Single Fraction Research Articles

MICP treated sand: insights into the impact of particle size on mechanical parameters and pore network after biocementation

Microbiologically Induced Calcium Carbonate Precipitation (MICP) is a technology for improving soil characteristics, especially strength, that has been gaining increasing interest in literature during the last few years. Although a lot of influencing factors on the result of MICP are known, particle size and shape of the particles remain poorly understood. While destructive measuring of compressive strength or calcium carbonate content are important for the characterization of samples these methods give no insight into the internal structures and pore networks of the samples. X-ray microcomputed tomography (micro-CT) is a technique that is used to characterize the internals of rocks and to a certain degree MICP-treated soils. However, the impact of filtering and image processing of micro-CT Data depending on the type of MICP sample is poorly described in the literature. In this study, single fractions of local quarry were treated with MICP through the ureolytic microorganism Sporosarcina pasteurii to investigate the influence of particle size distribution on calcium carbonate content, unconfined compressive strength and the reduction of water permeability. Additionally, micro-CT was conducted to obtain insights into the resulting pore system. The impact of the Gauss filter und Non-local means filter on the resulting images and data on the pore network are discussed. The results show that particle size has a significant impact on the result of all tested parameters of biosandstone with lower particle size leading to higher strength and generally higher calcium carbonate content. Micro-CT data showed that the technology is feasible to gain valuable insights into the internal structures of biosandstone but the resolution and signal-to-noise ratio remain challenging, especially for samples with particle sizes smaller than 125 µm.

Long-Term Outcomes After Cyberknife Radiosurgery for Nonfunctioning Pituitary Adenomas.

Stereotactic radiosurgery (SRS) has been widely adopted as an important adjunctive treatment modality for managing nonfunctioning pituitary adenomas (NFPAs). However, current studies on the long-term effects of SRS on pituitary adenomas have been largely limited by small sample sizes and short follow-up periods. The aim of this study was to evaluate the long-term outcomes of SRS for NFPAs. We conducted a retrospective review of 178 patients with NFPAs who received Cyberknife radiosurgery at a single institution between February 2008 and July 2021. Long-term outcomes of tumor control, new-onset hypopituitarism, and new visual disorders were assessed. During a median radiological follow-up of 49.7 months (range, 2.5-158.1 months), only 11 (7.0%) patients experienced tumor progression. The progression-free survival at 3, 5, and 10 years was 97.47%, 95.57%, and 93.04%, respectively. New-onset hypopituitarism was diagnosed in 27 (16.9%) patients with a median clinical follow-up duration of 71.2 months (range, 11.5-175.4 months). The median time from SRS to new-onset hypopituitarism was 28.3 months (range, 2.8-101.7 months). The cumulative incidence of new-onset hypopituitarism at 3, 5, and 10 years was 8.47%, 12.43%, and 15.25%, respectively. Biological effective dose >140 Gy and single fraction equivalent dose >16.0 Gy were significant risk factors for new-onset hypopituitarism (P = .046). Other adverse events were experienced by 15 (8.4%) patients, 9 (5.1%) of whom presented with new visual disorders. Development of new visual disorders was associated with a pretreatment tumor volume of >2.5 mL (P = .044). SRS is an effective and relatively safe means of managing both primary and residual/recurrent NFPAs.

NaOH-assisted hydrothermal reduction of graphene oxide

The influence of the pH of the reaction medium on the structural characteristics of hydrothermally reduced graphene oxide, synthesized by the Tour method, has been investigated. Varying the pH of the reaction medium within the range of 8.0, 10.0 and 12.0
(adjusted with NaOH) has revealed distinct effects on the morphology and properties of the resulting reduced graphene oxide. At a pH of 8.0 the hydrothermal treatment yielded reduced graphene oxide comprising of two particle fractions with a thickness equivalent to 4-5 graphitic layers each. In contrast, pH of 10.0 resulted in two particle fractions corresponding to 2-3 and 4 layers, respectively, while pH of 12.0 produced a single fraction with a particle thickness of 0.70 nm, encompassing 3 graphitic layers. Increasing the pH led to a decrease in the average lateral size of reduced graphene oxide particles to about 8 nm. All rGOs had micro- and mesopores with a specific surface area up to 226 m2/g, showing a proportional increase in mesopores with increasing pH. Analysis of slit-like micropores revealed a minimum fractal dimension (D = 2.18) at pH = 8.0. The obtained results provide valuable insights into tailoring the structural properties of hydrothermally reduced graphene oxide by controlling the pH of the reaction medium, offering potential applications in various fields, including nanotechnology and materials science.&#xD.

Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs. spread-out-Bragg-peak [SOBP]) on acute radiation-induced gastrointestinal toxicity (RIGIT) in mice. We also compared RIGIT between synchrotron-based protons and linac-based electrons with matched mean dose rates. We administered abdominal irradiation (12-14 Gy single fraction) to female C57BL/6J mice with an 87 MeV synchrotron-based proton beamline (2 cm diameter field size as a lateral beam). Dose rates were 0.2 Gy/s (S-T pCONV), 0.3 Gy/s (SOBP pCONV), 150 Gy/s (S-T pFLASH), and 230 Gy/s (SOBP pFLASH). RIGIT was assessed by the jejunal regenerating crypt assay and survival. We also compared responses to proton [pFLASH and pCONV] with responses to electron CONV (eCONV, 0.4 Gy/s) and electron FLASH (eFLASH, 188-205 Gy/s). The number of regenerating jejunal crypts at each matched dose was lowest for pFLASH (similar between S-T and SOBP), greater and similar between pCONV (S-T and SOBP) and eCONV, and greatest for eFLASH. Correspondingly, mice that received pFLASH SOBP had the lowest survival rates (50% at 50 days), followed by pFLASH S-T (80%), and pCONV SOBP (90%), but 100% of mice receiving pCONV S-T survived (log-rank P = 0.047 for the four groups). Our findings are consistent with an increase in RIGIT after synchrotron-based pFLASH versus pCONV. This negative proton-specific FLASH effect versus linac-based electron irradiation underscores the importance of understanding the physical and biological factors that will allow safe and effective clinical translation.

Dose tracking assessment for magnetic resonance guided adaptive radiotherapy of rectal cancers

BackgroundMagnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient’s daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy.MethodsNineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{T}\ ext{P}}_{\ ext{a}\ ext{d}\ ext{a}\ ext{p}}$$\\end{document}), a second plan (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{T}\ ext{P}}_{\ ext{I}\ ext{G}\ ext{R}\ ext{T}}$$\\end{document}) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{T}\ ext{P}}_{\ ext{a}\ ext{d}\ ext{a}\ ext{p}}$$\\end{document} and\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:{\ ext{T}\ ext{P}}_{\ ext{I}\ ext{G}\ ext{R}\ ext{T}}$$\\end{document}was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters.ResultsNinety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{D}}_{15\ ext{c}\ ext{c}}$$\\end{document} values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{D}}_{5\ ext{c}\ ext{c}}$$\\end{document} values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements.ConclusionsMRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

Radiosurgery for Facial Pain: A Narrative Review.

The surgical treatment of pain has been an integral part of neurosurgery since the early 20th century when Harvey Cushing pioneered ganglionectomy for trigeminal neuralgia. Over the ensuing years, as anatomic and physiologic knowledge of pain systems grew, new techniques aimed at new targets were developed for various pain conditions. Our objective was to provide an informative and up-to-date summary of radiosurgery for chronic facial pain, emphasizing trigeminal neuralgia and discussing the advantages and challenges of this modality. A PubMed search with keywords ("trigeminal neuralgia" or "cluster headache" or "glossopharyngeal neuralgia") and ("radiosurgery") and ("systematic review" or "review") was conducted. Relevant publications in English published from January 2000 to May 2022 were screened manually for their title, abstract, and even full text to determine their relevance. References from the searched articles were also searched as other supplementary articles. We excluded original articles and personal series from the analysis and only considered systematic reviews to maintain the transparency in the record. A total of 19 studies for trigeminal neuralgia (n > 100), 52 cases of cluster headache, and 42 cases of glossopharyngeal neuralgia were found. Radiosurgery remains the safest among various treatment options with equitable pain control with other percutaneous procedures. MVD remains the gold standard for long-term pain control. There is no difference in efficacy or tolerance between patients treated with gamma knife, linear accelerator, or CyberKnife. The minimum recommended prescription dose was 70 Gy (level of evidence II), and the maximum dose was 90 Gy (level of evidence III) in a single fraction. Radiosurgery provides 5-year pain control in 50% of patients without medication (85% of patients with/without medication) with an average latency period of 1-3 months. Approximately 8-15% of patients will experience a recurrence of pain after an average period of 1 year. Prospective pain relief will be about 60% at 3 years, 40% at 7 years, and 37% in 10 years. The main complication was facial hypoesthesia occurring in 25-50% of patients within 6 months-3 years and disabling in 10% of cases. Cluster headache and glossopharyngeal neuralgia are emerging conditions for treatment with GKRS, although long-term efficacy remains to be studied. Having searched PubMed and other databases and summarized the application of radiosurgery for facial pain, we concluded that radiosurgery is undoubtedly a promising tool for chronic facial pain, but further studies are needed to realize its long-term efficiency and advanced applications of the same.

Treatment plan quality for stereotactic treatment of multiple cranial metastases: Comparison of C-arm and O-ring treatment platforms

C-arm linacs have been used widely to treat multiple cranial metastases using stereotactic radiosurgery (SRS). A new generation of O-ring linacs offer several workflow advantages when compared to C-arm platforms. However, O-ring linacs are not able to employ couch rotations for noncoplanar beams used in SRS treatments. This study was conducted in order to simulate further possible developments of O-ring treatment units by assessing their geometrical efficiency. In this work we compare the plan quality for C-arm versus an O-ring platform including metrics that are relevant to SRS for multiple metastases. The comparison is conducted by incorporating tilted arcs on the O-ring platform therefore introducing noncoplanarity.Total 40 patients previously treated for SRS with 20 Gy single fraction were replanned for C-arm with a standard noncoplanar 5-arc arrangement and O-ring with both coplanar and noncoplanar beams. For the O-ring plans, we considered a default 3-arc coplanar arrangement, as well as 3- and 5-arc arrangements with arcs tipped up to 10 degrees from the axial plane. Target coverage, organ-at-risk (OAR) doses, monitor unit (MU) efficiency, conformity and gradient indices were assessed for all plans.For most metrics the O-ring geometries, even the coplanar arrangement, produced statistically comparable results to the C-arm. Small but significant differences were found for the 3 arc O-ring for PTV: D90%, D2% and MU/Gy and for the 5 arc O-ring at D2% when both were compared to the C-arm. Cumulative dose volume histograms (DVHs) for normal brain showed a cross-over between the C-arm and coplanar O-ring geometry at a low dose (2.3 ± 1.8 Gy), with O-ring associated with higher volumes above this cross-over dose. However, no statistical difference was seen in the brainstem, optic pathway and volumes of normal brain receiving 12 Gy or 20 Gy.This study has found that O-ring geometry linacs can produce SRS plans of comparable quality to those from a C-arm for multiple cranial metastases.

144 a Single Institution Retrospective Study of Palliative Single Fraction Whole/Near-Whole Liver Radiotherapy for Primary and Secondary Liver Disease

144 a Single Institution Retrospective Study of Palliative Single Fraction Whole/Near-Whole Liver Radiotherapy for Primary and Secondary Liver Disease

Single pre-operative radiation therapy (SPORT-CK) trial for low-risk breast cancer: Early results of a phase 2 study

Background and purposePreoperative partial breast irradiation (PBI) is a novel technique that can be used in patients with early-stage breast cancer with the goal of limiting the irradiated breast volume, toxicity and number of fractions. The aim of this trial is to assess the toxicity, surgical, oncologic and cosmetic outcomes of preoperative PBI. Materials and MethodsIn this single-arm phase II trial, we enrolled women ≥ 60 years, with unifocal low-risk breast invasive ductal carcinoma (cT1N0, grade 1–2, ER+, Her2-). Patients were treated with a single fraction of 20 Gy of preoperative PBI using volumetric modulated arc therapy (VMAT). Patients then underwent breast-conserving surgery (BCS) +/- sentinel lymph node biopsy within 72 h of radiation. Primary outcomes were rate of surgical complications and early toxicity. Secondary outcomes were cosmesis at 12 months, chronic toxicity and ipsilateral breast tumor recurrence. ResultsTwenty-five patients were recruited with a median age of 67 years, and a median follow-up of 60 months. Sentinel biopsy was positive in 1 out of 24 patients (4 %). Two patients received adjuvant RT for close margins or positive lymph nodes. Within the first 90 days, none of the patients had surgical complications; almost all had grade 0 to 1 acute and late RTOG skin toxicity. The cosmetic outcome was rated between good and excellent in all cases by physicians and patients, except for one patient who self-rated her cosmesis as fair as of the third year. There were no recurrences. ConclusionPreoperative single-fraction PBI is a safe and feasible treatment for elderly patients with low-risk early-stage breast cancer, with no surgical complications, very low rates of acute and late radiation toxicity, and excellent cosmetic outcomes. Randomized controlled trials are needed to compare preoperative to adjuvant PBI in this patient population.

Characterization of a Modified Clinical Linear Accelerator for Ultra-High Dose Rate Beam Delivery

Irradiations at Ultra-High Dose Rate (UHDR) regimes, exceeding 40 Gy/s in single fractions lasting less than 200 ms, have shown an equivalent antitumor effect compared to conventional radiotherapy with reduced harm to normal tissues. This work details the hardware and software modifications implemented to deliver 10 MeV UHDR electron beams with a linear accelerator Elekta SL 18 MV and the beam characteristics obtained. GafChromic EBT XD films and an Advanced Markus chamber were used for dosimetry characterization, while a silicon sensor assessed the machine’s beam pulses stability and repeatability. The dose per pulse, average dose rate and instantaneous dose rate in the pulse were evaluated for four experimental settings, varying the source-to-surface distance and the beam collimation, i.e., with and without the use of a cylindrical applicator. The results showed a dose per pulse from 0.6 Gy to a few tens of Gy and an average dose rate up to 300 Gy/s. The obtained results demonstrate the possibility to perform in vitro radiobiology experiments and test new technologies for beam monitoring and dosimetry at the upgraded LINAC, thus contributing to the electron UHDR research field.

Inter-subject cerebrovascular variability: a source of uncertainty for dose calculation to circulating blood cells for glioblastoma patients treated with modern radiotherapy techniques

Purpose. To assess how inter-subject variations in brain vasculature among glioblastoma (GBM) patients affects the calculated dose received by circulating blood cells (CBC) during radiotherapy and its subsequent impact on CBC depletion. Methods. Ten GBM patients treated with either intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) were selected. For each patient, 23 cerebrovascular models were developed based on 23 healthy subject MR-angiography data to simulate intra- and inter-subject blood vessel diversity. Based on the corresponding treatment plan of the patient, the dose to CBC was calculated for all the 230 scenarios. The impact of inter-subject variation on fraction of irradiated blood volume (VD >0 cGy) and lymphocyte kill rates as a function of the clinical target volume (CTV) size and treatment technique were analyzed. Results. The dose fluctuation to CBC was higher in IMRT plans compared to VMAT plans. The uncertainty in the VD >0 cGy was 18.3% for IMRT and 2.0% (CI95%) for VMAT and the dispersion of the D 2% index was 6 cGy for IMRT and 1 cGy for VMAT (CI95%) for one single treatment fraction of 200 cGy. The uncertainty in killed CBC due to inter-subject diversity in brain blood vessel increased with increasing CTV size and was σ = 11.2%. Conclusions. VMAT showed greater robustness against inter-subject variation in blood vessels compared to IMRT. We recommend considering the uncertainty in depleting CBC resulting from the use of less patient-specific and generic blood vessel phantoms to improve the radiation-induced lymphopenia assessments.

Morphological MRI features as prognostic indicators in brain metastases

BackgroundStereotactic radiotherapy is the preferred treatment for managing patients with fewer than five brain metastases (BMs). However, some lesions recur after irradiation. The purpose of this study was to identify patients who are at a higher risk of failure, which can help in adjusting treatments and preventing recurrence.MethodsIn this retrospective multicenter study, we analyzed the predictive significance of a set of interpretable morphological features derived from contrast-enhanced (CE) T1-weighted MR images as imaging biomarkers using Kaplan–Meier analysis. The feature sets studied included the total and necrotic volumes, the surface regularity and the CE rim width. Additionally, we evaluated other nonmorphological variables and performed multivariate Cox analysis.ResultsA total of 183 lesions in 128 patients were included (median age 61 [31–95], 64 men and 64 women) treated with stereotactic radiotherapy (57% single fraction, 43% fractionated radiotherapy). None of the studied variables measured at diagnosis were found to have prognostic value. However, the total and necrotic volumes and the CE rim width measured at the first follow-up after treatment and the change in volume due to irradiation can be used as imaging biomarkers for recurrence. The optimal classification was achieved by combining the changes in tumor volume before and after treatment with the presence or absence of necrosis (p < < 0.001).ConclusionThis study demonstrated the prognostic significance of interpretable morphological features extracted from routine clinical MR images following irradiation in brain metastases, offering valuable insights for personalized treatment strategies.

Neuroprotective effect of Myrtus communis against ionizing radiation-induced brain injury: Insights from histopathological and biochemical analysis in rats: TROD-GROG 005

AimTo investigate the potential radioprotective effects of Myrtus communis on brain tissue. MethodsThirty female rats were divided into four groups. The control group (C) was applied with oral saline solution (SF) for four days. Myrtus communis (MC) groups started to receive MC (100 mg/kg, oral) either four days before (R + preMC) or immediately after (R + MC) irradiation for four days. Irradiation was applied 10 Gy in a single fraction. All rats were sacrificed on the fourth day of irradiation. Malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) levels, myeloperoxidase (MPO), superoxide dismutase (SOD), and tissue factor activities (TFa) were determined for biochemical analysis. Hematoxylin&Eosin staining was done for histopathological analyses, and electrophoretic analyses were performed. ResultsNO, MDA, and MPO levels were higher in all irradiated groups compared with the C group. MC administration decreased NO, MDA, and MPO levels in R + preMC and R + MC groups. MC administration increased GSH levels. TFa activity decreased in R groups but did not change with MC administration compared to the C group. Radiation-induced brain tissue injury decreased, and morphologically normal neurons were observed in both MC-added groups. ConclusionMyrtus communis has a potential neuroprotective effect on brain tissue, attributed to its antioxidative, anti-inflammatory, and anti-lipid peroxidative properties.

Local delivery of carboplatin-loaded hydrogel and calcium carbonate enables two-stage drug release for limited-dose radiation to eliminate mouse malignant glioma

Postoperative radiotherapy remains the gold standard for malignant glioma treatment. Clinical limitations, including tumor growth between surgery and radiotherapy and the emergence of radioresistance, reduce treatment effectiveness and result in local disease progression. This study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy.We developed a compound of carboplatin-loaded hydrogel (CPH) incorporated with carboplatin-loaded calcium carbonate (CPCC) to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model.The doses of carboplatin in CPH and CPCC treatments were 150 μL (carboplatin concentration of 5 mg/mL) and 15 mg (carboplatin concentration of 4.1 μg/mg), respectively. Mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation.Local CPH-CPCC delivery synergized effectively with limited-dose radiation to eliminate mouse glioma, offering a promising solution for overcoming clinical limitations.

Biochemical, toxicological and genomic investigation of a high-biomass producing Limnothrix strain isolated from Italian shallow drinking water reservoir

The presence of cyanobacteria in water for drinking and recreational purposes is considered problematic due to their bloom-forming and toxigenic potential. While most cyanotoxins are produced by extensively studied cyanobacteria, little is known about other abundant genera not usually assessed for their toxic potential. Here, a new isolate of Limnothrix redekei from an Italian drinking water reservoir was cultured and investigated using biological, chemical, and genomic methods. Compared to other Limnothrix spp., the isolate yielded high biomass productivity and was mainly constituted by proteins. The isolate had genomic features similar to those of the other 10 genomes of Limnothrix spp. published so far, regardless of their geographical origin. Most genes were implicated in primary metabolism (e.g. photosynthesis, nutrients transport, cell division), while <1 % of the genome was dedicated to secondary metabolism. Two regions encoding for a cyanobactin and a polyketide were found, whereas those for known cyanotoxins were absent. Toxicological investigations based on the crustacean Artemia sp. bioassay revealed potential toxicity of Limnothrix aqueous extracts (mortality >90 %). The highest toxicity was observed in a single fraction of the extract, whose UV spectrum presented carotenoid-like characteristics. Although the structure of the putative toxin was not yet elucidated, these findings pose the basis for further investigations on Limnothrix spp. toxicity, for which the observed toxic aqueous extracts could not exclude possible implications for ecosystems and humans through drinking water resources.

Refining Treatment Planning in STereotactic Arrhythmia Radioablation: Benchmark Results and Consensus Statement From the STOPSTORM.eu Consortium

Background and purposeSTereotactic Arrhythmia Radioablation (STAR) showed promising results in patients with refractory ventricular tachycardia (VT). However, clinical data is scarce and heterogeneous. The STOPSTORM.eu consortium was established to investigate and harmonize STAR in Europe. The primary goal of this benchmark study was to investigate current treatment planning practice within the STOPSTORM project as a baseline for future harmonization. MethodsPlanning target volumes (PTV) overlapping extra-cardiac organs-at-risk and/or cardiac substructures were generated for three STAR cases. Participating centers were asked to create single fraction treatment plans with 25 Gy dose prescription based on in-house clinical practice. All treatment plans were reviewed by an expert panel and quantitative crowd knowledge-based analysis was performed with independent software using descriptive statistics for ICRU report 91 relevant parameters and crowd dose-volume-histograms. Thereafter, treatment planning consensus statements were established using a dual-stage voting process. ResultsTwenty centers submitted 67 treatment plans for this study. In most plans (75%) Intensity Modulated Arc Therapy (IMAT) with 6 MV flattening-filter-free beams was used. Dose prescription was mainly based on PTV D95% (49%) or D96-100% (19%). Many participants preferred to spare close extra-cardiac organs-at-risk (75%) and cardiac substructures (50%) by PTV coverage reduction. PTV D0.035cm3 ranged 25.5-34.6 Gy, demonstrating a large variety of dose inhomogeneity. Estimated treatment times without motion compensation or setup ranged 2-80 minutes. For the consensus statements, strong agreement was reached for beam technique planning, dose calculation, prescription methods and trade-offs between target and extra-cardiac critical structures. No agreement was reached on cardiac substructure dose limitations and on desired dose inhomogeneity in the target. ConclusionThis STOPSTORM multi-center treatment planning benchmark study showed strong agreement on several aspects of STAR treatment planning, but also revealed disagreement on others. To standardize and harmonize STAR in the future, consensus statements were established, however clinical data is urgently needed for actionable guidelines for treatment planning.

Cardiac SABR: Image matching techniques for accurate treatment delivery

BackgroundVentricular tachycardia is an irregular heartbeat conventionally treated using invasive cardiac catheter ablation and medication. However, when standard treatments have been exhausted, cardiac SABR provides a final treatment option to this high-mortality condition. Complex diagnostic mapping and planning scans enable multi-disciplinary target delineation for a 25Gy single fraction. However, organs at risk (OAR) near the target make this treatment challenging to plan and deliver. Publications from cardiologists report the efficacy of cardiac SABR, however there is limited data on the treatment delivery and image matching of this complex procedure. MethodsFour specialist therapeutic radiographers experienced in cardiac SABR reviewed 40 CBCTs from 10 patients treated in the UK. Each therapeutic radiographer conducted five image matches: a manual match (manual), an automatic match to the heart structure (auto) and the auto match followed by manual adjustment to the PTV (PTV), all using three degrees of freedom (DoF) only. The auto and PTV matches were also repeated using 6DoF. Inter-observer variability was quantified using 95% limits of agreement from a modified Bland-Altman analysis. ResultsThe limits of agreement were smallest in the automatic matches suggesting the algorithm is reliable. A manual adjustment from the auto match to the PTV is clinically appropriate to optimise target coverage. The limits of agreement were smaller in the 6DoF PTV match 1.06 mm, 1.24 mm, 1.68 mm than the 3DoF PTV match 1.57 mm, 2.06 mm, 2.11 mm (lateral, vertical, longitudinal). ConclusionThe 6DoF CBCT image match has less variability and therefore suggest using a 6DoF couch for treatment delivery. Implications for practiceCardiac SABR CBCT image matching at treatment delivery is complex, optimisation of CBCT acquisition parameters and therapeutic radiographer training is essential prior to implementation.

Neuro-Oncologic Veterinary Trial for the Clinical Transfer of Microbeam Radiation Therapy: Acute to Subacute Radiotolerance after Brain Tumor Irradiation in Pet Dogs.

Synchrotron Microbeam Radiation Therapy (MRT) has repeatedly proven its superiority compared with conventional radiotherapy for glioma control in preclinical research. The clinical transfer phase of MRT has recently gained momentum; seven dogs with suspected glioma were treated under clinical conditions to determine the feasibility and safety of MRT. We administered a single fraction of 3D-conformal, image-guided MRT. Ultra-high-dose rate synchrotron X-ray microbeams (50 µm-wide, 400 µm-spaced) were delivered through five conformal irradiation ports. The PTV received ~25 Gy peak dose (within microbeams) per port, corresponding to a minimal cumulated valley dose (diffusing between microbeams) of 2.8 Gy. The dogs underwent clinical and MRI follow-up, and owner evaluations. One dog was lost to follow-up. Clinical exams of the remaining six dogs during the first 3 months did not indicate radiotoxicity induced by MRT. Quality of life improved from 7.3/10 [±0.7] to 8.9/10 [±0.3]. Tumor-induced seizure activity decreased significantly. A significant tumor volume reduction of 69% [±6%] was reached 3 months after MRT. Our study is the first neuro-oncologic veterinary trial of 3D-conformal Synchrotron MRT and reveals that MRT does not induce acute to subacute radiotoxicity in normal brain tissues. MRT improves quality of life and leads to remarkable tumor volume reduction despite low valley dose delivery. This trial is an essential step towards the forthcoming clinical application of MRT against deep-seated human brain tumors.

Palliative Radiotherapy in Non-small Cell Lung Cancer: Patterns of Use and Predictors of 30-Day Mortality in End-of-Life Care.

Introduction Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) being the most common type. More than half of patients require radiotherapy throughout their treatment. Palliative radiotherapy (PRT) is an important tool for symptom control and quality of life improvement in advanced NSCLC patients. However, the benefits of PRT must be balanced against possible disadvantages, especially in end-of-life (EOL) care. This study aims to describe the profile of PRT-treated deceased NSCLC patients, quantify the proportion of PRT recipients in the last 30 days of life and identify short-term survival prognostic factors in this group. Materials and methods This retrospective analysis was performed at two radiotherapy facilities within the Kent Oncology Centre, UK, for two years, running from January 1, 2022, to January 1, 2024. Data were collected from 857 deceased NSCLC patients who received PRT. Demographics, cancer diagnosis, histology, tumour, node, metastasis (TNM) staging, radiotherapy details, recent treatments, performance status (PS) and comorbidities were analysed. Patients have been stratified as long-term survivors (more than 30 days after PRT initiation, LTS group) along with short-term survivors (STS) (died within 30 days, STS group). Descriptive statistics, chi-squared tests, t-tests and multivariable logistic regression have been used in the data analysis. Results Out of 857 patients, 148 (17.3%) died within 30 days of PRT initiation. PS was considerably worse (p = 0.027), Adult Comorbidity Evaluation 27 (ACE-27) scores were higher (p = 0.018), and metastatic disease was more prevalent (60.1% vs. 47.5%, p = 0.02) in STS group patients. Fewer patients in the STS group completed their treatment compared to the LTS group (63.5% vs. 82.8%, p < 0.001). The STS group also received lower mean radiation dose (17.7 Gy vs. 19.6 Gy, p = 0.022) and fewer fractions (4.4 vs. 5.2, p = 0.019). The most common RT regimen in both cohorts was 20 Gy in five fractions, used in 55.4% of STS and 49.8% of LTS patients, with no significant difference in single fraction RT use between groups (33.1% in STS vs. 36.8% in LTS, p = 0.401). Multivariate logistic regression identified significant predictors of 30-day mortality: poorer PS (adjusted OR: 1.981, 95% CI: 1.33-3.12, p = 0.001), metastatic disease (adjusted OR: 2.02, 95% CI: 1.246-3.571, p = 0.002), incomplete PRT (adjusted OR: 0.337, 95% CI: 0.21-0.514, p < 0.001) and no recent chemotherapy (adjusted OR: 0.542, 95% CI: 0.342-0.941, p = 0.044). Conclusion This study demonstrated that compared with previous reports, a higher proportion of NSCLC patients who received PRT died within 30 days of treatment initiation, and low treatment adherence rates highlight challenges in EOL settings. Identification of poor PS and metastatic disease as predictors of short-term mortality would help inform PRT decision-making. The underutilisation of single-fraction radiotherapy and the link between recent chemotherapy and lower 30-day mortality warrant further study. These results highlight the need for better prognostic tools and more selective use of PRT, including increased consideration of single-fraction radiotherapy, in NSCLC patients approaching end of life and emphasise the importance of balancing benefit against treatment burden in this vulnerable population.

A Prospective Randomised Comparative Study to Evaluate the Effect of Single Dose (6.25Gy Vs 8Gy) Palliative Radiotherapy with Zoledronic Acid in Patients with Painful Bone Metastases

Background: To assess the effectiveness of a single fraction dose of radiotherapy (6.25Gy versus 8 Gy) with zoledronic acid in cancer patients with painful bone metastases in treating pain; quality of life; duration of pain response and incidence of skeletal related events (SREs). Material and methods: A total of 80 patients with bone metastases presented in the department of Radiation Oncology, S.M.S hospital were randomly assigned to: Group A, received single dose of 6.25Gy with Zoledronic acid 4mg and Group B, received single dose of 8Gy with Zoledronic acid 4mg. The main variable was pain which was assessed with 11 point Numeric pain Rating Score (NRS). Results: There were total 80 patients, 40 in each group, with mean age 54.6 years and 54.5 years in group A and B respectively. Most frequent primary malignant sites were lung (36.2%), breast (28.7%), and prostate (8.7%). At 4 weeks post radiotherapy, complete response was 25% in group A, 27.5% in group B and overall response was 82.5% in group A, 85% in group B. At 2 months post radiotherapy complete response was observed in 25% of patients in group A, while 30% in group B and overall response in 85 % in group A and 87.5% in group B. Quality of life improved in both groups. Mean duration of pain relief was 13.5 weeks vs. 14.5 weeks respectively in group A and group B. Conclusion: There was improvement in pain relief and quality of life post radiotherapy in both the groups. On comparison between 2 groups, the overall pain relief was insignificant between the two dose schedules. So a lower dose 6.25Gy is almost as effective as 8 Gy single fractions for treatment of painful bone metastases.