Performance assessment of two motion management systems for frameless stereotactic radiosurgery.

BACKGROUND/PURPOSE: Frameless stereotactic radiosurgery (SRS) requires dedicated systems to monitor patient motion in order to avoid inaccurate radiation delivery due to involuntary shifts. The purpose of this study is to assess the accuracy and sensitivity of two distinct motion monitoring systems used for frameless SRS. METHODS: A surface image-guided system known as optical surface monitoring system (OSMS), and a fiducial marker-based system known as high definition motion management (HDMM) as part of the latest Gamma Knife Icon® were compared. A 3D printer-based cranial motion phantom was developed to evaluate the accuracy and sensitivity of these two systems in terms of: (1) the capability to recognize predefined shifts up to 3 cm, and (2) the capability to recognize predefined speeds up to 3 cm/s. The performance of OSMS, in terms of different reference surfaces, was also evaluated. RESULTS: Translational motion could be accurately detected by both systems, with an accuracy of 0.3 mm for displacement up to 1 cm, and 0.5 mm for larger displacements. The reference surface selection had an impact on OSMS performance, with flat surface resulting in less accuracy. HDMM was in general more sensitive when compared with OSMS in capturing the motion, due to its faster frame rate, but a delay in response was observed with faster speeds. Both systems were less sensitive in detection of superior-inferior motion when compared to lateral or vertical displacement directions. CONCLUSION: Translational motion can be accurately and sensitively detected by OSMS and HDMM real-time monitoring systems. However, performance variations were observed along different motion directions, as well as amongst the selection of reference images. Caution is needed when using real-time monitoring systems for frameless SRS treatment.

A machine learning approach to the accurate prediction of monitor units for a compact proton machine.

PURPOSE: Clinical treatment planning systems for proton therapy currently do not calculate monitor units (MUs) in passive scatter proton therapy due to the complexity of the beam delivery systems. Physical phantom measurements are commonly employed to determine the field-specific output factors (OFs) but are often subject to limited machine time, measurement uncertainties and intensive labor. In this study, a machine learning-based approach was developed to predict output (cGy/MU) and derive MUs, incorporating the dependencies on gantry angle and field size for a single-room proton therapy system. The goal of this study was to develop a secondary check tool for OF measurements and eventually eliminate patient-specific OF measurements. METHOD: The OFs of 1754 fields previously measured in a water phantom with calibrated ionization chambers and electrometers for patient-specific fields with various range and modulation width combinations for 23 options were included in this study. The training data sets for machine learning models in three different methods (Random Forest, XGBoost and Cubist) included 1431 (~81%) OFs. Ten-fold cross-validation was used to prevent "overfitting" and to validate each model. The remaining 323 (~19%) OFs were used to test the trained models. The difference between the measured and predicted values from machine learning models was analyzed. Model prediction accuracy was also compared with that of the semi-empirical model developed by Kooy (Phys. Med. Biol. 50, 2005). Additionally, gantry angle dependence of OFs was measured for three groups of options categorized on the selection of the second scatters. Field size dependence of OFs was investigated for the measurements with and without patient-specific apertures. RESULTS: All three machine learning methods showed higher accuracy than the semi-empirical model which shows considerably large discrepancy of up to 7.7% for the treatment fields with full range and full modulation width. The Cubist-based solution outperformed all other models (P < 0.001) with the mean absolute discrepancy of 0.62% and maximum discrepancy of 3.17% between the measured and predicted OFs. The OFs showed a small dependence on gantry angle for small and deep options while they were constant for large options. The OF decreased by 3%-4% as the field radius was reduced to 2.5 cm. CONCLUSION: Machine learning methods can be used to predict OF for double-scatter proton machines with greater prediction accuracy than the most popular semi-empirical prediction model. By incorporating the gantry angle dependence and field size dependence, the machine learning-based methods can be used for a sanity check of OF measurements and bears the potential to eliminate the time-consuming patient-specific OF measurements.

Commissioning and initial experience with the first clinical gantry-mounted proton therapy system.

The purpose of this study is to describe the comprehensive commissioning process and initial clinical experience of the Mevion S250 proton therapy system, a gantry-mounted, single-room proton therapy platform clinically implemented in the S. Lee Kling Proton Therapy Center at Barnes-Jewish Hospital in St. Louis, MO, USA. The Mevion S250 system integrates a compact synchrocyclotron with a C-inner gantry, an image guidance system and a 6D robotic couch into a beam delivery platform. We present our commissioning process and initial clinical experience, including i) CT calibration; ii) beam data acquisition and machine characteristics; iii) dosimetric commissioning of the treatment planning system; iv) validation through the Imaging and Radiation Oncology Core credentialing process, including irradiations on the spine, prostate, brain, and lung phantoms; v) evaluation of localization accuracy of the image guidance system; and vi) initial clinical experience. Clinically, the system operates well and has provided an excellent platform for the treatment of diseases with protons.

Measured Neutron Spectra and Dose Equivalents From a Mevion Single-Room, Passively Scattered Proton System Used for Craniospinal Irradiation.

PURPOSE: To measure, in the setting of typical passively scattered proton craniospinal irradiation (CSI) treatment, the secondary neutron spectra, and use these spectra to calculate dose equivalents for both internal and external neutrons delivered via a Mevion single-room compact proton system. METHODS AND MATERIALS: Secondary neutron spectra were measured using extended-range Bonner spheres for whole brain, upper spine, and lower spine proton fields. The detector used can discriminate neutrons over the entire range of the energy spectrum encountered in proton therapy. To separately assess internally and externally generated neutrons, each of the fields was delivered with and without a phantom. Average neutron energy, total neutron fluence, and ambient dose equivalent [H* (10)] were calculated for each spectrum. Neutron dose equivalents as a function of depth were estimated by applying published neutron depth-dose data to in-air H* (10) values. RESULTS: For CSI fields, neutron spectra were similar, with a high-energy direct neutron peak, an evaporation peak, a thermal peak, and an intermediate continuum between the evaporation and thermal peaks. Neutrons in the evaporation peak made the largest contribution to dose equivalent. Internal neutrons had a very low to negligible contribution to dose equivalent compared with external neutrons, largely attributed to the measurement location being far outside the primary proton beam. Average energies ranged from 8.6 to 14.5 MeV, whereas fluences ranged from 6.91 × 10(6) to 1.04 × 10(7) n/cm(2)/Gy, and H* (10) ranged from 2.27 to 3.92 mSv/Gy. CONCLUSIONS: For CSI treatments delivered with a Mevion single-gantry proton therapy system, we found measured neutron dose was consistent with dose equivalents reported for CSI with other proton beamlines.

Use of diverging apertures to minimize the edge scatter in passive scattering proton therapy.

The purpose of this study was to evaluate the use of diverging-cut aperture to minimize collimator contamination in proton therapy. Two sets of apertures with nondivergent and divergent edge were fabricated to produce a 10 cm × 10 cm field at the radiation isocenter of a single-room proton therapy unit. Transverse profiles were acquired in a scanning water tank with both aperture sets. Up to 9.5% extra dose was observed from aperture scattering near the field edges with the nondivergent aperture set at 2 cm above the water surface and remained 3.0% at depth of 10 cm. For the divergent set, the contamination was reduced to less than 3.5% and 1.3%, respectively. Our study demonstrated that scattering from apertures contaminated the dose distribution near the field edge at shallow depth. A diverging-cut aperture was capable of reducing the contamination and is recommended for use in passive scattering proton therapy, especially when critical organs are lateral and proximal to the target at shallow depth.

The impact of CT scan energy on range calculation in proton therapy planning.

The purpose of this study was to investigate the impact of tube potential (kVp) on the CT number (HU) to proton stopping power ratio (PSPR) conversion. The range and dosimetric change introduced by a mismatch in kVp used for the CT scan and the HU to PSPR table, based on a specific kVp, used to calculate dose are analyzed. Three HU to PSPR curves, corresponding to three kVp settings on the CT scanner, were created. A treatment plan was created for a single beam in a water phantom passing through a wedge-shaped bone heterogeneity. The dose was recalculated by changing only the HU to PSPR table used in the dose calculation. The change in the position of the distal 90% isodose line was recorded as a function of heterogeneity thickness along the beam path. The dosimetric impact of a mismatch in kVp between the CT and the HU to PSPR table was investigated by repeating this procedure for five clinical plans comparing DVH data and dose difference distributions. The HU to PSPR tables diverge for CT numbers greater than 200 HU. In the phantom plan, the divergence of the tables resulted in a difference in range of 1.6 mm per cm of bone in the beam path, for the HU used. For the clinical plans, the dosimetric effect of a kVp mismatch depends on the amount of bone in the beam path and the proximity of OARs to the distal range of the planned beams. A mismatch in kVp between the CT and the HU to PSPR table can introduce inaccuracy in the proton beam range. For dense bone, the measured range difference was approximately 1.6 mm per cm of bone along the beam path. However, the clinical cases analyzed showed a range change of 1 mm or less. Caution is merited when such a mismatch may occur.

Molecular detection and species-specific identification of medically important Aspergillus species by real-time PCR in experimental invasive pulmonary aspergillosis.

Diagnosis of invasive pulmonary aspergillosis (IPA) remains a major challenge to clinical microbiology laboratories. We developed rapid and sensitive quantitative PCR (qPCR) assays for genus- and species-specific identification of Aspergillus infections by use of TaqMan technology. In order to validate these assays and understand their potential diagnostic utility, we then performed a blinded study of bronchoalveolar lavage (BAL) fluid specimens from well-characterized models of IPA with the four medically important species. A set of real-time qPCR primers and probes was developed by utilizing unique ITS1 regions for genus- and species-specific detection of the four most common medically important Aspergillus species (Aspergillus fumigatus, A. flavus, A. niger, and A. terreus). Pan-Aspergillus and species-specific qPCRs with BAL fluid were more sensitive than culture for detection of IPA caused by A. fumigatus in untreated (P < 0.0007) and treated (P ≤ 0.008) animals, respectively. For infections caused by A. terreus and A. niger, culture and PCR amplification from BAL fluid yielded similar sensitivities for untreated and treated animals. Pan-Aspergillus PCR was more sensitive than culture for detection of A. flavus in treated animals (P = 0.002). BAL fluid pan-Aspergillus and species-specific PCRs were comparable in sensitivity to BAL fluid galactomannan (GM) assay. The copy numbers from the qPCR assays correlated with quantitative cultures to determine the pulmonary residual fungal burdens in lung tissue. Pan-Aspergillus and species-specific qPCR assays may improve the rapid and accurate identification of IPA in immunocompromised patients.

Comparison of an Aspergillus real-time polymerase chain reaction assay with galactomannan testing of bronchoalvelolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in lung transplant recipients.

BACKGROUND: Early diagnosis and treatment of invasive pulmonary aspergillosis (IPA) improves outcome. METHODS: We compared the performance of publicly available pan-Aspergillus, Aspergillus fumigatus-, and Aspergillus terreus-specific real-time polymerase chain reaction (PCR) assays with the Platelia galactomannan (GM) assay in 150 bronchoalveolar lavage (BAL) samples from lung transplant recipients (16 proven/probable IPA, 26 Aspergillus colonization, 11 non-Aspergillus mold colonization, and 97 negative controls). RESULTS: The sensitivity and specificity of pan-Aspergillus PCR (optimal quantification cycle [Cq], ≤35.0 by receiver operating characteristic analysis) and GM (≥.5) for diagnosing IPA were 100% (95% confidence interval, 79%-100%) and 88% (79%-92%), and 93% (68%-100%) and 89% (82%-93%), respectively. The sensitivity and specificity of A. fumigatus-specific PCR were 85% (55%-89%) and 96% (91%-98%), respectively. A. terreus-specific PCR was positive for the 1 patient with IPA due to this species; specificity was 99% (148 of 149 samples). Aspergillus PCR identified 1 patient with IPA not diagnosed by GM. For BAL samples associated with Aspergillus colonization, the specificity of GM (92%) was higher than that of pan-Aspergillus PCR (50%; P = .003). Among negative control samples, the specificity of pan-Aspergillus PCR (97%) was higher than that of BAL GM (88%; P = .03). Positive results for both BAL PCR and GM testing improved the specificity to 97% with minimal detriment to sensitivity (93%). CONCLUSIONS: A recently developed pan-Aspergillus PCR assay and GM testing of BAL fluid may facilitate the diagnosis of IPA after lung transplantation. A. fumigatus- and A. terreus-specific real-time PCR assays may be useful in rapidly identifying the most common cause of IPA and a species that is intrinsically resistant to amphotericin B, respectively.