Clinical impact of DVH uncertainties.

Dose-volume histograms (DVH), along with dose and volume metrics, are central to radiotherapy planning. As such, errors have the potential to significantly impact the selection of appropriate treatment plans. Dose distributions that pass tests in one TPS may fail the same tests when transferred to another, even if using identical structures and dose grid information. This work shows the design and implementation of methods for assessing the accuracy of dose and volume computations performed by treatment planning systems (TPS), and other analytical tools. We demonstrate examples where differences in calculations between systems can change the assessment of a plan's clinical acceptability. Our work also provides a more detailed DVH analysis of single targets than earlier published studies. This is relevant for SRS plans and small structure dose assessments. Very small structures are a particular problem because of their coarse digital representation, and the impact of this is thoroughly examined. Reference DVH curves were derived mathematically, based on Gaussian dose distributions centered on spherical structures. The structures and dose distributions were generated synthetically, and imported into RayStation, MasterPlan, and ProKnow. Corresponding DVHs were analytically derived and taken as ground truth references, for comparison with the commercial DVH calculations. Two commonly used dose metrics PCI and MGI were used to determine the limit of calculation accuracy for small structures. In addition, to measure the DVH differences between a larger range of commercial DVH calculators, the D95 metric from a set of real clinical plans was compared across both the 3 DVH calculators under test, and across a further six TPSs from other hospitals. We show that even slight deviations between the results of DVH calculators can lead to plan check failures, and we illustrate this with the commonly used D95 planning metric. We present clinical data across eight planning systems that highlight instances where plan checks would pass in one software and fail in another due to DVH calculation differences. For the smallest volumes tested, errors of up to 20% were observed in the DVHs. RayStation was tested down to a 3 mm radius sphere (≈0.1 cc) and this showed close to 10% error, reducing to 1% for 10 mm radius (≈4.0 cc) and 0.1% for 20 mm radius (≈33 cc). In clinical plans, the variation in D95 was up to 9% for the smallest volumes, and typically around 2% in the range 0.5 cc-20 cc, and 1% in 20 cc-70 cc, falling to <0.1% for large volumes. Paddick Conformity Index (PCI) and Modified Gradient Index (MGI) are commonly used plan quality indicators for very small volumes. For volumes ≈0.1 cc we observed errors of up to 40% in PCI, and up to 75% in MGI. Our study extends the range of tested DVH calculators in published work, and shows their performance over a wider range of volume sizes. We provide quantitative evidence of the critical need to test the accuracy of DVH calculators in the TPS before clinical use. This work is particularly relevant for both stereotactic plan evaluation and for assessment of small volume doses in published dose constraint recommendations. We demonstrate that significant errors can occur in DVHs for volumes less than 1 cc, even if the volumes themselves are calculated accurately. Even for large structures, deviations between the outputs of DVH calculators can lead to indicated or reported plan check failures if they do not include appropriate tolerances. We urge caution in the use of DVH metrics for these very small volumes and recommend that appropriate DVH uncertainty tolerances are set in organ dose constraints when using them to evaluate clinical plans.

Multi-institutional investigation into the robustness of intra-cranial multi-target stereotactic radiosurgery plans to patient setup errors.

PURPOSE: This study aimed to analyse correlations between planning factors including plan geometry and plan complexity with robustness to patient setup errors. METHODS: Multiple-target brain stereotactic radiosurgery (SRS) plans were obtained through the Trans-Tasman Radiation Oncology Group (TROG) international treatment planning challenge (2018). The challenge dataset consisted of five intra-cranial targets with a 20 Gy prescription. Setup error was simulated using an in-house tool. Dose to targets was assessed via dose covering 99 % (D99 %) of gross tumour volume (GTV) and 98 % of planning target volume (PTV). Dose to organs at risk was assessed using volume of normal brain receiving 12 Gy and maximum dose covering 0.03 cc of brainstem. Plan complexity was assessed via edge metric, modulation complexity score, mean multi-leaf collimator (MLC) gap, mean MLC speed and plan modulation. RESULTS: Even for small (0.5 mm/°) errors, GTV D99 % was reduced by up to 20 %. The strongest correlation was found between lower complexity plans (larger mean MLC gap and lower edge metric) and higher robustness to setup error. Lower complexity plans had 1 %-20 % fewer targets/scenarios with GTV D99 % falling below the specified tolerance threshold. These complexity metrics correlated with 100 % isodose volume sphericity and dose conformity, though similar conformity was achievable with a range of complexities. CONCLUSIONS: A higher level of importance should be directed towards plan complexity when considering plan robustness. It is recommended when planning multi-target SRS, larger MLC gaps and lower MLC aperture irregularity be considered during plan optimisation due to higher robustness should patient positioning errors occur.

Stereotactic Radiosurgery with Volumetric Modulated Arc Radiotherapy: Final Results of a Multi-arm Phase I Trial (DESTROY-2).

AIMS: To present the final results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumors in different extracranial sites. MATERIALS AND METHODS: The DESTROY-2 trial, planned as a prospective dose escalation study in oligometastatic (one to five lesions) cancer patients relied on the delivery of a single high dose of radiation utilizing high-precision technology. The primary study endpoint was the definition of the maximum tolerated dose (MTD) of SRS-VMAT. The secondary objectives of the study were the evaluation of safety, efficacy, and long-term outcomes. All patients consecutively observed at our radiotherapy unit matching the inclusion criteria were enrolled. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, other), and sequentially assigned to a particular dose level. RESULTS: Two hundred twenty seven lesions in 164 consecutive patients (male/female: 97/67, median age: 68 years; range: 29-92) were treated. The main primary tumors were: prostate cancer (60 patients), colorectal cancer (47 patients), and breast cancer (39 patients). The maximum planned dose level was achieved in all study arms, and the MTD was not exceeded. 34 Gy, 32 Gy, 24 Gy, and 24 Gy were established as the single-fraction doses for treating lung, liver, bone, and other extracranial lesions, respectively. The prescribed BED 2Gyα/ß:10 to the planning target volume ranged from 26.4 Gy to 149.6 Gy. Twenty-seven patients (16.5%) experienced grade 1-2 and only one grade 3 acute toxicity, which was a pulmonary one. In terms of late toxicity, we registered only 5 toxicity>G2: a G3 gastro-intestinal one, three G3 bone toxicity, and a G3 laryngeal toxicity. The overall response was available for 199 lesions: 107 complete response (53.8%), 50 partial response (25.1%), and 31 stable disease (15.6%), leading to an overall response rate of 94.5%. Progression was registered only in 11 cases (5.5%). The overall response rate in each arm ranged from 88.6% to 96.4%. The overall two-year local control, distant metastasis free survival, disease free survival, and overall survival were 81.7%, 33.0%, 25.4%, and 78.7% respectively. CONCLUSION: In conclusion, the planned doses of 34 Gy, 32 Gy, 24 Gy, and 24 Gy were successfully administered as single-fractions for the treatment of lung, liver, bone, and other extracranial lesions, respectively, in a prospective SRS dose-escalation trial. No dose-limiting toxicities were registered, and minimal acute and late toxicity were reported. New indications for SRS are currently being studied in oligoprogressive patients receiving targeted drugs or in combination with immunotherapy. The DESTROY-2 trial represents, in our opinion, a credible starting point for future modern radiosurgery trials.

Exploring feasibility criteria for stereotactic radiosurgical treatment of multiple brain metastases using five linac machines.

PURPOSE: This study aimed to find descriptors that correlates with normal brain dose to determine the feasibility of performing fractionated stereotactic radiosurgery (SRS) for multiple brain metastases (BMs) using five linac machines. METHODS: Thirty-two patients with 1-30 BMs were enrolled. Treatment plans were created using TrueBeam, Novalis Tx, TrueBeam Edge, Halcyon, and Tomotherapy linacs. The sum of all planning target volumes (PTVs) was defined as PTVall, and the brain region excluding PTVall was defined as normal brain. The total surface area (TSA) of the PTV was calculated from the sum of the surface areas of the equivalent spheres for each PTV. Volumes receiving more than 5, 12, and 18 Gy (V5Gy, V12Gy, and V18Gy, respectively) were used for evaluation of normal brain dose. Correlations between normal brain dose and each tumor characteristic (number, PTVall, and TSA) were investigated using the Spearman rank correlation coefficient. RESULTS: Correlations between each characteristic and normal brain dose were statistically significant (p < 0.05) across all machines. The correlation coefficients between each characteristic and V18Gy for the five machines were as follows: tumor number, 0.39-0.60; PTVall, 0.79-0.93; TSA, 0.93-0.99. The fit equations between TSA and V18Gy exhibited high coefficients of determination, ranging from 0.92 to 0.99 across five machines. CONCLUSION: This study devised fractionated SRS plans using for 1-30 BMs across five linac machines to find descriptors for determining SRS feasibility based on normal brain dose. TSA proved to be a promising descriptor of SRS feasibility for treating multiple BMs.

Accuracy of Beamscan Software in Determining the Inflection Point from the FFF Beam Profile Using Several Array Detectors.

OBJECTIVE: The goal of this study is to determine the accuracy of the PTW Beamscan program in determining the inflection point from Flattening Filter Free Beam Profile utilizing Multiple Detectors. METHODS: True Beam Linear Accelerator with 6FFF and 10FFF Photon Energies and 10 cm, 15 cm and 20 cm Field Sizes were used for this study. Profile measurements were taken with PTW's 729, 1,500, and 1,600 and the Starcheck system, the Pinpoint 3D with Beamscan system, and Linac's EPID. The first-order derivative was utilized in both the Excel spreadsheet and Beamscan software to analyse raw measured data to locate inflection point and the FWHM was calculated. The accuracy of inflection points and FWHM between the Excel sheet calculation and the software program were investigated. RESULTS: For 10X10 cm2 in the 729 Array, the greatest differences in FWHM were 5.16 mm and 5.04 mm for the X6 FFF and X10 FFF Energies, respectively. The largest difference was 2.26 mm for 1,600 SRS arrays with a 15×15 cm2 field size. The difference in FWHM between Manual and software analysis for 10X10 cm2 and 20X20 cm2 Field Sizes is in decreasing order for detectors from 729, 1,500, 1,600 SRS, Starcheck, Pinpoint 3D, and EPID. In contrast, there is no climbing or declining pattern detected in the difference in Field Width for the 15×15 cm2 Field Size. Similarly, for all detectors except the 1,600 SRS array, the peak of the first-order derivative occurs at the chamber position for a 15X15 cm2 field size. CONCLUSION: The higher resolution of measurement yields more accuracy in inflection point and the FWHM. Irrespective of measurement resolution, the Beamscan software provided the FWHM closer to the respective nominal Field Size. Out of all detectors, results obtained with Excel Starcheck and EPID are good in agreement with values obtained by the software analysis. Thus, it is shown that Beamscan software is so accurate in determining inflection point of a FFF beam profile and used for routine profile analysis.

A novel DNA vaccine encoding the SRS13 protein administered by electroporation confers protection against chronic toxoplasmosis.

Toxoplasma gondii is an obligate intracellular parasite that can infect a variety of mammals including humans and causes toxoplasmosis. Unfortunately, a protective and safe vaccine against toxoplasmosis hasn't been developed yet. In this study, we developed a DNA vaccine encoding the SRS13 protein and immunized BALB/c mice thrice with pVAX1-SRS13 through the intramuscular route (IM) or intradermally using an electroporation device (ID + EP). The immunogenicity of pVAX1-SRS13 was analyzed by ELISA, Western blot, cytokine ELISA, and flow cytometry. The protective efficacy of the pVAX1-SRS13 was investigated by challenging mice orally with T. gondii PRU strain tissue cysts. The results revealed that pVAX1-SRS13 administered through IM or ID + EP routes induced high level of anti-SRS13 IgG antibody responses (P = 0.0037 and P < 0.0001). The IFN-γ level elicited by the pVAX1-SRS13 (ID + EP) was significantly higher compared to the control group (P = 0.00159). In mice administered with pVAX1-SRS13 (ID + EP), CD8+ cells secreting IFN-γ was significantly higher compared to pVAX1-SRS13 (IM) (P = 0.0035) and the control group (P = 0.0068). Mice vaccinated with the SRS13 DNA vaccine did not induce significant IL-4 level. Moreover, a significant reduction in the number of tissue cysts and the load of T. gondii DNA was detected in brains of mice administered with pVAX1-SRS13 through ID + EP and IM routes compared to controls. In conclusion, the SRS13 DNA vaccine was found to be highly immunogenic and confers strong protection against chronic toxoplasmosis.

Contributing factors for reduction in maternal mortality ratio in India.

Maternal mortality ratio (MMR) estimates have been studied over time for understanding its variation across the country. However, it is never sufficient without accounting for presence of variability across in terms of space, time, maternal and system level factors. The study endeavours to estimate and quantify the effect of exposures encompassing all maternal health indicators and system level indicators along with space-time effects influencing MMR in India. Using the most recent level of possible -factors of MMR, maternal health indicators from the National Family Health Survey (NFHS: 2019-21) and system level indicators from government reports a heatmap compared the relative performance of all 19 SRS states. Facet plots with a regression line was utilised for studying patterns of MMR for different states in one frame. Using Bayesian Spatio-temporal random effects, evidence for different MMR patterns and quantification of spatial risks among individual states was produced using estimates of MMR from SRS reports (2014-2020). India has witnessed a decline in MMR, and for the majority of the states, this drop is linear. Few states exhibit cyclical trend such as increasing trends for Haryana and West Bengal which was evident from the two analytical models i.e., facet plots and Bayesian spatio- temporal model. Period of major transition in MMR levels which was common to all states is identified as 2009-2013. Bihar and Assam have estimated posterior probabilities for spatial risk that are relatively greater than other SRS states and are classified as hot spots. More than the individual level factors, health system factors account for a greater reduction in MMR. For more robust findings district level reliable estimates are required. As evident from our study the two most strong health system influencers for reducing MMR in India are Institutional delivery and Skilled birth attendance.

Identification and impact of failure of pelvic compensation in patients with adult spinal deformity.

BACKGROUND CONTEXT: Previous research has identified a specific subtype known as failure of pelvic compensation (FPC) in patients with adult spinal deformity (ASD). However, the criteria for assessing FPC remain inconsistent, and its impacts on spinal sagittal alignment and health-related quality-of-life (HRQoL) scores remain unclear. PURPOSE: To propose a novel criterion for identifying FPC based on variations in spinopelvic alignment during the transition from the supine to upright position and to evaluate the effects of FPC on patients' spinal sagittal alignment and HRQoL scores. STUDY DESIGN/SETTING: Retrospective cross-sectional study. PATIENT SAMPLE: Patients with ASD from a monocenter database. OUTCOME MEASURES: Radiographic measures, including thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt, pelvic incidence (PI), and sagittal vertical axis (SVA), were measured on lateral whole-spine radiographs. LL and SS were also measured on reconstructed lumbar computed tomography images in the sagittal view taken in the supine position. The relative functional cross-sectional area (rFCSA) of paraspinal muscles was evaluated via lumbar magnetic resonance imaging. HRQoL measures, encompassing visual analog scale for back pain (VAS-BP), Oswestry Disability Index (ODI), and Scoliosis Research Society-22R (SRS-22R), were collected. METHODS: A total of 154 patients were enrolled. Based on the calculated minimum detectable change of SS, FPC was defined as the change in SS of less than 3.4° between supine and upright positions. Patients were divided into 3 groups: sagittal balance with pelvic compensation (SI-PC), sagittal imbalance with pelvic compensation (SI-PC), and sagittal imbalance with failure of pelvic compensation (SI-FPC). Radiographic parameters and HRQoL scores were compared among the groups. RESULTS: Thirty-six patients were categorized into the SB-PC group, 87 into the SI-PC group, and 31 into the SI-FPC group. Patients with low PI and small paraspinal muscles rFCSA were more prone to experiencing FPC accompanied by severe sagittal imbalance. The SI-FPC group exhibited less TK and a larger SS than the SI-PC group exhibited and had a similar SVA as that of the SI-PC group. Additionally, they displayed worse VAS-BP, ODI, SRS-function, and SRS-22 total scores than the SB-PC group displayed. CONCLUSIONS: In patients with ASD, an inherently low pelvic compensatory reserve and a high fatty infiltration in paraspinal muscles are pivotal factors contributing to FPC. Compared with SI-PC patients, SI-FPC patients demonstrate a thoracic-dominant compensatory pattern for sagittal malalignment. In addition, these patients experienced more severe pain and functional decline than the SB-PC patients experienced.

Self-image in spinal deformity: a state-of-the-art review.

PURPOSE: To review the current literature surrounding the assessment of self-image in pediatric and adult spinal deformity. METHODS: The literature were reviewed for studies examining patient-reported outcome measurements (PROM) and self-image in pediatric and adult spinal deformity. PROM performance metrics were collected and described. The relationships between self-image PROM and patient outcomes, including satisfaction, were described. RESULTS: Several self-image PROM exist, including the Scoliosis Research Society-22r (SRS-22r) self-image domain, the Body Image Disturbance Questionnaire (BIDQ), and the Spinal Appearance Questionnaire (SAQ). The most commonly used is the self-image domain of the SRS-22r. It is validated in adult and pediatric spinal deformity and is correlated with patient desire for surgery and satisfaction after surgery. This domain is limited by floor and ceiling effects. CONCLUSION: Self-image assessment is critical to both pediatric and adult spinal deformity surgeries. The SRS-22r self-image domain is the most frequently reported PROM for this health domain. While valid in both surgical cohorts, this PROM is affected by floor and ceiling effects which limits the ability to discriminate between health states. Given the overall importance of this domain to patients with spinal deformity further efforts are needed to improve discrimination without gross increases in PROM question burden, which may limit broad acceptance and use.

Technical note: Patient-specific quality assurance for multi-target single-isocenter SRS-A target-specific approach.

BACKGROUND: As radiotherapy techniques advance, so do planning methods for multi-target intracranial SRS cases. Multi-target-single-isocenter (MTSI) planning offers high-precision beam delivery with shortened duration. However, accommodating all targets in a single Patient-Specific-Quality-Assurance (PSQA) with QA devices like SRS MapCHECK (SRS MC) is generally impractical. PURPOSE: Consequently, we conducted PSQA, using a custom script, by relocating each Target or Neighboring-Target-Group (T-NTG) relative to the beam isocenter on the PSQA device, ensuring each target's dose coverage at high precision. METHODS: SRS treatment plans use 6MV-FFF beams, consisting of four Volumetric Modulated ARC Therapy (VMAT) arcs, including one full-arc and three half arcs with couch-kicks. A custom script calculated T-NTG coordinates relative to the beam isocenter. QA verification plans were created for each T-NTG, redefining the beam isocenter for precise alignment with the center of the SRS MC. CBCT images were acquired during PSQA for SRS MC alignment, and gamma-index analysis (GIA) was performed. A single-tail paired t-test assessed the passing rate (PR) for 75 QA verification plans. RESULTS: GIA with l.0 mm/2.0% criteria for each QA plan yielded a PR > 95.5%, with an average of 98.9%. Plans achieving PR > 99.0% and > 97.0% constituted 63% and 92% of studied plans, respectively. Statistical significance was observed in a t-test with an ideal PR value of 100%, while insignificance was found with a PR value of 99%, suggesting that PSQA for individual targets consistently approaches 99% PR. In MTSI cases using 6MV-FFF beams, targets within the lateral dose-fall-off region require careful verification for acceptability. Our clinical study on individual T-NTG relocation demonstrates that the presented PSQA methods are generally acceptable, supported by a statistically insignificant PR against a 99% PR value. CONCLUSIONS: Presented statistical analysis results indicate that the proposed PSQA approach can serve as a reliable tool in clinical settings.

Dual-type quantile regression approach for mean estimation incorporating sampled and non-sampled data.

Drawing inspiration from recent advancements in robust mean estimation within finite sampling theory, we introduce a novel dual-type class of mean estimators in a design-based framework. The dual-type class is based on quantile regression and is specifically designed to be effective in the presence of extreme observations. Significantly, it integrates the averages of both sampled observations and non-sampled observations of auxiliary variable. In the initial discussion of this class, it is presumed that the target variable is non-sensitive, signifying its relevance to subjects that respondents do not consider embarrassing when queried directly. In this standard setting, we present specific estimators within the class and determine their theoretical properties. The class's scope broadens to include scenarios where the target variable incorporates sensitive topics, giving rise to nonresponse rates and inaccurate reporting. To alleviate these errors, one can promote respondent cooperation by employing scrambled response methods that obscure the actual value of the sensitive variable. Accordingly, the article delves into discussions on additive methods. Subsequently, a numerical study is conducted using asymmetric data to evaluate the effectiveness of the dual-type class by comparing it with several existing estimators, both in the absence and presence of scrambled responses.

The Impact of Multileaf Collimator Size on Single Isocenter Dynamic Conformal Arcs-Based Radiosurgery for Brain Metastases.

PURPOSE: To compare the plan quality of stereotactic radiosurgery (SRS) between 2.5-mm and 5-mm multileaf collimator (MLC) and investigate the factors' influence on the differences by MLC size. METHODS: Seventy-six treatment plans including 145 targets calculated with a single isocenter multiple noncoplanar dynamic conformal arc (DCA) technique using automatic multiple brain metastases (MBM) treatment planning system. Conformity index (CI), gradient index (GI), lesion underdosage volume factor (LUF), healthy tissue overdose volume factor (HTOF), geometric conformity index (g), and mean dose to normal organs were compared between 2.5-mm and 5-mm MLC. Then the factors that influenced the differences of these parameters were investigated. The impact of target size was also investigated for CI and GI values of individual targets (n=145), and differences between 2.5-mm and 5-mm MLC were analyzed. RESULTS: All parameters except for LUF were significantly better in plans with 2.5 mm MLC. Target size was a significant factor for difference in HTOF, and distance between targets was a significant factor for difference in brain dose and GI. Among 145 metastases, the average inverse CI was 1.35 and 1.47 with 2.5-mm and 5-mm MLC, respectively (p<0.001). The average GI was 3.21 and 3.53, respectively (p<0.001). For individual targets, target size was a significant factor in CI and GI both with 2.5-mm and 5-mm MLC (p-value: <0.001, each). CI and GI were significantly better with 2.5-mm than 5-mm MLC. CI was almost >0.67 except for ≤5mm targets with 5-mm MLC. Also, GI was almost smaller than 3.0 for >10 mm targets both with 2.5-mm and 5-mm MLC. CONCLUSIONS: MBM with 5-mm MLC was almost fine. However, it may be better to use a conservative margin for larger metastases. It may also be better to avoid SRS with 5-mm MLC for patients with ≤5 mm target size.

Long-Term Results of Stereotactic Radiotherapy in Patients with at Least 10 Brain Metastases at Diagnosis.

PURPOSE: to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis. METHODS: This is a monocentric prospective cohort of patients treated by SRT, followed by a brain MRI every two months. Subsequent SRT could be delivered in cases of new BMs during follow-up. The main endpoints were local control rate (LCR), overall survival (OS), and strategy success rate (SSR). Acute and late toxicity were evaluated. RESULTS: Seventy patients were included from October 2014 to January 2019, and the most frequent primary diagnosis was non-small-cell lung cancer (N = 36, 51.4%). A total of 1174 BMs were treated at first treatment, corresponding to a median number of 14 BMs per patient. Most of the patients (N = 51, 72.6%) received a single fraction of 20-24 Gy. At 1 year, OS was 62.3%, with a median OS of 19.2 months, and SSR was 77.8%. A cumulative number of 1537 BM were treated over time, corresponding to a median cumulative number of 16 BM per patient. At 1-year, the LCR was 97.3%, with a cumulative incidence of radio-necrosis of 2.1% per lesion. Three patients (4.3%) presented Grade 2 toxicity, and there was no Grade ≥ 3 toxicity. The number of treated BMs and the treatment volume did not influence OS or SSR (p > 0.05). CONCLUSIONS: SRT was highly efficient in controlling the BM, with minimal side effects. In this setting, an SRT treatment should be proposed even in patients with ≥10 BMs at diagnosis.

Radiosurgical thalamotomy for essential tremor: state of the art, current challenges and future directions.

INTRODUCTION: Essential tremor (ET) is the most frequent movement disorder, affecting up to 5% of adults > 65 years old. In 30-50% of cases, optimal medical management provides insufficient tremor relief and surgical options are considered. Thalamotomy is a time-honored intervention, which can be performed using radiofrequency (RF), stereotactic radiosurgery (SRS), or magnetic resonance-guided focused ultrasounds (MRgFUS). While the latter has received considerable attention in the last decade, SRS has consistently been demonstrated as an effective and well-tolerated option. AREAS COVERED: This review discusses the evidence on SRS thalamotomy for ET. Modern workflows and emerging techniques are detailed. Current outcomes are analyzed, with a specific focus on tremor reduction, complications and radiological evolution of the lesions. Challenges for the field are highlighted. EXPERT OPINION: SRS thalamotomy improves tremor in > 80% patients. The efficacy appears comparable to other modalities, including DBS, RF and MRgFUS. Side effects result mostly from idiosyncratic hyper-responses to radiation, which occur in up to 10% of treatments, are usually self-resolving, and are symptomatic in < 4% of patients. Future research should focus on accumulating more data on bilateral treatments, collecting long-term outcomes, refining targeting, and improving lesion consistency.

Feasibility of determining external beam radiotherapy dose using LuSy dosimeter.

INTRODUCTION: Radiation dose measurement is an essential part of radiotherapy to verify the correct delivery of doses to patients and ensure patient safety. Recent advancements in radiotherapy technology have highlighted the need for fast and precise dosimeters. Technologies like FLASH radiotherapy and magnetic-resonance linear accelerators (MR-LINAC) demand dosimeters that can meet their unique requirements. One promising solution is the plastic scintillator-based dosimeter with high spatial resolution and real-time dose output. This study explores the feasibility of using the LuSy dosimeter, an in-house developed plastic scintillator dosimeter for dose verification across various radiotherapy techniques, including conformal radiotherapy (CRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and stereotactic radiosurgery (SRS). MATERIALS AND METHODS: A new dosimetry system, comprising a new plastic scintillator as the sensing material, was developed and characterized for radiotherapy beams. Treatment plans were created for conformal radiotherapy, IMRT, VMAT, and SRS and delivered to a phantom. LuSy dosimeter was used to measure the delivered dose for each plan on the surface of the phantom and inside the target volumes. Then, LuSy measurements were compared against an ionization chamber, MOSFET dosimeter, radiochromic films, and dose calculated using the treatment planning system (TPS). RESULTS: For CRT, surface dose measurement by LuSy dosimeter showed a deviation of -5.5% and -5.4% for breast and abdomen treatment from the TPS, respectively. When measuring inside the target volume for IMRT, VMAT, and SRS, the LuSy dosimeter produced a mean deviation of -3.0% from the TPS. Surface dose measurement resulted in higher TPS discrepancies where the deviations for IMRT, VMAT, and SRS were -2.0%, -19.5%, and 16.1%, respectively. CONCLUSION: The LuSy dosimeter was feasible for measuring radiotherapy doses for various treatment techniques. Treatment delivery verification enables early error detection, allowing for safe treatment delivery for radiotherapy patients.

Construction of Toxoplasma gondii SRS29C nucleic acid vaccine and comparative immunoprotective study of an SRS29C and SAG1 combination.

Toxoplasma gondii is an intracellular protozoan parasite that infects all nucleated cells except the red blood cells. Currently, nucleic acid vaccines are being widely investigated in Toxoplasma gondii control, and several nucleic acid vaccine candidate antigens have shown good protection in various studies. The aim of this study was to construct a nucleic acid vaccine with Toxoplasma gondii SRS29C as the target gene. We explored the nucleic acid vaccine with Toxoplasma surface protein SRS29C and the combined gene of SRS29C and SAG1 and evaluated its immunoprotective effect against Toxoplasma gondii. To amplify the gene fragment and clone it to the expression vector, the recombinant plasmid pEGFP-SRS29C was constructed by PCR. Eukaryotic cells were transfected with the plasmid, and the expression of the target protein was assessed using the Western blot method. The level of serum IgG was determined via ELISA, and the splenic lymphocyte proliferation ability was detected using the CCK-8 method. The percentages of CD4+ and CD8+ T cells were measured by flow cytometry. Mice were immunised three times with single-gene nucleic acid vaccine and combination vaccine. Splenic lymphocytokine expression was determined using ELISA kits. The mice's survival time was monitored and recorded during an in vivo insect assault experiment, and the vaccine's protective power was assessed. The outcomes showed that PCR-amplification of an SRS29C gene fragment was successful. The 4,733-bp vector fragment and the 1,119-bp target segment were both recognised by double digestion. Additionally, after transfection of the recombinant plasmid pEGFP-SRS29C, Western blot examination of the extracted protein revealed the presence of a target protein strip at 66 kDa. The test results demonstrated that the IgG content in the serum of the pEGFP-SRS29C group and the co-immunization group was significantly higher than that of the PBS group and the empty vector group. The IgG potency induced by the co-immunization group was higher than that of the pEGFP-SRS29C group and the pEGFP-SAG1 group, the number of splenic lymphocyte proliferation number was higher than that of the PBS group and the empty vector group. The CD4+/CD8+ T ratio was higher than that of the PBS group and the empty vector group. The expression of IFN-γ and TNF-α in the splenocytes of the pEGFP-SRS29C group and the combined immunisation group was significantly higher following antigen stimulation. In the worm attack experiments, mice in the PBS and empty vector groups perished within 9 days of the worm attack, whereas mice in the pEGFP-SRS29C group survived for 18 days, mice in the pEGFP-SAG1 group survived for 21 days, and mice in the co-immunization group survived for 24 days. This demonstrates that the constructed Toxoplasma gondii nucleic acid vaccine pEGFP-SRS29C and the combined gene vaccine can induce mice to develop certain humoral and cellular immune responses, and enhance their ability to resist Toxoplasma gondii infection.

Nanoplastics Detected in Commercial Sea Salt.

People of all ages consume salt every day, but is it really just salt? Plastic nanoparticles [nanoplastics (NPs)] pose an increasing environmental threat and have begun to contaminate everyday salt in consumer goods. Herein, we developed a combined surface enhanced Raman scattering (SERS) and stimulated Raman scattering (SRS) approach that can realize the filtration, enrichment, and detection of NPs in commercial salt. The Au-loaded (50 nm) anodic alumina oxide substrate was used as the SERS substrate to explore the potential types of NP contaminants in salts. SRS was used to conduct imaging and quantify the presence of the NPs. SRS detection was successfully established through standard plastics, and NPs were identified through the match of the hydrocarbon group of the nanoparticles. Simultaneously, the NPs were quantified based on the high spatial resolution and rapid imaging of the SRS imaging platform. NPs in sea salts produced in Asia, Australasia, Europe, and the Atlantic were studied. We estimate that, depending on the location, an average person could be ingesting as many as 6 million NPs per year through the consumption of sea salt alone. The potential health hazards associated with NP ingestion should not be underestimated.

Posterior Corrective Surgery for Type II Congenital Kyphosis: SRS-Schwab Grade 4 Osteotomy or Vertebral Column Resection?

OBJECTIVE: Surgical decision-making for congenital kyphosis (CK) with failure of anterior segmentation (type II) has been contradictory regarding the trade-off between the pursuit of correction rate and the inherent risk of the osteotomy procedure. This study was designed to compare the clinical and radiographic measurement in type II CK underwent SRS-Schwab Grade 4 osteotomy and vertebral column resection (VCR), the most-adapted osteotomy techniques for CK, and to propose the strategy to select between the two procedures. METHODS: This retrospective observational comparative study evaluated surgical outcomes in type II CK patients underwent VCR or SRS-Schwab Grade 4 osteotomy at our institution between January 2015 and January 2020. Patients operated with VCR and SRS-Schwab Grade 4 osteotomy were allocated to Group 1 and Group 2 respectively. Radiographic parameters and SRS-22 quality of life metrics were assessed at pre-operation, post-operation, and during follow-up visits for both groups, allowing for a comprehensive comparison of surgical outcomes. RESULTS: Thirty-one patients (19 patients in Group 1 and 12 patients in Group 2) aged 16.3 ± 10.4 years were recruited. Correction of segmental kyphosis was similar between groups (51.1 ± 17.6° in Group 1 and 48.4 ± 19.8° in Group 2, p = 0.694). Group 1 had significantly longer operation time (365.9 ± 81.2 vs 221.4 ± 78.9, p < 0.001) and more estimated blood loss (975.2 ± 275.8 ml vs 725.9 ± 204.3 mL, p = 0.011). Alert event of intraoperative sensory and motor evoked potential (SEP and MEP) monitoring was observed in 1 patient of Group 2. Both groups had 1 transient post operative neurological deficit respectively. CONCLUSION: SRS-Schwab Grade 4 osteotomy was suitable for kyphotic mass when its apex is the upper unsegmented vertebrae or the neighboring disc, or when the apical vertebrae with an anterior/posterior (A/P) height ratio of vertebral body higher than 1/3. VCR is suitable when the apex is located within the unsegmented mass with its A/P height ratio lower than 1/3. Proper selection of VCR and SRS-Schwab Grade 4 osteotomy according to our strategy, could provide satisfying radiographic and clinical outcomes in type II CK patients during a minimum of 2 years follow-up. Patients undergoing VCR procedure might have longer operation time, more blood loss and higher incidence of peri- and post-operative complications.

Pattern of recurrence after stereotactic body radiotherapy of nodal lesions: a single-institution analysis.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) and/or single fraction stereotactic body radiosurgery (SRS) are effective treatment options for the treatment of oligometastatic disease of lymph nodes. Despite the encouraging local control rate, progression-free survival remains unfair due to relapses that might occur in the same district or at other sites. The recurrence pattern analysis after nodal local ablative RT (laRT) in oligometastatic patients is presented in this study. METHODS: The pattern of failure of patients with nodal metastases who were recruited and treated with SBRT in the Destroy-1 or SRS in the Destroy-2 trials was investigated in this single-institution, retrospective analysis. The different relapsed sites following laRT were recorded. RESULTS: Data on 190 patients who received SBRT or SRS on 269 nodal lesions were reviewed. A relapse rate of 57.2% (154 out of 269 nodal lesions) was registered. The pattern of failure was distant in 88 (57.4%) and loco-regional in 66 (42.6%) patients, respectively. The most frequent primary malignancies among patients experiencing loco-regional failure were genitourinary and gynaecological cancers. Furthermore, the predominant site of loco-regional relapse (62%) was the pelvic area. Only 26% of locoregional relapses occurred contra laterally, with 74% occurring ipsilaterally. CONCLUSIONS: The recurrence rates after laRT for nodal disease were more frequent in distant regions compared to locoregional sites. The most common scenarios for locoregional relapse appear to be genitourinary cancer and the pelvic site. In addition, recurrences often occur in the same nodal station or in a nodal station contiguous to the irradiated nodal site. ADVANCES IN KNOWLEDGE: Local ablative radiotherapy is an effective treatment in managing nodal oligometastasis. Despite the high local control rate, the progression free survival remains dismal with recurrences that can occur both loco-regionally or at distance. To understand the pattern of failure could aid the physicians to choose the best treatment strategy. This is the first study that reports the recurrence pattern of a significant number of nodal lesions treated with laRT.

The Effect of an Attenuated Live Vaccine against Salmonid Rickettsial Septicemia in Atlantic Salmon (Salmo salar) Is Highly Dependent on Water Temperature during Immunization.

Salmonid Rickettsial Septicemia (SRS), caused by the bacterium Piscirickettsia salmonis, is the main reason for antibiotic usage in the Chilean aquaculture industry. In 2016, a live attenuated vaccine (ALPHA JECT LiVac® SRS, PHARMAQ AS) was licensed in Chile and has been widely used in farmed salmonids since then. In experimental injection and cohabitation laboratory challenge models, we found that the vaccine is effective in protecting Atlantic salmon (Salmo salar) for at least 15 months against P. salmonis-induced mortality. However, the protection offered by the vaccine is sensitive to temperature during immunization. Fish vaccinated and immunized at 10 °C and above were well protected, but those immunized at 7 °C and 8 °C (the lower end of the temperature range commonly found in Chile) experienced a significant loss of protection. This temperature-dependent loss of effect correlated with the amount of vaccine-strain RNA detected in the liver the first week after vaccination and with in vitro growth curves, which failed to detect any growth at 8 °C. We found that good vaccine efficacy can be restored by exposing fish to 15 °C for the first five days after vaccination before lowering the temperature to 7 °C for the remaining immunization period. This suggests that maintaining the correct temperature during the first few days after vaccination is crucial for achieving a protective immune response with ALPHA JECT LiVac® SRS. Our results emphasize the importance of temperature control when vaccinating poikilothermic animals with live vaccines.