Impact of magnetic resonance imaging-related geometric distortion of dose distribution in fractionated stereotactic radiotherapy in patients with brain metastases.

PURPOSE: The geometric distortion related to magnetic resonance (MR) imaging in a diagnostic radiology (MRDR) and radiotherapy (MRRT) setup is evaluated, and the dosimetric impact of MR distortion on fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases is simulated. MATERIALS AND METHODS: An anthropomorphic skull phantom was scanned using a 1.5­T MR scanner, and the magnitude of MR distortion was calculated with (MRDR-DC and MRRT-DC) and without (MRDR-nDC and MRRT-nDC) distortion-correction algorithms. Automated noncoplanar volumetric modulated arc therapy (HyperArc, HA; Varian Medical Systems, Palo Alto, CA, USA) plans were generated for 53 patients with 186 brain metastases. The MR distortion at each gross tumor volume (GTV) was calculated using the distance between the center of the GTV and the MR image isocenter (MIC) and the quadratic regression curve derived from the phantom study (MRRT-DC and MRRT-nDC). Subsequently, the radiation isocenter of the HA plans was shifted according to the MR distortion at each GTV (HADC and HAnDC). RESULTS: The median MR distortions were approximately 0.1 mm when the distance from the MIC was < 30 mm, whereas the median distortion varied widely when the distance was > 60 mm (0.23, 0.47, 0.37, and 0.57 mm in MRDR-DC, MRDR-nDC, MRRT-DC, and MRRT-nDC, respectively). The dose to the 98% of the GTV volume (D98%) decreased as the distance from the MIC increased. In the HADC plans, the relative dose difference of D98% was less than 5% when the GTV was located within 70 mm from the MIC, whereas the underdose of GTV exceeded 5% when it was 48 mm (-26.5% at maximum) away from the MIC in the HAnDC plans. CONCLUSION: Use of a distortion-correction algorithm in the studied MR diagnoses is essential, and the dosimetric impact of MR distortion is not negligible, particularly for tumors located far away from the MIC.

Relationship between hydrogel spacer distribution and dosimetric parameters in linear-accelerator-based stereotactic body radiotherapy for prostate cancer.

PURPOSE: To explore the potential of quantitative parameters of the hydrogel spacer distribution as predictors for separating the rectum from the planning target volume (PTV) in linear-accelerator-based stereotactic body radiotherapy (SBRT) for prostate cancer. METHODS: Fifty-five patients underwent insertion of a hydrogel spacer and were divided into groups 1 and 2 of the PTV separated from and overlapping with the rectum, respectively. Prescribed doses of 36.25-45 Gy in five fractions were delivered to the PTV. The spacer cover ratio (SCR) and hydrogel-implant quality score (HIQS) were calculated. RESULTS: Dosimetric and quantitative parameters of the hydrogel spacer distribution were compared between the two groups. For PTV, D99% in group 1 (n = 29) was significantly higher than that in group 2 (n = 26), and Dmax, D0.03cc, D1cc, and D10% for the rectum were significantly lower in group 1 than in group 2. The SCR for prostate (89.5 ± 12.2%) in group 1 was significantly higher (p < 0.05) than that in group 2 (74.7 ± 10.3%). In contrast, the HIQS values did not show a significant difference between the groups. An area under the curve of 0.822 (95% confidence interval, 0.708-0.936) for the SCR was obtained with a cutoff of 93.6%, sensitivity of 62.1%, and specificity of 100%. CONCLUSIONS: The SCR seems promising to predict the separation of the rectum from the PTV in linear-accelerator-based SBRT for prostate cancer.

A virtual audit system for intensity-modulated radiation therapy credentialing in Japan Clinical Oncology Group clinical trials: A pilot study.

PURPOSE: The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data. METHODS: We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 mm criteria (the dose denominator was 2 Gy), 30% threshold dose, no scaling of the datasets, and 90% tolerance level. In addition, 21 datasets from nine institutions were obtained for array evaluation. Five institutions used ArcCHECK, while the others used Delta4. Global gamma analysis was performed with 3%/2 mm criteria (the dose denominator was the maximum calculated dose), 10% threshold dose, and 95% tolerance level. The film calibration and gamma analysis were conducted with in-house software developed using Python (version 3.9.2). RESULTS: The means ± standard deviations of the gamma passing rates were 99.4 ± 1.5% (range, 92.8%-100%) and 99.2 ± 1.0% (range, 97.0%-100%) in the film and array evaluations, respectively. CONCLUSION: This pilot study demonstrated the feasibility of virtual audits. The proposed virtual audit system will contribute to more efficient, cheaper, and more rapid trial credentialing than on-site and postal audits; however, the limitations should be considered when operating our virtual audit system.

Deep learning-based auto segmentation using generative adversarial network on magnetic resonance images obtained for head and neck cancer patients.

PURPOSE: Adaptive radiotherapy requires auto-segmentation in patients with head and neck (HN) cancer. In the current study, we propose an auto-segmentation model using a generative adversarial network (GAN) on magnetic resonance (MR) images of HN cancer for MR-guided radiotherapy (MRgRT). MATERIAL AND METHODS: In the current study, we used a dataset from the American Association of Physicists in Medicine MRI Auto-Contouring (RT-MAC) Grand Challenge 2019. Specifically, eight structures in the MR images of HN region, namely submandibular glands, lymph node level II and level III, and parotid glands, were segmented with the deep learning models using a GAN and a fully convolutional network with a U-net. These images were compared with the clinically used atlas-based segmentation. RESULTS: The mean Dice similarity coefficient (DSC) of the U-net and GAN models was significantly higher than that of the atlas-based method for all the structures (p < 0.05). Specifically, the maximum Hausdorff distance (HD) was significantly lower than that in the atlas method (p < 0.05). Comparing the 2.5D and 3D U-nets, the 3D U-net was superior in segmenting the organs at risk (OAR) for HN patients. The DSC was highest for 0.75-0.85, and the HD was lowest within 5.4 mm of the 2.5D GAN model in all the OARs. CONCLUSIONS: In the current study, we investigated the auto-segmentation of the OAR for HN patients using U-net and GAN models on MR images. Our proposed model is potentially valuable for improving the efficiency of HN RT treatment planning.

[Study of Dose Recalculation Method on Overriding Lung Density Using CBCT Image in the Thorax].

It is a useful method for the adaptive radiotherapy (ART) to calculate absorbed dose accurately on the image set taken by on-board cone beam computed tomography (CBCT) attached to linac for image-guided radiation therapy (IGRT). For this purpose, a simple and accurate calculation method is necessary. Several papers report that it is possible to calculate easily and accurately by using several methods of researches in the neck and prostate, but the lung density varies greatly depending on patient thorax condition. In this study, we propose a new dose recalculation method, which is a simple procedure and can achieve accurate dose calculation considered different lung densities in each patient. By using this method, it is possible to calculate exclusive of artifacts in CBCT because of overriding the lung density. The dose error between dose recalculation of the CBCT image and treatment plan agreed within±1%. Therefore, this method is expected to be a useful method for accurate dose calculation with CBCT image for ART.

Evaluation of radioactivity in the bodies of mice induced by neutron exposure from an epi-thermal neutron source of an accelerator-based boron neutron capture therapy system.

This study aimed to evaluate the residual radioactivity in mice induced by neutron irradiation with an accelerator-based boron neutron capture therapy (BNCT) system using a solid Li target. The radionuclides and their activities were evaluated using a high-purity germanium (HP-Ge) detector. The saturated radioactivity of the irradiated mouse was estimated to assess the radiation protection needs for using the accelerator-based BNCT system. 24Na, 38Cl, 80mBr, 82Br, 56Mn, and 42K were identified, and their saturated radioactivities were (1.4 ± 0.1) × 102, (2.2 ± 0.1) × 101, (3.4 ± 0.4) × 102, 2.8 ± 0.1, 8.0 ± 0.1, and (3.8 ± 0.1) × 101 Bq/g/mA, respectively. The 24Na activation rate at a given neutron fluence was found to be consistent with the value reported from nuclear-reactor-based BNCT experiments. The induced activity of each nuclide can be estimated by entering the saturated activity of each nuclide, sample mass, irradiation time, and proton current into the derived activation equation in our accelerator-based BNCT system.

Radiosensitization by PARP inhibition to proton beam irradiation in cancer cells.

The poly(ADP-ribose) polymerase (PARP)-1 regulates DNA damage responses and promotes base excision repair. PARP inhibitors have been shown to enhance the cytotoxicity of ionizing radiation in various cancer cells and animal models. We have demonstrated that the PARP inhibitor (PARPi) AZD2281 is also an effective radiosensitizer for carbon-ion radiation; thus, we speculated that the PARPi could be applied to a wide therapeutic range of linear energy transfer (LET) radiation as a radiosensitizer. Institutes for biological experiments using proton beam are limited worldwide. This study was performed as a cooperative research at heavy ion medical accelerator in Chiba (HIMAC) in National Institute of Radiological Sciences. HIMAC can generate various ion beams; this enabled us to compare the radiosensitization effect of the PARPi on cells subjected to proton and carbon-ion beams from the same beam line. After physical optimization of proton beam irradiation, the radiosensitization effect of the PARPi was assessed in the human lung cancer cell line, A549, and the pancreatic cancer cell line, MIA PaCa-2. The effect of the PARPi, AZD2281, on radiosensitization to Bragg peak was more significant than that to entrance region. The PARPi increased the number of phosphorylated H2AX (γ-H2AX) foci and enhanced G2/M arrest after proton beam irradiation. This result supports our hypothesis that a PARPi could be applied to a wide therapeutic range of LET radiation by blocking the DNA repair response.

Late toxicity of proton beam therapy for patients with the nasal cavity, para-nasal sinuses, or involving the skull base malignancy: importance of long-term follow-up.

BACKGROUND: Although several reports have shown that proton beam therapy (PBT) offers promise for patients with skull base cancer, little is known about the frequency of late toxicity in clinical practice when PBT is used for these patients. Here, we conducted a retrospective analysis to clarify the late toxicity profile of PBT in patients with malignancies of the nasal cavity, para-nasal sinuses, or involving the skull base. METHODS: Entry to this retrospective study was restricted to patients with (1) malignant tumors of the nasal cavity, para-nasal sinuses, or involving the skull base; (2) definitive or postoperative PBT (>50 GyE) from January 1999 through December 2008; and (3) more than 1 year of follow-up. Late toxicities were graded according to the common terminology criteria for adverse events v4.0 (CTCAE v4.0). RESULTS: From January 1999 through December 2008, 90 patients satisfied all criteria. Median observation period was 57.5 months (range, 12.4-162.7 months), median time to onset of grade 2 or greater late toxicity except cataract was 39.2 months (range, 2.7-99.8 months), and 3 patients had toxicities that occurred more than 5 years after PBT. Grade 3 late toxicities occurred in 17 patients (19%), with 19 events, and grade 4 late toxicities in 6 patients (7%), with 6 events (encephalomyelitis infection 2, optic nerve disorder 4). CONCLUSIONS: In conclusion, the late toxicity profile of PBT in patients with malignancy involving the nasal cavity, para-nasal sinuses, or skull base malignancy was partly clarified. Because late toxicity can still occur at 5 years after treatment, long-term follow-up is necessary.

Scintillation of polyester fabric and clothing via proton irradiation and its utilization in surface imaging of proton pencil beams.

In the realm of radiation therapy, a conspicuous obstacle lies in the dearth of external observation concerning radiation beams aimed at the patient. While real-time monitoring of such beams on the patient's surface during therapy holds promise, the imaging of particle beams has thus far proven to be a formidable task. Here, we show our discovery of polyester fabrics and cloths as auspicious scintillating materials, ideally suited for the visualization of radiation beams upon the patient's surface. The light output of polyester fabrics ranged from 10 to 20% of that observed in plastic scintillators. When exposed to spot scanning proton beams, clear beam spots emerged on the surface of the polyester cloths. The movement of these scanning beams was effectively captured using a CMOS camera in a light-shield-free with lights-off environment. The resulting images provided a means for evaluating spills of the proton beams. The inherent flexibility of polyester fabrics and clothing enhances their appeal for applications in the intricate landscape of radiation therapy, promising a bright future for surface beam imaging endeavors.

Assessing tumor volumetric reduction with consideration for setup errors based on mathematical tumor model and microdosimetric kinetic model in single-isocenter VMAT for brain metastases.

The volumetric reduction rate (VRR) was evaluated with consideration for six degrees-of-freedom (6DoF) patient setup errors based on a mathematical tumor model in single-isocenter volumetric modulated arc therapy (SI-VMAT) for brain metastases. Simulated gross tumor volumes (GTV) of 1.0 cm and dose distribution were created (27 Gy/3 fractions). The distance between the GTV center and isocenter (d) was set at 0-10 cm. The GTV was translated within 0-1.0 mm (Trans) and rotated within 0-1.0° (Rot) in the three axis directions using affine transformation. The tumor growth volume was calculated using a multicomponent mathematical model (MCTM), and lethal effects of irradiation and repair from damage during irradiation were calculated by a microdosimetric kinetic model (MKM) for non-small cell lung cancer (NSCLC) A549 and NCI-H460 (H460) cells. The VRRs were calculated 5 days after the end of irradiation using the physical dose to the GTV for varying d and 6DoF setup errors. The tolerance value of VRR, the GTV volume reduction rate, was set at 5%, based on the pre-irradiation GTV volume. With the exception of the only one A549 condition where (Trans, Rot) = (1.0 mm, 1.0°) was repeated for 3 fractions, all conditions met all the tolerance VRR values for A549 and H460 cells with varying d from 0 to 10 cm. Evaluation based on the mathematical tumor model suggested that if the 6DoF setup errors at each irradiation could be kept within 1.0 mm and 1.0°, there would be little effect on tumor volume regardless of the distance from the isocenter in SI-VMAT.

Preliminary study of luminescence phenomena from various materials under ultra-high dose rate proton beam irradiation for dose management.

This research aimed to identify materials capable of emitting visible light useful for dose management at ultra-high dose rate (uHDR). Various materials were irradiated with proton beams at a normal dose rate (NDR) and uHDR, and the resulting surface luminescence was captured using a high-sensitivity camera. The luminescence images were compared with the corresponding dose distributions. The luminescence of Tough Water Phantoms (Kyoto Kagaku Co. Ltd.) with various thicknesses was also observed to evaluate the depth distributions. Dose distributions were measured using two-dimensional ionization chamber detector arrays. The Tough Bone Phantom (Kyoto Kagaku Co. Ltd.) exhibited the strongest luminescence among the materials, followed by the Tough Water Phantom. The metals exhibited relatively weak luminescence. The luminescence profiles of the Tough Water Phantom, water, the Tough Lung Phantom (Kyoto Kagaku Co. Ltd.), and an acrylic were similar to the dose profiles. The luminescence distribution of the Tough Water Phantom in the depth direction was similar to that of the dose distributions. The luminescence at uHDR and NDR were approximately equivalent. The Tough Water Phantom was found to be a suitable material for dosimetry, even at uHDR. More detailed measurement data, such as wavelength data, must be collected to elucidate the luminescence mechanism.

Variation in Hounsfield unit calculated using dual-energy computed tomography: comparison of dual-layer, dual-source, and fast kilovoltage switching technique.

The purpose of the study is to investigate the variation in Hounsfield unit (HU) values calculated using dual-energy computed tomography (DECT) scanners. A tissue characterization phantom inserting 16 reference materials were scanned three times using DECT scanners [dual-layer CT (DLCT), dual-source CT (DSCT), and fast kilovoltage switching CT (FKSCT)] changing scanning conditions. The single-energy CT images (120 or 140 kVp), and virtual monochromatic images at 70 keV (VMI70) and 140 keV (VMI140) were reconstructed, and the HU values of each reference material were measured. The difference in HU values was larger when the phantom was scanned using the half dose with wrapping with rubber (strong beam-hardening effect) compared with the full dose without the rubber (reference condition), and the difference was larger as the electron density increased. For SECT, the difference in HU values against the reference condition measured by the DSCT (3.2 ± 5.0 HU) was significantly smaller (p < 0.05) than that using DLCT with 120 kVp (22.4 ± 23.8 HU), DLCT with 140 kVp (11.4 ± 12.8 HU), and FKSCT (13.4 ± 14.3 HU). The respective difference in HU values in the VMI70 and VMI140 measured using the DSCT (10.8 ± 17.1 and 3.5 ± 4.1 HU) and FKSCT (11.5 ± 21.8 and 5.5 ± 10.4 HU) were significantly smaller than those measured using the DLCT120 (23.1 ± 27.5 and 12.4 ± 9.4 HU) and DLCT140 (22.3 ± 28.6 and 13.1 ± 11.4 HU). The HU values and the susceptibility to beam-hardening effects varied widely depending on the DECT scanners.

A method for delivering the required neutron fluence in an accelerator-based boron neutron capture therapy system employing a lithium target.

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction.

Long-term geometric quality assurance of radiation focal point and cone-beam computed tomography for Gamma Knife radiosurgery system.

To investigate the geometric accuracy of the radiation focal point (RFP) and cone-beam computed tomography (CBCT) over long-term periods for the ICON Leksell Gamma Knife radiosurgery system. This phantom study utilized the ICON quality assurance tool plus, and the phantom was manually set on the patient position system before the implementation of treatment for patients. The deviation of the RFP position from the unit center point (UCP) and the positions of the four ball bearings (BBs) in the CBCT from the reference position were automatically analyzed. During 544 days, a total of 269 analyses were performed on different days. The mean ± standard deviation (SD) of the deviation between measured RFP and UCP was 0.01 ± 0.03, 0.01 ± 0.03, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively. The deviations with offset values after the cobalt-60 source replacement (0.00 ± 0.03, -0.01 ± 0.01, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively) were significantly (p = 0.001) smaller than those before the replacement (0.02 ± 0.03, 0.02 ± 0.01, and -0.02 ± 0.01 mm in the X, Y, and Z directions, respectively). The overall mean ± SD of four BBs was -0.03 ± 0.03, -0.01 ± 0.05, and 0.01 ± 0.03 mm in the X, Y, and Z directions, respectively. Geometric positional accuracy was ensured to be within 0.1 mm on most days over a long-term period of more than 500 days.

Development and characterization of a dedicated dose monitor for ultrahigh-dose-rate scanned carbon-ion beams.

The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DRspot)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8-12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DRspot). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.

CT number calibration audit in photon radiation therapy.

BACKGROUND: Inadequate computed tomography (CT) number calibration curves affect dose calculation accuracy. Although CT number calibration curves registered in treatment planning systems (TPSs) should be consistent with human tissues, it is unclear whether adequate CT number calibration is performed because CT number calibration curves have not been assessed for various types of CT number calibration phantoms and TPSs. PURPOSE: The purpose of this study was to investigate CT number calibration curves for mass density (ρ) and relative electron density (ρe ). METHODS: A CT number calibration audit phantom was sent to 24 Japanese photon therapy institutes from the evaluating institute and scanned using their individual clinical CT scan protocols. The CT images of the audit phantom and institute-specific CT number calibration curves were submitted to the evaluating institute for analyzing the calibration curves registered in the TPSs at the participating institutes. The institute-specific CT number calibration curves were created using commercial phantom (Gammex, Gammex Inc., Middleton, WI, USA) or CIRS phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA)). At the evaluating institute, theoretical CT number calibration curves were created using a stoichiometric CT number calibration method based on the CT image, and the institute-specific CT number calibration curves were compared with the theoretical calibration curve. Differences in ρ and ρe over the multiple points on the curve (Δρm and Δρe,m , respectively) were calculated for each CT number, categorized for each phantom vendor and TPS, and evaluated for three tissue types: lung, soft tissues, and bones. In particular, the CT-ρ calibration curves for Tomotherapy TPSs (ACCURAY, Sunnyvale, CA, USA) were categorized separately from the Gammex CT-ρ calibration curves because the available tissue-equivalent materials (TEMs) were limited by the manufacturer recommendations. In addition, the differences in ρ and ρe for the specific TEMs (ΔρTEM and Δρe,TEM , respectively) were calculated by subtracting the ρ or ρe of the TEMs from the theoretical CT-ρ or CT-ρe calibration curve. RESULTS: The mean ± standard deviation (SD) of Δρm and Δρe,m for the Gammex phantom were -1.1 ± 1.2 g/cm3 and -0.2 ± 1.1, -0.3 ± 0.9 g/cm3 and 0.8 ± 1.3, and -0.9 ± 1.3 g/cm3 and 1.0 ± 1.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm and Δρe,m for the CIRS phantom were 0.3 ± 0.8 g/cm3 and 0.9 ± 0.9, 0.6 ± 0.6 g/cm3 and 1.4 ± 0.8, and 0.2 ± 0.5 g/cm3 and 1.6 ± 0.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm for Tomotherapy TPSs was 2.1 ± 1.4 g/cm3 for soft tissues, which is larger than those for other TPSs. The mean ± SD of Δρe,TEM for the Gammex brain phantom (BRN-SR2) was -1.8 ± 0.4, implying that the tissue equivalency of the BRN-SR2 plug was slightly inferior to that of other plugs. CONCLUSIONS: Latent deviations between human tissues and TEMs were found by comparing the CT number calibration curves of the various institutes.

Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition.

OBJECTIVE: The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. METHODS: Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. RESULTS: One local recurrence was observed at Meckel's cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. CONCLUSIONS: Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

Extracting the gradient component of the gamma index using the Lie derivative method.

Objective. The gamma index (γ) has been extensively investigated in the medical physics and applied in clinical practice. However,γhas a significant limitation when used to evaluate the dose-gradient region, leading to inconveniences, particularly in stereotactic radiotherapy (SRT). This study proposes a novel evaluation method combined withγto extract clinically problematic dose-gradient regions caused by irradiation including certain errors.Approach. A flow-vector field in the dose distribution is obtained when the dose is considered a scalar potential. Using the Lie derivative from differential geometry, we definedL,S, andUto evaluate the intensity, vorticity, and flow amount of deviation between two dose distributions, respectively. These metrics multiplied byγ(γL,γS,γU), along with the threshold valueσ, were verified in the ideal SRT case and in a clinical case of irradiation near the brainstem region using radiochromic films. Moreover, Moran's gradient index (MGI), Bakai's χ factor, and the structural similarity index (SSIM) were investigated for comparisons.Main results. A highL-metric value mainly extracted high-dose-gradient induced deviations, which was supported by highSandUmetrics observed as a robust deviation and an influence of the dose-gradient, respectively. TheS-metric also denotes the measured similarity between the compared dose distributions. In theγdistribution,γLsensitively detected the dose-gradient region in the film measurement, despite the presence of noise. The thresholdσsuccessfully extracted the gradient-error region whereγ> 1 analysis underestimated, andσ= 0.1 (plan) andσ= 0.001 (film measurement) were obtained according to the compared resolutions. However, the MGI, χ, and SSIM failed to detect the clinically interested region.Significance. Although further studies are required to clarify the error details, this study demonstrated that the Lie derivative method provided a novel perspective for the identifying gradient-induced error regions and enabled enhanced and clinically significant evaluations ofγ.

Mathematical model combined with microdosimetric kinetic model for tumor volume calculation in stereotactic body radiation therapy.

We proposed a new mathematical model that combines an ordinary differential equation (ODE) and microdosimetric kinetic model (MKM) to predict the tumor-cell lethal effect of Stereotactic body radiation therapy (SBRT) applied to non-small cell lung cancer (NSCLC). The tumor growth volume was calculated by the ODE in the multi-component mathematical model (MCM) for the cell lines NSCLC A549 and NCI-H460 (H460). The prescription doses 48 Gy/4 fr and 54 Gy/3 fr were used in the SBRT, and the effect of the SBRT on tumor cells was evaluated by the MKM. We also evaluated the effects of (1) linear quadratic model (LQM) and the MKM, (2) varying the ratio of active and quiescent tumors for the total tumor volume, and (3) the length of the dose-delivery time per fractionated dose (tinter) on the initial tumor volume. We used the ratio of the tumor volume at 1 day after the end of irradiation to the tumor volume before irradiation to define the radiation effectiveness value (REV). The combination of MKM and MCM significantly reduced REV at 48 Gy/4 fr compared to the combination of LQM and MCM. The ratio of active tumors and the prolonging of tinter affected the decrease in the REV for A549 and H460 cells. We evaluated the tumor volume considering a large fractionated dose and the dose-delivery time by combining the MKM with a mathematical model of tumor growth using an ODE in lung SBRT for NSCLC A549 and H460 cells.

Improvement of target coverage using automated non-coplanar volumetric modulated arc therapy planning in stereotactic radiotherapy for cervical metastatic spinal tumors.

This study aimed to compare dosimetric parameters for targets and organs at risk (OARs) between volumetric modulated arc therapy (VMAT) and automated VMAT (HyperArc, HA) plans in stereotactic radiotherapy for patients with cervical metastatic spine tumors. VMAT plans were generated for 11 metastases using the simultaneous integrated boost technique to deliver 35 to 40 and 20 to 25 Gy for high dose and elective dose planning target volume (PTVHD and PTVED), respectively. The HA plans were retrospectively generated using 1 coplanar and 2 noncoplanar arcs. Subsequently, the doses to the targets and OARs were compared. The HA plans provided significantly higher (p < 0.05) Dmin (77.4 ± 13.1%), D99% (89.3 ± 8.9%), and D98% (92.5 ± 7.7%) for gross tumor volume (GTV) than those of the VMAT plans (73.4 ± 12.2%, 84.2 ± 9.6 and 87.3 ± 8.8% for Dmin, D99% and D98%, respectively). In addition, D99% and D98% for PTVHD were significantly higher in the HA plans, whereas dosimetric parameters were comparable between the HA and VMAT plans for PTVED. The Dmax values for the brachial plexus, esophagus, and spinal cord were comparable, and no significant difference was observed in the Dmean for the larynx, pharyngeal constrictor, thyroid, parotid grand (left and right), and Submandibular gland (left and right). The HA plans provided significantly higher target coverage of GTV and PTVHD, with a comparable dose for OARs with VMAT plans. The results of this study may contribute to the improvement of local control in clinical practice.