Local Failure Research Articles

The role of radiotherapy in extensive-stage small cell lung cancer: insights from treatment failure patterns in the era of immunotherapy

BackgroundThe therapeutic advantage of radiotherapy (RT) as an adjunct to first-line immunotherapy and chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC) remains unclear. This study aimed to elucidate the value of RT based on the first failure pattern of ES-SCLC.MethodsIn this study, we retrospectively analyzed ES-SCLC patients treated with first-line chemotherapy and immune checkpoint inhibitors (ICIs) at Shanghai Chest Hospital from August 2018 to October 2023. Our study recorded the first failure pattern in ES-SCLC, analyzed the main sites of disease progression, explored factors that may affect prognosis and estimated the value of RT in extending patient survival in the immunotherapy era. Key endpoints included the first failure pattern, progression-free survival (PFS) and overall survival (OS).ResultsAmong 344 patients, 70 (20%) had local failure, 105 (31%) had distant failure, 69 (20%) experienced both types of failure, and 100 (29%) showed no disease progression. Disease progression occurred in 244 patients (71%). They were divided into two groups: 183 without pre-progression RT and 61 with pre-progression RT. In the non-pre-progression RT group, 55 patients (30%) had local failure, 72 patients (39%) had distant failure, and 56 patients (31%) had both. In the pre-progression RT group, 15 patients (25%) had local failure, 33 patients (54%) had distant failure, and 13 patients (21%) had both. Univariate and multivariate analyses identified RT as an independent prognostic factor for improved OS (P < 0.05). Subgroup analysis further confirmed these findings. Pre-progression RT was associated with superior PFS (P < 0.05). The median overall survival (mOS) was 20.1 months (95% confidence interval [CI]: 15.5–24.7 months) in the pre-progression RT group, compared to 13.4 months (95% CI: 13.4–19.2 months) in the non-pre-progression RT group.ConclusionRT improved OS in these patients, and pre-progression RT improved PFS further. Pre-progression RT shows a trend toward OS benefit.

Efficacy and Failure Patterns Following Target Volume and Dose Reduction After Neoadjuvant Therapy in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma.

In this study, we aimed to analyze the efficacy and failure patterns of contouring target volume based on the residual tumor and decreasing the dose to the area of tumor regression after neoadjuvant therapy in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). We retrospectively analyzed the patients with locoregionally advanced HNSCC treated by our group from May 2011 to June 2023. All patients received neoadjuvant therapy followed by intensity-modulated radiation therapy. Gross tumor volumes for the primary tumor and metastatic lymph nodes were delineated according to postneoadjuvant extension. The tumor shrinkage after neoadjuvant therapy was included in the high-risk clinical target volume (CTV1) and prescribed a dose of 60 Gy. Kaplan-Meier analysis was employed to calculate local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), overall survival (OS), and distant metastasis-free survival (DMFS). Failure patterns were analyzed by mapping the location and extent of locoregional recurrence onto pretreatment planning CT. This study included a total of 114 patients, with a median follow-up of 34 months. The 5-year LRFS, RRFS, OS, and DMFS rates were 70.2%, 70.7%, 74.8%, and 73.8%, respectively. Among the 14 patients with recurrences, there were 5 local failures, 6 regional recurrences, and 3 both local and regional recurrences. All local recurrences occurred within the 95% isodose line, classified as in-field failures. Only one regional recurrence was marginal failure. No out-of-field failure was observed. Reduction of target volume after neoadjuvant therapy and distribution of 60 Gy of dose to the tumor regression area may be feasible.

Outcomes of Stereotactic Body Radiotherapy Compared with Surgical Resection in Patients with Hepatocellular Carcinoma and Macrovascular Invasion: A Propensity Score-Matched Analysis.

Patients with advanced hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) are recommended to receive systemic therapy according to guidelines. Stereotactic body radiotherapy (SBRT) and surgery are increasingly used in this patient population. This study compares outcomes from these local treatments. Patients diagnosed with HCC with MVI and treated with surgery or SBRT between 1999 and 2022 were included. Propensity score matching minimized bias from confounders. Overall survival (OS) was analyzed using the Kaplan-Meier method,. and local, regional, and distant recurrences were assessed via competing risk methods. Univariable and multivariable analyses adjusted by the Lasso method evaluated OS predictors. Among 175 patients, 38 underwent surgery and 137 received SBRT. The median age was 61 years, tumor volume was 158.6cc, and α-fetoprotein level was 197 IU/mL. Most surgical patients had major resection (74%) via an open approach (97%). The median biologically effective dose (BED) for SBRT was 53.7Gy. After matching, 35 patients per group had a median OS of 16 months. Local failure was higher in the SBRT group (20%) than in the surgery group (12%) at 1year (p=0.028). Distant failure was more frequent in surgery (54%) compared with SBRT (17%) [p=0.003]. Excluding SBRT patients receiving adjuvant systemic therapy did not change the results. In-hospital mortality was 9% post-surgery and 14% experienced post-SBRT liver impairment. Both surgery and SBRT offer good long-term OS and control. Surgery provides better local control, while SBRT had lower distant relapse. While SBRT has acceptable toxicity, surgery carries a significant mortality risk.

Effects of pore water and pore air pressure on the slope failure mechanisms due to rainfall in centrifuge investigation

BackgroundThe slope failures triggered by heavy rainfall are challenging to predict. However, their severe impact and potential for extensive damage emphasize the urgent need for effective strategies to mitigate these risks. This study aimed to investigate the effects of pore water pressures (PWPs) and pore air pressures (PAPs) on slope failure during heavy rainfall under centrifuge condition. Three centrifuge rainfall model tests were conducted with varying rainfall intensities (I) and relative densities (Dr). In this experiment, the slope model was subjected to a centrifugal acceleration of 30 G.ResultsIn all cases, slope failures started at the slope toes when the PWPs became positive and phreatic surfaces appeared on the slope surface. In the Toyoura sand case, the PAPs increased slightly at the slope crest, hardly changed at the slope toe, and oscillated at the slope shoulder due to rainwater infiltration. The entire slope failure was observed in this case. In the Silica sand cases, only localized slope toe failures were observed. The PAPs slightly oscillated with small changes in the silica sand case with a relative density of Dr = 50%. However, in the case with a Dr = 25%, the PAPs at the slope toe significantly increased compared to the other parts, and the oscillations were comparatively large. After the first failure occurred at the slope toe in the silica sand case with a Dr = 25%, cracks and slip lines appeared at the slope crest.ConclusionsThe three cases illustrated the complex relationship between soil properties, rainfall intensity, and the dynamics of pore water and pore air pressure on slope stability during heavy rainfall. From the behaviour of PAPs and PWPs in all cases, it was found that the transition from air to water occurred smoothly, and the isolation of air was not observed even during heavy rainfall. Changes in PAPs were far smaller than those in PWPs, indicating a smaller impact on slope stability than PWPs.

Towards a Meaningful Understanding of Organizational Leaders' Localized and Contextualized Implementation of UNSDGs in Bahrain's Changing Energy Sector Businesses

ABSTRACTDespite Network Leadership scholarship's emphasis on localizing and contextualizing leadership practices during organizational change, there is a dearth in the current theoretical framings on “how” to address the implementation failure of localization and contextualization towards broader SDGs/organizational sustainability. This paper fills this gap by offering deeper insightful theoretical and practical understanding of how organizational leaders can address socio‐economic and ecological sustainability concerns, and how a more meaningful reconceptualization and implementation of leadership practices can help Business and Management academics and practitioners address the organizational growth, human, and ecological well‐being dilemma in the energy sector. By drawing on Network Leadership, SDG, organizational change literature and 26 senior leaders' semi‐structured interviews, this study uses (Braun and Clarke's 2006) Thematic Analysis Procedure to resolve the theoretical and practical implementation lag in Business and Management scholarship. We contribute 4 novel implementation practices: (1) Operational; (2) strategic; (3) cultural and (4) interorganizational knowledge exchange alignment and a model on wider socio‐economic‐ecological well‐being. Showing ‘what’ leadership characteristics are needed and “how” to meaningfully reconceptualize the dominant localization and contextualization model of organizational change towards broader sustainability goals has been practically and scholarly overdue.

Patterns of failure after stereotactic radiosurgery for brain metastases from small cell lung cancer: outcomes in the immunotherapy era.

Small cell lung cancer (SCLC) is known to have high rates of development of brain metastases. Standard treatment has been whole brain radiation therapy (WBRT) but the role for more focused treatment and hippocampal avoidance has arisen in the past decade. In addition, with possible penetration of the central nervous system by more modern immunotherapies, the risk of distant failure may be lower. As such, we reviewed patients at our institution treated with stereotactic radiosurgery (SRS) to look at patterns, locations, and predictors of failure in the brain. A retrospective review and analysis of charts was done on 46 patients treated with SRS (no history of prior WBRT) for their brain metastases from SCLC. Multivariate analysis was used to determine significant prognostic factors influencing survival and local/distant failure. We tracked timing and type of immunotherapy, if any, as well as if patients failed in the hippocampus or required WBRT. There were 46 patients with 97 total brain metastases treated with SRS in this study. Median number of metastases was 2 (1-5). The median dose of radiation was 20Gy (20-30) in 3 fractions (1-5) for all 97 tumors. 11 patients did not receive immunotherapy, whereas 35 patients had immunotherapy of some sort. Median overall survival (OS) for the entire cohort was 13months, with a 12month OS of 59% and 2year OS of 30%. Cox regression did not reveal any significant predictors of OS, including age, sex, total volume, extracranial disease, KPS, immunotherapy, or number of metastases. 12month and 24month local control of disease was 95% and 80%, respectively. There were no significant predictors of local failure including volume, dose, or immunotherapy. 25 of the patients had distant brain failure, with a rate of distant failure of 38% and 64% for 6 and 12months, respectively. Immunotherapy, number of metastases, total target volume, nor presence of extracranial disease was predictive of distant brain failure. WBRT free survival was also measured and found to be 73% at 1year. There were no significant predictors for this measure. Lastly, five patients in this cohort showed failure in the hippocampus, where the rate of failure at 6 and 12months was 16%. Rates of distant brain failure in SCLC patients after SRS remain similar to those of NSCLC patients in the immunotherapy era. We did not show a decrease in distant failure rate based on immunotherapy use. The rate of hippocampal failure was quite low and should provide reassurance that SRS and techniques such as HA-IMRT can be reasonably used in these patients. Ongoing clinical trials will help provide more definitive answers in this arena.

Do Pre-Treatment Biopsy Characteristics Predict Early Tumour Progression in Feline Diffuse Large B Cell Nasal Lymphoma Treated With Radiotherapy?

The standard of care treatment for localised feline nasal lymphoma (FeNL) is radiation therapy (RT). Early local or systemic failure occurs in 17%-45% of cats treated with RT with or without chemotherapy. The aim of this study was to determine if pre-treatment biopsy characteristics could predict early tumour progression in FeNL. Inclusion criteria consisted of histologically confirmed FeNL, available paraffin blocks of diagnostic quality, localised to the sinonasal cavity on staging pre-RT, treated with IMRT/IGRT (10 × 4.2 Gy) without chemotherapy and at least 1 year follow-up. All pre-RT biopsies were reviewed and evaluated with CD3, CD20, CD79a, pan-CK and Ki-67 immunohistochemistry and the mitotic activity index was determined. The primary endpoint was progression-free survival (PFS) at 1 year and hazard-ratios (HR) with confidence interval (CI) were calculated. Twenty-eight cats fit the inclusion criteria, and all had diffuse large B-cell lymphoma. Seventeen cats (61%) were progression free at 1 year. Of the 11 cats that progressed in the first year, two had local progression, two had both local and systemic progression and seven had systemic progression. The mitotic index (HR: 1.03, CI 0.9-1.19, p = 0.645), Ki-67 (HR: 1.00, CI 0.98-1.02, p = 0.845) and > 30% of tumour-infiltrating T cells (HR: 0.38, CI 0.09-1.56, p = 0.175) were not significantly associated with PFS. In this uniformly RT treated population of FeNL, none of the evaluated pre-RT histologic parameters could predict early treatment failure.

Interpretable survival network for progression risk analysis of multimodality imaging biomarkers in poor-prognosis head and neck cancers

This study explores the predictive utility of multi-time point, multi-modality quantitative imaging biomarkers (QIBs) and clinical factors in patients with poor-prognosis head and neck cancers (HNCs) using interpretable machine learning. We examined 93 patients with p16 + oropharyngeal squamous cell carcinoma or locally advanced p16- HNCs enrolled in a phase II adaptive radiation dose escalation trial. FDG-PET and multiparametric MRI scans were conducted before radiation therapy and at the 10th fraction (2 weeks). A survival network analyzed MRI and PET-derived biomarkers such as gross tumor volume (GTV), blood volume (BV), and metabolic tumor volume (MTV50), along with clinical factors to predict local (LF) and distant failures (DF). Feature attributions and interactions were assessed using Expected Gradients (EG) and Expected Hessian (EH). Through rigorous cross-validation, the model for predicting LF, incorporating biomarkers like p16 status and radiation boost, achieved a c-index of 0.758. Similarly, the DF prediction model showed a c-index of 0.695. The analysis of feature attributions and interactions enhanced understanding of important features and complex factor interplays, potentially guiding more personalized and intensified treatment approaches for HNC patients.

Effects of undulating printing paths on axial compressive behaviors of 3D-printed continuous fiber-reinforced multi-cell thin-walled structure

Thin-walled structures are widely used in passive safety systems of the vehicles because of their excellent lightweight and stable progressive deformation behavior. Recently, continuous fiber 3D printing technique has been successfully applied in the manufacturing of thin-walled structures, providing a promising path to meet increasing requirements for energy absorbers as vehicle speed increases. This paper proposed a range of novel undulating printing paths to fabricate two kinds of continuous Kevlar fiber reinforced multi-cell thin-walled structures (CFMSs) with different cross-section shapes, named MT1 and MT2, respectively. For each type of CFMS, three different printing paths (moving back and forth between two layers) were designed to manufacture CFMS with the wall thickness comprised of only a single deposited line. The axial compressive tests were conducted to investigate the compressive response of CFMSs. It was found that undulating printing paths affect both the mechanical behavior and collapse mode of CFMSs. During the compression process, MT1 and MT2 printed with path 3 showed progressively folding deformation modes (differed from the progressive crushing mode of composite laminated thin-walled structures). Thus, compared to MT2 printed with path 1 and path 2, which exhibit global buckling, MT1 and MT2 printed with path 3 exhibited more stable energy absorption performance. Besides, although the local failure mode in different CFMSs caused by the same path was similar, the same printing path had different influences on the axial compressive properties of different CFMSs.

Stress-strain ratio on stabilization work in the saturated zone causes rapid road failure

Abstract Road construction frequently encounters difficulties with soil with low bearing capacity, such as soil subsidence, which results in the deformation or waves of the surface road. The investigation was conducted at the Paya Tumpi quarry and quarry in Krueng Raya-Laweung, which are the providers of soil material used in road construction. These two quarries, due to their extensive clay soil criteria, are unsuitable for use as road subgrade material. Hence, to utilize this soil, it is necessary to stabilize it by incorporating volcanic ash. This will be accomplished by evaluating the shear strength of mixed soil, the optimum water content for compaction, and the stress-strain ratio’s behaviour as a result of the stabilization effect. To determine the cohesion and shear angles at a defined shear stress and the response of each test object to strain and stress, a series of experiments were carried out. The research findings indicated that the cohesion and shear angles of the soil samples were enhanced by the addition of volcanic ash in comparison to natural soil. The cohesion (c) of sample-1, sample-2, and sample-3 increased from 0.034-0.223 kg/cm2, 0.093-0.118 kg/cm2, and 0.008–0.037 kg/cm2, respectively. Similarly, the shear angles (ϕ) increase from 32.30o to 40.30o, 27.20o to 30.10o, and 27.90o to 36.20o, respectively. The stress-strain ratio is intermediate between local failure and punching.

On the anatomy of acoustic emission.

Abrupt, local frictional fault failure comprises a displacement that is normally accompanied by acoustic emission (AE)-an impulsive elastic wave broadcast with an amplitude proportional to particle velocity. The aggregate of these displacements is the basic fault motion. In laboratory shear experiments, the examination of a sequence of laboratory earthquakes includes continuous measurements of fault motion and the associated AE that is broadcast. From these measurements, connections between the fault motion and cumulative sum of the AE amplitude can be identified. The composition of the AE broadcasts reveals inhomogeneity in the fault mechanical structure from which they arise. This inhomogeneity can be decomposed into a time invariant AE component and an articulated AE component. The articulated AE component serves as a "state of the fault diagnostic" that follows a distinctive pattern to fault failure. Thus, the articulated AE component can be used directly to monitor the state of the fault.

Outcomes of Management of Progressive Radiosurgery-Treated Brain Metastasis With Resection Followed by Pathology-Informed Management: A Retrospective Study

BACKGROUND AND OBJECTIVES: In patients treated with stereotactic radiosurgery (SRS) for brain metastases, follow-up imaging demonstrating progression may result from treatment effect/radionecrosis (RN) or tumor progression. We report long-term outcomes for a cohort of patients who demonstrated radiological progression on serial imaging after initial radiation and who underwent resection, at which point histology informed further management. METHODS: A retrospective chart review identified 76 patients with an associated 82 brain lesions between 2009 and 2022, that were initially treated with SRS, and then demonstrated suspicious imaging developing through at least 2 scan time points with either pathologic confirmation of tumor or RN. RESULTS: Of the 82 lesions, 55 lesions (67.1%) were found to be tumor and were treated with repeat radiation and 27 (32.9%) were found to have pathologically confirmed RN and conservatively managed. 14/27 lesions ultimately found to be radionecrotic required steroids preoperatively due to neurological symptoms. None of these lesions required further intervention with median postsurgery follow-up of 24.4 months (range 1-104 months). There were 55 instances (in 51 patients) of confirmed recurrent/progressive tumor who we treated with repeat aggressive radiation with either Cs-131 brachytherapy (12 [21.8%]) or SRS (43 [78.2%]). Among patients treated with reirradiation, the median follow-up to local failure was 15.2 months (95% CI 7.3-26.6 months). The 2-year local control rate was 79.5% (95% CI 68.3%-92.5%). CONCLUSION: These results support resection of radiosurgery-treated lesions with progression continuing through serial imaging, and this pathology-informed management results in excellent control of both RN and tumor progression after radiosurgery.

A prospective observational study of local failures in surgical stage III and IV squamous cell carcinoma of oral cavity

A prospective observational study of local failures in surgical stage III and IV squamous cell carcinoma of oral cavity

A Spatial-Temporal Method for Early Prediction of Fatigue Crack Region and Orientation in Metallic Cellular Materials Using In-Situ Infrared Thermography (IRT)

This study seeks an early prediction method of crack failure location and orientation due to low cycle fatigue in additively manufactured metallic cellular materials by leveraging experimentally observed accumulation of plastic deformation. To study this, a novel spatial-temporal approach for analyzing Infrared Thermographic (IRT) video was developed to detect heat generated by local plastic deformation. The method was validated experimentally by conducting fully reversed low cycle fatigue tests of Inconel 718 (IN718) honeycomb specimens manufactured using Laser Powder Bed Fusion (LPBF). Using the approach developed, results showed that localized heating due to plastic work could be detected and used for early prediction of the most probable path, and orientation of crack propagation. Furthermore, the method developed was found to be able to predict these results within the first 1.5% of the total life of the specimen apriori to crack initiation.

Assessing the vulnerability of empirical infrastructure networks to natural catastrophes

Human-made infrastructures are complex systems continually exposed to events that threat their function, such as cascading failures, occurring when the flow of physical quantities is redistributed within the network as a consequence of localized disruptions. Nevertheless, the role played by exogenous catastrophic events and internal failures on the robustness of critical infrastructures is usually addressed independently, under simplifying assumptions and lacking a unified picture for realistic risk assessments. Here, we fill this gap by introducing the Operational-Affected-Dismantled (OAD) model that captures both local and nonlocal failure propagation mechanisms. The model combines reaction–diffusion processes for local spreading with a global field effect for long-range interactions, allowing us to quantitatively characterize the cascade dynamics in infrastructure networks. Moreover, we include information on external stressors to assess the robustness of empirical network infrastructures and build spatial risk maps. By using data from severe storms (2009–2016) and from earthquakes (2000–2023) as stressors of the North American power grid and the worldwide airline transportation system, respectively, we offer a quantitative way to rank events by their potential to trigger systemic effects. By analyzing the response of the European power grid to simulated severe storms, we find that it can show high levels of systemic risk. Uncertainty in global climate and the accelerating frequency of extreme events all over the globe call for novel strategies to quantify, adapt to and mitigate systemic risk. Our framework provides a suitable starting point to assess the robustness of empirical systems in realistic and what-if scenarios.

Research on the pressure fluctuations and hydraulic resonance phenomena in the high-pressure pipelines of marine common rail systems

Increasing injection pressures in marine high-pressure common rail systems can lead to reliability issues due to pressure fluctuations. This study investigates the mechanism of hydraulic resonance caused by these fluctuations. A test bench assessed pressure fluctuations under various conditions and fuel pipe parameters, where hydraulic resonance was observed. Time-domain and frequency-domain analyses were conducted on the test results. The system pipeline was then optimized to eliminate hydraulic resonance. Resultsindicate that pressure fluctuations exhibit both high- and low-frequency coupling. Abnormal fluctuations are caused by hydraulic resonance, triggered by the proximity between the excitation frequency of the high-pressure fuel pump and the first-order natural frequency of the system. Resonance speed is influenced by the fuel pipe's structural parameters and the fuel's hydraulic properties. The frequency-domain model shows high predictive accuracy, identifying the interface between the pump and the pipeline as the most probable failure location. Optimization reduced pressure fluctuations at the pump end and the common rail by 73 % and 35.7 %, respectively, and eliminated hydraulic resonance at the original resonance speed. The maximum pressure fluctuation amplitude at the pump end decreased from 410 bar to 167 bar, a 59.3 % reduction. The research methodology presented in this paper provides a theoretical foundation for the structural design of the high-pressure pipeline in high-pressure common rail systems.

Tuning load redistribution and damage near heterogeneous interfaces

We investigate interface failure of model materials representing architected thin films in contact with heterogeneous substrates. We find that, while systems with statistically isotropic distributions of impurities derive their fracture strength from the ability to develop rough detachment fronts, materials with hierarchical microstructures confine failure near a prescribed surface, where crack growth is arrested and crack surface correlations are suppressed. We develop a theory of network Green’s functions for the systems at hand, and we find that the ability of hierarchical microstructures to control failure mode and locations comes at no performance cost in terms of peak stress and specific work of failure and derives from the quenched local anistotropy of the elastic interaction kernel.

Experimental Study of Mechanical Behavior of Dry-Stone Structure Contact

Dry-stone structures are traditional constructions that are present everywhere around the world, with their stability working mostly by gravity. Contrarily to their in-plane behavior, their out-of-plane response is very brittle and is fully controlled by the geometry, as well as the contact properties, between units (stones). Two main local failure modes of dry-joint contact are identified to lead to the global failure of the structure: (i) sliding and (ii) joint opening. Most of the existing studies investigated full structures to obtain the global response and/or couplet only, with the aim of only characterizing the contact. The present experimental work studies the effect of sliding and joint opening between stones at different scales: couplets, structures made of a few (up to five) blocks, and full walls, as well as varying the way the masonry units are assembled within a single structure. Different stones are employed to quantify potential differences. All the structures are loaded up to the collapse with a tilting table to induce out-of-plane actions. Repeatability tests are also conducted to better understand the effect of contact variability. This study unveils that the heterogeneity of the dry-joint contact, as well as the repartition of the blocks, affects the global response (both in terms of load capacity and failure mode). It also confirms that the most critical local failure mode is produced by the joint opening.

Evolutionary topology optimization with stress control for composite laminates using Tsai-Wu criterion

In this study, a topology optimization technique with stress control is proposed for the composite laminates. The bi-directional evolutionary structural optimization (BESO) method is selected to avoid the stress singularity. The technique expresses the failure index based on the Tsai-Wu criterion, thereby ensuring a comprehensive consideration of the anisotropy. To address the local nature of stress and multi-layer structure of laminates, a nested p-norm is employed, providing a global approximation of the local maximum failure index. To mitigate the highly non-linear stress behaviors, filter schemes are applied to both sensitivity numbers and design variables. Sensitivity numbers are derived via adjoint sensitivity analysis and Lagrange multipliers to address stress-based and stress-constrained problems. The proposed framework is validated through systematic numerical studies across various examples and conditions, offering insights into the topological behaviors of composite laminates. This study underscores the importance of considering distinct tensile and compressive strength in composite materials, which represents a key innovation. Additionally, the relationships among stiffness-based, stress-constrained, and stress-based designs are explored in depth.

Analysis of linear accelerator-based fractionated stereotactic radiotherapy in brain metastases: efficacy, safety, and dose tolerances

ObjectiveTo assess the efficacy and safety of linear accelerator-based fractionated stereotactic radiotherapy (LINAC-FSRT) in patients with brain metastases (BM).MethodsWe retrospectively analyzed 214 patients treated with LINAC-FSRT, categorized based on biologically effective dose (BED10, α/β = 10) into two groups (≤55 Gy, &amp;gt;55 Gy). Stratified analyses were conducted based on targeted therapy to compare survival outcomes. To examine brain tissue dose-tolerance volume, patients were divided into two groups: the standard Hypofractionated Treatment Effects in the Clinic (HyTEC) protocol group and an adjusted HyTEC protocol group where dose-volume restrictions exclude the planning target volume (PTV).ResultsResults as of December 2023 showed median intracranial progression-free survival (iPFS) at 12.4 months, with median overall survival (OS) not reached and a one-year local control (LC) rate of 68.7%. Mild to moderate toxicity affected 17.3% of patients, while severe toxicity occurred in 2.8%. Multivariate Cox analysis indicated that uncontrolled extracranial disease significantly reduced iPFS (HR = 2.692, 95%CI:1.880–3.853, P &amp;lt; 0.001) and OS (HR = 3.063, 95%CI:1.987–4.722, P &amp;lt; 0.001). BED10 &amp;gt;55 Gy (HR = 0.656, 95%CI:0.431–0.998, P = 0.049) improved OS, showing statistical significance (P = 0.037) without affecting iPFS or CNS toxicity (P = 0.127, P = 0.091). Stratified analysis highlighted nearly significant OS improvements with high-dose FSRT and targeted therapy (P = 0.054), while concurrent therapy markedly enhanced iPFS (P = 0.027). No significant differences were observed in intracranial local failure (ILF—which represents progression in previously treated areas during follow-up), one-year LC rates, iPFS, or OS between dose-volume groups. Adjusting HyTEC volume restrictions did not significantly increase CNS adverse reactions (P = 0.889).ConclusionsLINAC-FSRT is safe and effective in BM. BED10&amp;gt;55 Gy notably enhances OS post-LINAC-FSRT and may benefit LC. High BED10 FSRT with targeted therapy likely boosts synergy, and concurrent targeted therapy significantly improves iPFS. Diminishing dose volume constraints at different fractions based on the HyTEC guidelines is feasible.