinical workflow.

PURPOSE: This work investigated effects of implementing the Delta4 Discover diode transmission detector into the clinical workflow. METHODS: PDD and profile scans were completed with and without the Discover for a number of photon beam energies. Transmission factors were determined for all beam energies and included in Eclipse TPS to account for the attenuation of the Discover. A variety of IMRT plans were delivered to a Delta4 Phantom+ with and without the Discover to evaluate the Discover's effects on IMRT QA. An imaging QA phantom was used to assess the detector's effects on MV image quality. OSLDs placed on the Phantom+ were used to determine the detector's effects on superficial dose. RESULTS: The largest effect on PDDs after dmax was 0.5%. The largest change in beam profile symmetry and flatness was 0.2% and 0.1%, respectively. An average difference in gamma passing rates (2%/2 mm) of 0.2% was observed between plans that did not include the Discover in the measurement and calculation to plans that did include the Discover in the measurement and calculation. The Discover did not significantly change the MV image quality, and the largest observed increase in the relative superficial dose when the Discover was present was 1%. CONCLUSIONS: The effects the Discover has on the linac beam were found to be minimal. The device can be implemented into the clinic without the need to alter the TPS beam modeling, other than accounting for the device's attenuation. However, a careful workflow review to implement the Discover should be completed.

Using failure mode and effects analysis (FMEA) to generate an initial plan check checklist for improved safety in radiation treatment.

PURPOSE: To apply failure mode and effect analysis (FMEA) to generate an effective and efficient initial physics plan checklist. METHODS: A team of physicists, dosimetrists, and therapists was setup to reconstruct the workflow processes involved in the generation of a treatment plan beginning from simulation. The team then identified possible failure modes in each of the processes. For each failure mode, the severity (S), frequency of occurrence (O), and the probability of detection (D) was assigned a value and the risk priority number (RPN) was calculated. The values assigned were based on TG 100. Prior to assigning a value, the team discussed the values in the scoring system to minimize randomness in scoring. A local database of errors was used to help guide the scoring of frequency. RESULTS: Twenty-seven process steps and 50 possible failure modes were identified starting from simulation to the final approved plan ready for treatment at the machine. Any failure mode that scored an average RPN value of 20 or greater was deemed "eligible" to be placed on the second checklist. In addition, any failure mode with a severity score value of 4 or greater was also considered for inclusion in the checklist. As a by-product of this procedure, safety improvement methods such as automation and standardization of certain processes (e.g., dose constraint checking, check tools), removal of manual transcription of treatment-related information as well as staff education were implemented, although this was not the team's original objective. Prior to the implementation of the new FMEA-based checklist, an in-service for all the second checkers was organized to ensure further standardization of the process. CONCLUSION: The FMEA proved to be a valuable tool for identifying vulnerabilities in our workflow and processes in generating a treatment plan and subsequently a new, more effective initial plan checklist was created.

Preliminary clinical experience with Calypso anchored beacons for tumor tracking in lung SBRT.

PURPOSE: To present our preliminary experience with the recently released Calypso lung beacons to track lung tumor location during stereotactic body radiation therapy (SBRT). MATERIALS/METHODS: Five recent lung SBRT patients had Calypso lung beacons implanted for tumor tracking during treatment. Beacons were placed by a pulmonologist using fluoroscopic navigation within 1 week prior to planning four-dimensional computed tomography (4DCT) acquisition. Patients were immobilized in a full-body double-vacuum bag. For the first three patients, a verification 4DCT was obtained prior to the first fraction with the patient in the treatment position to assess both beacon migration and motion of tumor and beacons relative to planning day. For each treatment fraction, Calypso was used to position the patient. A verification cone-beam CT (CBCT) confirmed the Calypso-defined target position was appropriate. Real-time Calypso tracking information was also acquired and compared to an action level that was used to determine if the tumor migrated outside of the planning target volume. RESULTS: For four patients, the implant procedure was well tolerated, with average CBCT-based shifts being within 0.2 mm of the shifts reported by Calypso at the time of imaging. The other patient had a small pneumothorax due to very peripheral tumor location and experienced beacon migration. However, the patient quickly recovered from the pneumothorax, and after deactivating that beacon, motion tracking was possible throughout his treatment. CONCLUSIONS: All patients were successfully treated with SBRT using the newly released Calypso lung beacons, with initial positioning confirmed by this clinic's current clinical standard of CBCT. The system allowed us to validate, with real-time confirmation, that the planned internal target volumes were appropriate to each day's extent of actual tumor motion. An efficient and effective workflow for utilizing the new lung beacons for SBRT treatments was developed.

A systematic evaluation of the error detection abilities of a new diode transmission detector.

Transmission detectors meant to measure every beam delivered on a linear accelerator are now becoming available for monitoring the quality of the dose distribution delivered to the patient daily. The purpose of this work is to present results from a systematic evaluation of the error detection capabilities of one such detector, the Delta4 Discover. Existing patient treatment plans were modified through in-house-developed software to mimic various delivery errors that have been observed in the past. Errors included shifts in multileaf collimator leaf positions, changing the beam energy from what was planned, and a simulation of what would happen if the secondary collimator jaws did not track with the leaves as they moved. The study was done for simple 3D plans, static gantry intensity modulated radiation therapy plans as well as dynamic arc and volumetric modulated arc therapy (VMAT) plans. Baseline plans were delivered with both the Discover device and the Delta4 Phantom+ to establish baseline gamma pass rates. Modified plans were then delivered using the Discover only and the predicted change in gamma pass rate, as well as the detected leaf positions were evaluated. Leaf deviations as small as 0.5 mm for a static three-dimensional field were detected, with this detection limit growing to 1 mm with more complex delivery modalities such as VMAT. The gamma pass rates dropped noticeably once the intentional leaf error introduced was greater than the distance-to-agreement criterion. The unit also demonstrated the desired drop in gamma pass rates of at least 20% when jaw tracking was intentionally disabled and when an incorrect energy was used for the delivery. With its ability to find errors intentionally introduced into delivered plans, the Discover shows promise of being a valuable, independent error detection tool that should serve to detect delivery errors that can occur during radiotherapy treatment.

Technical Note: The use of DirectDensityTM and dual-energy CT in the radiation oncology clinic.

PURPOSE: Two new tools available in Radiation Oncology clinics are Dual-energy CT (DECT) and Siemens' DirectDensity™ (DD) reconstruction algorithm, which allows scans of any kV setting to use the same calibration. This study demonstrates why DD scans should not be used in combination with DECT and quantifies the magnitude of potential errors in image quality and dose. METHODS: A CatPhan 504 phantom was scanned with a dual-pass DECT and reconstructed with many different kernels, including several DD kernels. The HU values of various inserts were measured. The RANDO® man phantom was also scanned. Bone was contoured and then histograms of the bone HU values were analyzed for Filtered-Backprojection (FBP) and DD reconstructions of the 80 and 140 kV scans, as well as several virtual, monoenergetic reconstructions generated from FBP and DD reconstructions. "Standard" dose distributions were calculated on several reconstructions of both phantoms for comparison. RESULTS: The DD kernel overcorrected the high-Z material inserts relative to bone, giving an excessively low relative electron density (RED). A unique artifact was observed in the high density inserts of the CatPhan in the monoenergetic scans when utilizing a DD kernel, due to the overcorrection in the DD scan of the material, especially at lower kV. CONCLUSIONS: While DD and DECT perform as expected when used independently, errors from their combined use were demonstrated. Dose errors from misuse of the DD kernel with DECT post-processing were as large as 2.5%. The DECT post-processing was without value because the HU differences between low and high energy were removed by the DD kernel. When using DD and DECT, we recommend the use of a DD reconstruction of the high energy scan for the dose calculation, and use of a FBP filter for the low and high energy scans for the DECT post-processing.

An evaluation of the consistency of shifts reported by three different systems for non-coplanar treatments.

Treatment of intra-cranial lesions sometimes requires a non-coplanar beam configuration. One of the most commonly used IGRT modalities, kV conebeam CT, cannot typically be used when large couch rotations are introduced. However, multiple other systems allow for imaging/tracking the patient for such situations. This work compares shift consistency from three independent systems, namely Varian's Advanced Imaging, Brainlab's Exactrac and Varian's OSMS, all installed on the same linear accelerator. After a phantom was first positioned using conebeam CT, the three systems were used to determine shifts at different couch positions. This was done with and without intentional shifts inserted in the original phantom position. Results show that the difference in shifts between the three systems was never more than 0.7 mm (average of 0.2 mm, standard deviation of 0.2 mm). These results confirm that all three systems are equivalent to within 1 mm and may potentially be uses interchangeably, especially in cases where the PTV margin is on the order of 1 mm.

Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by using a microCT irradiator capable of targeted treatment in small animals. Within several days of irradiation, teratomas derived from injection of undifferentiated hESCs and hiPSCs demonstrated complete growth arrest lasting several months. In addition, EBRT reduced reseeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1 × 103 higher doses to form new teratomas. We demonstrate that irradiation induces teratoma cell apoptosis, senescence, and growth arrest, similar to established radiobiology mechanisms. Taken together, these results provide proof of concept for the use of EBRT in the treatment of existing teratomas and highlight a strategy to increase the safety of stem cell-based therapies. Stem Cells 2017;35:1994-2000.

Improved targeting accuracy of lung tumor biopsies with scanning-beam digital x-ray tomosynthesis image guidance.

PURPOSE: Electromagnetic navigation bronchoscopy (ENB) provides improved targeting accuracy during transbronchial biopsies of suspicious nodules. The greatest weakness of ENB-based guidance is the registration divergence that exists between the planning CT, acquired days or weeks before the intervention, and the patient on the table on the day of the intervention. Augmenting ENB guidance with real-time tomosynthesis imaging during the intervention could mitigate the divergence and further improve the yield of ENB-guided transbronchial biopsies. The real-time tomosynthesis prototype, the scanning-beam digital x-ray (SBDX) system, does not currently display images reconstructed by the iterative algorithm that was developed for this lung imaging application. A protocol using fiducial markers was therefore implemented to permit evaluation of potential improvements that would be provided by the SBDX system in a clinical setting. METHODS: Ten 7 mm lesions (5 per side) were injected into the periphery of each of four preserved pig lungs. The lungs were then placed in a vacuum chamber that permitted simulation of realistic motion and deformation due to breathing. Standard clinical CT scans of the pig lung phantoms were acquired and reconstructed with isotropic resolution of 0.625 mm. Standard ENB-guided biopsy procedures including target identification, path planning, CT-to-lung registration and navigation to the lesion were carried out, and a fiducial marker was placed at the location at which a biopsy would have been acquired. The channel-to-target distance provided by the ENB system prior to fiducial placement was noted. The lung phantoms were then imaged using the SBDX system, and using high-resolution conebeam CT. The distance between the fiducial marker tip and the lesion was measured in SBDX images and in the gold-standard conebeam-CT images. The channel-to-target divergence predicted by the ENB system and measured in the SBDX images was compared to the gold standard to determine if improved targeting accuracy could be achieved using SBDX image guidance. RESULTS: As expected, the ENB system showed poorer targeting accuracy for small peripheral nodules. Only 20 nodules of the 40 injected could be adequately reached using ENB guidance alone. The SBDX system was capable of visualizing these small lesions, and measured fiducial-to-target distances on SBDX agreed well with measurements in gold-standard conebeam-CT images (p = 0.0001). The correlation between gold-standard conebeam-CT distances and predicted fiducial-to-target distances provided by the ENB system was poor (p = 0.72), primarily due to inaccurate ENB CT-to-body registration and movement due to breathing. CONCLUSIONS: The SBDX system permits visualization of small lung nodules, as well as accurate measurement of channel-to-target distances. Combined use of ENB with SBDX real-time image guidance could improve accuracy and yield of biopsies, particularly of those lesions located in the periphery of the lung.

Modality comparison for small animal radiotherapy: a simulation study.

PURPOSE: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. METHODS: This paper presents a comparison of dose distributions generated by the three approaches-a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. RESULTS: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. CONCLUSIONS: The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.