Hypofractionation Research Articles

Predicting Efficacies of Fractional Doses of Vaccines by Using Neutralizing Antibody Levels: Systematic Review and Meta-Analysis.

With the emergence of SARS-CoV-2 variants that have eluded immunity from vaccines and prior infections, vaccine shortages and vaccine effectiveness pose unprecedented challenges for governments in expanding booster vaccination programs. The fractionation of vaccine doses might be an effective strategy for helping society to face these challenges, as fractional doses may have efficacies comparable with those of the standard doses. This study aims to investigate the relationship between vaccine immunogenicity and protection and to project efficacies of fractional doses of vaccines for COVID-19 by using neutralizing antibody levels. In this study, we analyzed the relationship between in vitro neutralization levels and the observed efficacies against both asymptomatic infection and symptomatic infection, using data from 13 studies of 10 COVID-19 vaccines and from convalescent cohorts. We further projected efficacies for fractional doses, using neutralization as an intermediate variable, based on immunogenicity data from 51 studies included in our systematic review. In comparisons with the convalescent level, vaccine efficacy against asymptomatic infection and symptomatic infection increased from 8.8% (95% CI 1.4%-16.1%) to 71.8% (95% CI 63%-80.7%) and from 33.6% (95% CI 23.6%-43.6%) to 98.6% (95% CI 97.6%-99.7%), respectively, as the mean neutralization level increased from 0.1 to 10 folds of the convalescent level. Additionally, mRNA vaccines provided the strongest protection, which decreased slowly for fractional dosing with dosages between 50% and 100% of the standard dose. We also observed that although vaccine efficacy increased with the mean neutralization level, the rate of this increase was slower for vaccine efficacy against asymptomatic infection than for vaccine efficacy against symptomatic infection. Our results are consistent with studies on immune protection from SARS-CoV-2 infection. Based on our study, we expect that fractional-dose vaccination could provide partial immunity against SARS-CoV-2 and its variants. Our findings provide a theoretical basis for the efficacy of fractional-dose vaccines, serving as reference evidence for implementing fractional dosing vaccine policies in areas facing vaccine shortages and thereby mitigating disease burden. Fractional-dose vaccination could be a viable vaccination strategy comparable to full-dose vaccination and deserves further exploration.

Left atrial strain after paroxysmal atrial fibrillation linac-based cardiac radioablation in elderly population.

Catheter ablation of atrial fibrillation (AF) may increase the risk of complication in aged patients. Stereotactic arrhythmia radioablation (STAR) is a non-invasive therapeutic alternative for cardiac arrhythmia. This sub-study evaluated left atrial strain (LAS) in elderly AF patients underwent STAR. Symptomatic paroxysmal AF patients aged > 70 years, with antiarrhythmic drugs failure or intolerance, enrolled in a phase II trial that have demonstrated the feasibility of LINAC-based STAR (total dose of 25Gy single fraction delivered in 3min), performed a 15-day electrocardiogram Holter monitoring to detect AF episodes (≥ 30s) and an echocardiographic LAS evaluation before and after STAR (at 1-, 3-, 6- and 12-month). Out 18 patients underwent STAR in the trial, 16 (7 males, 78 ± 5 years) completed the follow-up for LAS study. No baseline difference in echocardiographic and LAS parameters was observed between the 9 patients with AF recurrence during follow-up and those who maintained sinus rhythm. At 6- and 12-month after STAR, LAS reservoir was lower in patients with AF episodes than those without (respectively, p = 0.039 and p = 0.001). Values of left atrial area and volume as well as LAS conduit and contractile phase were not statistically significant different by patient's outcome across evaluations. Although no baseline LAS parameter before STAR seems predict AF recurrence after treatment in elderly patients, lower values of reservoir phase were observed during follow-up in those experiencing AF episodes. More research is needed to better assess the value of LAS monitoring in paroxysmal AF patients underwent Stereotactic cardiac radioablation.

A new approach to combined proton-photon therapy for metastatic cancer patients

Objective. Proton therapy is a limited resource and is typically not available to metastatic cancer patients. Combined proton-photon therapy (CPPT), where most fractions are delivered with photons and only few with protons, represents an approach to distribute proton resources over a larger patient population. In this study, we consider stereotactic radiotherapy of multiple brain or liver metastases, and develop an approach to optimally take advantage of a single proton fraction by optimizing the proton and photon dose contributions to each individual metastasis. Approach. CPPT treatments must balance two competing goals: (1) deliver a larger dose in the proton fractions to reduce integral dose, and (2) fractionate the dose in the normal tissue between metastases, which requires using the photon fractions. Such CPPT treatments are generated by simultaneously optimizing intensity modulated proton therapy (IMPT) and intensity modulated radiotherapy (IMRT) plans based on their cumulative biologically effective dose (BED α /β ). The dose contributions of the proton and photon fractions to each individual metastasis are handled as additional optimization variables in the optimization problem. The method is demonstrated for two patients with 29 and 30 brain metastases, and two patients with 4 and 3 liver metastases. Main results. Optimized CPPT plans increase the proton dose contribution to most of the metastases, while using photons to fractionate the dose around metastases which are large or located close to critical structures. On average, the optimized CPPT plans reduce the mean brain BED2 by 29% and the mean liver BED4 by 42% compared to IMRT-only plans. Thereby, the CPPT plans approach the dosimetric quality of IMPT-only plans, for which the mean brain BED2 and mean liver BED4 are reduced by 28% and 58%, respectively, compared to IMRT-only plans. Significance. CPPT with optimized proton and photon dose contributions to individual metastases may benefit selected metastatic cancer patients without tying up major proton resources.

Deciphering the therapeutic actions of Brenania brieyi (Rubiaceae) fractions on oxidoinflammatory anomalies

A decline in the antioxidant network during the inflammatory response plays a critical role in the pathogenesis of numerous diseases. We designed this study to decipher the therapeutic efficacy of Brenania brieyi in reducing oxidative stress caused by the inflammatory response to cotton pellets. Graded doses of methanol and chloroform fractions of B. brieyi (MFBB and CFBB) and indomethacin were administered to Wistar rats for seven days after implanting sterilised cotton pellets (20 mg). Thereafter, biochemical indices of oxidative stress were determined using blood samples taken through cardiac puncture. Furthermore, molecular interactions, drug-likeness, and toxicity features of B. brieyi phytochemicals were also assessed. Compared with the untreated group, the groups treated with MFBB and CFBB had a significant (p < 0.05) decrease in granuloma tissue weight and MDA levels while increasing glutathione levels, SOD, and CAT activities. In addition, a substantial increase in inflammatory-induced changes in antioxidant nutrients, together with a decline in liver enzymes, was obtained in the treated groups. The docking tests revealed that the top-scoring phytoconstituents of B. brieyi, n-hexadecanoic acid, and 9-octadecanoic acid interacted well with catalase, having docking scores of -6.19 and -7.58 kcal/mol, respectively. Moreover, the hits had good oral drug-likeness features and a safe toxicity profile. The findings of the study provide evidence that B. brieyi has antioxidant and anti-inflammatory properties, suggesting that it could be used as an alternative therapy to regulate oxidative stress-related diseases.

Tigliane metabolites in Hyles frass after feeding experiments with TPA and Euphorbia cyparissias

Within the genus Hyles, Euphorbia feeding appears to have evolved twice independently, in H. euphorbiae but also in H. nicaea, a species which had not been studied for its detoxification processes before. Euphorbia is known to contain toxic secondary metabolites, including diterpene esters, preventing most herbivores from feeding on them. We investigated the metabolisation of the standard phorbol ester Phorbol 12-myristate 13-acetate (TPA) and the diterpenes contained in Euphorbia cyparissias by the two species Hyles euphorbiae and Hyles nicaea (subspecies nicaea). For the first time, we report (1) The gut disposition of Hyles n. nicaea for this standard phorbol ester, which is commonly used in cancer and tumour research and (2) The disposition of the food plant tiglinaes of Euphorbia cyparissias after gut passage in both species and (3) Tigliane metabolites in the frass of TPA and of E. cyparissias feeding larvae. For both species around 5–25% of the TPA dose was recovered in the frass of the larvae, along with the metabolites phorbol and phorbol-13-acetate in very small amounts and traces. While the amounts of phorbol found did not differ much between the species frass, phorbol-13-acetate could be found in higher amounts in Hyles n. nicaea frass, indicating a difference in metabolisation. Moreover, enzymatic hydrolysis of TPA to phorbol-13-acetate and phorbol are postulated not to be the main metabolisation pathway, seeing that the amounts found only represent a small fraction of the TPA dose consumed.

Evaluating the effect of sodium alginate and sodium carboxymethylcellulose on pulmonary delivery of levofloxacin spray-dried microparticles.

Patients with cystic fibrosis commonly suffer from lung infections caused by Pseudomonas aeruginosa. Recently, the Levofloxacin (LVF) nebulizing solution (Quinsair®) has been prescribed for the antimicrobial management. The sustained-release (SR) dry powder formulation of LVF is a convenient alternative to Quinsair®. It has the potential to enhance patient convenience and decrease the likelihood of drug resistance over time. In this paper, we set forth to formulate and evaluate the potential application of sodium alginate (SA) and sodium carboxymethylcellulose (SCMC) for sustained pulmonary delivery of LVF. The spray-dried (SD) LVF microparticles were formulated using SCMC and SA along with L-leucine (Leu). The microparticles were analyzed in terms of particle size, morphology, x-ray diffraction (XRD), in-vitro drug release, and aerodynamic properties. Selected formulations were further proceeded to short-term stability test. The polymer-containing samples displayed process yield of 33.31%-39.67%, mean entrapment efficiency of 89% and volume size within the range of 2-5 μm. All the hydrogel microparticles were amorphous and exhibited rounded morphology with surface indentations. Formulations with a drug-to-excipient ratio of 50:50 and higher, showed a 24-h SR. The aerodynamic parameters were fine particle fraction and emitted dose percentage ranging between 46.21%-60.6% and 66.67%-87.75%, respectively. The short-term stability test revealed that the formulation with a 50:50 drug-to-excipient ratio, containing SA, demonstrated better physical stability. The selected formulation containing SA has the potential to extend the release duration. However, further enhancements are required to optimize its performance.

Stereotactic Body Radiation Therapy for Primary Renal Cell Carcinoma: A Case-Based Radiosurgery Society Practice Guide

Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment.

Delta radiomics to track radiation response in lung tumors receiving stereotactic magnetic resonance-guided radiotherapy

Background and purposeLung cancer is a leading cause of cancer-related mortality, and stereotactic body radiotherapy (SBRT) has become a standard treatment for early-stage lung cancer. However, the heterogeneous response to radiation at the tumor level poses challenges. Currently, standardized dosage regimens lack adaptation based on individual patient or tumor characteristics. Thus, we explore the potential of delta radiomics from on-treatment magnetic resonance (MR) imaging to track radiation dose response, inform personalized radiotherapy dosing, and predict outcomes. Materials and methodsA retrospective study of 47 MR-guided lung SBRT treatments for 39 patients was conducted. Radiomic features were extracted using Pyradiomics, and stability was evaluated temporally and spatially. Delta radiomics were correlated with radiation dose delivery and assessed for associations with tumor control and survival with Cox regressions. ResultsAmong 107 features, 49 demonstrated temporal stability, and 57 showed spatial stability. Fifteen stable and non-collinear features were analyzed. Median Skewness and surface to volume ratio decreased with radiation dose fraction delivery, while coarseness and 90th percentile values increased. Skewness had the largest relative median absolute changes (22 %–45 %) per fraction from baseline and was associated with locoregional failure (p = 0.012) by analysis of covariance. Skewness, Elongation, and Flatness were significantly associated with local recurrence-free survival, while tumor diameter and volume were not. ConclusionsOur study establishes the feasibility and stability of delta radiomics analysis for MR-guided lung SBRT. Findings suggest that MR delta radiomics can capture short-term radiographic manifestations of the intra-tumoral radiation effect.

Re-treatment of bone metastases for pain control: 2023 ASTRO education panel.

Bone metastases are a common and debilitating consequence of advanced cancer, often necessitating palliative radiation therapy (RT) for pain relief. Reirradiation (reRT) of bone metastases is often considered after lack of pain relief following an initial course of RT, after a partial but unsatisfying pain response to an initial course of radiotherapy, or after pain recurrence following a complete or partial pain response to an initial course of RT. The NCIC CTG SC.20 trial, a landmark multicenter, randomized, non-blinded, controlled non-inferiority trial, addressed the critical question of optimal dose fractionation for reRT in this patient population. This trial compared the efficacy and toxicity of a single 8 Gy fraction to multiple fractions totaling 20 Gy in 850 patients with painful bone metastases requiring reRT. The primary endpoint was overall pain response at 2 months, with secondary endpoints of quality of life (QoL) measures, functional interference, and toxicity profiles assessed using patient-reported questionnaires and the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. The intention-to-treat analysis revealed no significant difference in pain response between the two arms, meeting the pre-specified non-inferiority criteria. The per-protocol analysis suggested a potential benefit for a subset of patients receiving multiple fractions, although this was not statistically robust. Acute toxicities were more prevalent in the multiple fractions arm, with implications for patient comfort and healthcare utilization. Importantly, responders to reRT reported significant improvements in functional interference and QoL. The trial's findings support the use of a patient-centric approach to palliative RT, highlighting the viability of a single 8 Gy fraction as a less toxic and more convenient treatment option, albeit with consideration for individual patient circumstances. These results have significant implications for clinical practice, potentially reducing healthcare burdens while optimizing patient convenience during palliative care for painful bone metastases.

Hemostatic radiotherapy: a narrative review of the literature.

In locally advanced cancer, bleeding is a common clinical presentation and radiotherapy (RT) provides a noninvasive, well-tolerated, cost-effective treatment. However, the choice for fractionation dose and schedule seem to merely depend on physician's preference rather than specific guidelines. We reviewed the available literature on palliative hemostatic RT for response rate (RR) and bleeding duration in relation with the given dose. The PubMed database was used to search for articles, which were assessed by predetermined inclusion and exclusion criteria. A total of 54 articles, published over the last 20 years until December 2023 were analyzed for dose and/or fractionation regimen and their relation to the RR. A variety of fractionation schedules are used for palliative symptom control, including hemostasis. Research focusing on hemostatic irradiation specifically and prospective studies are rare. Moreover, to our knowledge, there are no specific (prospective) studies ongoing. Both external beam radiotherapy (EBRT) and brachytherapy lead to bleeding control and daily or weekly hypofractionated irradiation is safe and effective for both high and low biological equivalent dose (BED) regimens. If feasible, based on patient condition, some studies favor higher BED regimens to obtain more durable tumor/higher bleeding response. Higher radiation dose for thoracic irradiation may be indicative for simultaneous presentation of obstruction and/or dysphagia. Brachytherapy may be used solely or in combination with EBRT or in the setting of re-irradiation. Short-course regimens are preferred in patients in with low performance index scores. For future studies, multivariate analysis, including BED, can be important to assess efficacy of different fractionation schedules for a variety of tumor etiologies. Hemostatic RT, both by EBRT and brachytherapy, appears to be a safe and effective palliative treatment that clinically and statistically significantly reduces bleeding in cancer patients. The available literature is limited regarding prospective and uniform evaluation of hemostatic RT, including fractionation schedules. BED seems to be indicative for a better RR for specific indications. Current evidence suggests that treatment decisions should be tailored according to the patients' condition, tumor etiology and other clinical symptoms. More (prospective) research focusing on hemostasis is necessary to develop clear guidelines.

Intradermal fractional dose vaccination as a method to vaccinate individuals with suspected allergy to mRNA COVID-19 vaccines

Suspected allergic reactions after mRNA COVID-19 vaccination withheld multiple individuals from getting fully vaccinated during the pandemic. We vaccinated adults who had experienced possible allergic symptoms after their first intramuscular dose of a COVID-19 mRNA vaccine with a 1/5th fractional intradermal test dose of the mRNA-1273 (Moderna) COVID-19 vaccine. No anaphylactic reactions were observed after intradermal vaccination (n = 56). Serum anti-S1 IgG concentrations were measured using a bead-based multiplex assay four weeks after vaccinations. Antibody concentrations were compared with a previously collected nationwide cohort that had received two intramuscular doses of mRNA-1273. Antibody responses in all subjects tested (n = 47) were comparable to standard of care intramuscular dosing. Fractional intradermal dosing of mRNA COVID-19 vaccines may provide a pragmatic solution that is safe, time efficient compared to skin prick testing, dose sparing and immunogenic in individuals with suspected vaccine allergy.

Hydrodynamics of a dual-orifice needle-free jet injector

In the recent literature, it has been shown that an enhanced, multi-faceted, balanced immune response can be generated using a combined intradermal (ID) and intramuscular (IM) delivery of vaccines, especially for novel DNA vaccines. However, needle-based injection for a combined ID/IM delivery may require separate injections, which may prove to be time consuming, and impractical for mass immunizations. In contrast, a novel multi-orifice jet injector could be used to deliver drugs at multiple penetration depths simultaneously, which may provide advantages such as ease of operation, elimination of sharps, and short injection timeframe (O (10 m)).Here, we consider a dual-orifice geometry with both a wide orifice (200 μm–400 μm) for IM drug delivery and a narrow orifice (100 μm) for ID drug delivery. Using numerical simulations, we found that, at a fixed upstream pressure, jet velocities through wide and narrow orifices do not vary significantly for low-viscosity fluids (≲4%). However, it was previously hypothesized that the jet power, Pj=π8ρdj2vj3, is a more appropriate parameter to characterize tissue penetration depth. Thus, the jet power could vary by a factor of ∼10, yielding different depths for the two orifices. Using non-dimensional analysis via Euler (Eu) and Reynolds (Re) numbers, we characterize the role of orifice geometry and driving pressure, to generate geometry-specific correlations in the Eu–Re parameter space to estimate the jet velocity and pressure losses. We also elucidate the orifice size ratios that are best suited for fractional doses of ∼100 μL to intradermal tissue from a total injection of 1 ml.Preliminary experiments to visualize the penetration of wide and narrow jet streams into gelatin and pork substrates showed that the wide jet stream leads to substantially greater penetration depth than the narrow jet stream. In summary, we provide the initial feasibility of simultaneous delivery of a drug to multiple penetration depths from the same injection cartridge using the needle-free jet injection technique.

Evaluation of size–segregated bioaerosols concentration, deposition fraction and inhalation dose in individuals of an educational institute: a case study for health risk assessment

Evaluation of size–segregated bioaerosols concentration, deposition fraction and inhalation dose in individuals of an educational institute: a case study for health risk assessment

Predictive Factors and the Role of Conventionally Fractionated Radiation Therapy for Bone Metastasis from Renal Cell Carcinoma in the Era of Targeted Therapy.

Background and Objectives: Despite rapid advances in targeted therapies for renal cell carcinoma (RCC), bone metastases remain a major problem that significantly increases morbidity and reduces patients' quality of life. Conventional fractionated radiotherapy (CF-RT) is known to be an important local treatment option for bone metastases; however, bone metastases from RCC have traditionally been considered resistant to CF-RT. We aimed to investigate the effectiveness of CF-RT for symptomatic bone metastasis from RCC and identify the predictive factors associated with treatment outcomes in the targeted therapy era. Materials and Methods: Between January 2011 and December 2023, a total of 73 lesions in 50 patients treated with a palliative course of CF-RT for symptomatic bone metastasis from RCC were evaluated, and 62 lesions in 41 patients were included in this study. Forty-five lesions (72.6%) were treated using targeted therapy during CF-RT. The most common radiation dose fractionations were 30 gray (Gy) in 10 fractions (50%) and 39 Gy in 13 fractions (16.1%). Results: Pain relief was experienced in 51 of 62 lesions (82.3%), and the 12-month local control (LC) rate was 61.2%. Notably, 72.6% of the treatment course in this study was combined with targeted therapy. The 12-month LC rate was 74.8% in patients who received targeted therapy and only 10.9% in patients without targeted therapy (p < 0.001). Favorable Eastern Cooperative Oncology Group performance status (p = 0.026) and pain response (p < 0.001) were independent predictors of improved LC. Radiation dose escalation improved the LC in radiosensitive patients. A consistent treatment response was confirmed in patients with multiple treatment courses. Conclusions: CF-RT enhances pain relief and LC when combined with targeted therapy. Patients who responded well to initial treatment generally showed consistent responses to subsequent CF-RT for additional painful bone lesions. CF-RT could therefore be an excellent complementary local treatment modality for targeted therapy.

Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer.

This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer. Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2-3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded. The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4-5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates. This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.

Optimal minimum MU for intensity-modulated proton therapy with pencil-beam scanning proton beams.

A higher minimum monitor unit (minMU) for pencil-beam scanning proton beams in intensity-modulated proton therapy is preferred for more efficient delivery. However, plan quality may be compromised when the minMU is too large. This study aimed to identify the optimal minMU (OminMU) to improve plan delivery efficiency while maintaining high plan quality. We utilized clinical plans including six anatomic sites (brain, head and neck, breast, lung, abdomen, and prostate) from 23 patients previously treated with the Varian ProBeam system. The minMU of each plan was increased from the current clinical minMU of 1.1 to 3-24 MU depending on the daily prescribed dose (DPD). The dosimetric parameters of the plans were evaluated for consistency against a 1.1-minMU plan for target coverage as well as organs-at-risk dose sparing. DPD/minMU was defined as the ratio of DPD to minMU (cGy/MU) to find the OminMU by ensuring that dosimetric parameters did not differ by>1% compared to those of the 1.1-minMU plan. All plans up to 5 minMU showed no significant dose differences compared to the 1.1-minMU plan. Plan qualities remained acceptable when DPD/minMU ≥35 cGy/MU. This suggests that the 35 cGy/MU criterion can be used as the OminMU, which implies that 5 MU is the OminMU for a conventional fraction dose of 180 cGy. Treatment times were decreased by an average of 32% (max 56%, min 7%) and by an average of 1.6min when the minMU was increased from 1.1 to OminMU. A clinical guideline for OminMU has been established. The minMU can be increased by 1 MU for every 35 cGy of DPD without compromising plan quality for most cases analyzed in this study. Significant treatment time reduction of up to 56% was observed when the suggested OminMU is used.

A review on 4D cone-beam CT (4D-CBCT) in radiation therapy: Technical advances and clinical applications.

Cone-beam CT (CBCT) is the most commonly used onboard imaging technique for target localization in radiation therapy. Conventional 3D CBCT acquires x-ray cone-beam projections at multiple angles around the patient to reconstruct 3D images of the patient in the treatment room. However, despite its wide usage, 3D CBCT is limited in imaging disease sites affected by respiratory motions or other dynamic changes within the body, as it lacks time-resolved information. To overcome this limitation, 4D-CBCT was developed to incorporate a time dimension in the imaging to account for the patient's motion during the acquisitions. For example, respiration-correlated 4D-CBCT divides the breathing cycles into different phase bins and reconstructs 3D images for each phase bin, ultimately generating a complete set of 4D images. 4D-CBCT is valuable for localizing tumors in the thoracic and abdominal regions where the localization accuracy is affected by respiratory motions. This is especially important for hypofractionated stereotactic body radiation therapy (SBRT), which delivers much higher fractional doses in fewer fractions than conventional fractionated treatments. Nonetheless, 4D-CBCT does face certain limitations, including long scanning times, high imaging doses, and compromised image quality due to the necessity of acquiring sufficient x-ray projections for each respiratory phase. In order to address these challenges, numerous methods have been developed to achieve fast, low-dose, and high-quality 4D-CBCT. This paper aims to review the technical developments surrounding 4D-CBCT comprehensively. It will explore conventional algorithms and recent deep learning-based approaches, delving into their capabilities and limitations. Additionally, the paper will discuss the potential clinical applications of 4D-CBCT and outline a future roadmap, highlighting areas for further research and development. Through this exploration, the readers will better understand 4D-CBCT's capabilities and potential to enhance radiation therapy.

Seasonal variation in exposure to particulate matter among children attending different levels of education: Comparison of two dosimetry models

Exposure to particulate matter (PM) has been associated with several adverse health outcomes. Studies indicate that children may be exposed to much higher concentrations of PM at school than in other environments. There exists very little data on the deposited dose of PM while children attend classes. This study was carried out in a school located near an industrial complex in Portugal and attended by children aged 3–12 years. Indoor PM10, PM2.5 and PM1 were measured over two seasons in classrooms representing different school year groups. Particle deposition fractions in the respiratory tract, as well as the deposited doses, were calculated using the Multiple-Path Particle Dosimetry (MPPD) and the Exposure Dose Model (ExDoM2). Both models were implemented assuming an 8-h exposure scenario to represent the school day. In general, differences in PM concentrations were observed depending on room occupancy periods and season. The highest mean PM2.5 concentration was recorded in winter when the classroom was vacant (23.7 ± 20.5 μg m−3), while the highest mean PM10 level was observed in spring during school hours (61.7 ± 24.2 μg m−3). Regardless of the dosimetry model, the highest deposition of PM10 and PM2.5 was in the upper region, while the lowest was in the tracheobronchial (TB) region. The results indicate that deposited dose and deposition fraction in spring may be more harmful to pupils’ health than in winter. PM10 presented the highest doses, ranging from 54.2 to 128 μg and from 83.9 to 185 μg, according to MPPD and ExDoM2 estimates, respectively.

Simulation of Fire Evacuation in a Naturally Ventilated Bifurcated Tunnel

The natural wind velocities in tunnels under different natural conditions are distinct, and the longitudinal ventilation velocity significantly impacts the evacuation environment. This paper examines the evacuation conditions and strategies under varying wind velocities in bifurcated tunnels. Using Fire Dynamics Simulator (FDS) and Pathfinder software, the fire development and evacuation of three distinct longitudinal positions in a bifurcated tunnel are simulated. The simulation results demonstrate that the evacuation conditions for disparate fire sources at varying wind velocities are markedly disparate. In consideration of the construction cost and the maximization of evacuation capacity, the width of the evacuation doors at the three locations should be set to 2 m, 1.5 m, and 1.5 m, respectively. Furthermore, an analysis of the safety of individual personnel through Fractional Effective Dose (FED) revealed that directing evacuees towards the upstream of the fire after the fire is detected can significantly reduce individual personnel injuries while ensuring the overall success of the evacuation.

Vertebral body collapse after spine stereotactic body radiation therapy: a single-center institutional experience.

Spine stereotactic body radiation therapy (SBRT) for the treatment of metastatic disease is increasingly utilized owing to improved pain and local control over conventional regimens. Vertebral body collapse (VBC) is an important toxicity following spine SBRT. We investigated our institutional experience with spine SBRT as it relates to VBC and spinal instability neoplastic score (SINS). Records of 83 patients with 100 spinal lesions treated with SBRT between 2007 and 2022 were reviewed. Clinical information was abstracted from the medical record. The primary endpoint was post-treatment VBC. Logistic univariate analysis was performed to identify clinical factors associated with VBC. Median dose and number of fractions used was 24 Gy and 3 fractions, respectively. There were 10 spine segments that developed VBC (10%) after spine SBRT. Median time to VBC was 2.4 months. Of the 11 spine segments that underwent kyphoplasty prior to SBRT, none developed subsequent VBC. No factors were associated with VBC on univariate analysis. The rate of vertebral body collapse following spine SBRT is low. Prophylactic kyphoplasty may provide protection against VBC and should be considered for patients at high risk for fracture.