Initial Clinical Experience With Novel Directional Low-Dose Rate Brachytherapy for Retroperitoneal Sarcoma.

BACKGROUND: A novel Palladium-103 low-dose rate (LDR) brachytherapy device was developed to provide dose-escalation to the tumor bed after resection while shielding adjacent tissues. This multicenter report describes the initial experience with this device in patients with retroperitoneal sarcoma (RPS). MATERIALS AND METHODS: Patients with recurrent RPS, prior radiotherapy, and/or concern for positive margins were considered. An LDR brachytherapy dose of 20-60 Gy was administered, corresponding to biologically effective dose values of 15-53 Gy and equivalent dose values of 12-43 Gy. RESULTS: Six patients underwent implantation at four institutions. Of these, five had recurrent disease in the retroperitoneum or pelvic sidewall, one had untreated locally advanced leiomyosarcoma, two had prior external beam radiation therapy at the time of initial diagnosis, and four received neoadjuvant external beam radiation therapy plus brachytherapy. The device was easily implanted and conformed to the treatment area. Median follow-up was 16 mo; radiation was delivered to the at-risk margin with minimal irradiation of adjacent structures. No local recurrences at the site of implantation, device migration, or radiation-related toxicities were observed. CONCLUSIONS: The novel LDR directional brachytherapy device successfully delivered a targeted dose escalation to treat RPS high-risk margins. Lack of radiation-related toxicity demonstrates its safety.

A model for predicting the dose to the parotid glands based on their relative overlapping with planning target volumes during helical radiotherapy.

The sparing of the parotid glands in the treatment of head and neck cancers is of clinical relevance as high doses to the salivary glands may result in xerostomia. Xerostomia is a major cause of decreased quality of life for head and neck patients. This paper explores the relationship between the overlap of the target volumes and their expansions with the parotid glands for helical delivery plans and their ability to be spared. Various overlapping volumes were examined, and an overlap with a high statistical relevance was found. A model that predicts exceeding tolerance parotid mean dose based on its fractional overlapping volume with PTVs was developed. A fractional overlapping volume of 0.083 between the parotid gland and the high dose PTV plus 5 mm expansion - was determined to be the threshold value to predict parotid Dmean  > 26 Gy for parotids that overlap with the high dose PTV plus 5 mm expansion. If the parotid gland only overlaps with the intermediate dose target (and/or low dose target) and the overlapping volume of the parotid gland and the intermediate dose target is less than 25%, the parotid mean dose is likely less than 26 Gy. If the parotid overlaps with the low dose target only then the mean dose to the parotid is likely to be less than 26 Gy. This finding will prove as a very useful guide for the physicians and planners involved in the planning process to know prior whether the parotid glands will be able to be spared with the current set of target volumes or if revisions are necessary. This work will serve as a helpful guide in the planning process of head and neck target cases.

The sensitivity of ArcCHECK-based gamma analysis to manufactured errors in helical tomotherapy radiation delivery.

Three-dimensional measurement arrays are an efficient means of acquiring a distribution of data for patient plan delivery QA. However, the tie between plan integrity and traditional gamma-based analysis of these data are not clear. This study explores the sensitivity of such analysis by creating errors in Helical Tomotherapy delivery and measuring the passing rates with an ArcCHECK cylindrical diode array. Errors were introduced in each of the couch speed, leaf open time, and gantry starting position in increasing magnitude while the resulting gamma passing rates were tabulated. The error size required to degrade the gamma passing rate to 90% or below was on average a 3% change in couch speed, 5° in gantry synchronization, or a 5 ms in leaf closing speed for a 3%/3 mm Van Dyk gamma analysis. This varied with plan type, with prostate plans exhibiting less sensitivity than head and neck plans and with gamma analysis criteria, but in all cases the error magnitudes were large compared to actual machine tolerances. These findings suggest that the sensitivity of ArcCHECK-based gamma analysis to single-mode errors in tomotherapy plans is dependent upon plan and analysis type and at traditional passing thresholds unable to detect small defects in the plan.

Multiparametric Magnetic Resonance Imaging- Guided Dose-Escalated Radiation Therapy for Localized Prostate Cancer: A Prospective Phase 2 Trial.

PURPOSE: This trial's purpose was to determine the late toxicity associated with dose escalation to Prostate Imaging Reporting and Data System (PI-RADS) III-V lesions on multiparametric magnetic resonance imaging (MRI) with an image guided combined IMRT-stereotactic body radiation therapy (SBRT) approach in men with localized prostate cancer. METHODS AND MATERIALS: In this phase 2 trial patients with localized prostate cancer with clinical tumor stage T1-T3bN0 and at least one PIRADS III-V lesion were recruited to receive 45 Gy in 25 fractions to the prostate and seminal vesicles followed by a boost of 18 Gy in 3 fractions to the prostate with a simultaneous integrated boost 21 Gy in 3 fractions to the PI-RADS lesion(s). The primary endpoint was the cumulative incidence of late grade ≥3 genitourinary and gastrointestinal toxicity by 18 months (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). RESULTS: Overall, 50 patients were enrolled in this study, and 43 patients completed at least 18 months of follow-up. The cumulative incidence of grade 1, 2, and 3 late genitourinary toxicity at 18 months was 18%, 53%, and 2%. One patient was noted to have grade 3 hematuria and needed cystoscopy-guided cauterization. No acute grade 3 gastrointestinal or genitourinary toxicities were observed. The cumulative incidence of grade 1, 2, and 3 late gastrointestinal toxicity at 18 months was 31%, 4%, and 0%, respectively. At a median follow-up of 43.5 months, 3 patients developed biochemical recurrence, each with distant bone metastases without local or nodal recurrence. At 3 years, freedom from biochemical failure rate was 95.3% (95% CI, 89.2%-100%). CONCLUSIONS: Multiparametric MRI-guided dose escalation to PI-RADS III-V lesions using a combined image guided IMRT-SBRT approach is associated with an acceptable risk of late gastrointestinal and genitourinary toxicity. The results should be interpreted with caution considering their single institutional nature, small sample size, and short follow-up and should be validated in a larger study.

A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity.

PURPOSE: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. METHODS: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lung dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. RESULTS: Whole body midplane dose uniformity of ±10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within ±5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. CONCLUSIONS: The proposed TBI technique can achieve dose uniformity within ±10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.

Dosimetric characteristics of the small diameter BrainLab™ cones used for stereotactic radiosurgery.

The purpose was to study the dosimetric characteristics of the small diameter (≤ 10.0 mm) BrainLAB cones used for stereotactic radiosurgery (SRS) treatments in conjunction with a Varian Trilogy accelerator. Required accuracy and precision in dose delivery during SRS can be achieved only when the geometric and dosimetric characteristics of the small radiation fields is completely understood. Although a number of investigators have published the dosimetric characteristics of SRS cones, to our knowledge, there is no generally accepted value for the relative output factor (ROF) for the 5.0 mm diameter cone. Therefore, we have investigated the dosimetric properties of the small (≤ 10.0 mm) diameter BrainLAB SRS cones used in conjunction with the iPlan TPS and a Trilogy linear accelerator with a SRS beam mode. Percentage depth dose (PDD), off-axis ratios (OAR), and ROF were measured using a SRS diode and verified with Monte Carlo (MC) simulations. The dependence of ROF on detector material response was studied. The dependence of PDD, OAR, and ROF on the alignment of the beam CAX with the detector motion line was also investigated using MC simulations. An agreement of 1% and 1 mm was observed between measurements and MC for PDD and OAR. The calculated ROF for the 5.0 mm diameter cone was 0.692 ± 0.008--in good agreement with the measured value of 0.683 ± 0.007 after the diode response was corrected. Simulations of the misalignment between the beam axis and detector motion axis for angles between 0.5°-1.0° have shown a deviation > 2% in PDD beyond a certain depth. We have also provided a full set of dosimetric data for BrainLAB SRS cones. Monte Carlo calculated ROF values for cones with diameters less than 10.0 mm agrees with measured values to within 1.8%. Care should be exercised when measuring PDD and OAR for small cones. We recommend the use of MC to confirm the measurement under these conditions.

A novel use of 3D-printed template in vaginal HDR brachytherapy.

PURPOSE: The High-Dose-Rate (HDR) vaginal cylinder treatment is typically designed using the initial CT, while the subsequent implants are verified using rudimentary methods (i.e., visual inspection, ruler measurements, etc.) and/or X-ray imaging. We are proposing the use of a 3D-printed individualized template that could provide simple and reproducible vaginal cylinder insertion. MATERIAL AND METHODS: Six patients were included in the study with prescriptions of 6 Gy/fraction for 2 to 5 fractions (total 27 treatments). The first 1 to 2 treatments were delivered without the template and the rest with the CT-based 3D-printed templates. Cone beam CTs (CBCTs) were acquired to verify the cylinder placement for all treatments. D2cc of the bladder and rectum are recorded on both planning CT and the following on-treatment CBCTs. RESULTS: By using the templates, the tip position variation on average (±1 SD) reduced from 0.8±0.5 cm to 0.6±0.4 cm, and angular difference decreased from 5.3±3.5° to 4.7±2.4°. The pitch and yaw deviation are reduced from 0.9 ± 5.8° and 0.4±2.9° to 0.0±3.9° and -0.2±3.0°, respectively. The deviation of D2cc to bladder from the plan reduced from 6±4% to 5±3%, and rectum from 5±2% to 4±4%. CONCLUSION: The 3D-printed patient-specific cylinder templates could potentially improve the geometrical reproducibility of cylinder treatments at no cost of additional imaging. The D2cc for the bladder and rectum are determined by the treatment length rather than their respective volumes.

Quantitative Medical Physics National Job Data Distribution Analysis.

PURPOSE: The purpose of this study was to investigate the contemporary distribution of medical physics (MP) employment opportunities across the United States. METHODS AND MATERIALS: An annual record (2018-2019) of advertised full-time MP jobs was created using publicly available information from the American Association of Physicists in Medicine and Indeed websites. Listed jobs were categorized based on position name, work experience, job function, and geographic region. To account for regional population differences, a preponderance of employment opportunities per 10 million people was computed. Using Commission on Accreditation of Medical Physics Education Programs residency accreditation data, the nationwide locations of the MP training centers and the number of residency positions per annum were identified. A chi-square goodness-of-fit test was used for statistical analysis. RESULTS: A total of 441 unique MP jobs were identified nationwide per annum (2018-2019). The highest percentage of MP jobs was reported from the South region (33.6%), and the lowest (17.2%) was from the West. Analysis revealed that 148 jobs (33.6%) were academic and 293 (66.4%) were nonacademic. The South had the most academic jobs overall (31.8%), whereas the West had the fewest (13.5%). Regionally, the highest percentage of academic jobs (46.9%) was reported from the Northeast, whereas the West had the lowest percentage (26.3%). The analysis of academic versus nonacademic job comparison by regions showed statistically significant differences (P = .0133). The Midwest and the West regions, respectively, showed the highest (18.2) and lowest (10.24) number of jobs per unit population, measured in 10 million. CONCLUSIONS: To our knowledge, this is one of the first national quantitative job data analyses of MP job distributions. This study revealed the level of demand for qualified candidates in 2018 to 2019, showing an imbalance between academic and nonacademic positions across the regions of the United States. Moreover, the geographic distribution of job listings deviated significantly from expectation given the relative population of each region.

Intracranial metastatic disease rarely involves the pituitary: retrospective analysis of 935 metastases in 155 patients and review of the literature.

We present a case report of a patient recently treated at our institution for an isolated non-small cell lung cancer metastatic lesion to the sella, report the lack of involvement of the pituitary gland in a large single-institution series of treated intracranial parenchymal metastases, and review the pertinent literature. We reviewed cranial imaging studies (CT and MRI) for 935 metastases in 155 patients treated at our institution over the previous 3 years for intracranial metastatic disease. Special attention was paid to the skull base to document the presence of any metastatic disease involving the pituitary gland, infundibular stalk, sella turcica (including anterior and posterior clinoids), or diaphragm sellae. We found no other involvement of the pituitary gland or other sellar structures by metastatic disease in this series. Intracranial metastatic disease rarely involves the pituitary gland and infundibular stalk parenchyma, suggesting that this structure may be safely omitted from the treatment field during WBRT and prophylactic cranial irradiation (PCI). This treatment approach should reduce the late sequelae of treatment to this critical organ.

Scatter imaging during lung stereotactic body radiation therapy characterized with phantom studies.

By collecting photons scattered out of the therapy beam, scatter imaging creates images of the treated volume. Two phantoms were used to assess the possible application of scatter imaging for markerless tracking of lung tumors during stereotactic body radiation therapy (SBRT) treatment. A scatter-imaging camera was assembled with a CsI flat-panel detector and a 5 mm diameter pinhole collimator. Scatter images were collected during the irradiation of phantoms with megavoltage photons. To assess scatter image quality, spherical phantom lung tumors of 2.1-2.8 cm diameters were placed inside a static, anthropomorphic phantom. To show the efficacy of the technique with a moving target (3 cm diameter), the position of a simulated tumor was tracked in scatter images during sinusoidal motion (15 mm amplitude, 0.25 Hz frequency) in a dynamic lung phantom in open-field, dynamic conformal arc (DCA), and volumetric modulated arc therapy (VMAT) deliveries. Anatomical features are identifiable on static phantom scatter images collected with 10 MU of delivered dose (2.1 cm diameter lung tumor contrast-to-noise ratio of 4.4). The contrast-to-noise ratio increases with tumor size and delivered dose. During dynamic motion, the position of the 3.0 cm diameter lung tumor was identified with a root-mean-square error of 0.8, 1.2, and 2.9 mm for open field (0.3 s frame integration), DCA (0.5 s), and VMAT (0.5 s), respectively. Based on phantom studies, scatter imaging is a potential technique for markerless lung tumor tracking during SBRT without additional imaging dose. Quality scatter images may be collected at low, clinically relevant doses (10 MU). Scatter images are capable of sub-millimeter tracking precision, but modulation decreases accuracy.

Heart dose and coronary artery calcification in patients receiving thoracic irradiation for lung cancer.

BACKGROUND: Thoracic irradiation (TIR) is associated with an increased risk of coronary artery disease (CAD) and coronary-related death. Lung cancer patients receive considerable doses of TIR, making them a high-risk population that may benefit from post-therapy surveillance. Coronary artery calcium (CAC) is a known biomarker of CAD development and may serve as a useful indicator of disease progression in this population. We hypothesized greater CAC progression in lung cancer patients subjected to higher whole heart radiation doses. METHODS: CAC progression (pre- and >2 years post-TIR) from chest CT scans of lung cancer patients were evaluated. A 2:1 matched control population was established controlling for age, gender, race, and CT scan interval. Vessel-specific CAC presence, progression, and extension in pre- and post-interval CT studies was evaluated by two blinded reviewers using the ordinal method. Dosimetric treatment files were restored and contours of the whole heart and proximal left anterior descending artery (LAD) were created within existing plans to compute radiation doses (Pinnacle Treatment Planning Software). Binary logistic regression analysis identified factors predictive for CAC development. Multiple logistic regression analysis with hierarchal method was used to assess covariates. RESULTS: Thirty-five patients and 65 controls (50% female) were evaluated; mean age 57 years, mean follow-up post-radiation 4.9±2.2 years. Average mean and maximum left anterior descending coronary artery (LAD) radiation doses were 19.9 Gy (95% CI, 14.1-25.7) and 30.7 Gy (95% CI, 23.8-37.5), respectively; 91.6% inter-observer variability. There was greater incidence of coronary calcification in irradiated patients (48.6% vs. 24.6%; P=0.01). In interval CT scans, a greater proportion of radiated patients demonstrated new coronary calcification (P=0.007) and extension within the LAD (P=0.003). Radiation exposure was the only independent predictor of new calcification (OR 3.1; 95% CI: 1.09-9.2). CONCLUSIONS: We identified both an increase in the development and progression of CAC in lung cancer patients receiving TIR. Future studies utilizing alternative cancer populations and larger sample sizes are necessary to further correlate radiographic and dosimetric observations to cardiovascular events.

Detection of electron beam energy variations using a computed radiography system.

A method to evaluate the electron beam energy constancy by employing the computed radiography (CR) system has been developed. In this method, a right triangular plastic wedge is used to produce a curve of the CR storage phosphor plate signal versus the wedge thickness. The curve, which resembles the percentage depth ionization curve of the clinical electron beams, can be used to derive the energy constancy metric EC(50). The sensitivity of the method was tested using polystyrene sheets of variable thicknesses. For electron energies up to 12 MeV, energy changes induced by 1.5 mm thick polystyrene can be detected, while a 2.3 mm thick polystyrene sheet is required for higher energies. The measurements were carried out over a two-year period. The results showed a good reproducibility with the use of the same CR plate and cassette, and without the requirement of calibration procedures. The two-year range of the EC(50) was within the 99% confidence intervals, and the standard deviation of the EC(50) was measured to be from 0.3 to 0.4 mm for different beam energies. This technique provides an efficient and accurate method to perform the electron beam energy check and could be used by centers equipped with the CR system without requiring additional detection devices.

Acoustic-based proton range verification in heterogeneous tissue: simulation studies.

Acoustic-based proton range verification (protoacoustics) is a potential in vivo technique for determining the Bragg peak position. Previous measurements and simulations have been restricted to homogeneous water tanks. Here, a CT-based simulation method is proposed and applied to a liver and prostate case to model the effects of tissue heterogeneity on the protoacoustic amplitude and time-of-flight range verification accuracy. For the liver case, posterior irradiation with a single proton pencil beam was simulated for detectors placed on the skin. In the prostate case, a transrectal probe measured the protoacoustic pressure generated by irradiation with five separate anterior proton beams. After calculating the proton beam dose deposition, each CT voxel's material properties were mapped based on Hounsfield Unit values, and thermoacoustically-generated acoustic wave propagation was simulated with the k-Wave MATLAB toolbox. By comparing the simulation results for the original liver CT to homogenized variants, the effects of heterogeneity were assessed. For the liver case, 1.4 cGy of dose at the Bragg peak generated 50 mPa of pressure (13 cm distal), a 2× lower amplitude than simulated in a homogeneous water tank. Protoacoustic triangulation of the Bragg peak based on multiple detector measurements resulted in 0.4 mm accuracy for a δ-function proton pulse irradiation of the liver. For the prostate case, higher amplitudes are simulated (92-1004 mPa) for closer detectors (<8 cm). For four of the prostate beams, the protoacoustic range triangulation was accurate to ⩽1.6 mm (δ-function proton pulse). Based on the results, application of protoacoustic range verification to heterogeneous tissue will result in decreased signal amplitudes relative to homogeneous water tank measurements, but accurate range verification is still expected to be possible.

Compton scatter imaging: A promising modality for image guidance in lung stereotactic body radiation therapy.

PURPOSE: Lung stereotactic body radiation therapy (SBRT) requires delivering large radiation doses with millimeter accuracy, making image guidance essential. An approach to forming images of patient anatomy from Compton-scattered photons during lung SBRT is presented. METHODS: To investigate the potential of scatter imaging, a pinhole collimator and flat-panel detector are used for spatial localization and detection of photons scattered during external beam therapy using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software is used to develop a model to simulate scatter images. This model is validated by comparing experimental and simulated phantom images. Patient scatter images are then simulated from 4DCT data. RESULTS: Experimental lung tumor phantom images have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU (0.5 s temporal resolution). The relative signal intensity from objects of different composition as well as lung tumor contrast for simulated phantom images agree quantitatively with experimental images, thus validating the Monte Carlo model. Scatter images are shown to display high contrast between different materials (lung, water, bone). Simulated patient images show superior (~double) tumor contrast compared to MV transmission images. CONCLUSIONS: Compton scatter imaging is a promising modality for directly imaging patient anatomy during treatment without additional radiation, and it has the potential to complement existing technologies and aid tumor tracking and lung SBRT image guidance.

Dosimetric effects of saline- versus water-filled balloon applicators for IORT using the model S700 electronic brachytherapy source.

PURPOSE: The Xoft Axxent Electronic Brachytherapy System (Xoft, Inc., San Jose, CA) is a viable option for intraoperative radiation therapy (IORT) treatment of early-stage breast cancer. The low-energy (50-kVp) X-ray source simplifies shielding and increases relative biological effectiveness but increases dose distribution sensitivity to medium composition. Treatment planning systems typically assume homogenous water for brachytherapy dose calculations, including precalculated atlas plans for Xoft IORT. However, Xoft recommends saline for balloon applicator filling. This study investigates dosimetric differences due to increased effective atomic number (Zeff) for saline (Zeff = 7.56) versus water (Zeff = 7.42). METHODS: Balloon applicator diameters range from 3 to 6 cm. Monte Carlo N-Particle software is used to calculate dose at the surface (Ds) of and 1 cm away (D1cm) from the water-/saline-filled balloon applicator using a single dwell at the applicator center as a simple estimation of the dosimetry and multiple dwells simulating the clinical dose distributions for the atlas plans. RESULTS: Single-dwell plans show a 4.4-6.1% decrease in Ds for the 3- to 6-cm diameter applicators due to the saline. Multidwell plans show similar results: 4.9% and 6.4% Ds decrease, for 4-cm and 6-cm diameter applicators, respectively. For the single-dwell plans, D1cm decreases 3.6-5.2% for the 3- to 6-cm diameter applicators. For the multidwell plans, D1cm decreases 3.3% and 5.3% for the 4-cm and 6-cm applicators, respectively. CONCLUSIONS: The dosimetric effect introduced by saline versus water filling for Xoft balloon applicator-based IORT treatments is ∼5%. Users should be aware of this in the context of both treatment planning and patient outcome studies.

Characterization of Compton-scatter imaging with an analytical simulation method.

By collimating the photons scattered when a megavoltage therapy beam interacts with the patient, a Compton-scatter image may be formed without the delivery of an extra dose. To characterize and assess the potential of the technique, an analytical model for simulating scatter images was developed and validated against Monte Carlo (MC). For three phantoms, the scatter images collected during irradiation with a 6 MV flattening-filter-free therapy beam were simulated. Images, profiles, and spectra were compared for different phantoms and different irradiation angles. The proposed analytical method simulates accurate scatter images up to 1000 times faster than MC. Minor differences between MC and analytical simulated images are attributed to limitations in the isotropic superposition/convolution algorithm used to analytically model multiple-order scattering. For a detector placed at 90° relative to the treatment beam, the simulated scattered photon energy spectrum peaks at 140-220 keV, and 40-50% of the photons are the result of multiple scattering. The high energy photons originate at the beam entrance. Increasing the angle between source and detector increases the average energy of the collected photons and decreases the relative contribution of multiple scattered photons. Multiple scattered photons cause blurring in the image. For an ideal 5 mm diameter pinhole collimator placed 18.5 cm from the isocenter, 10 cGy of deposited dose (2 Hz imaging rate for 1200 MU min-1 treatment delivery) is expected to generate an average 1000 photons per mm2 at the detector. For the considered lung tumor CT phantom, the contrast is high enough to clearly identify the lung tumor in the scatter image. Increasing the treatment beam size perpendicular to the detector plane decreases the contrast, although the scatter subject contrast is expected to be greater than the megavoltage transmission image contrast. With the analytical method, real-time tumor tracking may be possible through comparison of simulated and acquired patient images.

Truebeam Radiosurgery for the Treatment of Trigeminal Neuralgia: Preliminary Results at a Single Institution.

INTRODUCTION: Radiosurgery is now an established method of satisfactory pain control in patients with trigeminal neuralgia (TN). The Varian Truebeam STx (Varian Medical Systems, Palo Alto, CA) linear accelerator (LINAC) system is an arc-based, frameless stereotactic radiosurgery system used for the treatment of TN. To our knowledge, there has been only one published series of patient histories that documents the use of a frameless LINAC system for the treatment of TN. We describe the treatment parameters, patient outcomes, and complications associated with the treatment of TN. METHODS: All patients treated with the Truebeam system for TN between 2012 and 2015, with at least a six-month follow-up, were identified. A dose of 90 Gy was delivered to the isocenter using a 0.5 cm diameter cone. The cisternal segment of the trigeminal nerve was placed at the location of the LINAC isocenter using an ExacTrac™ (Brainlab, Munich, Germany) image guidance system. The radiosurgical dose, Barrow Neurologic Institute pain score (BNI PS), symptom recurrence, magnetic resonance imaging (MRI) radiographic changes, and other complications, including Barrow Neurologic Institute facial numbness score (BNI FN), were analyzed. RESULTS: A total of 18 patients-15 women and 3 men-with a mean age of 58 years (median: 59 years; range: 22-84 years) were treated at our institution. Fourteen patients (78%) had a BNI PS of IIIb or better, which was considered successful treatment. Twelve patients had excellent (BNI PS I) pain relief and two patients had good (BNI PS II-IIIB; recurrence after one year) pain relief. The pain of four patients recurred after a mean of 10 months. CONCLUSION: Truebeam radiosurgery can provide effective and safe treatment for patients suffering from TN. The efficacy appears similar to other frame- and frameless-based systems.

Mesenchymal stem cells enhance xenochimerism in NK-depleted hosts.

BACKGROUND: Xenogeneic hematopoietic engraftment holds promise as a strategy to achieve whole organ xenograft tolerance. We tested whether xenogeneic bone marrow grafts, engineered with mesenchymal stem cells (MSCs), might provide a new nontoxic approach to enhance xenogeneic engraftment. METHODS: ACI rat MSCs, cultured from whole bone marrow, were identified as CD29+ CD44+OX-18+, CD45-HIS36- and could differentiate into adipogenic and osteogenic tissue. Lethally irradiated B6 mice received ACI whole bone marrow either alone or in combination with ACI MSC. Xenogeneic engraftment was measured in murine peripheral blood on days 7, 50, and 100. Natural killer (NK)-cell-depleted murine recipients treated with or without MSC underwent rat skin graft transplants on the day of the bone marrow infusion. RESULTS: In NK-depleted hosts, control animals failed to survive 60 days; 40% MSC-treated hosts survived >100 days, P < 0 .05. Rat hematopoietic engraftment exceeded 89% on days 7 and 54 and decreased to <25% by day 100. No graft-versus-host disease was observed in MSC-treated animals, P < 0.05. Skin graft survival was prolonged in the MSC-treated group, (21 +/- 1.7 days, P = 0.2). CONCLUSIONS: Our findings present a new approach in engineering xenografts and provide an encouraging platform for additional studies.

Reporting small bowel dose in cervix cancer high-dose-rate brachytherapy.

Small bowel (SB) is an organ at risk (OAR) that may potentially develop toxicity after radiotherapy for cervix cancer. However, its dose from brachytherapy (BT) is not systematically reported as in other OARs, even with image-guided brachytherapy (IGBT). This study aims to introduce consideration of quantified objectives for SB in BT plan optimization and to evaluate the feasibility of sparing SB while maintaining adequate target coverage. In all, 13 patients were included in this retrospective study. All patients were treated with external beam radiotherapy (EBRT) 45Gy in 25 fractions followed by high dose rate (HDR)-BT boost of 28Gy in 4 fractions using tandem/ring applicator. Magnetic resonance imaging (MRI) and computed tomographic (CT) images were obtained to define the gross tumor volume (GTV), high-risk clinical target volume (HR-CTV) and OARs (rectum, bladder, sigmoid colon, and SB). Treatment plans were generated for each patient using GEC-ESTRO recommendations based on the first CT/MRI. Treatment plans were revised to reduce SB dose when the [Formula: see text] dose to SB was > 5Gy, while maintaining other OAR constraints. For the 7 patients with 2 sets of CT and MRI studies, the interfraction variation of the most exposed SB was analyzed. Plan revisions were done in 6 of 13 cases owing to high [Formula: see text] of SB. An average reduction of 19% in [Formula: see text] was achieved. Meeting SB and other OAR constraints resulted in less than optimal target coverage in 2 patients (D90 of HR-CTV < 77Gyαß10). The highest interfraction variation was observed for SB at 16 ± 59%, as opposed to 28 ± 27% for rectum and 21 ± 16% for bladder. Prospective reporting of SB dose could provide data required to establish a potential correlation with radiation-induced late complication for SB.

Studies of the route of administration and role of conditioning with radiation on unrelated allogeneic mismatched mesenchymal stem cell engraftment in a nonhuman primate model.

OBJECTIVE: The aim of this study was to examine the effects of the route of administration [intrabone marrow (IBM) vs intravenous (IV)] and the role of conditioning with irradiation in optimizing mesenchymal stem cell (MSC) transplantation. MATERIALS AND METHODS: To determine if irradiation resulted in depletion of colony-forming unit fibroblasts (CFU-F), which might favor the engraftment of donor MSC, the number of CFU-Fs was assayed from animals receiving either hemibody irradiation (HBI) or total body irradiation (TBI). RESULTS: TBI resulted in a marked reduction of CFU-F numbers that spontaneously resolved, whereas animals receiving HBI did not experience depletion of CFU-F. Animals receiving MSC grafts by the IV route had higher numbers of marrow CFU-F. MSC were transduced using retroviral vectors encoding the neomycin resistance gene (Neo(R)) and a second gene encoding either the human soluble tumor necrosis factor receptor (hsTNFRII) or beta-galactosidase (beta-Gal). MSCs were administered by either the IV or IBM route to animals receiving HBI. The Neo(R) transgene was detectable in hematopoietic tissues of all animals and nonhematopoietic tissues in a single animal. Evidence of transgene expression was documented by detection of beta-Gal(+) cells in BM smears and transiently elevated serum levels of hsTNFRII. CONCLUSION: These studies indicate that 1) MSC possess the ability to engraft and persist in an unrelated mismatched allogeneic hosts; 2) 250-cGy HBI did not favor engraftment of MSC; 3) the IBM route was not more effective than the IV route in delivering MSC grafts; and 4) transplanted MSC preferentially localized to the marrow rather than nonhematopoietic tissues.