Current and Emerging Radiotherapy Options for Uveal Melanoma.

What treatment options are there for patients having uveal melanoma? A randomized, prospective, multi-institutional clinical trial (COMS) showed no difference in survival between brachytherapy and enucleation for medium-sized lesions. With the obvious benefit of retaining the eye, brachytherapy has flourished and many different approaches have been developed such as low-dose-rate sources using alternate low-energy photon-emitting radionuclides, different plaque designs and seed-loading techniques, high-dose-rate brachytherapy sources and applicators, and low- and high-dose-rate beta-emitting sources and applicators. There also have been developments of other radiation modalities like external-beam radiotherapy using linear accelerators with high-energy photons, particle accelerators for protons, and gamma stereotactic radiosurgery. This article examines the dosimetric properties, targeting capabilities, and outcomes of these approaches. The several modalities examined herein have differing attributes and it may be that no single approach would be considered optimal for all patients and all lesion characteristics.

Monte Carlo investigation of dose distribution of uniformly and non-uniformly loaded standard and notched eye plaques.

To investigate the effect of using non-uniform loading and notched plaques on dose distribution for eye plaques. Using EGSnrc Monte Carlo (MC) simulations, we investigate eye plaque dose distributions in water and in an anatomically representative eye phantom. Simulations were performed in accordance with TG43 formalism and compared against full MC simulations which account for inter-seed and inhomogeneity effects. For standard plaque configurations, uniformly and non-uniformly loaded plaque dose distributions in water showed virtually no difference between each other. For standard plaque, the MC calculated dose distribution in planes parallel to the plaque is narrower than the TG43 calculation due to attenuation at the periphery of the plaque by the modulay. MC calculated the dose behind the plaque is fully attenuated. Similar results were found for the notched plaque, with asymmetric attenuation along the plane of the notch. Cumulative dose volume histograms showed significant reductions in the calculated MC doses for both tumor and eye structures, compared to TG43 calculations. The effect was most pronounced for the notch plaque where the MC dose to the optic nerve was greatly attenuated by the modulay surrounding the optic nerve compared to the TG43. Thus, a reduction of optic nerve D95% from 14 to 0.2 Gy was observed, when comparing the TG43 calculation to the MC result. The tumor D95% reduced from 89.2 to 79.95 Gy for TG43 and MC calculations, respectively. TG43 calculations overestimate the absolute dose and the lateral dose distribution of both standard and notched eye plaques, leading to the dose overestimation for the target and organs at risk. The dose matching along the central axis for the non-uniformly loaded plaques to that of uniformly loaded ones was found to be sufficient for providing comparable coverage and can be clinically used in eye-cancer-busy centers.

MRI-Guided Online Adaptive Stereotactic Body Radiation Therapy of Liver and Pancreas Tumors on an MR-Linac System.

PURPOSE: To describe a comprehensive workflow for MRI-guided online adaptive stereotactic body radiation therapy (SBRT) specific to upper gastrointestinal cancer patients with abdominal compression on a 1.5T MR-Linac system. Additionally, we discuss the workflow's clinical feasibility and early experience in the case of 16 liver and pancreas patients. METHODS: Eleven patients with liver cancer and five patients with pancreas cancer were treated with online adaptive MRI-guidance under abdominal compression. Two liver patients received single-fraction treatments; the remainder plus all pancreas cancer patients received five fractions. A total of 65 treatment sessions were investigated to provide analytics relevant to the online adaptive processes. The quantification of target and organ motion as well as definition and validation of internal target volume (ITV) margins were performed via multi-contrast imaging provided by three different 2D cine sequences. The plan generation was driven by full re-optimization strategies and using T2-weighted 3D image series acquired by means of a respiratory-triggered exhale phase or a time-averaged imaging protocol. As a pre-requisite for the clinical development of the procedure, the image quality was thoroughly investigated via phantom measurements and numerical simulations specific to upper abdominal sites. The delivery of the online adaptive treatments was facilitated by real-time monitoring with 2D cine imaging. RESULTS: Liver 1-fraction and 5-fraction online adaptive session time were on average 80 and 67.5 min, respectively. The total session length varied between 70-90 min for a single fraction and 55-90 min for five fractions. The pancreas sessions were 54-85 min long with an average session time of 68.2 min. Target visualization on the 2D cine image data varied per patient, with at least one of the 2D cine sequences providing sufficient contrast to confidently identify its location and confirm reproducibility of ITV margins. The mean/range of absolute and relative dose values for all treatment sessions evaluated with ArcCheck were 90.6/80.9-96.1% and 99/95.4-100%, respectively. CONCLUSION: MR-guidance is feasible for liver and pancreas tumors when abdominal compression is used to reduce organ motion, improve imaging quality, and achieve a robust intra- and inter-fraction patient setup. However, the treatment length is significantly longer than for the conventional linac, and patient compliance is paramount for the successful completion of the treatment. Opportunities for reducing the online adaptive session time should be explored. As the next steps, dose-of-the-day and dose accumulation analysis and tools are needed to enhance the workflow and to help further refine the online re-planning processes.

Design and evaluation of 3D printable patient-specific applicators for gynecologic HDR brachytherapy.

PURPOSE: The purpose of this study is to improve dose distribution and organ-at-risk sparing during gynecologic HDR brachytherapy with patient-specific applicators. The majority of applicators used today are generic in design and do not allow for dose modulation for patient-specific shaping of dose distributions. Their performance might be adjusted with commercially available wedge shields; however, this provides dose modulation in the orthogonal plane only and does not allow for variation along the length of the applicator. Generic applicators are available only in standard sizes and geometries, and provide suboptimal patient fit with limited dose modulation. METHODS: In this paper we use Monte Carlo modeling for comprehensive characterization of radiologic properties of various 3D printable biocompatible and sterilizable materials with comparison to water. Based on these results, we choose the optimal set of materials for a patient-specific applicator. We develop a novel method to design the patient-specific applicator without incurring a significant increase in treatment time or changes to clinical workflow. Finally, using an example of two selected vaginal cancers, we compare the performance of patient-specific and water-equivalent applicators in terms of target coverage and rectum sparing. RESULTS: In the energy range from 1 MeV to 4 MeV, all materials have similar attenuation coefficients. In the range from ~2 keV to 1 MeV and above 4 MeV, tungsten-polylactic acid composite (WPLA) was seen to have the highest attenuation coefficient. The dose distribution of the water-equivalent applicator was found to be symmetric about its central axis. At the same time patient-specific shielded applicators exhibit well-modulated dose distributions. Their isodose lines are seen to spread radially into the patient, while merging close to the applicator surface, where WPLA shielding has been applied. CONCLUSIONS: The patient-specific cylinders provide comparable dose to the target, while offering advanced healthy tissue sparing, not achievable with the generic design.

A Probe of Valence and Conduction Band Electronic Structure of Lead Oxide Films for Photodetectors.

We investigate how the electronic structure of amorphous lead oxide (a-PbO) films deposited on ITO substrate is changed after annealing at various temperatures. Both experimental soft X-ray spectroscopic and density functional theory (DFT) based computational techniques are used to explore the electronic structure of this material. X-ray emission, resonant X-ray inelastic scattering, and X-ray absorption spectroscopic techniques are employed to directly probe the valence and conduction bands. We discover that the films are very stable and remain amorphous when exposed to temperatures below 300 °C. An amorphous-to-polycrystalline (α-PbO phase) transformation occurs during annealing at 400 °C. At 500 °C, an alpha to beta phase change is observed. These structural modifications are accompanied by the band gap value changing from 1.4±0.2 eV to 2.0±0.2 eV upon annealing at 400 °C and to 2.6±0.2 eV upon annealing at 500 °C. A difference between surface and bulk structural properties is found for all samples annealed at 500 °C and above; these samples also exhibit an unexpected suppression of O : 2p density of states (DOS) near the bottom of the conduction band, whereas additional electronic states appear well within the valence band. This study provides a significant step forward to understanding the electronic properties of two polymorphic forms of PbO needed for optimization of this material for use in X-ray sensors.

Performance optimization of capacitive motion sensing (CMS) system for intra-fraction motion detection during stereotactic radiosurgery.

The purpose of this investigation is to improve intra-fractional motion detection during cranial stereotactic radiosurgery with a novel capacitive motion sensing (CMS) system. Previous work showed that a capacitive detection system, based on a MPR121 capacitance-to-digital converter, provided a number of advantages over existing patient imaging systems used in the clinic, by uniquely offering ionizing-radiation-free and continuous monitoring without modification to the immobilization mask or treatment room. However, in order to provide submillimeter detection accuracy, the MPR121-based CMS system required relatively large sensors in close proximity to the patient. Therefore, the aim of this investigation was to improve sensitivity of the system, allowing reduction in sensor size and preserving its stable operation in the linear accelerator environment. For this, we developed, characterized and compared motion detection capabilities of four CMS systems based on different capacitance-to-digital converters: MPR121, CPT212B, FDC1004 and FDC2214. Among all candidates, the FDC2214-based system was found to uniquely combine accurate 3D motion detection in real time, with stable performance under ionizing radiation. It exhibited an order of magnitude improvement in sensitivity in comparison with the proof-of-study system, allowing a spatial precision as low as 0.3 mm, and its overall performance was found to satisfy the AAPM practice guidelines of positioning tolerance within 1 mm. Furthermore, the high sensitivity of the system allows both reduction of the sensor area and location more distant from the patient surface, which are key improvements with regard to development of a clinical device.