Investigation of the Electrokinetic Properties of HIV-Based Virus-Like Particles.

The antigen density on the surface of HIV-based virus-like particles (VLPs) plays a crucial role in the improvement of HIV vaccine potency. HIV VLPs consist of a dense protein core, which is surrounded by a lipid bilayer and whose surface is usually decorated with antigenic glycoproteins. The successful downstream processing of these particles is challenging, and the high-resolution and cost-efficient purification of HIV-based VLPs has not yet been achieved. Chromatography, one of the major unit operations involved in HIV VLP purification strategies, is usually carried out by means of ion exchangers or ion-exchange membranes. Understanding the electrokinetic behavior of HIV-based VLPs may help to improve the adjustment and efficiency of the corresponding chromatographic processes. In this study, we investigated the electrokinetics and aggregation of both undecorated and decorated VLPs and interpreted the data from the perspective of the soft particle model developed by Ohshima (OSPM), which fails to fully predict the behavior of the studied VLPs. Post-Ohshima literature, and particularly the soft multilayer particle model developed by Langlet et al., provides an alternative theoretical framework to overcome the limits of the OSPM. We finally hypothesized that the electrophoretic mobility of HIV-based VLPs is controlled by an electrohydrodynamic interplay between envelope glycoproteins, lipid bilayer, and Gag envelope.

Hypofractionated stereotactic radiotherapy (HFSRT) versus single fraction stereotactic radiosurgery (SRS) to the resection cavity of brain metastases after surgical resection (SATURNUS): study protocol for a randomized phase III trial.

BACKGROUND: The brain is a common site for cancer metastases. In case of large and/or symptomatic brain metastases, neurosurgical resection is performed. Adjuvant radiotherapy is a standard procedure to minimize the risk of local recurrence and is increasingly performed as local stereotactic radiotherapy to the resection cavity. Both hypofractionated stereotactic radiotherapy (HFSRT) and single fraction stereotactic radiosurgery (SRS) can be applied in this case. Although adjuvant stereotactic radiotherapy to the resection cavity is widely used in clinical routine and recommended in international guidelines, the optimal fractionation scheme still remains unclear. The SATURNUS trial prospectively compares adjuvant HFSRT with SRS and seeks to detect the superiority of HFSRT over SRS in terms of local tumor control. METHODS: In this single center two-armed randomized phase III trial, adjuvant radiotherapy to the resection cavity of brain metastases with HFSRT (6 - 7 × 5 Gy prescribed to the surrounding isodose) is compared to SRS (1 × 12-20 Gy prescribed to the surrounding isodose). Patients are randomized 1:1 into the two different treatment arms. The primary endpoint of the trial is local control at the resected site at 12 months. The trial is based on the hypothesis that HFSRT is superior to SRS in terms of local tumor control. DISCUSSION: Although adjuvant stereotactic radiotherapy after resection of brain metastases is considered standard of care treatment, there is a need for further prospective research to determine the optimal fractionation scheme. To the best of our knowledge, the SATURNUS study is the only randomized phase III study comparing different regimes of postoperative stereotactic radiotherapy to the resection cavity adequately powered to detect the superiority of HFSRT regarding local control. TRIAL REGISTRATION: The study was retrospectively registered with ClinicalTrials.gov, number NCT05160818, on December 16, 2021. The trial registry record is available on  https://clinicaltrials.gov/study/NCT05160818 . The presented protocol refers to version V1.3 from March 21, 2021.

X-ray Dark-Field CT for Early Detection of Radiation-induced Lung Injury in a Murine Model.

Online supplemental material is available for this article.

Early detection of radiation-induced lung damage with X-ray dark-field radiography in mice.

OBJECTIVE: Assessing the advantage of x-ray dark-field contrast over x-ray transmission contrast in radiography for the detection of developing radiation-induced lung damage in mice. METHODS: Two groups of female C57BL/6 mice (irradiated and control) were imaged obtaining both contrasts monthly for 28 weeks post irradiation. Six mice received 20 Gy of irradiation to the entire right lung sparing the left lung. The control group of six mice was not irradiated. A total of 88 radiographs of both contrasts were evaluated for both groups based on average values for two regions of interest, covering (irradiated) right lung and healthy left lung. The ratio of these average values, R, was distinguished between healthy and damaged lungs for both contrasts. The time-point when deviations of R from healthy lung exceeded 3σ was determined and compared among contrasts. The Wilcoxon-Mann-Whitney test was used to test against the null hypothesis that there is no difference between both groups. A selection of 32 radiographs was assessed by radiologists. Sensitivity and specificity were determined in order to compare the diagnostic potential of both contrasts. Inter-reader and intra-reader accuracy were rated with Cohen's kappa. RESULTS: Radiation-induced morphological changes of lung tissue caused deviations from the control group that were measured on average 10 weeks earlier with x-ray dark-field contrast than with x-ray transmission contrast. Sensitivity, specificity, and accuracy doubled using dark-field radiography. CONCLUSION: X-ray dark-field radiography detects morphological changes of lung tissue associated with radiation-induced damage earlier than transmission radiography in a pre-clinical mouse model. KEY POINTS: • Significant deviations from healthy lung due to irradiation were measured after 16 weeks with x-ray dark-field radiography (p = 0.004). • Significant deviations occur on average 10 weeks earlier for x-ray dark-field radiography in comparison to x-ray transmission radiography. • Sensitivity and specificity doubled when using x-ray dark-field radiography instead of x-ray transmission radiography.

Craniospinal irradiation(CSI) in patients with leptomeningeal metastases: risk-benefit-profile and development of a prognostic score for decision making in the palliative setting.

BACKGROUND: The aim of our study was to assess the feasibility and oncologic outcomes in patients treated with spinal (SI) or craniospinal irradiation (CSI) in patients with leptomeningeal metastases (LM) and to suggest a prognostic score as to which patients are most likely to benefit from this treatment. METHODS: Nineteen patients treated with CSI at our institution were eligible for the study. Demographic data, primary tumor characteristics, outcome and toxicity were assessed retrospectively. The extent of extra-CNS disease was defined by staging CT-scans before the initiation of CSI. Based on outcome parameters a prognostic score was developed for stratification based on patient performance status and tumor staging. RESULTS: Median follow-up and overall survival (OS) for the whole group was 3.4 months (range 0.5-61.5 months). The median overall survival (OS) for patients with LM from breast cancer was 4.7 months and from NSCLC 3.3 months. The median OS was 7.3 months, 3.3 months and 1.5 months for patients with 0, 1 and 2 risk factors according to the proposed prognostic score (KPS < 70 and the presence of extra-CNS disease) respectively. Nonhematologic toxicities were mild. CONCLUSION: CSI demonstrated clinically meaningful survival that is comparable to the reported outcome of intrathecal chemotherapy. A simple scoring system could be used to better select patients for treatment with CSI in this palliative setting. In our opinion, the feasibility of performing CSI with modern radiotherapy techniques with better sparing of healthy tissue gives a further rationale for its use also in the palliative setting.

A proof of principle experiment for microbeam radiation therapy at the Munich compact light source.

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich compact light source (MuCLS), one of these novel compact X-ray facilities, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay. For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3 Gy or 5 Gy and tumor growth delay was measured. Microbeams had a width of 50 µm and a center-to-center distance of 350 µm with peak doses of either 21 Gy or 35 Gy. A dose rate of up to 5 Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that MRT can be successfully performed in vivo at compact inverse Compton sources.

The dosimetric impact of stabilizing spinal implants in radiotherapy treatment planning with protons and photons: standard titanium alloy vs. radiolucent carbon-fiber-reinforced PEEK systems.

BACKGROUND: Throughout the last years, carbon-fibre-reinforced PEEK (CFP) pedicle screw systems were introduced to replace standard titanium alloy (Ti) implants for spinal instrumentation, promising improved radiotherapy (RT) treatment planning accuracy. We compared the dosimetric impact of both implants for intensity modulated proton (IMPT) and volumetric arc photon therapy (VMAT), with the focus on uncertainties in Hounsfield unit assignment of titanium alloy. METHODS: Retrospective planning was performed on CT data of five patients with Ti and five with CFP implants. Carbon-fibre-reinforced PEEK systems comprised radiolucent pedicle screws with thin titanium-coated regions and titanium tulips. For each patient, one IMPT and one VMAT plan were generated with a nominal relative stopping power (SP) (IMPT) and electron density (ρ) (VMAT) and recalculated onto the identical CT with increased and decreased SP or ρ by ±6% for the titanium components. RESULTS: Recalculated VMAT dose distributions hardly deviated from the nominal plans for both screw types. IMPT plans resulted in more heterogeneous target coverage, measured by the standard deviation σ inside the target, which increased on average by 7.6 ± 2.3% (Ti) vs 3.4 ± 1.2% (CFP). Larger SPs lead to lower target minimum doses, lower SPs to higher dose maxima, with a more pronounced effect for Ti screws. CONCLUSIONS: While VMAT plans showed no relevant difference in dosimetric quality between both screw types, IMPT plans demonstrated the benefit of CFP screws through a smaller dosimetric impact of CT-value uncertainties compared to Ti. Reducing metal components in implants will therefore improve dose calculation accuracy and lower the risk for tumor underdosage.

Early and late toxicity profiles of patients receiving immediate postoperative radiotherapy versus salvage radiotherapy for prostate cancer after prostatectomy.

PURPOSE: The present study aims to evaluate both early and late toxicity profiles of patients receiving immediate postoperative radiotherapy (RT; adjuvant RT or additive RT) compared to salvage RT. METHODS: We evaluated 253 patients with prostate cancer treated with either immediate postoperative (adjuvant RT, n = 42; additive RT, n = 39) or salvage RT (n = 137). Thirty-five patients received salvage treatment but did not achieve a postoperative prostate specific antigen (PSA) level <0.1 ng/ml and thus were excluded from analysis. RESULTS: A significantly higher rate of early grade 1/2 proctitis in the immediate postoperative RT group without additional pelvic RT was observed (p = 0.02). Patients in the immediate postoperative RT group without additional pelvic RT showed significantly more early urinary tract obstructions (p = 0.003). Toxicity rates of early (<3 months) and late (3-6 months) postoperative RT were similar (p > 0.05). Baseline recovery rate of erectile dysfunction was better in patients with immediate postoperative RT without additional pelvic RT (p = 0.02; hazard ratio (HR) = 2.22, 95%-confidence interval, 95%-CI: 1.12-4.37). Recovery rate of urinary incontinence showed no significant difference in all groups (p > 0.05). CONCLUSION: Patients receiving immediate postoperative RT (adjuvant or additive RT) without additional pelvic RT experience early gastrointestinal (GI) side effect proctitis and, as well as early genitourinary (GU) toxicity urinary tract obstruction more frequently than patients treated with salvage RT. Therefore, complete recovery after surgery is essential. However, we suggest basing the treatment decision on the patient's postoperative clinical condition and evaluation of any adverse risk factors, since many studies demonstrate a clear benefit for immediate postoperative RT (adjuvant or additive RT) in terms of oncological outcome.

Interobserver variability of patient positioning using four different CT datasets for image registration in lung stereotactic body radiotherapy.

PURPOSE: To assess the impact of different reference CT datasets on manual image registration with free-breathing three-dimensional (3D) cone beam CTs (FB-CBCT) for patient positioning by several observers. METHODS: For 48 patients with lung lesions, manual image registration with FB-CBCTs was performed by four observers. A slow planning CT (PCT), average intensity projection (AIP), maximum intensity projection (MIP), and midventilation CT (MidV) were used as reference images. Couch shift differences between the four reference CT datasets for each observer as well as shift differences between the observers for the same reference CT dataset were determined. Statistical analyses were performed and correlations between the registration differences and the 3D tumor motion and the CBCT score were calculated. RESULTS: The mean 3D shift difference between different reference CT datasets was the smallest for AIPvsMIP (range 1.1-2.2 mm) and the largest for MidVvsPCT (2.8-3.5 mm) with differences >10 mm. The 3D shifts showed partially significant correlations to 3D tumor motion and CBCT score. The interobserver comparison for the same reference CTs resulted in the smallest ∆3D mean differences and mean ∆3D standard deviation for ∆AIP (1.5 ± 0.7 mm, 0.7 ± 0.4 mm). The maximal 3D shift difference between observers was 10.4 mm (∆MidV). Both 3D tumor motion and mean CBCT score correlated with the shift differences (Rs = 0.336-0.740). CONCLUSION: The applied reference CT dataset impacts image registration and causes interobserver variabilities. The 3D tumor motion and CBCT quality affect shift differences. The smallest differences were found for AIP which might be the most appropriate CT dataset for image registration with FB-CBCT.

Individualized radiotherapy by combining high-end irradiation and magnetic resonance imaging.

Image-guided radiotherapy (IGRT) has been integrated into daily clinical routine and can today be considered the standard especially with high-dose radiotherapy. Currently imaging is based on MV- or kV-CT, which has clear limitations especially in soft-tissue contrast. Thus, combination of magnetic resonance (MR) imaging and high-end radiotherapy opens a new horizon. The intricate technical properties of MR imagers pose a challenge to technology when combined with radiation technology. Several solutions that are almost ready for routine clinical application have been developed. The clinical questions include dose-escalation strategies, monitoring of changes during treatment as well as imaging without additional radiation exposure during treatment.

Pencil beam kernel-based dose calculations on CT data for a mixed neutron-gamma fission field applying tissue correction factors.

Objective.For fast neutron therapy with mixed neutron and gamma radiation at the fission neutron therapy facility MEDAPP at the research reactor FRM II in Garching, no clinical dose calculation software was available in the past. Here, we present a customized solution for research purposes to overcome this lack of three-dimensional dose calculation.Approach.The applied dose calculation method is based on two sets of decomposed pencil beam kernels for neutron and gamma radiation. The decomposition was performed using measured output factors and simulated depth dose curves and beam profiles in water as reference medium. While measurements were performed by applying the two-chamber dosimetry method, simulated data was generated using the Monte Carlo code MCNP. For the calculation of neutron dose deposition on CT data, tissue-specific correction factors were generated for soft tissue, bone, and lung tissue for the MEDAPP neutron spectrum. The pencil beam calculations were evaluated with reference to Monte Carlo calculations regarding accuracy and time efficiency.Main results.In water, dose distributions calculated using the pencil beam approach reproduced the input from Monte Carlo simulations. For heterogeneous media, an assessment of the tissue-specific correction factors with reference to Monte Carlo simulations for different tissue configurations showed promising results. Especially for scenarios where no lung tissue is present, the dose calculation could be highly improved by the applied correction method.Significance.With the presented approach, time-efficient dose calculations on CT data and treatment plan evaluations for research purposes are now available for MEDAPP.

In Vivo Microbeam Radiation Therapy at a Conventional Small Animal Irradiator.

Microbeam radiation therapy (MRT) is a still pre-clinical form of spatially fractionated radiotherapy, which uses an array of micrometer-wide, planar beams of X-ray radiation. The dose modulation in MRT has proven effective in the treatment of tumors while being well tolerated by normal tissue. Research on understanding the underlying biological mechanisms mostly requires large third-generation synchrotrons. In this study, we aimed to develop a preclinical treatment environment that would allow MRT independent of synchrotrons. We built a compact microbeam setup for pre-clinical experiments within a small animal irradiator and present in vivo MRT application, including treatment planning, dosimetry, and animal positioning. The brain of an immobilized mouse was treated with MRT, excised, and immunohistochemically stained against γH2AX for DNA double-strand breaks. We developed a comprehensive treatment planning system by adjusting an existing dose calculation algorithm to our setup and attaching it to the open-source software 3D-Slicer. Predicted doses in treatment planning agreed within 10% with film dosimetry readings. We demonstrated the feasibility of MRT exposures in vivo at a compact source and showed that the microbeam pattern is observable in histological sections of a mouse brain. The platform developed in this study will be used for pre-clinical research of MRT.

Reduced side effects by proton microchannel radiotherapy: study in a human skin model.

The application of a microchannel proton irradiation was compared to homogeneous irradiation in a three-dimensional human skin model. The goal is to minimize the risk of normal tissue damage by microchannel irradiation, while preserving local tumor control through a homogeneous irradiation of the tumor that is achieved because of beam widening with increasing track length. 20 MeV protons were administered to the skin models in 10- or 50-µm-wide irradiation channels on a quadratic raster with distances of 500 µm between each channel (center to center) applying an average dose of 2 Gy. For comparison, other samples were irradiated homogeneously at the same average dose. Normal tissue viability was significantly enhanced after microchannel proton irradiation compared to homogeneous irradiation. Levels of inflammatory parameters, such as Interleukin-6, TGF-Beta, and Pro-MMP1, were significantly lower in the supernatant of the human skin tissue after microchannel irradiation than after homogeneous irradiation. The genetic damage as determined by the measurement of micronuclei in keratinocytes also differed significantly. This difference was quantified via dose modification factors (DMF) describing the effect of each irradiation mode relative to homogeneous X-ray irradiation, so that the DMF of 1.21 ± 0.20 after homogeneous proton irradiation was reduced to 0.23 ± 0.11 and 0.40 ± 0.12 after microchannel irradiation using 10- and 50-µm-wide channels, respectively. Our data indicate that proton microchannel irradiation maintains cell viability while significantly reducing inflammatory responses and genetic damage compared to homogeneous irradiation, and thus might improve protection of normal tissue after irradiation.

Development of a PTV margin for preclinical irradiation of orthotopic pancreatic tumors derived from a well-known recipe for humans.

In human radiotherapy a safety margin (PTV margin) is essential for successful irradiation and is usually part of clinical treatment planning. In preclinical radiotherapy research with small animals, most uncertainties and inaccuracies are present as well, but according to the literature a margin is used only scarcely. In addition, there is only little experience about the appropriate size of the margin, which should carefully be investigated and considered, since sparing of organs at risk or normal tissue is affected. Here we estimate the needed margin for preclinical irradiation by adapting a well-known human margin recipe from van Herck et al. to the dimensions and requirements of the specimen on a small animal radiation research platform (SARRP). We adjusted the factors of the described formula to the specific challenges in an orthotopic pancreatic tumor mouse model to establish an appropriate margin concept. The SARRP was used with its image-guidance irradiation possibility for arc irradiation with a field size of 10 × 10 mm2 for 5 fractions. Our goal was to irradiate the clinical target volume (CTV) of at least 90% of our mice with at least 95% of the prescribed dose. By carefully analyzing all relevant factors we gain a CTV to planning target volume (PTV) margin of 1.5 mm for our preclinical setup. The stated safety margin is strongly dependent on the exact setting of the experiment and has to be adjusted for other experimental settings. The few stated values in literature correspond well to our result. Even if using margins in the preclinical setting might be an additional challenge, we think it is crucial to use them to produce reliable results and improve the efficacy of radiotherapy.

Roadmap for precision preclinical x-ray radiation studies.

This Roadmap paper covers the field of precision preclinical x-ray radiation studies in animal models. It is mostly focused on models for cancer and normal tissue response to radiation, but also discusses other disease models. The recent technological evolution in imaging, irradiation, dosimetry and monitoring that have empowered these kinds of studies is discussed, and many developments in the near future are outlined. Finally, clinical translation and reverse translation are discussed.

Comparison of 3 Positioning Techniques for Fractionated High-precision Radiotherapy in an Orthotopic Mouse Model of Pancreatic Cancer.

Small-animal irradiators are widely used in oncologic research, and many experiments use mice to mimic radiation treatments in humans. To improve fractionated high-precision irradiation in mice with orthotopic pancreatic tumors, we evaluated 3 positioning methods: no positioning aid, skin marker, and immobilization devices (immobilization masks). We retrospectively evaluated the translation vector needed for optimal tumor alignment (by shifting the mouse in left-right, in cranio-caudal, and in anterior-posterior direction) on cone-beam CT from our small-animal radiotherapy system. Of the 3 methods, the skin marker method yielded the smallest mean translation vector (3.8 mm) and was the most precise method overall for most of the mice. In addition, the skin marker method required supplemental rotation (that is, roll, pitch, and yaw) for optimal tumor alignment only half as often as positioning without a positioning aid. Finally, the skin marker method had the highest scores for the quality of the fusion results. Overall, we preferred the skin marker method over the other 2 positioning methods with regard to optimal treatment planning and radiotherapy in an orthotopic mouse model of pancreatic cancer.

A comprehensive and efficient quality assurance program for an image-guided small animal irradiation system.

In the field of preclinical radiotherapy, many new developments were driven by technical innovations. To make research of different groups comparable in that context and reliable, high quality has to be maintained. Therefore, standardized protocols and programs should be used. Here we present a guideline for a comprehensive and efficient quality assurance program for an image-guided small animal irradiation system, which is meant to test all the involved subsystems (imaging, treatment planning, and the irradiation system in terms of geometric accuracy and dosimetric aspects) as well as the complete procedure (end-to-end test) in a time efficient way. The suggestions are developed on a Small Animal Radiation Research Platform (SARRP) from Xstrahl (Xstrahl Ltd., Camberley, UK) and are presented together with proposed frequencies (from monthly to yearly) and experiences on the duration of each test. All output and energy related measurements showed stable results within small variation. Also, the motorized parts (couch, gantry) and other geometrical alignments were very stable. For the checks of the imaging system, the results are highly dependent on the chosen protocol and differ according to the settings. We received nevertheless stable and comparably good results for our mainly used protocol. All investigated aspects of treatment planning were exactly fulfilled and also the end-to-end test showed satisfying values. The mean overall time we needed for our checks to have a well monitored machine is less than two hours per month.

Dual energy CT for a small animal radiation research platform using an empirical dual energy calibration.

Objective.Dual energy computed tomography (DECT) has been shown to provide additional image information compared to conventional CT and has been used in clinical routine for several years. The objective of this work is to present a DECT implementation for a Small Animal Radiation Research Platform (SARRP) and to verify it with a quantitative analysis of a material phantom and a qualitative analysis with anex-vivomouse measurement.Approach.For dual energy imaging, two different spectra are required, but commercial small animal irradiators are usually not optimized for DECT. We present a method that enables dual energy imaging on a SARRP with sequential scanning and an Empirical Dual Energy Calibration (EDEC). EDEC does not require the exact knowledge of spectra and attenuation coefficients; instead, it is based on a calibration. Due to the SARRP geometry and reconstruction algorithm, the calibration is done using an artificial CT image based on measured values. The calibration yields coefficients to convert the measured images into material decomposed images.Main results.To analyze the method quantitatively, the electron density and the effective atomic number of a material phantom were calculated and compared with theoretical values. The electron density showed a maximum deviation from the theoretical values of less than 5% and the atomic number of slightly more than 6%. For use in mice, DECT is particularly useful in distinguishing iodine contrast agent from bone. A material decomposition of anex-vivomouse with iodine contrast agent was material decomposed to show that bone and iodine can be distinguished and iodine-corrected images can be calculated.Significance.DECT is capable of calculating electron density images and effective atomic number images, which are appropriate parameters for quantitative analysis. Furthermore, virtual monochromatic images can be obtained for a better differentiation of materials, especially bone and iodine contrast agent.

Treatment Planning Study for Microbeam Radiotherapy Using Clinical Patient Data.

Microbeam radiotherapy (MRT) is a novel, still preclinical dose delivery technique. MRT has shown reduced normal tissue effects at equal tumor control rates compared to conventional radiotherapy. Treatment planning studies are required to permit clinical application. The aim of this study was to establish a dose comparison between MRT and conventional radiotherapy and to identify suitable clinical scenarios for future applications of MRT. We simulated MRT treatment scenarios for clinical patient data using an inhouse developed planning algorithm based on a hybrid Monte Carlo dose calculation and implemented the concept of equivalent uniform dose (EUD) for MRT dose evaluation. The investigated clinical scenarios comprised fractionated radiotherapy of a glioblastoma resection cavity, a lung stereotactic body radiotherapy (SBRT), palliative bone metastasis irradiation, brain metastasis radiosurgery and hypofractionated breast cancer radiotherapy. Clinically acceptable treatment plans were achieved for most analyzed parameters. Lung SBRT seemed the most challenging treatment scenario. Major limitations comprised treatment plan optimization and dose calculation considering the tissue microstructure. This study presents an important step of the development towards clinical MRT. For clinical treatment scenarios using a sophisticated dose comparison concept based on EUD and EQD2, we demonstrated the capability of MRT to achieve clinically acceptable dose distributions.

Low-Energy X-Ray Intraoperative Radiation Therapy (Lex-IORT) for Resected Brain Metastases: A Single-Institution Experience.

BACKGROUND: Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest. METHOD: Eighteen consecutive patients undergoing BM resection followed by immediate lex-IORT with 16-30 Gy applied to the spherical applicator were retrospectively analyzed. Demographic, RT-specific, radiographic and clinical data were reviewed to evaluate the effectiveness and safety of IORT for BM. Descriptive statistics and Kaplan-Meyer analysis were applied. RESULTS: The mean follow-up time was 10.8 months (range, 0-39 months). The estimated local control (LC), distant brain control (DBC) and overall survival (OS) at 12 months post IORT were 92.9% (95%-CI 79.3-100%), 71.4% (95%-CI 50.2-92.6%) and 58.0% (95%-CI 34.1-81.9%), respectively. Two patients developed radiation necrosis (11.1%) and wound infection (CTCAE grade III); both had additional adjuvant treatment after IORT. For five patients (27.8%), the time to the start or continuation of systemic treatment was ≤15 days and hence shorter than wound healing and adjuvant RT would have required. CONCLUSION: In accordance with previous series, this study demonstrates the effectiveness and safety of IORT in the management of brain metastases despite the small cohort and the retrospective characteristic of this analysis.