A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Adaptation of stochastic microdosimetric kinetic model for charged-particle therapy treatment planning.

The microdosimetric kinetic (MK) model underestimates the cell-survival fractions for high linear energy transfer (LET) and high dose irradiations. To address the issue, some researchers previously extended the MK model to the stochastic microdosimetric kinetic (SMK) model. In the SMK model, the radiation induced cell-survival fractions were estimated from the specific energies z d and z n absorbed by a microscopic subnuclear structure domain and a cell nucleus, respectively. By taking the stochastic nature of z n as well as that of z d into account, the SMK model could reproduce the measured cell-survival fractions for radiations with wide LET and dose ranges. However, treatment planning based on the SMK model was unrealistic in clinical practice due to its long computation time and huge memory space required for the computation. In this study, we modified the SMK model to shorten the computation time and to reduce the memory space required for the computation. By using the dose-averaged cell-nucleus specific energy per event [Formula: see text] in the SMK formalism, the stochastic nature of z n was reflected onto the estimated cell-survival fractions. The accuracy of the modified SMK model was examined through the comparison between the estimated and the measured survival fractions of human salivary gland tumor cells and V79 cells. We then implemented the modified SMK model into the in-house treatment planning software for scanned charged-particle therapy to validate its applicability in clinical practice. As examples, treatment plans of helium-, carbon-, and neon-ion beams were made for an orbital tumor case. The modified SMK model could reproduce the measured cell-survival fractions more accurately compared to the MK model especially for high-LET and high-dose irradiations. In summary, the modified SMK model offers the accuracy and simplicity required in treatment planning of scanned charged-particle therapy for wide LET and dose ranges.

Tumour control in ion beam radiotherapy with different ions in the presence of hypoxia: an oxygen enhancement ratio model based on the microdosimetric kinetic model.

Few attempts have been made to include the oxygen enhancement ratio (OER) in treatment planning for ion beam therapy, and systematic studies to evaluate the impact of hypoxia in treatment with the beam of different ion species are sorely needed. The radiobiological models used to quantify the OER in such studies are mainly based on the dose-averaged LET estimates, and do not explicitly distinguish between the ion species and fractionation schemes. In this study, a new type of OER modelling, based on the microdosimetric kinetic model, taking into account the specificity of the different ions, LET spectra, tissues and fractionation schemes, has been developed. The model has been benchmarked with published in vitro data, HSG, V79 and CHO cells in aerobic and hypoxic conditions, for different ion irradiation. The model has been included in the simulation of treatments for a clinical case (brain tumour) using proton, lithium, helium, carbon and oxygen ion beams. A study of the tumour control probability (TCP) as a function of oxygen partial pressure, dose per fraction and primary ion type has been performed. The modelled OER depends on both the LET and ion type, also showing a decrease for an increased dose per fraction with a slope that depends on the LET and ion type, in good agreement with the experimental data. In the investigated clinical case, a significant increase in TCP has been found upon increasing the ion charge. Higher OER variations as a function of dose per fraction have also been found for low-LET ions (up to 15% varying from 2 to 8 Gy(RBE) for protons). This model could be exploited in the identification of treatment condition optimality in the presence of hypoxia, including fractionation and primary particle selection.

Optimum size of a calibration phantom for x-ray CT to convert the Hounsfield units to stopping power ratios in charged particle therapy treatment planning.

In charged-particle therapy treatment planning, the volumetric distribution of stopping power ratios (SPRs) of body tissues relative to water is used for patient dose calculation. The distribution is conventionally obtained from computed tomography (CT) images of a patient using predetermined conversion functions from the CT numbers to the SPRs. One of the biggest uncertainty sources of patient SPR estimation is insufficient correction of beam hardening arising from the mismatch between the size of the patient cross section and the calibration phantom for producing the conversion functions. The uncertainty would be minimized by selecting a suitable size for the cylindrical water calibration phantom, referred to as an 'effective size' of the patient cross section, Leffective. We investigated the Leffective for pelvis, abdomen, thorax, and head and neck regions by simulating an ideal CT system using volumetric models of the reference male and female phantoms. The Leffective values were 23.3, 20.3, 22.7 and 18.8 cm for the pelvis, abdomen, thorax, and head and neck regions, respectively, and the Leffective for whole body was 21.0 cm. Using the conversion function for a 21.0-cm-diameter cylindrical water phantom, we could reduce the root mean square deviation of the SPRs and their mean deviation to ≤0.011 and ≤0.001, respectively, in the whole body. Accordingly, for simplicity, the effective size of 21.0 cm can be used for the whole body, irrespective of body-part regions for treatment planning in clinical practice.

The FLUKA Monte Carlo code coupled with the NIRS approach for clinical dose calculations in carbon ion therapy.

Particle therapy facilities often require Monte Carlo (MC) simulations to overcome intrinsic limitations of analytical treatment planning systems (TPS) related to the description of the mixed radiation field and beam interaction with tissue inhomogeneities. Some of these uncertainties may affect the computation of effective dose distributions; therefore, particle therapy dedicated MC codes should provide both absorbed and biological doses. Two biophysical models are currently applied clinically in particle therapy: the local effect model (LEM) and the microdosimetric kinetic model (MKM). In this paper, we describe the coupling of the NIRS (National Institute for Radiological Sciences, Japan) clinical dose to the FLUKA MC code. We moved from the implementation of the model itself to its application in clinical cases, according to the NIRS approach, where a scaling factor is introduced to rescale the (carbon-equivalent) biological dose to a clinical dose level. A high level of agreement was found with published data by exploring a range of values for the MKM input parameters, while some differences were registered in forward recalculations of NIRS patient plans, mainly attributable to differences with the analytical TPS dose engine (taken as reference) in describing the mixed radiation field (lateral spread and fragmentation). We presented a tool which is being used at the Italian National Center for Oncological Hadrontherapy to support the comparison study between the NIRS clinical dose level and the LEM dose specification.

Adaptation of the microdosimetric kinetic model to hypoxia.

Ion beams present a potential advantage in terms of treatment of lesions with hypoxic regions. In order to use this potential, it is important to accurately model the cell survival of oxic as well as hypoxic cells. In this work, an adaptation of the microdosimetric kinetic (MK) model making it possible to account for cell hypoxia is presented. The adaptation relies on the modification of damage quantity (double strand breaks and more complex lesions) due to the radiation. Model parameters such as domain size and nucleus size are then adapted through a fitting procedure. We applied this approach to two cell lines, HSG and V79 for helium, carbon and neon ions. A similar behaviour of the parameters was found for the two cell lines, namely a reduction of the domain size and an increase in the sensitive nuclear volume of hypoxic cells compared to those of oxic cells. In terms of oxygen enhancement ratio (OER), the experimental data behaviour can be reproduced, including dependence on particle type at the same linear energy transfer (LET). Errors on the cell survival prediction are of the same order of magnitude than for the original MK model. Our adaptation makes it possible to account for hypoxia without modelling the OER as a function of the LET of the particles, but directly accounting for hypoxic cell survival data.

Effective particle energies for stopping power calculation in radiotherapy treatment planning with protons and helium, carbon, and oxygen ions.

The stopping power ratio (SPR) of body tissues relative to water depends on the particle energy. For simplicity, however, most analytical dose planning systems do not account for SPR variation with particle energy along the beam's path, but rather assume a constant energy for SPR estimation. The range error due to this simplification could be indispensable depending on the particle species and the assumed energy. This error can be minimized by assuming a suitable energy referred to as an 'effective energy' in SPR estimation. To date, however, the effective energy has never been investigated for realistic patient geometries. We investigated the effective energies for proton, helium-, carbon-, and oxygen-ion radiotherapy using volumetric models of the reference male and female phantoms provided by the International Commission on Radiological Protection (ICRP). The range errors were estimated by comparing the particle ranges calculated when particle energy variations were and were not considered. The effective energies per nucleon for protons and helium, carbon, and oxygen ions were 70 MeV, 70 MeV, 131 MeV, and 156 MeV, respectively. Using the determined effective energies, the range errors were reduced to ⩽0.3 mm for respective particle species. For SPR estimation of multiple particle species, an effective energy of 100 MeV is recommended, with which the range error is ⩽0.5 mm for all particle species.

A dose calculation algorithm with correction for proton-nucleus interactions in non-water materials for proton radiotherapy treatment planning.

In treatment planning for proton radiotherapy, the dose measured in water is applied to the patient dose calculation with density scaling by stopping power ratio [Formula: see text]. Since the body tissues are chemically different from water, this approximation may cause dose calculation errors, especially due to differences in nuclear interactions. We proposed and validated an algorithm for correcting these errors. The dose in water is decomposed into three constituents according to the physical interactions of protons in water: the dose from primary protons continuously slowing down by electromagnetic interactions, the dose from protons scattered by elastic and/or inelastic interactions, and the dose resulting from nonelastic interactions. The proportions of the three dose constituents differ between body tissues and water. We determine correction factors for the proportion of dose constituents with Monte Carlo simulations in various standard body tissues, and formulated them as functions of their [Formula: see text] for patient dose calculation. The influence of nuclear interactions on dose was assessed by comparing the Monte Carlo simulated dose and the uncorrected dose in common phantom materials. The influence around the Bragg peak amounted to -6% for polytetrafluoroethylene and 0.3% for polyethylene. The validity of the correction method was confirmed by comparing the simulated and corrected doses in the materials. The deviation was below 0.8% for all materials. The accuracy of the correction factors derived with Monte Carlo simulations was separately verified through irradiation experiments with a 235 MeV proton beam using common phantom materials. The corrected doses agreed with the measurements within 0.4% for all materials except graphite. The influence on tumor dose was assessed in a prostate case. The dose reduction in the tumor was below 0.5%. Our results verify that this algorithm is practical and accurate for proton radiotherapy treatment planning, and will also be useful in rapidly determining fluence correction factors for non-water phantom dosimetry.

Influence of nuclear interactions in body tissues on tumor dose in carbon-ion radiotherapy.

PURPOSE: In carbon-ion radiotherapy treatment planning, the planar integrated dose (PID) measured in water is applied to the patient dose calculation with density scaling using the stopping power ratio. Since body tissues are chemically different from water, this dose calculation can be subject to errors, particularly due to differences in inelastic nuclear interactions. In recent studies, the authors proposed and validated a PID correction method for these errors. In the present study, the authors used this correction method to assess the influence of these nuclear interactions in body tissues on tumor dose in various clinical cases. METHODS: Using 10-20 cases each of prostate, head and neck (HN), bone and soft tissue (BS), lung, liver, pancreas, and uterine neoplasms, the authors first used treatment plans for carbon-ion radiotherapy without nuclear interaction correction to derive uncorrected dose distributions. The authors then compared these distributions with recalculated distributions using the nuclear interaction correction (corrected dose distributions). RESULTS: Median (25%/75% quartiles) differences between the target mean uncorrected doses and corrected doses were 0.2% (0.1%/0.2%), 0.0% (0.0%/0.0%), -0.3% (-0.4%/-0.2%), -0.1% (-0.2%/-0.1%), -0.1% (-0.2%/0.0%), -0.4% (-0.5%/-0.1%), and -0.3% (-0.4%/0.0%) for the prostate, HN, BS, lung, liver, pancreas, and uterine cases, respectively. The largest difference of -1.6% in target mean and -2.5% at maximum were observed in a uterine case. CONCLUSIONS: For most clinical cases, dose calculation errors due to the water nonequivalence of the tissues in nuclear interactions would be marginal compared to intrinsic uncertainties in treatment planning, patient setup, beam delivery, and clinical response. In some extreme cases, however, these errors can be substantial. Accordingly, this correction method should be routinely applied to treatment planning in clinical practice.

Variation in patient position and impact on carbon-ion scanning beam distribution during prostate treatment.

OBJECTIVE: We assessed the impact of changes in patient position on carbon-ion scanning beam distribution during treatment for prostate cancer. METHODS: 68 patients were selected. Carbon-ion scanning dose was calculated. Two different planning target volumes (PTVs) were defined: PTV1 was the clinical target volume plus a set-up margin for the anterior/lateral sides and posterior side, while PTV2 was the same as PTV1 minus the posterior side. Total prescribed doses of 34.4 Gy [relative biological effectiveness (RBE)] and 17.2 Gy (RBE) were given to PTV1 and PTV2, respectively. To estimate the influence of geometric variations on dose distribution, the dose was recalculated on the rigidly shifted single planning CT based on two dimensional-three dimensional rigid registration of the orthogonal radiographs before and after treatment for the fraction of maximum positional changes. RESULTS: Intrafractional patient positional change values averaged over all patients throughout the treatment course were less than the target registration error = 2.00 mm and angular error = 1.27°. However, these maximum positional errors did not occur in all 12 treatment fractions. Even though large positional changes occurred during irradiation in all treatment fractions, lowest dose encompassing 95% of the target (D95)-PTV1 was >98% of the prescribed dose. CONCLUSION: Intrafractional patient positional changes occurred during treatment beam irradiation and degraded carbon-ion beam dose distribution. Our evaluation did not consider non-rigid deformations, however, dose distribution was still within clinically acceptable levels. ADVANCES IN KNOWLEDGE: Inter- and intrafractional changes did not affect carbon-ion beam prostate treatment accuracy.

Effects of beam interruption time on tumor control probability in single-fractionated carbon-ion radiotherapy for non-small cell lung cancer.

Carbon-ion radiotherapy treatment plans are designed on the assumption that the beams are delivered instantaneously, irrespective of actual dose-delivery time structure in a treatment session. As the beam lines are fixed in the vertical and horizontal directions at our facility, beam delivery is interrupted in multi-field treatment due to the necessity of patient repositioning within the fields. Single-fractionated treatment for non-small cell lung cancer (NSCLC) is such a case, in which four treatment fields in multiple directions are delivered in one session with patient repositioning during the session. The purpose of this study was to investigate the effects of the period of dose delivery, including interruptions due to patient repositioning, on tumor control probability (TCP) of NSCLC. All clinical doses were weighted by relative biological effectiveness (RBE) evaluated for instantaneous irradiation. The rate equations defined in the microdosimetric kinetic model (MKM) for primary lesions induced in DNA were applied to the single-fractionated treatment of NSCLC. Treatment plans were made for an NSCLC case for various prescribed doses ranging from 25 to 50 Gy (RBE), on the assumption of instantaneous beam delivery. These plans were recalculated by varying the interruption time τ ranging from 0 to 120 min between the second and third fields for continuous irradiations of 3 min per field based on the MKM. The curative doses that would result in a TCP of 90% were deduced for the respective interruption times. The curative dose was 34.5 Gy (RBE) for instantaneous irradiation and 36.6 Gy (RBE), 39.2 Gy (RBE), 41.2 Gy (RBE), 43.3 Gy (RBE) and 44.4 Gy (RBE) for τ = 0 min, 15 min, 30 min, 60 min and 120 min, respectively. The realistic biological effectiveness of therapeutic carbon-ion beam decreased with increasing interruption time. These data suggest that the curative dose can increase by 20% or more compared to the planned dose if the interruption time extends to 30 min or longer. These effects should be considered in carbon-ion radiotherapy treatment planning if a longer dose-delivery procedure time is anticipated.

Nuclear-interaction correction of integrated depth dose in carbon-ion radiotherapy treatment planning.

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.

A trichrome beam model for biological dose calculation in scanned carbon-ion radiotherapy treatment planning.

In scanned carbon-ion (C-ion) radiotherapy, some primary C-ions undergo nuclear reactions before reaching the target and the resulting particles deliver doses to regions at a significant distance from the central axis of the beam. The effects of these particles on physical dose distribution are accounted for in treatment planning by representing the transverse profile of the scanned C-ion beam as the superposition of three Gaussian distributions. In the calculation of biological dose distribution, however, the radiation quality of the scanned C-ion beam has been assumed to be uniform over its cross-section, taking the average value over the plane at a given depth (monochrome model). Since these particles, which have relatively low radiation quality, spread widely compared to the primary C-ions, the radiation quality of the beam should vary with radial distance from the central beam axis. To represent its transverse distribution, we propose a trichrome beam model in which primary C-ions, heavy fragments with atomic number Z ≥ 3, and light fragments with Z ≤ 2 are assigned to the first, second, and third Gaussian components, respectively. Assuming a realistic beam-delivery system, we performed computer simulations using Geant4 Monte Carlo code for analytical beam modeling of the monochrome and trichrome models. The analytical beam models were integrated into a treatment planning system for scanned C-ion radiotherapy. A target volume of 20 × 20 × 40 mm(3) was defined within a water phantom. A uniform biological dose of 2.65 Gy (RBE) was planned for the target with the two beam models based on the microdosimetric kinetic model (MKM). The plans were recalculated with Geant4, and the recalculated biological dose distributions were compared with the planned distributions. The mean target dose of the recalculated distribution with the monochrome model was 2.72 Gy (RBE), while the dose with the trichrome model was 2.64 Gy (RBE). The monochrome model underestimated the RBE within the target due to the assumption of no radial variations in radiation quality. Conversely, the trichrome model accurately predicted the RBE even in a small target. Our results verify the applicability of the trichrome model for clinical use in C-ion radiotherapy treatment planning.

Implementation of a target volume design function for intrafractional range variation in a particle beam treatment planning system.

OBJECTIVE: Treatment planning for charged particle therapy in the thoracic and abdominal regions should take account of range uncertainty due to intrafractional motion. Here, we developed a design tool (4Dtool) for the target volume [field-specific target volume (FTV)], which accounts for this uncertainty using four-dimensional CT (4DCT). METHODS: Target and normal tissue contours were input manually into a treatment planning system (TPS). These data were transferred to the 4Dtool via the picture archiving and communication system (PACS). Contours at the reference phase were propagated to other phases by deformable image registration. FTV was calculated using 4DCT on the 4Dtool. The TPS displays FTV contours using digital imaging and communications in medicine files imported from the PACS. These treatment parameters on the CT image at the reference phase were then used for dose calculation on the TPS. The tool was tested in single clinical case randomly selected from patients treated at our centre for lung cancer. RESULTS: In this clinical case, calculation of dose distribution with the 4Dtool resulted in the successful delivery of carbon-ion beam at the reference phase of 95% of the prescribed dose to the clinical target volume (CTV). Application to the other phases also provided sufficient dose to the CTV. CONCLUSION: The 4Dtool software allows the design of the target volume with consideration to intrafractional range variation and is now in routine clinical use at our institution. ADVANCES IN KNOWLEDGE: Our alternative technique represents a practical approach to four-dimensional treatment planning within the current state of charged particle therapy.

Implementation of a triple Gaussian beam model with subdivision and redefinition against density heterogeneities in treatment planning for scanned carbon-ion radiotherapy.

Challenging issues in treatment planning for scanned carbon-ion (C-ion) therapy are (i) accurate calculation of dose distribution, including the contribution of large angle-scattered fragments, (ii) reduction in the memory space required to store the dose kernel of individual pencil beams and (iii) shortening of computation time for dose optimization and calculation. To calculate the dose contribution from fragments, we modeled the transverse dose profile of the scanned C-ion beam with the superposition of three Gaussian distributions. The development of pencil beams belonging to the first Gaussian component was calculated analytically based on the Fermi-Eyges theory, while those belonging to the second and third components were transported empirically using the measured beam widths in a water phantom. To reduce the memory space for the kernels, we stored doses only in the regions of interest considered in the dose optimization. For the final dose calculation within the patient's whole body, we applied a pencil beam redefinition algorithm. With these techniques, the triple Gaussian beam model can be applied not only to final dose calculation but also to dose optimization in treatment planning for scanned C-ion therapy. To verify the model, we made treatment plans for a homogeneous water phantom and a heterogeneous head phantom. The planned doses agreed with the measurements within ±2% of the target dose in both phantoms, except for the doses at the periphery of the target with a high dose gradient. To estimate the memory space and computation time reduction with these techniques, we made a treatment plan for a bone sarcoma case with a target volume of 1.94 l. The memory space for the kernel and the computation time for final dose calculation were reduced to 1/22 and 1/100 of those without the techniques, respectively. Computation with the triple Gaussian beam model using the proposed techniques is rapid, accurate and applicable to dose optimization and calculation in treatment planning for scanned C-ion therapy.

Measurement of neutron ambient dose equivalent in carbon-ion radiotherapy with an active scanned delivery system.

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.

Effects of a difference in respiratory cycle between treatment planning and irradiation for phase-controlled rescanning and carbon pencil beam scanning.

OBJECTIVE: To evaluate the impact of variation in respiratory cycle between treatment planning and irradiation for pencil beam scanning and phase-controlled rescanning (PCR) on the resulting dose distribution, we conducted a simulation study based on four-dimensional CT (4DCT) data for lung cancer patients. METHODS: 4DCT data were acquired for seven patients with lung tumours. Treatment planning was designed to ensure the delivery of 95% of the prescribed dose to the clinical target volume in respective phases of the 4DCT by taking account of intrafractional beam range variations. Carbon ion pencil beam scanning dose distributions were calculated for various respiratory cycles that differed from the reference respiration (=4.4 s) but which stayed regular during irradiation. The number of rescannings was changed to 1, 4 or 8 times. PCR was correlated with the gating window in treatment planning to calculate the beam weighting map. RESULTS: 8×PCR improved dose conformation to the target for all irradiation respiratory cycles. Minimum dose (Dmin) and lowest dose encompassing 95% of the target (D95) values with 4×PCR were decreased from 94.1% and 98.1% to 88.4% and 93.5% with an altered irradiation respiratory cycle of 2.4 s. However, these values were improved with 8×PCR to over 94.9% for Dmin and 98.6% for D95 for respective irradiation respiratory cycles. CONCLUSION: Pencil beam scanning treatment with eight or more PCRs consistently improved dose conformation for moving lung targets even when different respiratory cycles were used for treatment planning and irradiation. ADVANCES IN KNOWLEDGE: Scanning treatment with eight or more rescannings consistently improved dose homogeneity to a moving target even though respiratory cycles varied during treatment.

Washout measurement of radioisotope implanted by radioactive beams in the rabbit.

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.