A generalized model for monitor units determination in ocular proton therapy using machine learning: A proof-of-concept study.

Objective.Determining and verifying the number of monitor units is crucial to achieving the desired dose distribution in radiotherapy and maintaining treatment efficacy. However, current commercial treatment planning system(s) dedicated to ocular passive eyelines in proton therapy do not provide the number of monitor units for patient-specific plan delivery. Performing specific pre-treatment field measurements, which is time and resource consuming, is usually gold-standard practice. This proof-of-concept study reports on the development of a multi-institutional-based generalized model for monitor units determination in proton therapy for eye melanoma treatments.Approach.To cope with the small number of patients being treated in proton centers, three European institutes participated in this study. Measurements data were collected to address output factor differences across the institutes, especially as function of field size, spread-out Bragg peak modulation width, residual range, and air gap. A generic model for monitor units prediction using a large number of 3748 patients and broad diversity in tumor patterns, was evaluated using six popular machine learning algorithms: (i) decision tree; (ii) random forest, (iii) extra trees, (iv) K-nearest neighbors, (v) gradient boosting, and (vi) the support vector regression. Features used as inputs into each machine learning pipeline were: Spread-out Bragg peak width, range, air gap, fraction and calibration doses. Performance measure was scored using the mean absolute error, which was the difference between predicted and real monitor units, as collected from institutional gold-standard methods.Main results.Predictions across algorithms were accurate within 3% uncertainty for up to 85.2% of the plans and within 10% uncertainty for up to 98.6% of the plans with the extra trees algorithm.Significance.A proof-of-concept of using machine learning-based generic monitor units determination in ocular proton therapy has been demonstrated. This could trigger the development of an independent monitor units calculation tool for clinical use.

Alanine/EPR dosimetry for mailed intercomparison at ocular proton therapy facilities-preliminary results for three centres for irradaitions at CCB IFJ PAN eyeline.

Quality control of therapeutic photon beams in the form of postal dose audits based on passive dosemeters is widely used in photon radiotherapy. On the other hand, no standardised dosimetry audit programme for proton centres has been established in Europe so far. We evaluated alanine/EPR dosimetry systems developed at the Istituto Superiore di Sanità (Italy), the Hasselt Universiteit (Belgium) and the Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences (Poland) for their applicability as a potential tool for routine mailed dose audits of passively scattered therapeutic proton beams. The evaluation was carried out in the form of an intercomparison. Dosemeters were irradiated in the 70 MeV proton beam at ocular proton therapy facility in the Cyclotron Centre Bronowice at the Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences in Krakow. A very good agreement was found between the dose measured by three laboratories and the delivered dose determined with an ionisation chamber. This, together with the inherent properties of alanine, such as non-destructive readout, tissue equivalence, weak energy dependence, dose rate independence and insignificant fading, makes alanine a good candidate for a dosemeter used in postal auditing in proton ocular radiotherapy.

Microdosimetric characterization of a clinical proton therapy beam: comparison between simulated lineal energy distributions in spherical water targets and experimental measurements with a silicon detector.

Objective. Treatment planning based on computer simulations wasproposed to account for the increased relative biological effectiveness (RBE) of proton radiotherapy beams near to the edges of the irradiated volume. Since silicon detectors could be used to validate the results of these simulations, it is important to explore the limitations of this comparison.Approach. Microdosimetric measurements with a MicroPlus Bridge V2 silicon detector (thickness = 10µm) were performed along the Bragg peak of a clinical proton beam. The lineal energy distributions, the dose-mean values, and the RBE calculated with a biological weighting function were compared with PHITS simulations (microdosimetric target = 1µm water sphere), and published clonogenic survivalin vitroRBE data for the V79 cell line. The effect of the silicon-to-water conversion was also investigated by comparing three different methodologies (conversion based on a single value, novel bin-to-bin conversions based on SRIM and PSTAR).Main results. Mainly due to differences in the microdosimetric targets, the experimental dose-mean lineal energy and RBE values at the distal edge were respectively up to 53% and 28% lower than the simulated ones. Furthermore, the methodology chosen for the silicon-to-water conversion was proven to affect the dose-mean lineal energy and the RBE10up to 32% and 11% respectively. The best methodology to compensate for this underestimation was the bin-to-bin silicon-to-water conversion based on PSTAR.Significance. This work represents the first comparison between PHITS-simulated lineal energy distributions in water targets and corresponding experimental spectra measured with silicon detectors. Furthermore, the effect of the silicon-to-water conversion on the RBE was explored for the first time. The proposed methodology based on the PSTAR bin-to-bin conversion appears to provide superior results with respect to commonly used single scaling factors and is recommended for future studies.

3D Dosimetry Based on LiMgPO4 OSL Silicone Foils: Facilitating the Verification of Eye-Ball Cancer Proton Radiotherapy.

A direct verification of the three-dimensional (3D) proton clinical treatment plan prepared for tumor in the eyeball, using the Eclipse Ocular Proton Planning system (by Varian Medical Systems), has been presented. To achieve this, a prototype of the innovative two-dimensional (2D) circular silicone foils, made of a polymer with the embedded optically stimulated luminescence (OSL) material in powder form (LiMgPO4), and a self-developed optical imaging system, consisting of an illuminating light source and a high-sensitive CCD camera has been applied. A specially designed lifelike eyeball phantom has been used, constructed from 40 flat sheet LMP-based silicone foils stacked and placed together behind a spherical phantom made by polystyrene, all to reflect the curvature of the real eyeball. Two-dimensional OSL signals were captured and further analyzed from each single silicone foil after irradiation using a dedicated patient collimator and a 58.8 MeV modulated proton beam. The reconstructed 3D proton depth dose distribution matches very well with the clinical treatment plan, allowing for the consideration of the new OSL system for further 3D dosimetry applications within the proton radiotherapy area.

Characterization of the HollandPTC proton therapy beamline dedicated to uveal melanoma treatment and an interinstitutional comparison.

PURPOSE: Eye-dedicated proton therapy (PT) facilities are used to treat malignant intraocular lesions, especially uveal melanoma (UM). The first commercial ocular PT beamline from Varian was installed in the Netherlands. In this work, the conceptual design of the new eyeline is presented. In addition, a comprehensive comparison against five PT centers with dedicated ocular beamlines is performed, and the clinical impact of the identified differences is analyzed. MATERIAL/METHODS: The HollandPTC eyeline was characterized. Four centers in Europe and one in the United States joined the study. All centers use a cyclotron for proton beam generation and an eye-dedicated nozzle. Differences among the chosen ocular beamlines were in the design of the nozzle, nominal energy, and energy spectrum. The following parameters were collected for all centers: technical characteristics and a set of distal, proximal, and lateral region measurements. The measurements were performed with detectors available in-house at each institution. The institutions followed the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice for absolute dose measurement, and the IAEA TRS-398 Code of Practice, its modified version or International Commission on Radiation Units and Measurements Report No. 78 for spread-out Bragg peak normalization. Energy spreads of the pristine Bragg peaks were obtained with Monte Carlo simulations using Geant4. Seven tumor-specific case scenarios were simulated to evaluate the clinical impact among centers: small, medium, and large UM, located either anteriorly, at the equator, or posteriorly within the eye. Differences in the depth dose distributions were calculated. RESULTS: A pristine Bragg peak of HollandPTC eyeline corresponded to the constant energy of 75 MeV (maximal range 3.97 g/cm2 in water) with an energy spread of 1.10 MeV. The pristine Bragg peaks for the five participating centers varied from 62.50 to 104.50 MeV with an energy spread variation between 0.10 and 0.70 MeV. Differences in the average distal fall-offs and lateral penumbrae (LPs) (over the complete set of clinically available beam modulations) among all centers were up to 0.25 g/cm2 , and 0.80 mm, respectively. Average distal fall-offs of the HollandPTC eyeline were 0.20 g/cm2 , and LPs were between 1.50 and 2.15 mm from proximal to distal regions, respectively. Treatment time, around 60 s, was comparable among all centers. The virtual source-to-axis distance of 120 cm at HollandPTC was shorter than for the five participating centers (range: 165-350 cm). Simulated depth dose distributions demonstrated the impact of the different beamline characteristics among institutions. The largest difference was observed for a small UM located at the posterior pole, where a proximal dose between two extreme centers was up to 20%. CONCLUSIONS: HollandPTC eyeline specifications are in accordance with five other ocular PT beamlines. Similar clinical concepts can be applied to expect the same high local tumor control. Dosimetrical properties among the six institutions induce most likely differences in ocular radiation-related toxicities. This interinstitutional comparison could support further research on ocular post-PT complications. Finally, the findings reported in this study could be used to define dosimetrical guidelines for ocular PT to unify the concepts among institutions.

Modeling the radiation-induced cell death in a therapeutic proton beam using thermoluminescent detectors and radiation transport simulations.

Changes in the relative biological effectiveness (RBE) of the radiation-induced cell killing of human salivary glands (HSG) were assessed along the Bragg peak of a 60 MeV clinical proton beam by means of coupling biophysical models with the results of Monte Carlo radiation transport simulations and experimental measurements with luminescent detectors. The fluence- and dose-mean unrestricted proton LET were determined along the Bragg peak using a recently developed methodology based on the combination of the response of 7LiF:Mg,Ti (MTS-7) and 7LiF:Mg,Cu,P (MCP-7) thermoluminescent detectors. The experimentally assessed LET values were compared with the results of radiation transport simulations using the Monte Carlo code PHITS, showing a good agreement. The cell survival probabilities and RBE were then calculated using the linear-quadratic model with the linear term derived using a phenomenological LET-based model (Carabe A et al 2012 Phys. Med. Biol. 57 1159) in combination with the experimentally-assessed or PHITS-simulated dose mean proton LET values. To the same aim, PHITS simulated microdosimetric spectra were used as input to the modified microdosimetric kinetic model (modified MKM, (Kase et al 2006 Radiat. Res. 166 629-38)). The RBE values calculated with the three aforementioned approaches were compared and found to be in very good agreement between each other, proving that by using dedicated pairs of thermoluminescent detectors it is possible to determine ionization density quantities of therapeutic proton beams which can be applied to predict the local value of the RBE.

Practice Patterns Analysis of Ocular Proton Therapy Centers: The International OPTIC Survey.

PURPOSE: To assess the planning, treatment, and follow-up strategies worldwide in dedicated proton therapy ocular programs. METHODS AND MATERIALS: Ten centers from 7 countries completed a questionnaire survey with 109 queries on the eye treatment planning system (TPS), hardware/software equipment, image acquisition/registration, patient positioning, eye surveillance, beam delivery, quality assurance (QA), clinical management, and workflow. RESULTS: Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014. Most centers treated a vast number of ocular patients (1729 to 6369). Three centers treated fewer than 200 ocular patients. Most commonly, the centers treated uveal melanoma (UM) and other primary ocular malignancies, benign ocular tumors, conjunctival lesions, choroidal metastases, and retinoblastomas. The UM dose fractionation was generally within a standard range, whereas dosing for other ocular conditions was not standardized. The majority (80%) of centers used in common a specific ocular TPS. Variability existed in imaging registration, with magnetic resonance imaging (MRI) rarely being used in routine planning (20%). Increased patient to full-time equivalent ratios were observed by higher accruing centers (P=.0161). Generally, ophthalmologists followed up the post-radiation therapy patients, though in 40% of centers radiation oncologists also followed up the patients. Seven centers had a prospective outcomes database. All centers used a cyclotron to accelerate protons with dedicated horizontal beam lines only. QA checks (range, modulation) varied substantially across centers. CONCLUSIONS: The first worldwide multi-institutional ophthalmic proton therapy survey of the clinical and technical approach shows areas of substantial overlap and areas of progress needed to achieve sustainable and systematic management. Future international efforts include research and development for imaging and planning software upgrades, increased use of MRI, development of clinical protocols, systematic patient-centered data acquisition, and publishing guidelines on QA, staffing, treatment, and follow-up parameters by dedicated ocular programs to ensure the highest level of care for ocular patients.

NUNDO: a numerical model of a human torso phantom and its application to effective dose equivalent calculations for astronauts at the ISS.

The health effects of cosmic radiation on astronauts need to be precisely quantified and controlled. This task is important not only in perspective of the increasing human presence at the International Space Station (ISS), but also for the preparation of safe human missions beyond low earth orbit. From a radiation protection point of view, the baseline quantity for radiation risk assessment in space is the effective dose equivalent. The present work reports the first successful attempt of the experimental determination of the effective dose equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular activity (IVA). This was achieved using the anthropomorphic torso phantom RANDO(®) equipped with more than 6,000 passive thermoluminescent detectors and plastic nuclear track detectors, which have been exposed to cosmic radiation inside the European Space Agency MATROSHKA facility both outside and inside the ISS. In order to calculate the effective dose equivalent, a numerical model of the RANDO(®) phantom, based on computer tomography scans of the actual phantom, was developed. It was found that the effective dose equivalent rate during an EVA approaches 700 µSv/d, while during an IVA about 20 % lower values were observed. It is shown that the individual dose based on a personal dosimeter reading for an astronaut during IVA results in an overestimate of the effective dose equivalent of about 15 %, whereas under an EVA conditions the overestimate is more than 200 %. A personal dosemeter can therefore deliver quite good exposure records during IVA, but may overestimate the effective dose equivalent received during an EVA considerably.

Spatial distributions of residuals produced inside a spallation target.

The spallation target model of an accelerator driven system (ADS), consisting of six 5 cm thick and 16 cm in diameter Pb segments, was constructed. Three sets of 17 Bi samples (1/2 inch in diameter and 1 mm thick) were placed in 3 Pb disc-shaped holders inside the target at 5, 10 and 15 cm from its front. After irradiation with 660 MeV proton beam gamma-spectra of radioisotopes produced in Bi were collected several times for each sample with the use of HPGe detectors in order to identify the radioisotopes and to determine their absolute activities. Their spatial distributions were then compared with respective values obtained in the calculations made with the use of FLUKA and/or MCNPX code. A fair agreement with the experiment has been observed.