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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., (© 2022 Institute of Physics and Engineering in Medicine.)

In this study, the survival fraction (SF) and relative biological effectiveness (RBE) of pancreatic cancer cells exposed to spread-out Bragg peak helium, carbon, oxygen, and neon ion beams are estimated from the measured microdosimetric spectra using a microdosimeter and the application of the microdosimetric kinetic (MK) model. To measure the microdosimetric spectra, a 3D mushroom silicon-on-insulator microdosimeter connected to low noise readout electronics (MicroPlus probe) was used. The parameters of the MK model were determined for pancreatic cancer cells such that the calculated SFs reproduced previously reported in vitro SF data. For a cuboid target of 10 × 10 × 6 cm 3 , treatment plans of helium, carbon, oxygen, and neon ion beams were designed using in-house treatment planning software (TPS) to achieve a 10% SF of pancreatic cancer cells throughout the target. The physical doses and microdosimetric spectra of the planned fields were measured at different depths in polymethyl methacrylate phantoms. The biological effects, such as SF, RBE, and RBE-weighted dose at different depths along the fields were predicted from the measurements. The predicted SFs at the target region were generally in good agreement with the planned SF from the TPS in most cases.

In treatment planning of charged-particle therapy, tissue heterogeneity is conventionally modeled as water with various densities, i.e. stopping effective densities ρ(S), and the integrated depth dose measured in water (IDD) is applied accordingly for the patient dose calculation. Since the chemical composition of body tissues is different from that of water, this approximation causes dose calculation errors, especially due to difference in nuclear interactions. Here, we propose and validate an IDD correction method for these errors in patient dose calculations. For accurate handling of nuclear interactions, ρ(S) of the patient is converted to nuclear effective density ρ(N), defined as the ratio of the probability of nuclear interactions in the tissue to that in water using a recently formulated semi-empirical relationship between the two. The attenuation correction factor Φ(w)(p), defined as the ratio of the attenuation of primary carbon ions in a patient to that in water, is calculated from a linear integration of ρ(N) along the beam path. In our treatment planning system, a carbon-ion beam is modeled to be composed of three components according to their transverse beam sizes: primary carbon ions, heavier fragments, and lighter fragments. We corrected the dose contribution from primary carbon ions to IDD as proportional to Φ(w)(p), and corrected that from lighter fragments as inversely proportional to Φ(w)(p). We tested the correction method for some non-water materials, e.g. milk, lard, ethanol and water solution of potassium phosphate (K2HPO4), with un-scanned and scanned carbon-ion beams. In un-scanned beams, the difference in IDD between a beam penetrating a 150 mm-thick layer of lard and a beam penetrating water of the corresponding thickness amounted to -4%, while it was +6% for a 150 mm-thick layer of 40% K2HPO4. The observed differences were accurately predicted by the correction method. The corrected IDDs agreed with the measurements within ±1% for all materials and combinations of them. In scanned beams, the dose estimation error in target dose amounted to 4% for a 150 mm-thick layer of 40% K2HPO4. The error is significantly reduced with the correction method. The planned dose distributions with the method agreed with the measurements within ±1.5% of target dose for all materials not only in the target region but also in the plateau and fragment-tail regions. We tested the correction method of IDD in some non-water materials to verify that this method would offer the accuracy and simplicity required in carbon-ion radiotherapy treatment planning.

In ion beam radiotherapy, secondary neutrons contribute to an undesired dose outside the target volume, and consequently the increase of secondary cancer risk is a growing concern. In this study, neutron ambient dose equivalents in carbon-ion radiotherapy (CIRT) with an active beam delivery system were measured with a rem meter, WENDI-II, at National Institute of Radiological Sciences. When the same irradiation target was assumed, the measured neutron dose with an active beam was at most ∼15 % of that with a passive beam. This percentage became smaller as larger distances from the iso-centre. Also, when using an active beam delivery system, the neutron dose per treatment dose in CIRT was comparable with that in proton radiotherapy. Finally, it was experimentally demonstrated that the use of an active scanned beam in CIRT can greatly reduce the secondary neutron dose., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: In treatment planning of charged-particle radiotherapy, patient heterogeneity is conventionally modeled as variable-density water converted from CT images to best reproduce the stopping power, which may lead to inaccuracies in the handling of multiple scattering and nuclear interactions. Although similar conversions can be defined for these individual interactions, they would be valid only for specific CT systems and would require additional tasks for clinical application. This study aims to improve the practicality of the interaction-specific heterogeneity correction., Methods: The authors calculated the electron densities and effective densities for stopping power, multiple scattering, and nuclear interactions of protons and ions, using the standard elemental-composition data for body tissues to construct the invariant conversion functions. The authors also simulated a proton beam in a lung-like geometry and a carbon-ion beam in a prostate-like geometry to demonstrate the procedure and the effects of the interaction-specific heterogeneity correction., Results: Strong correlations were observed between the electron density and the respective effective densities, with which the authors formulated polyline conversion functions. Their effects amounted to 10% differences in multiple-scattering angle and nuclear interaction mean free path for bones compared to those in the conventional heterogeneity correction. Although their realistic effect on patient dose distributions would be generally small, it could be at the level of a few percent when a carbon-ion beam traverses a large bone., Conclusions: The present conversion functions are invariant and may be incorporated in treatment planning systems with a common function relating CT number to electron density. This will enable improved beam dose calculation while minimizing initial setup and quality management of the user's specific system.

In order to effectively utilize the prominent properties of heavy ions in radiotherapy, it is important to evaluate both the position of the field irradiated with incident ions and the absorbed dose distribution in a patient's body. One of the methods for this purpose is the utilization of the positron emitters produced through the projectile fragmentation reactions of stable heavy ions with target nuclei. In heavy-ion therapy, spread-out Bragg peak (SOBP) beams are used to achieve uniform biological dose distributions in the whole tumor volume. Therefore, in this study, we designed SOBP beams of 30 and 50 mm water-equivalent length (mmWEL) in width for (12)C and (16)O, and carried out irradiation experiments using them. Water, polyethylene and polymethyl methacrylate were selected as targets to simulate a human body. Pairs of annihilation gamma rays were detected by means of a limited-angle positron camera for 500 s, and annihilation gamma-ray distributions were obtained. The maximum likelihood estimation (MLE) method was applied to the detected distributions for evaluating the positions of the distal and proximal edges of the SOBP in a target. The differences between the positions evaluated with the MLE method and those derived from the measured dose distributions were less than 1.7 mm and 2.5 mm for the distal and the proximal edge, respectively, in all irradiation conditions. When the positions of both edges are determined with the MLE method, the most probable shape of the dose distribution in a target can be estimated simultaneously. The close agreement between the estimated and the measured distributions implied that the shape of the dose distribution in an irradiated target could be evaluated from the detected annihilation gamma-ray distribution.

Purpose: The utility of positron emitter nuclei generated by photonuclear reactions was verified for X-ray beam monitoring in a phantom., Materials and Methods: Positron emission tomography-computed tomography (PET-CT) images of a gelatinous water phantom (H(2)O target) and a polyethylene phantom (CH(2) target) were acquired 5 min after delivering a dose of 17 Gy with an X-ray beam energy of 21 MV. Reconstructed PET images and the calculated half-life showed that the positron emitters of (15)O (half-life 122.2 s) in the H(2)O target and (11)C (half-life 20.4 min) in the CH(2) target were generated by photonuclear reactions., Results: A comparison was made between measured activity and dose distributions for each target. The measured times of annihilation gamma rays from the positron emitter nucleus were 10 and 30 min for the (15)O nucleus in the H(2)O target and the (11)C nucleus in the CH(2) target, respectively. The activity distributions of the (15)O and (11)C positron emitter nuclei were similar to the measured dose distributions for both depth and lateral directions except for dose buildup and collimator edge regions. It was confirmed that no activity was detected at an X-ray energy of 14 MV, which was far below the energy threshold for both photonuclear reactions., Conclusion: It was estimated that the PET-CT image acquired from the activity of the (15)O and (11)C positron emitter nuclei might provide the area of X-ray beam irradiation in a phantom.

In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an ionization chamber. The good agreement between the derived and the measured distributions implies that the deposited dose distribution in a target can be estimated from the detected annihilation gamma-ray distribution with a positron camera.

In radiation therapy with hadron beams, it is important to evaluate the range of incident ions and the deposited dose distribution in a patient body for the effective utilization of such properties as the dose concentration and the biological effect around the Bragg peak. However, there is some ambiguity in determining this range because of a conversion error from the x-ray CT number to the charged particle range. This is because the CT number is related to x-ray absorption coefficients, while the ion range is determined by the electron density of the substance. Using positron emitters produced in the patient body through fragmentation reactions during the irradiation has been proposed to overcome this problem. The activity distribution in the patient body can be deduced by detecting pairs of annihilation gamma rays emitted from the positron emitters, and information about the range of incident ions can be obtained. In this paper, we propose a quantitative comparison method to evaluate the mean range of incident ions and monitor the activity distribution related to the deposited dose distribution. The effectiveness of the method was demonstrated by evaluating the range of incident ions using the maximum likelihood estimation (MLE) method and Fisher's information was calculated under realistic conditions for irradiations with several kinds of ions. From the calculated Fisher's information, we compared the relative advantages of initial beams to determine the range of incident ions. The (16)O irradiation gave the most information among the stable heavy ions when we measured the induced activity for 500 s and 60 s just after the irradiation. Therefore, under these conditions, we concluded that the (16)O beam was the optimum beam to monitor the activity distribution and to evaluate the range. On the other hand, if the positron emitters were injected directly as a therapeutic beam, the (15)O irradiation gave the most information. Although the relative advantages of initial beams as well as the measured activity distributions slightly varied according to the measurement conditions, comparisons could be made for different conditions by using Fisher's information.

Washout of 10C and 11C implanted by radioactive beams in brain and thigh muscle of rabbits was studied. The biological washout effect in a living body is important in the range verification system or three-dimensional volume imaging in heavy ion therapy. Positron emitter beams were implanted in the rabbit and the annihilation gamma-rays were measured by an in situ positron camera which consisted of a pair of scintillation cameras set on either side of the target. The ROI (region of interest) was set as a two-dimensional position distribution and the time-activity curve of the ROI was measured. Experiments were done under two conditions: live and dead. By comparing the two sets of measurement data, it was deduced that there are at least three components in the washout process. Time-activity curves of both brain and thigh muscle were clearly explained by the three-component model analysis. The three components ratios (and washout half-lives) were 35% (2.0 s), 30% (140 s) and 35% (10 191 s) for brain and 30% (10 s), 19% (195 s) and 52% (3175 s) for thigh muscle. The washout effect must be taken into account for the verification of treatment plans by means of positron camera measurements.