A Bioinspired Gradient Design Strategy for Cellulose-Based Electromagnetic Wave Absorbing Structural Materials.

Cellulose nanofiber (CNF) possesses excellent intrinsic properties, and many CNF-based high-performance structural and functional materials have been developed recently. However, the coordination of the mechanical properties and functionality is still a considerable challenge. Here, a CNF-based structural material is developed by a bioinspired gradient structure design using hollow magnetite nanoparticles and the phosphorylation-modified CNF as building blocks, which simultaneously achieves a superior mechanical performance and electromagnetic wave absorption (EMA) ability. Benefiting from the gradient design, the flexural strength of the structural material reached ∼205 MPa. Meanwhile, gradient design improves impedance matching, contributing to the high EMA ability (-59.5 dB) and wide effective absorption width (5.20 GHz). Besides, a low coefficient of thermal expansion and stable storage modulus was demonstrated as the temperature changes. The excellent mechanical, thermal, and EMA performance exhibited great potential for application in stealth equipment and electromagnetic interference protecting electronic packaging materials.

Injectable Hydrogels Including Magnetic Nanosheets for Multidisciplinary Treatment of Hepatocellular Carcinoma via Magnetic Hyperthermia.

Relapse and unresectability have become the main obstacle for further improving hepatocellular carcinoma (HCC) treatment effect. Currently, single therapy for HCC in clinical practice is limited by postoperative recurrence, intraoperative blood loss and poor patient outcomes. Multidisciplinary therapy has been recognized as the key to improving the long-term survival rate for HCC. However, the clinical application of HCC synthetic therapy is restricted by single functional biomaterials. In this study, a magnetic nanocomposite hydrogel (CG-IM) with iron oxide nanoparticle-loaded mica nanosheets (Iron oxide nanoparticles@Mica, IM) is reported. This biocompatible magnetic hydrogel integrated high injectability, magnetocaloric property, mechanical robustness, wet adhesion, and hemostasis, leading to efficient HCC multidisciplinary therapies including postoperative tumor margin treatment and percutaneous locoregional ablation. After minimally invasive hepatectomy of HCC, the CG-IM hydrogel can facilely seal the bleeding hepatic margin, followed by magnetic hyperthermia ablation to effectively prevent recurrence. In addition, CG-IM hydrogel can inhibit unresectable HCC by magnetic hyperthermia through the percutaneous intervention under ultrasound guidance.

Automated identification and quantification of metastatic brain tumors and perilesional edema based on a deep learning neural network.

PURPOSE: This paper presents a deep learning model for use in the automated segmentation of metastatic brain tumors and associated perilesional edema. METHODS: The model was trained using Gamma Knife surgical data (90 MRI sets from 46 patients), including the initial treatment plan and follow-up images (T1-weighted contrast-enhanced (T1cWI) and T2-weighted images (T2WI)) manually annotated by neurosurgeons to indicate the target tumor and edema regions. A mask region-based convolutional neural network was used to extract brain parenchyma, after which the DeepMedic 3D convolutional neural network was in the segmentation of tumors and edemas. RESULTS: Five-fold cross-validation demonstrated the efficacy of the brain parenchyma extraction model, achieving a Dice similarity coefficient of 96.4%. The segmentation models used for metastatic tumors and brain edema achieved Dice similarity coefficients of 71.6% and 85.1%, respectively. This study also presents an intuitive graphical user interface to facilitate the use of these models in clinical analysis. CONCLUSION: This paper introduces a deep learning model for the automated segmentation and quantification of brain metastatic tumors and perilesional edema trained using only T1cWI and T2WI. This technique could facilitate further research on metastatic tumors and perilesional edema as well as other intracranial lesions.

Magnetic resonance radiomics-derived sphericity correlates with seizure in brain arteriovenous malformations.

OBJECTIVES: Angioarchitectural analysis of brain arteriovenous malformations (BAVMs) is qualitative and subject to interpretation. This study quantified the morphology of and signal changes in the nidal and perinidal areas by using MR radiomics and compared the performance of MR radiomics and angioarchitectural analysis in detecting epileptic BAVMs. MATERIALS AND METHODS: From 2010 to 2020, a total of 111 patients with supratentorial BAVMs were retrospectively included and grouped in accordance with the initial presentation of seizure. Patients' angiograms and MR imaging results were analyzed to determine the corresponding angioarchitecture. The BAVM nidus was contoured on time-of-flight MR angiography images. The perinidal brain parenchyma was contoured on T2-weighted images, followed by radiomic analysis. Logistic regression analysis was performed to determine the independent risk factors for seizure. ROC curve analysis, decision curve analysis (DCA), and calibration curve were performed to compare the performance of angioarchitecture-based and radiomics-based models in diagnosing epileptic BAVMs. RESULTS: In multivariate analyses, low sphericity (OR: 2012.07, p = .04) and angiogenesis (OR: 5.30, p = .01) were independently associated with a high risk of seizure after adjustment for age, sex, temporal location, and nidal volume. The AUC for the angioarchitecture-based, MR radiomics-based, and combined models was 0.672, 0.817, and 0.794, respectively. DCA confirmed the clinical utility of the MR radiomics-based and combined models. CONCLUSIONS: Low nidal sphericity and angiogenesis were associated with high seizure risk in patients with BAVMs. MR radiomics-derived tools may be used for noninvasive and objective measurement for evaluating the risk of seizure due to BAVM. CLINICAL RELEVANCE STATEMENT: Low nidal sphericity was associated with high seizure risk in patients with brain arteriovenous malformation and MR radiomics may be used as a noninvasive and objective measurement method for evaluating seizure risk in patients with brain arteriovenous malformation. KEY POINTS: • Low nidal sphericity was associated with high seizure risk in patients with brain arteriovenous malformation. • The performance of MR radiomics in detecting epileptic brain arteriovenous malformations was more satisfactory than that of angioarchitectural analysis. • MR radiomics may be used as a noninvasive and objective measurement method for evaluating seizure risk in patients with brain arteriovenous malformation.

Impact of crosslinking agents with steric cyclic groups on the properties of polymer-dispersed liquid crystals.

As a type of intelligent dimming film, polymer-dispersed liquid crystals (PDLCs) have been widely applied in various fields, such as smart windows, light shutters and displays. The properties of PDLCs are greatly influenced by the structure of the raw materials. In this work, the impact of crosslinking agents with different cyclic or chain groups was investigated by comparing the electro-optical performance and the morphology of the polymer matrix in the as-made PDLC films. It was found that the incorporation of large steric groups into the crosslinking agents can alter the morphology of the polymer matrix and thus affect the electro-optical properties. However, the impact is distinct when the spatial structure or rigidity is different. Besides, a combination of crosslinking agents with flexible alkyl-chain structures and steric structures can further reduce the threshold voltage while keeping the high contrast ratio. After detailed comparison, an optimized combination of BDDA/TCDDA in a weight ratio of 1/1 is selected to demonstrate the enhanced properties of the as-constructed film with a thickness of 20 µm. It exhibits low threshold voltage (8.2 V), low saturation voltage (21.2 V) and a high contrast ratio (203) simultaneously. This research offers an optimizing method from the crosslinking agent perspective and is anticipated to promote the further improvement of the PDLC's performance.

Graphene/Cholesteric Liquid-Crystal-Based Electro-Driven Thermochromic Light Modulators toward Wide-Gamut Dynamic Light Color-Tuning-Related Applications.

Light filters are ubiquitous in projection and display techniques, illumination engineering, image sensing, photography, etc., while those enabling wide-gamut dynamic light color tuning are still lacking. Herein, by combining the electro-heating capability of graphene and unique optical properties (thermochromism and circular dichroism) of small-molecule-weight cholesteric liquid crystal (ChLC), a brand-new thermochromic light modulator is constructed as actively tunable color filter. Transparent graphene/glass hybrid with reasonably high conductivity serves both as a high-performance heater for actuating the thermochromism of temperature-responsive ChLC and as neutral light attenuator for brightness control. Thanks to the temperature- and polarization-dependent spectral properties of the ChLC, widely tunable hue and saturation properties of transmission light color are achieved, respectively. Several intriguing applications, e.g., color-variable smart windows for backlight color tuning and color-variable filters for photography, are also demonstrated. This work hereby provides new paradigms for promoting the applications of graphene/ChLC-based light modulators in next-generation light-management-related scenarios.

Simultaneously Strengthening and Toughening All-Natural Structural Materials via 3D Nanofiber Network Interfacial Design.

Constructing structural materials from sustainable raw materials is considered an efficient way to reduce the potential threat posed by plastics. Nevertheless, challenges remain regarding combining excellent mechanical and thermal properties, especially the balance of strength and toughness. Here, we report a 3D nanofiber network interfacial design strategy to strengthen and toughen all-natural structural materials simultaneously. The introduced protonated chitosan at the interface between the surface oxidized 3D nanonetwork of bacterial cellulose forms the interfacial interlocking structure of nanonetworks, achieving a robust physical connection and providing enough physical contact sites for chemical crosslinking. The obtained sustainable structural material successfully integrates excellent mechanical and thermal properties on the nanoscale of cellulose nanofibers, such as light weight, high strength, and superior thermal expansion coefficient. The relationship between structural design and comprehensive mechanical property improvement is analyzed in detail, providing a universal perspective to design sustainable high-performance structural materials from nanoscale building blocks.

Dynamically Modulating the Dissymmetry Factor of Circularly Polarized Organic Ultralong Room-Temperature Phosphorescence from Soft Helical Superstructures.

Achieving circularly polarized organic ultralong room-temperature phosphorescence (CP-OURTP) with a high luminescent dissymmetry factor (glum ) is crucial for diverse optoelectronic applications. In particular, dynamically controlling the dissymmetry factor of CP-OURTP can profoundly advance these applications, but it is still unprecedented. This study introduces an effective strategy to achieve photoirradiation-driven chirality regulation in a bilayered structure film, which consists of a layer of soft helical superstructure incorporated with a light-driven molecular motor and a layer of room-temperature phosphorescent (RTP) polymer. The prepared bilayered film exhibits CP-OURTP with an emission lifetime of 805 ms and a glum value up to 1.38. Remarkably, the glum value of the resulting CP-OURTP film can be reversibly controlled between 0.6 and 1.38 over 20 cycles by light irradiation, representing the first example of dynamically controlling the glum in CP-OURTP.

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

BACKGROUND: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation. METHODS: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS: The cohort comprised 505 patients (254 [50.3%] males; median [interquartile range] age, 34 [15] years) from 14 centers. The median clinical and magnetic resonance imaging follow-up was 52 (interquartile range, 61) and 47 (interquartile range, 52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability, 50% [95% CI, 45%-55%]) and obliteration by 300 (59.4%) patients (5-year probability, 56% [95% CI, 51%-61%]). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4 cm3, subdistribution hazard, 0.61 [95% CI, 0.44-0.86]; P=0.005; >4 cm3, subdistribution hazard, 0.47 [95% CI, 0.32-0.7]; P<0.001) and brainstem/basal ganglia involvement (subdistribution hazard, 0.6 [95% CI, 0.45-0.81]; P<0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS: Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention.

Global Analysis of the WOX Transcription Factor Family in Akebia trifoliata.

Akebia trifoliata is an economically important, self-incompatible fruit tree in the Lardizabalaceae family. Asexual propagation is the main strategy used to maintain excellent agronomic traits. However, the generation of adventitious roots during asexual propagation is very difficult. To study the important role of the WUSCHEL-related homeobox (WOX) transcription factor in adventitious root growth and development, we characterized this transcription factor family in the whole genome of A. trifoliata. A total of 10 AktWOXs were identified, with the following characteristics: length (657~11,328 bp), exon number (2~5), isoelectric point (5.65~9.03), amino acid number (176~361 AA) and molecular weight (20.500~40.173 kDa), and their corresponding expression sequence could also be detectable in the public transcriptomic data for A. trifoliata fruit. A total of 10 AktWOXs were classified into modern (6), intermediate (2) and ancient clades (2) and all AktWOXs had undergone strong purifying selection during evolution. The expression profile of AktWOXs during A. trifoliata adventitious root formation indicated that AktWOXs play an important role in the regulation of adventitious root development. Overall, this is the first study to identify and characterize the WOX family in A. trifoliata and will be helpful for further research on A. trifoliata adventitious root formation.

Cholesteric Liquid Crystal Polymeric Coatings for Colorful Artificial Muscles and Motile Humidity Sensor Skin Integrated with Magnetic Composites.

Structural colorful cholesterics show impressive susceptibility to external stimulation, leading to applications in electro/mechano-chromic devices. However, out-of-plane actuation of structural colorful actuators based on cholesterics and the integration with other stimulation remains underdeveloped. Herein, colorful actuators and motile humidity sensors are developed using humidity-responsive cholesteric liquid crystal networks (CLCNs) and magnetic composites. The developed colorful actuator can exhibit synergistic out-of-plane shape morphing and color change in response to humidity, with CLCNs as colorful artificial muscles. Through the integration with magnetic control, the motile sensor can be navigated to open and confined spaces with the aid of friction to detect local relative humidity. The integration of multi-stimulation actuation of cholesteric magnetic actuators will expand the research frontier of structural colorful actuators and motile sensors for confined spaces.

Large-Area Uniaxially Oriented Sub-5†nm Line Patterns of Hybrid Liquid Crystals Constructed by Perylene Diimide and Oligo(Dimethylsiloxane).

Construction of sub-5 nm long-range ordered structures through self-assembly has received increasing attention. Herein, a series of ODMS-based thermotropic liquid crystals (LCs) containing perylene diimide (PDI) were designed and synthesized. These LCs can form ordered nanostructures with periodic sizes around 5 nm including smectic J (SmJ), oblique columnar (Colob ), and hexagonal columnar (Colh ) phases with change in the volume fraction of ODMS, where the layer spacing of the SmJ phase is less than 5 nm. Thin films with parallel oriented nanolines with line width less than 5 nm can be obtained on PDMS-modified silicon substrates by spin-casting and simple thermal annealing processes. Moreover, owing to the strong π-π interaction between PDI cores, these nanolines are long-range ordered with uniaxial orientation in relatively large areas (1.5×1.5 µm2 ) with over 300 continuous microdomains without pre-patterning. These nanostructures provide the possibility of preparing nanotemplates by oxygen plasma etching.

Federated Learning: A Cross-Institutional Feasibility Study of Deep Learning Based Intracranial Tumor Delineation Framework for Stereotactic Radiosurgery.

BACKGROUND: Deep learning-based segmentation algorithms usually required large or multi-institute data sets to improve the performance and ability of generalization. However, protecting patient privacy is a key concern in the multi-institutional studies when conventional centralized learning (CL) is used. PURPOSE: To explores the feasibility of a proposed lesion delineation for stereotactic radiosurgery (SRS) scheme for federated learning (FL), which can solve decentralization and privacy protection concerns. STUDY TYPE: Retrospective. SUBJECTS: 506 and 118 vestibular schwannoma patients aged 15-88 and 22-85 from two institutes, respectively; 1069 and 256 meningioma patients aged 12-91 and 23-85, respectively; 574 and 705 brain metastasis patients aged 26-92 and 28-89, respectively. FIELD STRENGTH/SEQUENCE: 1.5T, spin-echo, and gradient-echo [Correction added after first online publication on 21 August 2023. Field Strength has been changed to "1.5T" from "5T" in this sentence.]. ASSESSMENT: The proposed lesion delineation method was integrated into an FL framework, and CL models were established as the baseline. The effect of image standardization strategies was also explored. The dice coefficient was used to evaluate the segmentation between the predicted delineation and the ground truth, which was manual delineated by neurosurgeons and a neuroradiologist. STATISTICAL TESTS: The paired t-test was applied to compare the mean for the evaluated dice scores (p < 0.05). RESULTS: FL performed the comparable mean dice coefficient to CL for the testing set of Taipei Veterans General Hospital regardless of standardization and parameter; for the Taichung Veterans General Hospital data, CL significantly (p < 0.05) outperformed FL while using bi-parameter, but comparable results while using single-parameter. For the non-SRS data, FL achieved the comparable applicability to CL with mean dice 0.78 versus 0.78 (without standardization), and outperformed to the baseline models of two institutes. DATA CONCLUSION: The proposed lesion delineation successfully implemented into an FL framework. The FL models were applicable on SRS data of each participating institute, and the FL exhibited comparable mean dice coefficient to CL on non-SRS dataset. Standardization strategies would be recommended when FL is used. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

Management strategies for intracranial progression in ALK-positive non-small cell lung cancer: a real-world cohort study.

PURPOSE: ALK-positive NSCLC patients exhibit a particularly high propensity for the development of brain metastases. Current guidelines suggest transit to next-line therapy (SysTx) or local radiotherapy (RadTx) including whole-brain radiotherapy and radiosurgery. However, the clinical impact of these two strategies remains unclear. METHODS: We conducted a retrospective analysis focusing on patients with stage IV ALK-positive NSCLC who underwent first-line ALK TKI treatment. Patients with intracranial progression may receive two different treatment strategies: SysTx and RadTx. Our objective was to investigate the outcomes associated with these two distinct treatment pathways. RESULTS: A total 20 patients of ALK-positive NSCLC who received first-line ALK TKI therapy and subsequently developed intracranial progression were enrolled. About 55% of patients had brain metastasis initially. Nine patients (45%) were treated with crizotinib at first. Patients treated with crizotinib demonstrated a significantly shorter intracranial PFS1 (crizotinib: 8.27 months vs. others: 27.0 months, p = 0.006). Following intracranial progression, approximately 60% of patients transitioned to the next line of systemic treatment (SysTx), while the remaining 40% opted for local cranial radiotherapy (RadTx). Intriguingly, our analysis revealed no statistically significant difference in intracranial progression-free survival (PFS2) between these two distinct treatment strategies. (SysTx: 20.87 months vs. RadTx: 28.23 months, p = 0.461). CONCLUSION: The intracranial progression-free survival showed no difference between the two strategies suggesting that both local radiotherapy and systemic therapy may be valid options. Individualized strategy, molecular analysis, and multidisciplinary conferences may all play a pivotal role in decision-making.

Treatment and survival of patients with small cell lung cancer and brain metastasis.

PURPOSE: To elucidate treatment patterns and their outcomes in patients with small cell lung cancer (SCLC) and brain metastasis (BM). METHODS: In this retrospective study, patients with SCLC and BM were stratified by treatment modality into three groups: those treated with systemic therapy only, those treated with stereotactic radiosurgery (SRS) and systemic therapy, and those treated with whole-brain radiotherapy (WBRT) and systemic therapy. The primary outcomes were overall survival (OS) and time to central nervous system progression (TTCP). RESULTS: The analysis included 149 patients. After BM diagnosis, 48 patients (32.2%) received systemic therapy alone, 33 received SRS with systemic therapy, and 68 received WBRT with systemic therapy. The median OS and TTCP were 7.2 months and 8.7 months, respectively. Patients receiving WBRT with systemic therapy exhibited better intracranial control, but not better OS, than did the other patients. Key prognostic factors affecting OS were age, BM lesion count, chemotherapy, and immunotherapy. Notably, the Eastern Cooperative Oncology Group performance status and BM lesion count significantly influenced intracranial control in patients treated with SRS and systemic therapy. CONCLUSION: Although WBRT combined with systemic therapy offer better intracranial control in patients with SCLC and BM, this approach is not superior to the other approaches in terms of OS benefits. Emerging systemic therapies, such as immunotherapy, may be used as alternative or adjunctive treatments for specific patient populations. Further studies are warranted to refine treatment selection.

Stereotactic radiosurgery for pituitary and cavernous sinus metastases.

PURPOSE: Metastases extending to the pituitary gland and cavernous sinus are extremely rare; however, advances in neuroimaging have increased the reported incidence. Stereotactic radiosurgery (SRS) affords the precise delivery of focused radiation to minimize adverse radiation effects. This study assessed the efficacy and safety of SRS in the treatment of pituitary and cavernous sinus metastases. METHODS: Analysis was performed on 23 patients with pituitary and cavernous sinus metastases who underwent treatment using SRS between 1996 and 2021. The cohort was categorized into 2 groups in terms of metastasis location: pituitary involvement (Group 1, n = 11) and cavernous sinus involvement (Group 2, n = 12). Overall survival, local tumor control, and distal tumor control rates were compared between the two groups using Kaplan-Meier analysis. RESULTS: The median age of the cohort was 52.2 years and the median tumor volume was 4.5 mL. Overall survival rates were as follows: 1 year (72.9%), 2 years (51.8%), and 3 years (45.3%). Local tumor control rates were as follows: 1 year (82.3%), 2 years (82.3%), and 3 years (65.9%). Visual deficit and hypopituitarism were the most common presentations in Group 1, whereas cranial nerve deficit was the most common presentation in Group 2. CONCLUSIONS: SRS appears to be a safe and effective therapy for the treatment of pituitary and cavernous sinus metastases. GKRS is a relatively simple procedure, which places minimal stress on the patient, thereby facilitating further anti-cancer treatment. Considering the limited survival duration in cases of metastasis, it is very likely that post-GKRS complications (e.g., new onset cranial nerve deficit and hypopituitarism) would not become an issue before patient passes away.

Magnetic resonance imaging signal characteristics associated with prognosis of skull base chordoma after gamma knife radiosurgery.

OBJECTIVE: To investigate the association between the magnetic resonance imaging (MRI) signal characteristics of skull base chordoma and radiosurgical outcomes. METHODS: Twenty-four patients with skull base chordomas treated with Gamma Knife radiosurgery (GKRS) after previous surgical resection were retrospectively (2001-2021) examined. Pre-GKRS MRIs were analyzed for RT2 (tumor-to-brainstem signal intensity ratio on T2-weighted imaging), RCE (tumor-to-brainstem signal intensity ratio on contrast-enhanced T1-weighted imaging), and mean apparent diffusion coefficient (ADC). Correlations of the parameters with patient survival and local tumor progression were made by using Cox regression and Kaplan-Meier analyses. RESULTS: During a median follow-up of 46 months after GKRS, 9 patients died with significantly more local tumor progression events (median number: 2 vs 0, P = .012) than did 15 alive patients. On multivariable analysis, higher mean ADC was associated with longer patient survival (P = .016) after GKRS. The actuarial 5-year overall survival rates were 88.9% versus 54.7% for chordomas with an ADC of ≥ 1270 × 10-6 mm2/s versus < 1270 × 10-6 mm2/s. RT2 < 1.5 (P = .038) and RCE > 1.57 (P = .022) were associated with a lower probability of local tumor control. CONCLUSION: Lower mean ADC values are associated with shorter patient survival in skull base chordomas after GKRS. Diffusion-weighted imaging may help in GKRS planning and outcome prediction for these patients.

Improved survival and intracranial tumor control of EGFR-mutated NSCLC patients with newly developed brain metastases following stereotactic radiosurgery and EGFR-TKI: a large retrospective cohort study and meta-analyses.

PURPOSE: To examine the differential effects of SRS and TKI on EGFR-mutated NSCLC patients with brain metastases (BMs) and outcomes following continuation of the same TKI agent in case of new BMs. METHODS: This study included 608 NSCLC patients (2,274 BMs) while meta-analyses included 1,651 NSCLC patients (> 3,944 BMs). Overall survival (OS) and intracranial progression free survival (iPFS) were estimated using Kaplan-Meier methods. Hazard ratios (95% CI) of prognostic factors were estimated using Cox regression models. RESULTS: The median OS/iPFS (95% CI) (months) for patients with wildtype EGFR/ALK, EGFR mutations, and ALK rearrangements were 17.7 (12.9-23.6)/12.1 (9.8-15.6), 28.9 (23.8-33.3)/17.7 (14.8-21.2), and 118.0 (not reached)/71.7 (15.1-not reached), respectively. In EGFR-mutated patients, meta-analyses combining our data showed significantly improved OS and iPFS of patients who received SRS and TKI (OS:35.1 months, iPFS:20.0 months) when compared to those who have SRS alone (OS:20.8 months, iPFS:11.8 months) or TKI alone (OS:24.3 months, iPFS:13.8 months). Having SRS for newly diagnosed BMs while keeping the existing TKI agent yielded OS (30.0 vs. 32.1 months, p = 0.200) non-inferior to patients who started combined SRS and TKI therapy for their newly diagnosed NSCLC with BMs. Multivariable analyses showed that good performance score and TKI therapy were associated with improved outcomes. CONCLUSIONS: Combined SRS and TKI resulted in favorable outcomes in EGFR-mutated NSCLC patients with newly diagnosed BMs. Continuation of the same TKI agent plus SRS in case of new brain metastases yielded good clinical outcomes and may be considered a standard-of-care treatment.

Leukoencephalopathy in patients with brain metastases who received radiosurgery with or without whole brain radiotherapy.

BACKGROUND: Whole brain radiation therapy (WBRT) for brain metastases (BMs) is a common cause of radiation-induced leukoencephalopathy; however the safety of alternative stereotactic radiosurgery (SRS) remains unclear. This study examined the incidence of leukoencephalopathy in patients treated with SRS alone versus WBRT plus SRS for BMs with a focus on the relationship between prognostic factors and leukoencephalopathy. METHODS: Analysis was performed between 2002 and 2021. The total enrollment was 993 patients with the distribution: WBRT plus SRS (n = 291) and SRS only (n = 702). Leukoencephalopathy was graded from 0 to 3 for changes in white matter indicated by the MRI after WBRT or SRS. Patient characteristics and SRS dosimetric parameters were reviewed to identify factors that contributed to the incidence of leukoencephalopathy or overall survival. RESULTS: The incidence of leukoencephalopathy was consistently higher in WBRT plus SRS group than in SRS alone group (p < 0.001). Leukoencephalopathy was also associated with a larger total tumor volume (≧28cm3; p = 0.028) and age (> 77 years; p = 0.025). Nonetheless, the SRS integral dose to skull in the subgroup of WBRT plus SRS treatment was not demonstrated significance in development of leukoencephalopathy (p = 0.986 for integral dose 1-2 J, p = 0.776 for integral dose > 2 J). CONCLUSIONS: This study revealed that SRS is safe for oligo-BMs in terms of leukoencephalopathy development. Patient age and total tumor volume were identified as important factors in assessing the development of leukoencephalopathy. The additional of SRS (even at an integral dose > 2 J) did not increase the incidence of leukoencephalopathy.

Natural history of lung squamous cell brain metastases in patients treated with radiosurgery: a thirty-year experience at a tertiary medical center.

PURPOSE: In this study we report our 30-year experience in stereotactic radiosurgery (SRS) treatment of lung squamous cell carcinoma (LUSC) brain metastases (BMs). It will serve to provide detailed longitudinal outcomes and predictors of efficacy in treating LUSC-BMs with SRS. METHOD: We retrospectively reviewed 51 patients and 109 tumors treated with SRS at our center between 1993 and 2022. Patient demographics, PDL1 genotype, immunotherapy use and mortality cause were recorded. Radiological and clinical outcomes were followed at 1-3-month intervals post-SRS. Cox-regression analysis and Kaplan-Meier survival curves were performed in statistical analysis. RESULTS: We included 37 male and 14 female patients (median age 62.7 years at BM diagnosis). Median overall survival (OS) time was 6.9 months, 6-month OS rate was 62.1%, and Karnofsky performance scale (KPS) was the only independent predictor. Median time for local control maintenance was 7.6 months, 6-month local control rate was 69.1%, with TKI as the only independent predictor. Median time to distant failure was 5.13 months, 6-month distant failure rate was 51.1%, and factors with significant impact included gender (p = 0.002), presence of extracranial metastases (p < 0.001), use of immunotherapy(p < 0.001), PDL1 genotype (p = 0.034), and total intracranial metastases number (p = 0.008). However, no definitive benefits of immunotherapy were identified in patients with higher PDL1 mutational tumors. CONCLUSION: In this study we defined the natural history of disease progression and outcomes in SRS-treated LUSC-BM patients. We also identified predictors of OS and tumor control among these patients. The findings of this study will serve as a guide when counseling these patients for SRS.