A single center, inter-observer evaluation of vestibular schwannoma stereotactic radiosurgery and its dosimetric impact.

The aim of this work was to evaluate the inter- and intra-observer variation in contouring vestibular schwannoma (VS) and the organs-at-risk (OAR), and its dosimetric impact in Volumetric Modulated Arc Therapy (VMAT). Three VS typical cases were contoured by four clinicians. The Agreement Volume Index (AVI) appeared to be notably higher in VS than in OARs, such that the dose coverage of VS is fairly robust. In OARs, the largest variation was +1.02Gy in dmax for the brainstem, +0.78Gy in dmean for the cochlea and +1.05Gy in dmax of the trigeminal nerve. Accordingly, it was decided that all VS delineations for stereotactic radiosurgery (SRS), and all frame-based SRS contouring in general, should always be reviewed by a second physician. In addition, the retrospective presentation of VS cases at daily peer review meetings has also been adopted to ensure that the consensus is constantly updated, as well as for training purposes.

Impact of TP53 mutations on brain metastasis control in non-small cell lung cancer patients undergoing stereotactic radiosurgery.

Purpose: To investigate whether TP53 variants may be correlated with overall survival and local control following stereotactic radiosurgery (SRS) for brain metastases (BMs) from non-small cell lung cancer (NSCLC). Methods: Patients undergoing an initial course of SRS for NSCLC brain metastases between 1/2015 and 12/2020 were retrospectively identified. Overall survival and freedom from local intracranial progression (FFLIP) were estimated via Kaplan-Meier method. Cox models assessed TP53 variant status (pathogenic variant, PV; variant not detected, ND). Results: 255 patients underwent molecular profiling for TP53, among whom 144 (56%) had a TP53 PV. Median follow-up was 11.6 months. OS was not significantly different across TP53 status. A trend toward superior FFLIP was observed for PV (95% CI 62.9 months-NR) versus ND patients (95% CI 29.4 months-NR; p=0.06). Superior FFLIP was observed for patients with one TP53 variant versus those with TP53 ND. Conclusion: Among NSCLC patients with BMs, the potential association between TP53 status and post-SRS FFLIP warrants further investigation in a larger prospective cohort.

The Effect of Global Spinal Alignment on the Cervical Degeneration in Patients with Degenerative Lumbar Scoliosis.

PURPOSE: To elucidate the effect of global spinal alignment on the cervical degeneration in Patients with Degenerative Lumbar Scoliosis (DLS). METHODS: A total of 117 patients with DLS and 42 controls were analysed. DLS patients (study group) were categorized according to the SRS-Schwab classification. Patients with lumbar spinal stenosis were reviewed as a control group. Spinopelvic parameters were measured in cervical and full-length spine radiographs. Cervical degeneration was assessed using the Cervical Degeneration Index (CDI) scoring system. RESULTS: There were significant differences in C2-7 sagittal vertical axis, T1 Slope, thoracic kyphosis, Lumbar Lordosis (LL), and pelvic tilt between DLS and control groups. Although the DLS and control groups did not differ significantly with regard to CDI scores, a striking difference was noted when sagittal spinopelvic modifiers were considered individually. Patients with a Pelvic Incidence minus Lumbar Lordosis (PI-LL) modifier grade of ++ had significantly higher CDI scores than those with 0, and patients with a PI-LL or Sagittal Vertical Axis (SVA) modifier grade of ++ had significantly higher CDI scores than control group. Disk narrowing scores were highest in patients with a PI-LL modifier grades of ++ followed by those with +. Additionally, CDI scores were more associated with LL rather than cervical lordosis. CONCLUSIONS: Patients with DLS may be at greater risk of cervical spine degeneration, especially those with a PI-LL or SVA modifier grade of ++. Surgical strategy for DLS patients should be more carefully selected considering the restoration of LL.

Determinants of cerebral radionecrosis in animal models: A systematic review.

BACKGROUND: Radionecrosis is a common complication in radiation oncology, while mechanisms and risk factors have yet to be fully explored. We therefore conducted a systematic review to understand the pathogenesis and identify factors that significantly affect the development. METHODS: We performed a systematic literature search based on the PRISMA guidelines using PubMed, Ovid, and Web of Science databases. The complete search strategy can be found as a preregistered protocol on PROSPERO (CRD42023361662). RESULTS: We included 83 studies, most involving healthy animals (n = 72, 86.75 %). High doses of hemispherical irradiation of 30 Gy in rats and 50 Gy in mice led repeatedly to radionecrosis among different studies and set-ups. Higher dose and larger irradiated volume were associated with earlier onset. Fractionated schedules proved limited effectiveness in the prevention of radionecrosis. Distinct anatomical brain structures respond to irradiation in various ways. White matter appears to be more vulnerable than gray matter. Younger age, more evolved animal species, and genetic background were also significant factors, whereas sex was irrelevant. Only 13.25 % of the studies were performed on primary brain tumor bearing animals, no studies on brain metastases are currently available. CONCLUSION: This systematic review identified various factors that significantly affect the induction of radionecrosis. The current state of research neglects the utilization of animal models of brain tumors, even though patients with brain malignancies constitute the largest group receiving brain irradiation. This latter aspect should be primarily addressed when developing an experimental radionecrosis model for translational implementation.

Safety, Tolerability, and EEG-Based Target Engagement of STP1 (PDE3,4 Inhibitor and NKCC1 Antagonist) in a Randomized Clinical Trial in a Subgroup of Patients with ASD.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a clinically and biologically defined subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

Off-iso Winston-Lutz test on seven linear accelerators.

PURPOSE: The aim of this study is to find optimal gantry, collimator, and couch angles for performing single isocenter, multiple target stereotactic radiosurgery (SIMT-SRS). Nineteen angle sets were tested across seven linear accelerators for radiation-isocenter coincidence and off-isocenter coincidence. The off-isocenter Winston-Lutz test was performed to evaluate the accuracy of isocenter alignment for each angle set, and optimal angle sets as well as maximum off-isocenter distance to target for each angle set was determined. The influence of simulated patient weight on off-iso Winston-Lutz test accuracy was also inspected. METHOD: The SNC MultiMet-WL phantom and MultiMet-WL QA Software v2.1 were used for the direct measurement and analysis of the off-iso Winston-Lutz test (also referred to as Winston-Lutz-Gao test). A two-step method was developed to ensure precise initial placement of the target. Nineteen beams were delivered at 6X energy and 2 × 2 cm field size to each of six targets on the MultiMet Cube with couch kicks at five cardinal angles (90°, 45°, 0°, 315°, and 270°). To reduce imaging uncertainty, only EPID was used in target alignment and test image acquisition. A total of 200 Ibs (90.7 kg) of weight was also used to mimic patient weight. All tests were performed on both the free table and the weighted table. RESULTS: For two new TrueBeam machines, the maximum offset was within the 1 mm tolerance when the off-iso distance is less than 7 cm. Two older VitalBeam machines exhibited unfavorable gantry, couch, and collimator (GCC) angle sets: Linac No. 3 at (0,90,0), (0,270,0) and Linac No. 4 at (0,45,45) and (0,90,0). The C-Series Linacs failed in the majority of GCC angle sets, with Linac No. 5 exhibiting a maximum offset of 1.53 mm. Four of seven machines show a clear trend that offset increases with off-isocenter distance. Additionally, the IGRT table was less susceptible to the addition of simulated patient weight than the ExactCouch. CONCLUSION: Among the seven linear accelerators addressed, newer model machines such as the Varian TrueBeam were more precise than older models, especially in comparison to the C-Series Linacs. The newer machines are more suitable for delivering SIMT-SRS procedures in all GCC angle sets, and the results indicate that newer TrueBeams are capable of performing SIMT-SRS procedures at all angle sets for targets of off-iso distances up to 7 cm. The trend that offset between the target center and radiation field center increases with off-iso distance, however, does not always hold true across machines. This may be comprised by the EPID's severe off-axis horn effect. Lastly, the IGRT couch was less susceptible to patient weight compared to ExactCouch in the off-isocenter Winston-Lutz test.

Evaluating stereotactic accuracy with patient-specific MRI distortion corrections for frame-based radiosurgery.

PURPOSE: This study examines how MRI distortions affect frame-based SRS treatments and assesses the need for clinical distortion corrections. METHODS: The study included 18 patients with 80 total brain targets treated using frame-based radiosurgery. Distortion within patients' MRIs were corrected using Cranial Distortion Correction (CDC) software, which utilizes the patient's CT to alter planning MRIs to reduce inherent intra-cranial distortion. Distortion was evaluated by comparing the original planning target volumes (PTVORIG) to targets contoured on corrected MRIs (PTVCORR). To provide an internal control, targets were also re-contoured on uncorrected (PTVRECON) MRIs. Additional analysis was done to assess if 1 mm expansions to PTVORIG targets would compensate for patient-specific distortions. Changes in target volumes, DICE and JACCARD similarity coefficients, minimum PTV dose (Dmin), dose to 95% of the PTV (D95%), and normal tissue receiving 12 Gy (V12Gy), 10 Gy (V10Gy), and 5 Gy (V5Gy) were calculated and evaluated. Student's t-tests were used to determine if changes in PTVCORR were significantly different than intra-contouring variability quantified by PTVRECON. RESULTS: PTVRECON and PTVCORR relative changes in volume were 6.19% ± 10.95% and 1.48% ± 32.92%. PTVRECON and PTVCORR similarity coefficients were 0.90 ± 0.08 and 0.73 ± 0.16 for DICE and 0.82 ± 0.12 and 0.60 ± 0.18 for JACCARD. PTVRECON and PTVCORR changes in Dmin were -0.88% ± 8.77% and -12.9 ± 17.3%. PTVRECON and PTVCORR changes in D95% were -0.34% ± 5.89 and -8.68% ± 13.21%. The 1 mm expanded PTVORIG targets did not entirely cover 14 of the 80 PTVCORR targets. Normal tissue changes (V12Gy, V10Gy, V5Gy) calculated with PTVRECON were (-0.09% ± 7.39%, -0.38% ± 5.67%, -0.08% ± 2.04%) and PTVCORR were (-2.14% ± 7.34%, -1.42% ± 5.45%, -0.61% ± 1.93%). Except for V10Gy, all PTVCORR changes were significantly different (p < 0.05) than PTVRECON. CONCLUSION: MRIs used for SRS target delineation exhibit notable geometric distortions that may compromise optimal dosimetric accuracy. A uniform 1 mm expansion may result in geometric misses; however, the CDC algorithm provides a feasible solution for rectifying distortions, thereby enhancing treatment precision.

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.

Effect of modulation factor and low dose threshold level on gamma pass rates of single isocenter multi-target SRT treatment plans.

PURPOSE: SRS MapCHECK (SMC) is a commercially available patient-specific quality assurance (PSQA) tool for stereotactic radiosurgery (SRS) applications. This study investigates the effects of degree of modulation, location off-axis, and low dose threshold (LDT) selection on gamma pass rates (GPRs) between SMC and treatment planning system, Analytical Anisotropic Algorithm (AAA), or Vancouver Island Monte Carlo (VMC++ algorithm) system calculated dose distributions. METHODS: Volumetric-modulated arc therapy (VMAT) plans with modulation factors (MFs) ranging from 2.7 to 10.2 MU/cGy were delivered to SMC at isocenter and 6 cm off-axis. SMC measured dose distributions were compared against AAA and VMC++ via gamma analysis (3%/1 mm) with LDT of 10% to 80% using SNC Patient software. RESULTS: Comparing on-axis SMC dose against AAA and VMC++ with LDT of 10%, all AAA-calculated plans met the acceptance criteria of GPR ≥ 90%, and only one VMC++ calculated plan was marginally outside the acceptance criteria with pass rate of 89.1%. Using LDT of 80% revealed decreasing GPR with increasing MF. For AAA, GPRs reduced from 100% at MF of 2.7 MU/cGy to 57% at MF of 10.2 MU/cGy, and for VMC++ calculated plans, the GPRs reduced from 89% to 60% in the same MF range. Comparison of SMC dose off-axis against AAA and VMC++ showed more pronounced reduction of GPR with increasing MF. For LDT of 10%, AAA GPRs reduced from 100% to 83% in the MF range of 2.7 to 9.8 MU/cGy, and VMC++ GPR reduced from 100% to 91% in the same range. With 80% LDT, GPRs dropped from 100% to 42% for both algorithms. CONCLUSIONS: MF, dose calculation algorithm, and LDT selections are vital in VMAT-based SRT PSQA. LDT of 80% enhances sensitivity of gamma analysis for detecting dose differences compared to 10% LDT. To achieve better agreement between calculated and SMC dose, it is recommended to limit the MF to 4.6 MU/cGy on-axis and 3.6 MU/cGy off-axis.

Evaluating effectiveness of clustering algorithms in multiple target stereotactic radiosurgery.

OBJECTIVE: Single-isocenter-multiple-target technique for stereotactic radiosurgery (SRS) can reduce treatment duration but risks compromised dose coverage due to potential rotational errors. Clustering targets into two groups can reduce isocenter-target distances, mitigating the rotational uncertainty. However, a comprehensive evaluation of clustering algorithms for SRS is absent. This study addresses this gap by introducing the SRS Target Clustering Framework (Framework), a comprehensive tool that utilizes commonly used clustering algorithms to generate efficient cluster configurations. Approach. The Framework incorporates four distinct optimization objectives based on two key metrics: the isocenter-target distance and the ratio of this distance to the target radius. Agglomerative and weighted agglomerative clustering are employed for minimax and weighted minimax objectives, respectively. K-means and weighted k-means are utilized for sum-of-squares and weighted sum-of-squares objectives. We applied the Framework to 126 SRS plans, comparing results to ground truth solutions obtained through a brute force algorithm. Main results. For the minimax objective, the average maximum isocenter-target distance from agglomerative clustering (4.8 cm) was slightly higher than the ground truth (4.6 cm). Similarly, the weighted agglomerative clustering achieved an average maximum ratio of 15.1 compared to the ground truth of 14.6. Notably, both k-means and weighted k-means clustering showed close agreement (within a precision of 0.1) with the ground truth for average root-mean-square target-isocenter distance and ratio (3.6 cm and 11.1, respectively). Significance. These results demonstrate the Framework's effectiveness in generating clusters for SRS targets. The proposed approach has the potential to become a valuable tool in SRS treatment planning. Furthermore, this study is the first to investigate clustering algorithms for both minimizing maximum and sum-of-squares uncertainty in SRS. .

Repeated HyperArc radiosurgery for recurrent intracranial metastases and dosimetric analysis of recurrence pattern to account for diffuse dose effect on microscopical disease.

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods: 56 patients were treated for 702 BMs with 197 (range 2-8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). Results: The 1-year OS was 70 %, and the median was 20.8 months (17-36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0-7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.

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.

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.

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.

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.

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.

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.

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.