Background:Glioblastoma is the most common and aggressive central nervous system malignancy with poor prognosis. Tumor-treating fields (TTFields), approved in China in May 2020, represents a significant advancement in GBM treatment. Leveraging the extensive real-world data accumulated in the Chinese Medical Information and Big Data Association (CHMIA) database, this study aims to assess clinical outcomes of Chinese patients with glioblastoma on TTFields therapy. Methods:This ambispective, observational study assessed post-marketing safety (data cut-off: November 15, 2021) and effectiveness (data cut-off: May 18, 2024) of TTFields in Chinese patients with newly diagnosed glioblastoma (ndGBM) and recurrent glioblastoma (rGBM). Safety outcomes included incidence and severity of skin adverse events (AEs); effectiveness was measured by overall survival (OS) and landmark OS rates. Results:Of 648 patients screened for this study, 315 were eligible and enrolled for analysis (ndGBM: n = 210; rGBM: n = 105). In the ndGBM cohort, the median OS was 19.9 months (95% CI: 13.4-24.8), with a 12-month OS rate of 63.5% (95% CI: 54.8-71.0). In the rGBM cohort, the median OS was 8.1 months (95% CI: 5.3-9.8), and 3-month and 6-month OS rates were 80.2% (95% CI: 70.4-87.1) and 58.7% (95% CI: 47.0-68.7), respectively. Most treatment-emergent AEs (TEAEs), including skin TEAEs, were mild to moderate (Grade 1-2). Conclusions:This study provided the largest real-world dataset to-date on TTFields in Chinese patients with glioblastoma. These patients showed survival outcomes similar to those in prior pivotal studies, without new safety concerns identified, supporting its use in Chinese glioblastoma population.

Background Accurate glioma diagnosis relies on tissue biopsy, which is often challenging. Liquid biopsy offers an alternative, but single-component circulating free DNA (cfDNA) or circulating free RNA (cfRNA) approaches have limited comprehensiveness. We developed and validated GlioKit, a platform for simultaneous cfDNA and cfRNA extraction from cerebrospinal fluid (CSF) to enhance diagnostic coverage, and evaluated its accuracy by correlating CSF-derived molecular profiles with tumor characteristics.Methods We retrospectively analyzed 71 patients from the China Glioma Liquid Biopsy MultiOmics Atlas (C-Glioma) database, including 31 GBM, 36 IDH-mutant gliomas, and 4 diffuse midline gliomas (DMGs). Using GlioKit, we simultaneously extracted and analyzed CSF cfDNA and cfRNA, targeting 6 mutations (IDH1, IDH2, H3F3A, HIST1H3B, TERT, BRAF) and 2 fusions (EGFR, MET). Concordance between CSF-derived mutations and matched tumor tissue features was assessed overall and stratified by CSF collection method (lumbar puncture, surgery, or Ommaya reservoir).Results Among 71 glioma CSF samples, cfDNA mutations were detected in 55 (77%), cfRNA in 15 of 44 (34%). Overall, cfDNA-tumor concordance was 89%, and cfRNA was 73%. Subgroup analysis revealed cfDNA detection rates of 33/41 (surgery), 11/15 (Ommaya), and 11/15 (lumbar puncture); cfRNA detection rates were 5/25, 6/11, and 4/8, respectively. Corresponding concordance rates were cfDNA-30/33 (surgery), 10/11 (Ommaya), and 9/11 (lumbar puncture); cfRNA-4/5, 5/6, and 2/4.Conclusions Cerebrospinal fluid-derived cfDNA and cfRNA variations closely align with tumor genomic alterations, validating CSF as a minimally invasive source for glioma molecular subtyping. GlioKit has potential for glioma diagnosis and therapy planning.

Laser-driven surface waves and terahertz (THz) radiation from a metal wire provides an efficient scheme for intense terahertz generation. The resulting THz radiation usually exhibits an asymmetrical beam pattern with an off-axis radial polarization, which should be measured and analyzed comprehensively. Here, we present a detailed experimental investigation of the THz beam emitted from a laser-irradiated metal wire using electro-optic (EO) sampling technique. By measuring the EO signal at different radial positions and azimuthal angles within the THz beam, we indicate that the emitted THz field constitutes an off-axis radially polarized vector beam. Moreover, analysis of the time-domain waveforms and corresponding spectra reveals a spatially dependent spectral composition: the THz beam comprises both low-frequency (<1 THz) and high-frequency (>1 THz) components, whose relative intensities vary with radial position. Specifically, the outer regions of the THz beam are dominated by low-frequency emission, whereas the high-frequency component becomes increasingly prominent toward the beam center. These findings experimentally verify a two-component nature of THz emission from laser-irradiated metal wires and will advances its applications in THz-driven particle acceleration, biomedical imaging, and nonlinear THz science.

Stereotactic body radiotherapy (SBRT) is effective for localized prostate cancer, yet many recurrences originate from the intraprostatic tumor mass (ITM). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) and multiparametric magnetic resonance imaging (mpMRI) enable precise ITM localization and support focal dose escalation. This trial assesses whether PSMA-PET/mpMRI-guided boosting during SBRT improves biochemical control without excess toxicity. This is a single-center, prospective, randomized (1:1), controlled, open-label clinical trial conducted at Huashan Hospital, Fudan University. A total of 128 men with newly diagnosed localized prostate adenocarcinoma will be enrolled and randomized to receive either (1) standard SBRT (39 Gy in 6 fractions) or (2) PSMA-PET/mpMRI-guided focal dose-escalated SBRT (up to 48 Gy in 6 fractions). All participants will receive androgen deprivation therapy (ADT) according to National Comprehensive Cancer Network (NCCN) risk group and clinical practice. The primary endpoint is biochemical progression-free survival (PSA-PFS), defined by the Phoenix criteria. Secondary endpoints include local progression-free survival (LPFS), distant metastasis-free survival (DMFS), overall survival (OS), prostate cancer-specific survival (PCSS), toxicity (CTCAE v5.0), and patient-reported quality of life (EPIC-26 and SF-12). Survival outcomes will be analyzed using Kaplan-Meier estimates and compared via log-rank testing.Clinical trial registration:www.chictr.org.cnidentifier ChiCTR2500114310.

Primary central nervous system large B-cell lymphoma (PCNS-LBCL) exhibits the worst prognosis among all extranodal LBCLs, with the enriched genetic mutations in MyD88L265P, CD79B and PIM1. However, the upfront incorporation of targeted therapies remains an unmet need in newly diagnosed (ND) patients. In this study, we found that in the presence of MyD88L265P context, B-cell receptor downstream bruton’s tyrosine kinase (BTK) was significantly overexpressed, which subsequently enhanced the stability of PIM1 oncoprotein. To evaluate the intracranial delivery of BTK inhibitor(BTKi), patient-derived PCNS-LBCL xenografted mice models were treated with highly-selective BTKi orelabrutinib, either monotherapeutically or in combining with methotrexate. Interestingly, orelabrutinib showed excellent efficiency crossing BBB with the functional BTK blockade and promoted PIM1 degradation, providing the molecular basis of incorporating BTKi into PCNS-LBCL therapy. Thus, we determined the efficacy and toxicity of orelabrutinib in combination with high-dose methotrexate in a prospective dose-escalating cohort and real-world practice. The patients being treated with orelabrutinib-included ORMD regimen showed better response and more prolonged survival compared to those with RMD regimen. We further investigated the genetic mutations of PCNS-LBCL across tumor tissue, cerebrospinal fluid (CSF) and plasma. The mutations in CSF circulating tumor DNA (ctDNA) rather than plasma-ctDNA were more consistent to those in tumor tissue, indicating that CSF-ctDNA is a useful tool for monitoring PCNS-LBCL. In summary, our data provided the molecular rationale as well as clinical evidences that incorporation of BTKi into frontline induction therapy is a promising strategy for ND PCNS-LBCL.

Differentiating recurrence from treatment-induced changes (TIC) in post-therapy gliomas remains a significant diagnostic challenge. This prospective study evaluated the diagnostic efficacy and prognostic value of dynamic contrast-enhanced MRI (DCE-MRI) distributed parameter (DP) model versus 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) in differentiating gliomas recurrence from TIC. Adults with new or increasing contrast-enhancing lesions in MRI after treatment were prospectively included. Patients were additionally examined using 18F-FET PET and DCE-MRI. DCE parameters was processed using DP and compared with maximum standardized uptake value (SUVmax), mean standardized uptake value and mean tumor-to-brain ratio measured from 18F-FET PET images. Diagnostic test properties and prognosis value of DCE-MRI were determined. Normalized cerebral blood volume (nCBV ≥ 2.32) and normalized cerebral blood flow (nCBF ≥ 1.11) demonstrated sensitivities of 0.78 and 0.75, specificities of 0.88 and 1.00, diagnostic accuracy of ​0.80​ for both, and areas under the receiver operating characteristic curves (AUCs) of ​0.86​ and ​0.85, respectively. For ​FET-PET​, SUVmax cutoff of 2.36​ achieved sensitivity of ​0.93, specificity of ​0.57, accuracy of ​0.85, and AUCs of ​0.72. Weak correlations existed between DCE-MRI and FET-PET parameters (r: -0.05–0.20; p > 0.05). Over a median follow-up of 11 months (IQR 8.75–15), patients with nCBV ≥ 2.32 had significantly shorter median progression-free survival (9 months vs. not-reached; p = 0.02). DCE-MRI incorporating DP demonstrated strong diagnostic performance in distinguishing recurrent gliomas from TIC, with diagnostic accuracy comparable to 18F-FET PET. Furthermore, nCBV demonstrated prognostic value for clinical outcomes in glioma patients.

Glioma recurrence and resistance to therapy remain major challenges in neuro-oncology, driven in part by profound cellular and spatial heterogeneity within the tumor microenvironment. Malignant and immune populations dynamically coexist and transition during disease progression, yet their coordinated organization remains poorly understood, and standard bulk RNA sequencing cannot resolve cell-type composition. To address these limitations, we established GliomaDeconv, a glioma-specific reference and interpretation framework for bulk RNA-seq deconvolution, derived from multi-subtype scRNA-seq datasets and implemented using established probabilistic deconvolution architecture. Application of GliomaDeconv to spatially annotated IVY GAP datasets and large bulk RNA-seq cohorts enabled systematic mapping of cellular composition, spatial organization, and dynamic evolution across glioma subtypes and disease stages. Single-cell analyses identified distinct malignant cell states, including a neural progenitor-like (NPC-like) population with strong tumor-propagating capacity, as well as multiple functionally specialized tumor-associated macrophage subsets enriched in grade- and subtype-specific patterns. GliomaDeconv-derived estimates showed biological concordance with single-cell-derived molecular programs in bulk datasets and suggested that histologically defined tumor regions are associated with distinct malignant and immune cell-state enrichments. Large-cohort analyses further identified subtype-specific cellular programs and therapy-associated phenotypic transitions. Functional validation in an orthotopic model showed that SNAP25-high/NPC-like glioma cells exhibited enhanced tumor-propagating capacity, supporting an association between this cell state and glioma progression. Collectively, GliomaDeconv bridges single-cell resolution and large-cohort transcriptomics, enabling precise dissection of glioma microenvironmental composition across subtypes and disease stages. The tool provides a practical framework for biological interpretation and is freely available at http://www.szflab.site/gliomadeconv/.

Abstract Cerebrospinal fluid contributes to homeostasis in the central nervous system, but how its dynamics are altered in glioblastoma is unclear. We find that glioblastoma drives leptomeningeal perivascular fibrosis that is associated with impaired fluid transport and clearance. Lineage tracing and single-cell analyses in male tumor-bearing mice identify leptomeningeal fibroblasts as the principal source of this fibrotic response, with limited contribution from pericytes. Fibrosis is linked to activation of nuclear factor kappa B signaling in collagen-producing fibroblasts, extracellular matrix deposition around perivascular spaces, reduced intratumoural cytotoxic T cell accumulation and a less permissive immune microenvironment. Here, we show that inhibiting nuclear factor kappa B signaling in leptomeningeal fibroblasts reduces fibrosis, improves fluid clearance, enhances intratumoural cytotoxic T cell accumulation and restores responsiveness to programmed cell death protein 1 blockade, identifying this pathway as a therapeutic target in glioblastoma.

To minimize the radiation injury for white matter (WM) pathways during brain arteriovenous malformation (bAVM) stereotactic radiosurgery (SRS), the WM tractography is integrated into treatment planning to identify WM pathways and restrict receiving dose. Manual segmentation of eloquent bAVM adjacent to WM pathways is time-consuming and prone to substantial inter-practitioner variability due to intricate entanglement within eloquent brain areas. The objective of this study is to develop and evaluate a deep learning (DL) system for the segmentation of eloquent bAVM in a clinical setting. A total of 191 eloquent bAVM patients who underwent WM tractography and 3D time-of-flight magnetic resonance angiography (TOF-MRA) images were enrolled. 153 patients were used to construct a two-stage DL bAVM segmentation ensemble (TBASE) consisting of 2D detection and 3D segmentation models to segment the bAVM, the other 38 to test performance. Comparative experiments with ResNet and U-Net were conducted to validate the effectiveness of the proposed network. A randomized multi-reader evaluation was then conducted to assess the impact of TBASE assistance for bAVM segmentation using ten algorithm-unseen cases. Six medical professionals contoured the same series of cases in both assisted and unassisted modes, with a 6-week memory washout period between each session. The aided and unaided Dice Similarity Coefficients (DSC), Hausdorff Distance (HD), along with contouring times were compared. The mean values and standard deviations for DSC and HD of TBASE are 0.87 ± 0.03 and 3.51 ± 0.26, respectively, while Res-Net and U-Net results are 0.75 ± 0.12 and 4.14 ± 0.99, 0.77 ± 0.09 and 3.94 ± 0.82, respectively. The average volume difference across all patients in test dataset is 0.25 ± 1.39 cc, with no statistically significant variation observed. With TBASE assistance, the mean DSC of readers improved from 0.76 ± 0.07 to 0.86 ± 0.05 (P < 0.001), with corresponding values of mean HD reducing from 4.31 ± 0.68 to 3.35 ± 0.17 (P < 0.001) and a mean time saving of 52.15

ABSTRACT Purpose There is ongoing debate regarding the therapeutic approach and prognosis for IDH‐mutant grade 4 astrocytoma, a newly defined subtype of diffuse glioma in the 2021 WHO classification system for central nervous system tumors (WHO CNS 5). The aim of this study was to explore the clinical outcome and prognosticators for newly diagnosed IDH‐mutant grade 4 astrocytoma based on our single institutional data. Methods This retrospective analysis included 53 consecutive patients with newly diagnosed IDH‐mutant grade 4 astrocytoma, who underwent radiotherapy between September 2021 and December 2023. All patients were administered concurrent and adjuvant temozolomide. Eleven patients received adjuvant tumor‐treating fields (TTFields). Results The median follow‐up was 15.7 months. Twenty patients had tumor relapse; three patients died, all of whom were without TTFields therapy. The median PFS for the entire cohort was 19.3 months, and the median OS was not reached. Univariate analysis indicated patients younger than 40 years (p = 0.11) or without homozygous deletion of CDKN2A/B (p = 0.11) tended to have better PFS. In addition, the TTFields group tended to have longer median PFS than the non‐TTFields group in both analyses before and after propensity score matching (PSM) (24.4 vs. 18.5 months, p = 0.097, before PSM; 24.4 vs. 15.9 months, p = 0.080, after PSM). No significant independent prognostic factor was found in the multivariate analysis. Conclusions The study reveals important insights into clinical practice for IDH‐mutant grade 4 astrocytoma. Younger age and tumor without deleted CDKN2A/B might be predictive of better outcomes. The addition of TTFields trended towards improved PFS, necessitating prospective clinical trials for further investigation.

BACKGROUND:High-frequency irreversible electroporation (H-FIRE) has gradually become an attractive alternative treatment of intracranial tumors due to its clinically favorable characteristics, such as mild muscle contractions, precise ablation margins, and preservation of vessel structures. Encouraging results have been obtained in pre-clinical trials with animal models. However, a more comprehensive understanding of spatiotemporal distributions of electric field and temperature in clinically relevant intracranial tissue during the treatment of H-FIRE is still required prior to its clinical implementation. PURPOSE:In this study, we performed the first attempt to numerically investigate the electric field and temperature distributions for the conformal ablation of intracranial tumors in patient-specific glioma tumor models. METHODS:Four representative 3D patient-specific glioma models were constructed based on T1-weighted MR images of four clinical patients. The treatment protocols of H-FIRE were optimized for the conformal ablation of these glioma patients by using a multi-objective optimization genetic algorithm. To alleviate the temperature increase during the H-FIRE administration, a new ablation procedure was designed and tested numerically. RESULTS:The results achieved in this study demonstrated that the conformal ablation of gliomas with differing sizes and shapes can be achieved by optimizing the number of electrodes, applied pulse voltage, active tip length, electrode gap, and electrode insertion depth. The temperature increases due to the administration of H-FIRE pulses can be effectively alleviated by introducing a pulse-off time between two ablation procedures. CONCLUSION:This study contributes to the field of H-FIRE in the treatment of intracranial tumors and promotes its clinical implementation.

Cerebrospinal fluid (CSF) maintains the homeostasis of central nervous system (CNS) through its unique biochemical composition. Although impaired CSF dynamics is increasingly recognized in glioblastoma (GBM) patients, the mechanistic basis and pathological consequences of GBM-induced CSF defects remain poorly defined. Here, we demonstrate that GBM induces leptomeningeal fibrosis - a previously unrecognized process that disrupts cerebrospinal fluid (CSF) drainage. Mechanistically, this occurs through the activation of NF-κB signaling in leptomeningeal fibroblasts. The resulting signaling cascade triggers pathological activation of fibroblasts, ultimately leading to perivascular fibrosis that physically obstructs CSF drainage pathways. Crucially, compromised CSF clearance creates an immunosuppressive microenvironment that fosters tumor progression. Clinically, leptomeningeal fibrosis in GBM patients correlates with exhausted T cell accumulation. Pharmacological inhibition or conditional P65 (NF-κB subunit) ablation in murine leptomeningeal fibroblasts attenuates fibrosis, enhances T cell infiltration, and restores anti-PD-1 responsiveness in orthotopic GBM models. These findings reveal a critical axis linking CSF dysfunction to GBM immunosuppression, positioning NF-κB/P65 signaling in leptomeningeal fibroblasts as a strategic target to enhance immunotherapy efficacy.

In the application of pulsed electric fields for tumor ablation, bipolar pulses are preferred over unipolar pulses due to their more uniform therapeutic effects and reduced muscle contractions. This study designs a linear transformer driver (LTD) source based on a reverse-series topology structure for generating bipolar pulses. During the discharge phase, the LTD primary modules at all levels are grounded, offering the advantages of low isolation voltage levels and simple and reliable switch control, with theoretically unrestricted induction stacking modules. The bipolar pulse source is composed of structurally identical unipolar modules connected in reverse series in their secondary windings. However, this structure introduces the side effect of reverse inductive adder of induced electromotive forces. Therefore, this study proposes a bipolar complementary short-circuit circuit to eliminate the effects of reverse inductive adder. In addition, a primary charging power supply using a negative-polarity capacitor charging power supply (CCPS) was employed to enhance the stability of the triggering circuit. Finally, a magnetic core reset circuit was designed to achieve a wider output pulse duration and improve the utilization of the magnetic core. The multiscale experiment results demonstrate the robust and stable capability of the bipolar pulse source in the pulse discharge and tumor ablation, with the following parameters: voltage amplitude ranging from 0 to +/- 5000 V, current amplitude ranging from 0 to +/- 100 A, pulse duration ranging from 300 ns to 1 mu s, and intervals between positive and negative pulses ranging from 0 to 1 ms. All pulse parameters can be flexibly adjusted using a custom-made computer system.

H3K27-altered diffuse midline gliomas (H3-DMGs) represent aggressive tumors with fatal outcome and exceedingly rare cases have a long-term survival (LTS). We included 5 adult thalamic H3-DMG LTS and 13 short-term survivors (STS), and performed whole exome sequencing, RNA-seq and DNA methylation array. The median overall survival was 48.0 ± 12.1 months for LTS and 12.5 ± 5.9 months for STS. There was no significant difference in clinical characteristics and treatment received between LTS and STS. LTS exhibited more copy number gain and amplification (P = 0.007), and tumor microenvironment analysis revealed increased accumulation of M1 macrophage (P = 0.005) alongside a notable reduction in cancer-associated fibroblast in LTS (P = 0.037). The signatures of LTS and STS were signature 30 (similarity = 76.7

INTRODUCTION:This study evaluated local control and overall survival following hypofractionated stereotactic radiosurgery (HF-SRS) using the CyberKnife system for brain metastases ≥ 10 cm3, addressing the challenges of balancing efficacy and toxicity in larger lesions. METHODS:We enrolled patients with 1-4 newly diagnosed brain metastases from lung or breast cancer. The primary endpoint was local control of the treated metastases. The secondary endpoints were overall survival and incidence of radiation necrosis. Survival endpoints were evaluated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to test for significant associations between clinical factors and outcomes. RESULTS:Between December 2016 and December 2018, 63 patients with 65 large brain metastases were included in this study. Of all the 63 cases, 55 cases were initially treated with HF-SRS; eight had tumour recurrence after gamma knife treatment. The radiosurgical margin dose (median, 30 Gy; range, 25-34 Gy) was prescribed at an isodose curve of 60%-75% (median, 67%) with multiple fractions (median, three fractions; range, 2-4), targeting a median tumour volume of 18.1 cm3 (range, 10.1-39.6 cm3). The median follow-up was 19 months. The local tumour control rates were 100%, 100%, and 92.58% at 6, 12, and 18 months, respectively. The 6-, 12-, and 18-month survival rates were 95.24%, 82.51%, and 68.61%, respectively. The cumulative incidence of radiation necrosis in patients who underwent primary HF-SRS was 7.02% and 14.04% at 1 year and 18 months, respectively. CONCLUSION:We report our experience treating large brain metastases with HF-SRS. HF-SRS showed favourable local control with low incidence of complications.

Tumor-treating fields (TTFields) therapy and radiotherapy may have synergistic anti-glioma effect based on preclinical studies. The combination of chemoradiation therapy (CRT) with TTFields therapy has noticeably attracted clinicians’ attention. This study aimed to provide insights into the clinical outcomes of patients with newly diagnosed glioblastoma who received either concurrent CRT and TTFields therapy or adjuvant TTFields therapy following CRT. The findings were based on a cohort of patients who were treated at Huashan Hospital (Shanghai, China). This retrospective study analyzed ndGBM patients’ clinical outcomes who were treated at Huashan Hospital and received TTFields therapy. Patients were categorized into two groups: one group received adjuvant TTFields therapy after completing CRT (referred to as the A-TTF group), while the other received TTFields therapy concurrently with CRT and continued TTFields after treatment (referred to as the CA-TTF group). The study evaluated treatment efficacy and toxicities, comparing outcomes between the two groups. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan–Meier method. To mitigate confounding factors, efficacy was assessed using the Cox proportional hazards regression model, propensity score matching, and inverse probability of treatment weighting (IPTW) based on the propensity score. A total of 72 patients with ndGBM were included in the study. Among them, 41 patients received concurrent and adjuvant TTFields therapy in combination with CRT (CA-TTF group), and 31 patients received adjuvant TTFields therapy with temozolomide (A-TTF group). The median follow-up time was 18.0 months. No significant differences were observed in median PFS (14.2 vs. 15.0 months, P = 0.92) or OS (20.8 vs. 20.0 months, P = 0.92) between the CA-TTF and A-TTF groups. Skin toxicity was common, while manageable, with no significant difference between the two groups. Following IPTW adjustment, the hazard ratios for PFS and OS indicated a potential advantage for the CA-TTF group, although this difference was not statistically significant. Concurrent CRT and TTFields therapy emerged safe for newly diagnosed GBM patients. Although no significant survival differences were found between the CA-TTF and A-TTF groups, the potential benefit of concurrent TTFields warrants further investigation through large-scale clinical trials.

Glioblastoma (GBM) stands as the most aggressive and prevalent primary brain malignancy. Tumor Treating Fields (TTFields), an innovative therapy complementing chemotherapy for GBM treatment, which can significantly enhance overall survival, disease progression-free survival, and patient’s quality of life. However, there is a dearth of health economics evaluation on TTFields therapy both domestically and internationally. The study aims to assess the cost-effectiveness of TTFields + temozolomide (TMZ) in comparison to TMZ alone for newly diagnosed GBM patients. The intent is to provide robust economic evidence to serve as a foundation for policymaking and decision-making processes in GBM treatment. We estimated outcomes for newly diagnosed GBM patients over a lifetime horizon using a partitioned survival model with three states: Progression-Free Survival, Progression Disease, and Death. The survival model was derived from a real-world study in China, with long-term survival data drawn from GBM epidemiology literature. Adverse event rates were sourced from the EF-14 trial data. Cost data, validated by expert consultation, was obtained from public literature and databases. Utility values were extracted from published literature. Using Microsoft Excel, we calculated expected costs and quality-adjusted life years (QALYs) over 15 years from a health system perspective. The willingness-to-pay threshold was set at three times the Chinese per capita Gross Domestic Product (GDP) in 2022, amounting to CN¥242,928 (US37,655) /QALY. A 5

Significance The rapid development of ultra-intense and ultra-short lasers has provided unprecedented new experimental methods and extreme physical conditions, made it possible to reach new frontiers of ultra-fast and intense interactions between lasers and matter, and given birth to a large number of new principles, new phenomena, and revolutionary techniques. Plasma-based acceleration driven by an ultra-intense and ultra-short laser may contribute to the emergence of new particle-acceleration technologies and generation of novel ultra-fast radiation sources. These novel particle and radiation sources can provide new means and opportunities for frontier interdisciplinary studies in areas such as high-energy particle physics, nuclear photonics, materials science, and biomedicine, making it a hot spot and emerging field on the world scientific and technological frontiers. The accelerating electric field of a laser-driven plasma wakefiled can reach 100 GV/m, which is more than three orders of magnitude higher than that of a traditional electron accelerator. A high-energy GeV electron beam can thus be produced over a centimeter-scale acceleration length, thus greatly reducing the scale and cost of the accelerator. The electron beams produced via laser wakefield acceleration also have the advantages of an ultrashort pulse duration and inherent high-precision synchronization with the driving laser. In addition, by designing an appropriate and effective scheme, the electron-injection and acceleration processes can be optimized to produce high-quality and high-energy ultrafast electron sources with ultrahigh brightness comparable to that from a traditional accelerator. Laser-wakefield-driven electron beams can be used as low-cost and desktop femtosecond radiation sources such as for betatron X-ray radiation, inverse Compton scattering, bremsstrahlung radiation, and undulator radiation. These novel radiation sources usually have high brightness, good collimation, a femtosecond pulse duration, and energy tunability, covering a wide spectral range from extreme ultraviolet to gamma rays. Therefore, research in this area is occurring around the world, and this is an important research topic for high-field laser physics and new accelerators. Such laser wakefield acceleration and novel radiation sources are thus of great scientific significance for the development and application of synchrotron radiation, free electron lasers, and high-energy particle physics. Progress After nearly 20 years of development, great progress has been made in both experimental and theoretical studies on laser-driven plasma acceleration. It is now transitioning from laser acceleration to laser accelerators. On one hand, the energy gain of laser wakefield electron acceleration has been significantly extended to 7.8 GeV. On the other hand, the specific qualities of the accelerated electron beams produced via laser wakefield acceleration, such as the energy spread, divergence, emittance, and stability of the electron beam, are also being optimized to a great extent. However, the comprehensive performance has to meet higher requirements for practical application, and there are still many key scientific issues and technical difficulties that need to be further explored and solved in the future. In particular, the energy spread of the electron beam is usually on the order of several percent, and such a large energy spread has greatly hindered its practical application. In order to obtain more stable and brighter high-energy electron beams, the electron injection and acceleration in the plasma wakefield should be accurately controlled and optimized to minimize the energy spread and divergence, which can also improve the application performance of novel radiation sources. Therefore, the basic principles and parameter characteristics of a plasma wakefield driven by a femtosecond intense laser are first briefly introduced. The mechanisms and characteristics of different electron injection methods are then analyzed and compared (Table 1). Second, based on the research results and progress made by our group in recent years, the schemes and technologies for exploring energy chirp control in a plasma wakefield with a structured plasma profile are summarized and analyzed in relation to the generation of ultrahigh-brightness electron beams with an ultralow energy spread at a per-mille level (Fig.5). Third, we discuss how these high-quality electron beams are used to produce novel radiation sources and greatly improve their application performance, including enhanced betatron X-ray radiation (Fig.9), quasi-monoenergetic all-optical self-synchronized Compton scattering gamma-rays (Fig.18), and free-electron lasing in an undulator (Fig.22). Some of the progress in other related frontier research fields is also discussed in relation to laser wakefield electron acceleration and novel radiation source generation. Finally, the prospects for a laser wakefield electron accelerator and its further practical applications are outlined. Conclusions and Prospects A high-quality electron beam source and novel radiation source based on laser wakefield acceleration have the advantages of a compact size, easy tuning, small source size, femtosecond pulse duration, high brightness, good collimation, and high-precision synchronization control, which can provide new methods and tools for frontier interdisciplinary research such as high-energy particle physics, nuclear photonics, materials science, and biomedicine. Although significant progress has been made in the past decade in improving the quality of an electron beam such as its energy spread and six-dimensional brightness, the wakefield accelerator is still in a very early phase in view of the energy spread and stability of the electron beam ,especially for electron beams with energy levels below 100 MeV or above 1 GeV, when compared with traditional accelerators. This dilemma is mainly limited by the scalability and stability of the existing schemes. The key issue or challenge facing the wakefield acceleration community is to devise more effective schemes to generate electron beams with an ultralow energy spread (0.1%-0.01%), ultralow emittance (similar to 1 mu m.mrad), high repetition rate, and stability. Benefiting from the rapid and continuous development of ultrashort pulse laser technology in terms of the repetition rate, waveform control, and stability of the high-power laser, it is believed that the qualities and brightness of these high-energy ultrafast electron beams will be further improved by advancing the existing schemes, which will further facilitate the development of novel radiation sources. All these advances will greatly promote the continuous development of high-quality laser wakefield electron accelerators and their practical applications in the years to come.