Dose Gradient Research Articles

P11.25.B Adjuvant high precision hypofractionated radiotherapy for resected brain metastases: single-institutional experience

Abstract Background The proportion of patients with solid tumor who develop brain metastases may be as high as 35%. Whenever possible, resection should be the first treatment option. Unfortunately, resection alone has recurrence rates up to 50-60%. In order to improve local control, adjuvant radiation to the surgical cavity is highly recommended. Single dose stereotactic radiosurgery (SRS) as well as hypofractionated stereotactic radiotherapy (HFSRT) have shown one-year local control rates from 70 to 90% with low incidence of radiation-induced toxicity. High precision hypofractionated radiotherapy (HFRT) using Volumetric Modulated Arc Therapy (VMAT) combines sharp dose gradients of SRS with a fractionated scheme, allowing high radiation doses per fraction while minimizing adverse events. Therefore, it could be used as an alternative to SRS for target volumes larger than 3 cm or close to sensitive brain areas. This study aims to analyze control parameters and toxicity of High precision HFRT after brain metastasis resection. Material and Methods We retrospectively analyzed 38 patients diagnosed with brain metastases underwent complete or subtotal surgical resection followed by adjuvant High precision HFRT between January and December 2019 at Catalan Institute of Oncology, Badalona. Radiation was delivered using VMAT technique with 6 MV photon beams. Patient immobilization was achieved using commercial radiotherapy-thermoplastic-mask and daily image guide control with CBCT (cone beam computed tomography) was performed. Statistical analysis was performed with SPSS.PASW.Statistics.v18. Results We identified 38 patients (47.4% men, 52.6% women) with a median age at diagnosis of 61 years [37 - 83 years]. Most of the primary neoplasms were from lung (50%) and breast cancer (24%). The median size of cavities was 10,5cc [0.4 - 75.5cc]. Radiation scheme was selected depending on size and location of the surgical cavity, primary tumor histology and patient’s performance status. Forty-two percent of patients received 27 Gy/3 fractions, 39% received 24 Gy/3 fractions and 7% received 18Gy/3fractions. The remaining four patients received 35 Gy/5fr (3%), 15 Gy/3fr (3%), 16 Gy/2fr (3%) and 30Gy/10fr (3%) respectively. With a median follow-up of 9.9 months, brain recurrence was observed in 23 patients (60%), with only 7 patients (18.4%) showing local relapse at surgical cavity. One-year local control rate was 81% for all patients. Radiation necrosis was confirmed by Positron Emission Tomography in 3 patients (7.8%). Leptomeningeal disease was observed in 5 patients (13.2%). No significant differences were observed between radiation schemes nor primary tumor histology. Conclusion Surgery followed by High precision HFRT delivered with VMAT technique is an effective and safe treatment alternative to SRS for selected patients with brain metastases.

Personalized Superficial HDR Brachytherapy-Dosimetric Verification of Dose Distribution with Lead Shielding of Critical Organs in the Head and Neck Region.

Background: Surface brachytherapy, usually characterized by a high dose gradient, allows the dose to be precisely deposited in the irradiated area while protecting critical organs. When the lesion is located in the nasal or ocular region, the organ of vision must be protected. The aim of this study was to verify the dose distributions near critical organs in the head and neck region during a brachytherapy procedure using lead shielding of the eye. Methods: Anthropomorphic phantom using 3D-printing technology was prepared. The doses deposited at a point in the lens of the eye and on the surface of the eyelid, directly under the lead shield were calculated and measured using EBT3 radiochromic films. Comparison of doses planned in the treatment planning system using the TG-43 formalism, TG-186 formalism, and measured were also performed. Results: Comparing the planned and calculated doses with TG186 formalism it can be assumed that the use of lead shields is a method for protecting the organ of vision from the adverse effects of ionizing radiation. Conclusions: The decision to use a lead shield during facial surface brachytherapy procedures should be made on a patient-by-patient basis and based on model-based calculation methods recommended by TG186.

Assessment of dose-volume histogram precision for five clinical systems.

To investigate the dependency of dose-volume histogram (DVH) behavior and precision on underlying discretization using shapes and dose distributions with known analytical DVHs for five commercial DVH calculators. DVHs and summary metrics were extracted from all five systems using synthetic cone and cylinder objects for which the true volume and DVH curves were known. Trends in the curves and metrics were explored by varying the underlying voxelization of the CT image, structure set, and dose grid as well by varying the geometry of the structure and direction of a linear dose gradient. Using synthetic structures allowed for comparison with ground truth DVH curves to assess their accuracy while an algorithm was additionally developed to assess the precision of each system. The precision was calculated with a novel algorithm that treats any "stair step" behavior in a DVH curve as an uncertainty band and calculates the width, characterized as a percent difference, of the band for various DVH metrics. The underlying voxelization was additionally changed and DVHs were extracted for two clinical examples. The details of how each system calculated DVHs were also investigated and tendencies in the calculated curves, metrics, and precision were related to choices made in the calculation methodology. Calculation methodology differences that had a noticeable impact on the DVH curves and summary metrics include supersampling beyond the input grids and interpretation of the superior and inferior ends of the structures. Among the systems studied, the median precision ranged from 0.902% to 3.22%, and interquartile ranges varied from 1.09% to 3.91%. Commercial dose-evaluation solutions can calculate different DVH curves, structure volume measures, and dose statistics for the same input data due to differences in their calculation methodologies. This study highlights the importance of understanding and investigating the DVH calculation when considering a new clinical system and when using more than one system for data transfer.

Preclinical validation and treatment of volumetric modulated arc therapy based total bone marrow irradiation in Halcyon™ ring gantry linear accelerator

AimThis study aims​ to report preclinical validation, and the first clinical treatment of total bone marrow irradiation (TMI) and total bone marrow and lymph nodal irradiation (TMLI) using Volumetric modulated arc therapy in Halcyon-E ring gantry linear accelerator. Preclinical validation includes simulation, planning, patient-specific QA, and dry run.Material and methodFour patients, two female and two male, with body weights of 116 kg, 52 kg, 64 kg, and 62 kg; with two with chronic myeloid leukemia, one each with acute lymphoblastic leukemia and acute myeloid leukemia (AML) were simulated and planned for TMI/TMLI. Patients were immobilized with a full-body vacuum bag. Head first supine (HFS) and Feet first supine (FFS) CT scans were acquired from head to knee and knee to toe. Planning target volume (PTV) was created with a uniform margin of 6 mm over the total bone marrow/bone marrow + lymph nodes. HFS and FFS PTVs were optimized independently using 6MV unflatten energy for 12 Gy in 6 fractions. Plans were merged to create the resultant dose distribution using a junction bias dose matching technique. The total number of isocenters was ≤ 10 per CT set, and two to four full arcs were used for each isocenter. A junction dose gradient technique was used for dose feathering between arcs between adjacent isocenters.ResultOnly one female patient diagnosed as AML received the TMLI treatment, while the other three patients dropped out due to clinical complications and comorbidities that developed in the time between simulation and treatment. The result presented has been averaged over all four patients. For PTV, 95% dose was normalised to 95% volume, PTV_V107% receiving 3.3 ± 3.1%. Total lung mean and V12Gy were 1048.6 ± 107.1 cGy and 19.5 ± 12.1%. Maximum lens doses were 489.5 ± 35.5 cGy (left: L) and 497 ± 69.2 cGy (right: R). The mean cardiac and bilateral kidney doses were 921.75 ± 89.2 cGy, 917.9 ± 63.2 cGy (L), and 805.9 ± 9.7 cGy (R). Average Monitor Unit was 7738.25 ± 1056.6. The median number of isocenters was 17(HFS+FFS), average MU/Dose (cGy) ratio per isocenter was 2.28 ± 0.3.ConclusionHalcyon-E ring gantry linear accelerator capable of planning and delivering TMI/TMLI.​​

A novel multichannel deep learning model for fast denoising of Monte Carlo dose calculations: preclinical applications

Objective. In preclinical radiotherapy with kilovolt (kV) x-ray beams, accurate treatment planning is needed to improve the translation potential to clinical trials. Monte Carlo based radiation transport simulations are the gold standard to calculate the absorbed dose distribution in external beam radiotherapy. However, these simulations are notorious for their long computation time, causing a bottleneck in the workflow. Previous studies have used deep learning models to speed up these simulations for clinical megavolt (MV) beams. For kV beams, dose distributions are more affected by tissue type than for MV beams, leading to steep dose gradients. This study aims to speed up preclinical kV dose simulations by proposing a novel deep learning pipeline. Approach. A deep learning model is proposed that denoises low precision (∼106 simulated particles) dose distributions to produce high precision (109 simulated particles) dose distributions. To effectively denoise the steep dose gradients in preclinical kV dose distributions, the model uses the novel approach to use the low precision Monte Carlo dose calculation as well as the Monte Carlo uncertainty (MCU) map and the mass density map as additional input channels. The model was trained on a large synthetic dataset and tested on a real dataset with a different data distribution. To keep model inference time to a minimum, a novel method for inference optimization was developed as well. Main results. The proposed model provides dose distributions which achieve a median gamma pass rate (3%/0.3 mm) of 98% with a lower bound of 95% when compared to the high precision Monte Carlo dose distributions from the test set, which represents a different dataset distribution than the training set. Using the proposed model together with the novel inference optimization method, the total computation time was reduced from approximately 45 min to less than six seconds on average. Significance. This study presents the first model that can denoise preclinical kV instead of clinical MV Monte Carlo dose distributions. This was achieved by using the MCU and mass density maps as additional model inputs. Additionally, this study shows that training such a model on a synthetic dataset is not only a viable option, but even increases the generalization of the model compared to training on real data due to the sheer size and variety of the synthetic dataset. The application of this model will enable speeding up treatment plan optimization in the preclinical workflow.

5-Fluorouracil combined with cisplatin via arterial induction for advanced T-stage nasopharyngeal carcinoma: A 10-year outcome of a phase I/II study.

Background and PurposeCurrently, there is no optimal dose recommendation for a 120-h continuous infusion of 5-fluorouracil via arterial cannulation for advanced T-stage nasopharyngeal carcinoma (NPC). Thus, the aim of this study was to determine the maximum tolerated dose (MDT), along with the efficacy, late adverse events, and 10-year survival outcome of 5-fluorouracil administered continuously for 120 h combined with cisplatin via the superficial temporal artery in patients with advanced T-stage NPC.Materials and MethodsFifty-one patients with histologically confirmed advanced T-stage NPC were eligible for inclusion in this clinical trial. The patients received induction chemotherapy consisting of cisplatin (20 mg/m2/d for 1–5 d) and 5-fluorouracil, administered continuously for 120 h at different dose gradients via a superficial temporal artery. To identify the MTD of 5-fluorouracil infused arterially, we employed a 3 + 3 design during study phase I. The initial dose administered was 200 mg/m2/d, which then was gradually escalated by 50 mg/m2/d until the MTD was reached. Following two cycles of induction chemotherapy, current radical chemoradiotherapy commenced. We assessed the efficacy, survival, toxicity, and quality of life of patients following treatment.ResultsThe overall response (complete response + partial response) rates following induction chemotherapy in the primary mass and lymph nodes were 100% and 100%, respectively. All 51 (100%) patients achieved T-category down-staging after intra-arterial chemotherapy. The MTD was 450 mg/m2/d for 120 h. No late neurological toxicities, such as brain stem injury, temporal lobe necrosis, and spinal cord injury, were observed. The 5- and 10-year overall survival (OS) rates were 78.0% and 71.7%, respectively, with a median OS of 131 months.ConclusionContinuous infusion of 5-fluorouracil combined with cisplatin via the superficial temporal artery showed promising survival benefits and few toxicities in patients with advanced T-stage NPC.

Treatment Planning in Intraoperative Radiation Therapy (IORT): Where Should We Go?

Simple SummaryIntraoperative radiation therapy is evolving towards new treatment regimens, including ultrahigh dose rates, while in-room imaging systems are increasingly being used for treatment planning and verification. Furthermore, the combination of multiple treatment modalities is being investigated and suggested in some studies, with the aim to improve clinical outcomes. This evolution calls for newly designed treatment planning systems in which several features shall be integrated. In this article, an attempt is made to identify emerging needs and foresee the possible evolution of treatment planning technology and strategies for intraoperative radiation therapy in the near future.As opposed to external beam radiation therapy (EBRT), treatment planning systems (TPS) dedicated to intraoperative radiation therapy (IORT) were not subject to radical modifications in the last two decades. However, new treatment regimens such as ultrahigh dose rates and combination with multiple treatment modalities, as well as the prospected availability of dedicated in-room imaging, call for important new features in the next generation of treatment planning systems in IORT. Dosimetric accuracy should be guaranteed by means of advanced dose calculation algorithms, capable of modelling complex scattering phenomena and accounting for the non-tissue equivalent materials used to shape and compensate electron beams. Kilovoltage X-ray based IORT also presents special needs, including the correct description of extremely steep dose gradients and the accurate simulation of applicators. TPSs dedicated to IORT should also allow real-time imaging to be used for treatment adaptation at the time of irradiation. Other features implemented in TPSs should include deformable registration and capability of radiobiological planning, especially if unconventional irradiation schemes are used. Finally, patient safety requires that the multiple features be integrated in a comprehensive system in order to facilitate control of the whole process.

A measure tool for evaluating dose falloff outside the target volume in high precision radiotherapy

IntroductionA reliable and high resolution systemic with all aspects plan evaluation indices has been proposed in this study to measure the dose falloff outside the target volume. The essential goal of this study is to compensate the shortcomings for the judgment of planning target volume and dose-volume histogram by visual verification slice by slice in high precision modern radiotherapy techniques like stereotactic radiation surgery, volumetric arc therapy, and stereotactic body radiation therapy. Materials and methodsDynamic Gradient Index has been proposed both geometric and dosimetric orientated in all aspects plan evaluation indices to measure the dose falloff outside the target volume. Organ at Risk Integral Dose, and Target Specific Gain Ratio are created for evaluating highly conformal plans and provide better sparing of normal tissue. Users can do the plan evaluation indices calculation proposed in this study just simply with a sequence of exported data including normal tissue volume covered by every isodose line, target volume covered by every isodose line, and organ at risk volume covered by every isodose line from the approved planning system. The results here were also compared with several indices usually used such as gradient index developed by various authors. ResultsDGI avoids the mistaken judgment counted on a single gradient index on one referenced isodose line recommended by other published results for the evaluation of SRS, SBRT high precision needed plan. Dynamic Gradient Index is a measure of steep dose gradient outside the target volume; therefore; this index plays a significant role in SRS as a measure of plan quality, especially a judgment of complication cases. Furthermore, taking into consideration the Organ at Risk Integral Dose and normal tissue integral dose to evaluate the target therapeutic gain lets Target Specific Gain Ratio becomes a comprehensive evaluation tool for pros and cons tangled cases. ConclusionsThe function of DGI successfully reflects the advantage of fast expanded isodose lines (low dose gradient) could be easily examined. The plan superiority is determined by how close the DGI and the other indices are to the line of the benchmark. The growing speed of DGI for the SRS curve is slower similar to VMAT than the other two treatment techniques. The DGI of SRS beyond 100% inside the target area shows the advantage of the plateau between 100% and 110%, which means the change of dose gradient is smaller and this phenomenon could not be checked in DVH as well in other plan evaluation indices.

Assessment of dose gradient index variation during simultaneously integrated boost intensity‐modulated radiation therapy for head and neck cancer patients

AbstractObjectiveDose gradient index (DGI) is a tool used to evaluate radiation dose gradient outside the target. This study aimed to analyze the consistency of this tool through the long course of radiotherapy due to patient anatomical changes, such as body weight loss and tumor shrinkage.MethodsA total of 30 patients diagnosed with different head and neck cancer were treated with the simultaneous integrated boost intensity‐modulated radiation therapy technique; the patients underwent new computed tomography (CT) simulations after 10 and 20 treatment sessions. The gradient index was compared for the initial, reconstructed, and adaptive plans.ResultsAll patients showed a significant decrease (p < 0.001) in weight at reconstructed CT1 (RCT1) and reconstructed CT2 compared with original CT. Also, primary gross tumor volume was significantly decreased (p < 0.001) at reconstructed CT1 and reconstructed CT2. In the dosimetric part, all organs showed a significant increase in dose delivery at reconstructed plans (Rplans) compared with the original plan (Oplan). Meanwhile, at adaptive plans (Aplans), all organs showed a significant decrease in dose delivery compared with Oplan. The DGI was significantly increased at Rplan1 and Rplan2 compared with Oplan, with a median value of 29 (15.5–41.3) and 30 (15.1–38) at Rplan1 and Rplan2, respectively, and 25.8 (14.9–37.6) at Oplan. Whereas DGI value decreased significantly at Aplan1 compared with Oplan, and then insignificantly increased at Aplan2 compared with Aplan1.ConclusionDGI must be evaluated during the intensity‐modulated radiation therapy course in the treatment of head and neck cancers, which clearly varies significantly as a result of a patient's anatomical changes during the radiotherapy course, and it can be improved or maintained to its original value by using adaptive planning strategy.

Inhibitory Effect of Seawater Pearl Hydrolysate on UVA-Induced Photoaging of Human Skin Fibroblasts.

This study is an investigation into the inhibitory effect of seawater pearl hydrolysate (SPH) on the UVA-induced photoaging of human skin fibroblast (HSF) cells, and the mechanism thereof. HSF cells were cultured and irradiated with a UVA 0–50 J·cm−2 dose gradient. The cell inhibition rate was detected using the CCK8 method, and the half-inhibitory dose was determined. Based on this, the dose of UVA irradiation for the follow-up experiment was selected to establish a photoaging model of the HSF cells. The cells were divided into a normal (N) group, UVA-irradiated (UVA) group, SPH low dose (SPHL) group, SPH medium dose (SPHM) group, and SPH high dose (SPHH) group. The photoaging model of HSF cells was established by UVA irradiation in the UVA, SPHL, SPHM, and SPHH groups; the SPHL, SPHM, and SPHH groups were treated with SPH at concentrations of 50, 100, and 200 mg·L−1, respectively, at the same time. After 24 and 48 h of culture, the reactive oxygen species (ROS) level of the HSF cells was detected by flow cytometry, and the required culture time of the HSF cells for the follow-up experiment was selected. The malondialdehyde and glutathione contents, as well as the activities of the superoxide dismutase, catalase, and glutathione peroxidase in the HSF cells, were detected by biochemical methods. The levels of expression of MMP-1 and collagen I protein in HSF cells were detected by the western blot test, the extent of aging of HSF cells was detected by β-galactosidase staining, and the apoptosis level of HSF cells was detected by flow cytometry. The results show that SPH inhibits the UVA-induced photoaging of HSF cells in a dose-dependent manner within a certain concentration range, and the effect of a concentration of 200 mg·L–1 was the most significant. The mechanism is related to improving the antioxidant activity of photoaging HSF cells to eliminate excessive ROS. It can inhibit apoptosis, reduce the protein expression of MMP-1, and effectively control the degradation of collagen I protein in photoaging HSF cells. Therefore, SPH offers potential for use in sunscreen cosmetics.

ПЕРСПЕКТИВЫ РАЗВИТИЯ ПРОТОННОЙ ТЕРАПИИ В РОССИИ

It is generally accepted that a proton therapy is one of the most effective method of external beam radiotherapy. Proton therapy has the highest conformal factor even compared with the most modern facilities for radiotherapy which use electron beam or gamma rays. Accuracy of combination of the 90–95 % isodose surface with PTV is better and dose gradients outside PTV is steeper, also integral dose of radiation from proton therapy for a healthy tissue is less than two times that for gamma irradiation. We can clearly see it comparing a HDV of treatment plan for gamma irradiation and proton therapy for the same clinical cases. In last years a lifespan of patient after radiotherapy treatment is a quit extended, so a question for quality of life for them is more significant. Decreasing of integral dose for a healthy tissue reduces a chance of negative effects from radiotherapy that would mostly appear after a lot years after treatment, so named late side effects. Quality of life is even more important in the case of pediatric oncology, when we not only expect a long healthy life for them, but also have aim to exclude side effects from their development. There was a long term clinical investigation in 1954–1990 years in ten experimental centers (among them clinical data: 50% in USA, 30% in USSR/Russia) that had confirmed the described advantages of proton therapy. These clinical results formed a foundation of quick development proton therapy clinical centers in developed countries in 1990s. These centers are based on oncology and multidisciplinary hospitals and treat 1000 and more patients per year. There are 96 working and 38 constructing PTCs in the world for today. Although we have a lot of experience in proton therapy in Russia, we didn’t take part in this new stage. In fact a patient treatment was over in all of three experimental PTCs (Moscow, Dubna, St. Petersburg) up to 2014. Thus we have a delay in a development of proton therapy for 30 years from a world level. Government of the Russian Federation Decree № 287 of 16th March 2020 establishes Program, which has to overcome this delay in development. Main science executer of the Program is National Research Center «Kurchatov Institute», which has an experience, scientific potential and competence for it. The main aims, stages and objects of the Program are presented.

Improved treatment robustness of postoperative breast cancer radiotherapy including supraclavicular nodes.

A combination of a three-dimensional conformal radiation therapy (3D-CRT) plan with a dose gradient of the chest wall area and a volumetric modulated arc therapy (VMAT) plan of the supraclavicular area might improve the dose distribution robustness in the junction. To investigate the impact of patient motion on the dose distribution, hybrid 3D-CRT and VMAT plans were recalculated by shifting the isocenter of the VMAT plan. Compared to the nominal plan, the target D98% for high- vs low-dose gradients decreased by 24% vs 12%. Hybrid VMAT with a low-dose gradient 3D-CRT plan was found to be robust towards patient motion.

Investigating the number of radiation fields in intensity-modulated radiotherapy plans of optic nerve sheath meningioma patients using dose gradient index

Purpose: In optic nerve radiotherapy, vital organs are very close to the target volume, they are highly sensitive to radiation and have low dose tolerance. In this regard, evaluating dose fall-off steepness around the target volume is required to assess various intensity-modulated radiation therapy (IMRT) plans in the treatment of the optic nerve sheath meningioma (ONSM) patients. Materials and Methods: Thirteen ONSM patients were analyzed with three IMRT techniques, including three (IMRT-3F), five (IMRT-5F), and seven fields (IMRT-7F). These plans were studied using Dmean, Dmax, D2%, D98%, V100%, uniformity index (UI), homogeneity index (HI), conformity index (CI), and specifically the dose gradient indices (DGIs). Results: The values of Dmax and Dmean for IMRT-3F, IMRT-5F and IMRT-7F were (5637.42 ± 57.08, 5322.84 ± 83.86), (5670.51 ± 67.87, 5383.00 ± 58.45), and (5692.99 ± 31.65, 5405.72 ± 51.73), respectively, which were increased with increment in the number of IMRT fields from 3 to 7. The UI and HI indices were significantly different between IMRT-3F and IMRT-7F (p = 0.010 and p = 0.005, respectively), and CI was close to the ideal value (0.99 ± 0.01) in IMRT-7F. The significant findings of the dose gradient indices represented smaller values in IMRT-7F, which led to a faster dose fall-off, particularly at the 70%-85% isodose levels around the target. Conclusion: Increasing the number of radiation fields in IMRT treatment plans of ONSM patients had a considerable difference in both the dosimetric parameters of the target volume and at-risk organs, as well as the dose gradient indices. Overall, IMRT-7F could be considered as a preferred technique in the treatment of this meningioma.

Evaluation of a New Inverse, Globally Convex Treatment Planning System Algorithm for Gamma Knife Radiation Surgery Within a Prospective Trial: Advantages and Disadvantages in Practical Application

PurposeA new inverse planning software called IntuitivePlan (IP) based on a global convex optimization algorithm was adopted for the Gamma Knife radiation surgery. We investigated IP's suitability for daily clinical use and its applicability for different cerebral entities. Methods and MaterialsFor 230 target volumes, IP was tested in a prospective trial. The computed treatment plans were compared with conventional expert preplans, which included forward planning by the expert and local internal optimization. Based on the same dose constraints, we used the default settings for the inverse calculation of the treatment plans. Plan quality metrics such as the Paddick conformity index were compared for both planning techniques with additional subdivisions into the 3 selectable IP planning strategies and different entity groups. ResultsIP calculated treatment plans of quality similar to that of preplans created by expert planners. Some plan quality metrics, especially those related to conformity and dose gradient, attained statistically significantly higher scores combined with high coverage for the inversely generated plans except for the selectivity optimizing strategy. Normal brain volume receiving 10 Gy or 12 Gy or higher (V10Gy or V12Gy) did not show significant differences for the coverage optimizing strategies. The IP software demonstrated significantly shorter planning times versus manual planning as well as greater numbers of isocenters, often associated with longer treatment times. In terms of total time, these differences almost balanced out again. ConclusionsOur results suggest that IP is advantageous for complex tumors. We observed general clinical significance for conformity and superiority for the selectivity optimizing strategy. In addition, the high-quality calculation from IP enables novices in the profession to achieve pre-treatment plans of a quality similar to that of expert planners. IP allows for optimizing the sparing of surrounding tissue and conformity for benign tumors within a short time. Thus, IP forms a solid basis for further planning on the treatment day.

Possibilities and challenges when using synthetic computed tomography in an adaptive carbon-ion treatment workflow

Background and purposeAnatomical surveillance during ion-beam therapy is the basis for an effective tumor treatment and optimal organ at risk (OAR) sparing. Synthetic computed tomography (sCT) based on magnetic resonance imaging (MRI) can replace the X-ray based planning CT (X-rayCT) in photon radiotherapy and improve the workflow efficiency without additional imaging dose. The extension to carbon-ion radiotherapy is highly challenging; complex patient positioning, unique anatomical situations, distinct horizontal and vertical beam incidence directions, and limited training data are only few problems. This study gives insight into the possibilities and challenges of using sCTs in carbon-ion therapy. Materials and methodsFor head and neck patients immobilised with thermoplastic masks 30 clinically applied actively scanned carbon-ion treatment plans on 15 CTs comprising 60 beams were analyzed. Those treatment plans were re-calculated on MRI based sCTs which were created employing a 3D U-Net. Dose differences and carbon-ion spot displacements between sCT and X-rayCT were evaluated on a patient specific basis. ResultsSpot displacement analysis showed a peak displacement by 0.2 cm caused by the immobilisation mask not measurable with the MRI. 95.7% of all spot displacements were located within 1 cm. For the clinical target volume (CTV) the median D50% agreed within −0.2% (−1.3 to 1.4%), while the median D0.01cc differed up to 4.2% (−1.3 to 25.3%) comparing the dose distribution on the X-rayCT and the sCT. OAR deviations depended strongly on the position and the dose gradient. For three patients no deterioration of the OAR parameters was observed. Other patients showed large deteriorations, e.g. for one patient D2% of the chiasm differed by 28.1%. ConclusionThe usage of sCTs opens several new questions, concluding that we are not ready yet for an MR-only workflow in carbon-ion therapy, as envisaged in photon therapy. Although omitting the X-rayCT seems unfavourable in the case of carbon-ion therapy, an sCT could be advantageous for monitoring, re-planning, and adaptation.

Clinical validation of novel lightning dose optimizer for gamma knife radiosurgery of irregular-shaped arteriovenous malformations and pituitary adenomas.

PurposeTo demonstrate the clinical feasibility of a novel treatment planning algorithm via lightning dose optimizer (LDO) on Leksell Gamma Knife (LGK) GammaPlan with significantly faster planning times for stereotactic radiosurgery (SRS) of the complex and difficult arteriovenous malformations (AVMs) and pituitary adenomas.Methods and materialsAfter completing the in‐house end‐to‐end phantom testing and independent dose verification of the recently upgraded LDO algorithm on GammaPlan using the MD Anderson's IROC anthropomorphic SRS head phantom irradiation credentialing, 20 previously treated GK‐SRS patients (10 AVM, average volume 3.61 cm3 and 10 pituitary adenomas, average volume 0.86 cm3) who underwent manual forward planning on GammaPlan were retrospectively replanned via LDO. These pathologies were included because of the need for adequate dose delivery with organs at risk in very close proximity. LDO finds the target curvature boundary by well‐formulated linear programing objectives and inversely optimizes the GK‐SRS plan by isocenter placement, optimization, and sequencing. For identical target coverage, the LDO and original manual plans were compared for target conformity, gradient index, dose to critical organs, and surrounding normal brain. Additionally, various treatment delivery parameters, including beam‐on time were recorded.ResultsFor both patient cohorts, LDO provided similar target coverage with better dose conformity, tighter radiosurgical dose distribution with a lower value of gradient indices (all p < 0.001), and lower dose to critical organs. For AVMs, there was a significant reduction of normal brain V 10Gy, V 12Gy, and V 14Gy by 4.74, 3.67, and 2.67 cm3 (all p < 0.001). LDO had twice the number of shots (p < 0.001), and longer beam‐on time (p = 0.012) by a factor of 1.44. For pituitary adenomas, LDO provided systematically lower values of V 10Gy, V 12Gy, and V 14Gy by 1.08, 0.86, and 0.68 cm3 (all p < 0.001), and lower maximum dose to optic pathway by 0.7 Gy (p = 0.005), but had almost twice the numbers of shots (p < 0.001) and increased beam‐on time (p = 0.005) by a factor of 1.2. However, for both patient groups, the average planning time for the LDO was <5 min, compared to the estimated 30–90 min of manual planning times.ConclusionGK‐SRS treatment on Leksell Perfexion GammaPlan using the LDO provided highly conformal target coverage with a steep dose gradient, spared critical organs, and significantly reduced normal brain dose for complex targets at the cost of slightly higher treatment times. LDO generated high‐quality treatment plans and could significantly reduce planning time. If available, the LDO algorithm is suggested for validation and clinical use for complex and difficult GK cases.

Time-Resolved Dosimetry of Pulsed Photon Beams for Radiotherapy Based on Diamond Detector

The widespread diffusion of precision radiotherapy techniques, geared toward the release of larger dose gradients in shorter time frames, is leading to new challenges in dosimetry. Accurate dose measurements are essential to check for beam anomalies and inaccuracies to ensure treatment efficacy and patient safety during radiotherapy. This work describes the main features of a diamond dosimeter coupled to an extremely compact front-end electronics. The detection system was tested under the X-ray pulses generated by a medical LINAC for both the 6 MV and the 18 MV accelerating voltages. Located in the LINAC's bunker, it eliminates the need for a long cable connection between the detector and the electronics, detrimental for the system response speed. Signal acquisition was performed synchronously with the impinging X-ray pulses with a sampling period as low as 20 us, allowing for a real-time beam monitoring. The dosimeter demonstrated a very good stability despite the high value of the absorbed dose during the performed experiments (about 100 Gy). The measured dose-per-pulse values of 278 uGy and 556 uGy at 6 MV and 18 MV, respectively, are in excellent agreement with the nominal values expected for the LINAC apparatus used for the tests. In addition to single-pulse measurements, fundamental for dynamic radiotherapy, the proposed system also allows for the calculation of both the total collected charge and the photocurrent generated by the detector. In this regards, despite the compactness, it demonstrates its effectiveness as a tool for source diagnostics in terms of both beam intensity and emission timing.

Treatment Planning for Cardiac Radioablation: Multicenter Multiplatform Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial

Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is necessary for multicenter clinical studies such as the RAdiosurgery for VENtricular TAchycardia trial. Planning computed tomography data and consensus structures from 3 patients were sent to 5 academic centers for independent plan development using a variety of platforms and techniques with the RAdiosurgery for VENtricular TAchycardia study protocol serving as guideline. Three-dimensional dose distributions and treatment plan details were collected and analyzed. In addition, an objective relative plan quality ranking system for ventricular tachycardia treatments was established. For each case, 3 coplanar volumetric modulated arc (VMAT) plans for C-arm linear accelerators (LINAC) and 3 noncoplanar treatment plans for robotic arm LINAC were generated. All plans were suitable for clinical applications with minor deviations from study guidelines in most centers. Eleven of 18 treatment plans showed maximal one minor deviation each for target and cardiac substructures. However, dose-volume histograms showed substantial differences: in one case, the planning target volume ≥30 Gy ranged from 0.0% to 79.9% and the ramus interventricularis anterior V14Gy ranged from 4.0% to 45.4%. Overall, the VMAT plans had steeper dose gradients in the high-dose region, while the plans for the robotic arm LINAC had smaller low-dose regions. Thereby, VMAT plans required only about half as many monitor units, resulting in shorter delivery times, possibly an important factor in treatment outcome. Cardiac radioablation is feasible with robotic arm and C-arm LINAC systems with comparable plan quality. Although cross-center training and best practice guidelines have been provided, further recommendations, especially for cardiac substructures, and ranking of dose guidelines will be helpful to optimize cardiac radioablation outcomes.

Proton radiography using discrete range modulation method – A Monte Carlo study

The advantage of proton therapy is the Bragg peak, but its range uncertainties can also lead to a certain dose deviation. This uncertainty can be reduced by using proton radiography to determine the water equivalent path length (WEPL). In this study, a discrete range modulation (DRM) method is introduced and its image quality compared with that of the previously reported continuous range modulation (CRM) method. MCNPX2.7.0 was used to simulate parallel proton beams with energies from 70 to 230 MeV at 2.5 MeV/step. In the DRM method, the WEPL can be related to R80 using the relationship between the proton energy and energy deposition at 80% of the fall-off (E80). For the CRM method, a dose gradient plan was created to estimate the relationship between WEPL and accumulated dose. DRM and CRM were compared using four different phantoms. For the slab, CIRS 062M head and cake phantoms, DRM had a good agreement with the theoretic WEPL: within 2 mm or 1%, and with a standard deviation of less than 0.5 mm. For the sphere phantom, DRM can achieve a GammapRG passing rate of 0.999, passing the criteria of a WEPL deviation of less than 2 mm and a distance-to-agreement of less than 3 mm. Proton radiographs made by the DRM method are more accurate and precise than those made by CRM. Two algorithms are proposed to solve the range mixing problems. DRM can also save unnecessary doses that do not contribute to imaging.

MTOR INHIBITOR IMPROVES TESTOSTERONE-INDUCED MYOCARDIAL HYPERTROPHY IN HYPERTENSIVE RATS

Objective: Compelling evidence have described the incidence of hypertension and left ventricular hypertrophy (LVH) in postmenopausal women is significantly increased worldwide. Our team’s previous research identified that androgen was an underlying factor contributing to increased blood pressure and LVH in postmenopausal women. However, little is known about how androgens affect LVH in postmenopausal hypertensive women. The purpose of this study was to evaluate the role of mTOR signaling pathway in myocardial hypertrophy in androgen-induced postmenopausal hypertension and whether mTOR inhibitors can protect the myocardium from androgen-induced interference to prevent and treat cardiac hypertrophy. Design and method: For that, ovariectomized (OVX) spontaneously hypertensive rats (SHR) aged 12 weeks were used to study the effects of testosterone (T 2.85 mg/kg/weekly im) on blood pressure and myocardial tissue. On the basis of antihypertensive therapy (chlorthalidone 8 mg/kg/day ig), the improvement of blood pressure and myocardial hypertrophy in rats treated with different dose gradients of rapamycin (0.8 mg/kg/day Vs 1.5 mg/kg/day Vs 2 mg/kg/day ip) in OVX+ estrogens (E 9.6 mg/Kg/day, ig)+T group was further evaluated. Results: After T intervention, the OVX female rats exhibited significant increments in the heart weight / tibial length (TL), cross-sectional area of cardiomyocytes and the mRNA expressions of atrial natriuretic peptide, B- myosin heavy chain and matrix metalloproteinase 9 accompanied by a significant reduction in the uterine weight/TL and issue inhibitor of metalloproteinase 1. Mammalian rapamycin receptor (mTOR), ribosomal protein S6 kinase (S6K1), 4E-bindiong protein 1(4EBP1) and eukaryotic translation initiation factor 4E in myocardial tissue of OVX+E+T group were expressed at higher levels than those of the other four groups. On the other hand, rapamycin abolished the effects of T-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/ S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Conclusions: Collectively, these data suggest that the mTOR/S6K1/4EBP1 pathway is an important therapeutic target for the prevention of LVH in postmenopausal hypertensive women with high T levels. Our findings also support the standpoint that the mTOR inhibitor, rapamycin, can eliminate T-induced cardiomyocyte hypertrophy.