[Safety Analysis Using Event Tree Analysis for Multi-Ion Therapy].

At the National Institutes for Quantum Science and Technology (QST), a multi-ion therapy using helium, carbon, oxygen, and neon ions has been studied for charged particle therapy with more optimal biological effects. To make multi-ion therapy clinically feasible, a new treatment system was developed to realize the changes of the ion species in each irradiation using the Heavy Ion Medial Accelerator in Chiba (HIMAC). Since radiation therapy is safety-critical, it is necessary to construct a safety system that includes multiple safety barriers in the new treatment system for multi-ion therapy and to perform a safety analysis for the prevention of serious accidents. In this study, we conducted a safety analysis using event tree analysis (ETA) for newly introduced processes in the treatment planning, accelerator, and irradiation system of the multi-ion therapy. ETA is an optimal method to verify multiple safety barriers that are essential for medical safety and to shorten the time for safety analysis by focusing only on the new processes. Through ETA, we clarified the types of malfunctions and human errors that may lead to serious accidents in the new system for multi-ion therapy, and verified whether safety barriers such as interlock systems and human check procedures are sufficient to prevent such malfunctions and human errors. As a result, 6 initial events which may lead to serious accidents were listed in the treatment planning process, 16 initial events were listed in the accelerator system, and 13 initial events were listed in the irradiation system. Among these 35 initial events, 5 cautionary initial events were identified that could lead to serious final events and they had a probability of occurrence higher than 10-4. Meanwhile, the others were all initial events that do not lead to serious accidents, or the initial events that can lead to serious accidents but were considered to have sufficient safety barriers. The safety analysis using ETA successfully identified the system malfunctions and the human errors that can lead to serious accidents, and the multiple safety barriers against them were systematically analyzed. It became clear that the multiple safety barriers were not sufficient for some initial events. We plan to improve the safety barriers for the five cautionary initial events before the start of the clinical trial. Based on these findings, we achieved our objective to conduct a safety analysis for a new treatment system for multi-ion therapy. The safety analysis procedure using ETA proposed by this study will be effective when new systems for radiotherapy are established at QST and other facilities in the future as well.

End-to-end dosimetry audit for three-dimensional image-guided brachytherapy for cervical cancer.

BACKGROUND: End-to-end dosimetry audit for brachytherapy is challenging due to the steep dose gradient. However, it is an efficient method to detect unintended errors in actual clinical practice. PURPOSE: We aimed to develop an on-site end-to-end test phantom for three-dimensional image-guided brachytherapy (IGBT) for cervical cancer. METHODS: The test phantom we developed consisted of a water tank with an applicator/detector holder. The holder was designed to accommodate the applicator and insert an ionization chamber (PinPoint; PTW, Freiburg, Germany) to measure the dose at point A. Imaging and reconstruction were performed in the same way as performed for a patient. The feasibility of our test phantom was assessed in two different hospitals using tandem and ovoid (made of either metal or carbon) applicators that the hospitals provided. RESULTS: The measured and calculated doses at point A were compared for each applicator. We observed that the values obtained using metal applicators were consistently lower, on an average by -2.3%, than the calculated values, while those obtained using carbon applicators were comparable to the calculated values. This difference can be attributed to the attenuation of the dose by the metal applicators, resulting in a lower dose at point A. The majority of treatment planning system, including the one used in this study, do not account for the material of applicator. CONCLUSIONS: An end-to-end test phantom for IGBT was developed, tested, and applied in a dosimetry audit in hospitals and showed favorable results for evaluating the point A dose.

Clinical dose assessment for scanned carbon-ion radiotherapy using linear energy transfer measurements and Monte Carlo simulations.

Objective. Dosimetric commissioning of treatment planning systems (TPS) focuses on validating the agreement of the physical dose with experimental data. For carbon-ion radiotherapy, the commissioning of the relative biological effectiveness (RBE) is necessary to predict the clinical outcome based on the radiation quality of the mixed radiation field. In this study, we proposed a approach for RBE commissioning using Monte Carlo (MC) simulations, which was further strengthen by RBE validation based on linear energy transfer (LET) measurements.Approach. First, we tuned the MC simulation based on the results of dosimetric experiments including the beam ranges, beam sizes, and MU calibrations. Furthermore, we compared simulated results to measured depth- and radial-LET distributions of the 430 MeV u-1carbon-ion spot beam with a 1.5 mm2, 36µm thick silicon detector. The measured dose-averaged LET (LETd) and RBE were compared with the simulated results. The RBE was calculated based on the mixed beam model with linear-quadratic parameters depending on the LET. Finally, TPS-calculated clinical dose profiles were validated through the tuned MC-based calculations.Main results. A 10 keVµm-1and 0.15 agreement for LETdand RBE, respectively, were found between simulation and measurement results obtained for a 2σlateral size of 430 MeV u-1carbon-ion spot beam in water. These results suggested that the tuned MC simulation can be used with acceptable precision for the RBE and LET calculations of carbon-ion spot beam within the clinical energy range. For physical and clinical doses, the TPS- and MC-based calculations showed good agreements within 1.0% at the centre of the spread-out Bragg peaks.Significance. The tuned MC simulation can accurately reproduce the actual carbon-ion beams, and it can be used to validate the physical and clinical dose distributions calculated by TPS. Moreover, the MC simulation can be used for dosimetric commissioning, including clinical doses, without LET measurements.

Microdosimetric investigation for multi-ion therapy by means of silicon on insulator (SOI) microdosimeter.

Objective.Ion radiotherapy with protons or carbon ions is one of the most advanced clinical methods for cancer treatment. To further improve the local tumor control, ion radiotherapy using multiple ion species has been investigated. Due to complexity of dose distributions delivered by multi-ion therapy in a tumor, a validation strategy for the planned treatment efficacy must be established that can be potentially used in the quality assurance (QA) protocol for the multi-ion treatment plans. In previous work, we demonstrated that the microdosimetric approach using the silicon on insulator (SOI) microdosimeter is practical for validating cell surviving fraction (SF) of MIA PaCa-2 cells in the independent fields of helium, carbon, oxygen, and neon ion beams.Approach.This paper extends the previous study, and we demonstrate a microdosimetry based approach as a pilot study to build the QA protocol in the multi-ion therapy predicting the cell SF along the spread-out Bragg peak obtained by combined irradiations of He+O and C+Ne ions. Across the study, the SOI microdosimeter system MicroPlus was used for measurement of the lineal energy in individual ion fields followed by deriving the lineal energy of combined ion fields delivered by a pencil beam scanning system at HIMAC.Main results.The predicted cell SF based on derived lineal energy and dose in the combined fields was in good agreement with the planned cell SF by our in-house treatment planning system.Significance.The presented results indicated the potential benefit of the SOI microdosimeter system MicroPlus as the QA system in the multi-ion radiotherapy.

Dose response of a radiophotoluminescent glass dosimeter for TomoTherapy, CyberKnife, and flattening-filter-free linear accelerator output measurements in dosimetry audit.

PURPOSE: We experimentally determined the radiophotoluminescent glass dosimeter (RPLD) dose responses for TomoTherapy, CyberKnife, and flattening-filter-free (FFF) linear accelerator (linac) outputs for dosimetry audits in Japan. METHODS: A custom-made solid phantom with a narrow central-axis spacing of three RPLD elements was used for output measurement to minimise the dose-gradient effect of the non-flattening filter beams. For RPLD dose estimation, we used the ISO 22127 formalism. Additional unit-specific correction factors were introduced and determined via the measured data. For TomoTherapy (7 units) and CyberKnife (4 units), the doses were measured under machine-specific reference fields. For FFF linac (5 units), in addition to the reference condition, we obtained the field-size effects for the range from 5×5 cm to 25×25 cm. RESULTS: The correction factors were estimated as 1.008 and 0.999 for TomoTherapy and CyberKnife, respectively. For FFF linac, they ranged from 1.011 to 0.988 for 6 MV and from 1.011 to 0.997 for 10 MV as a function of the side length of the square field from 5 to 25 cm. The estimated uncertainties of the absorbed dose to water measured by RPLD for the units were 1.32%, 1.35%, and 1.30% for TomoTherapy, CyberKnife, and FFF linac, respectively. A summary of the dosimetry audits of these treatment units using the obtained correction factors is also presented. The average percentage differences between the measured and hospital-stated doses were <1% under all conditions. CONCLUSION: RPLD can be successfully used as a dosimetry audit tool for modern treatment units.

Application of lung substitute material as ripple filter for multi-ion therapy with helium-, carbon-, oxygen-, and neon-ion beams.

A development project for hypo-fractionated multi-ion therapy has been initiated at the National Institute of Radiological Sciences in Japan. In the treatment, helium, carbon, oxygen, and neon ions will be used as primary beams with pencil beam scanning. A ripple filter (RiFi), consisting of a thin plastic or aluminum plate with a fine periodic ridge and groove structure, has been used to broaden the Bragg peak of heavy-ion beams in the beam direction. To sufficiently broaden the Bragg peak of helium-, carbon-, oxygen-, and neon-ion beams with suppressed lateral scattering and surface dose inhomogeneity, in this study, we tested a plate made of a lung substitute material, Gammex LN300, as the RiFi. The planar integrated dose distribution of a 183.5 MeV u-1neon-ion beam was measured behind a 3 cm thick LN300 plate in water. The Bragg peak of the pristine beam was broadened following the normal distribution with the standard deviationσvalue of 1.29 mm, while the range of the beam was reduced by 8.8 mm by the plate. To verify the LN300 performance as the RiFi in multi-ion therapy, we measured the pencil beam data of helium-, carbon-, oxygen- and neon-ion beams penetrating the 3 cm thick LN300 plate. The data were then modeled and used in a treatment planning system to achieve a uniform 10% survival of human undifferentiated carcinoma cells within a cuboid target by the beam for each of the different ion species. The measured survival fractions were reasonably reproduced by the planned ones for all the ion species. No surface dose inhomogeneity was observed for any ion species even when the plate was placed close to the phantom surface. The plate made of lung substitute material, Gammex LN300, is applicable as the RiFi in multi-ion therapy with helium-, carbon-, oxygen- and neon-ion beams.