Ming Yang

Background: Salvage options for recurrent grade 4 glioma (GBM) remain limited and no single standard of care has been established after recurrence. Teniposide (VM-26) has been reintroduced into clinical practice, but its benefit when added to temozolomide (TMZ) plus bevacizumab (Bev) in recurrent grade 4 glioma remains unclear. Methods: This single-center, real-world exploratory study retrospectively enrolled 53 patients with recurrent grade 4 glioma who received either teniposide plus TMZ and Bev (VM26 + TMZ + Bev, n = 26) or TMZ plus Bev (TMZ + Bev, n = 27). The control group combined patients treated before teniposide became available again in China (2020–2022) with those treated concurrently with the triplet (2023–2026). Safety was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0; tumor response was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria on an intention-to-treat basis, and survival was estimated by the Kaplan–Meier method. Results: Median progression-free survival (PFS) was 7.8 months (95% confidence interval (CI), 4.9–10.9) in the VM26 + TMZ + Bev group versus 5.1 months (95% CI, 4.4–6.8) in the TMZ + Bev group (log-rank p = 0.037; unadjusted hazard ratio (HR) 0.50, 95% CI, 0.25–0.97), and median overall survival (OS) was 12.7 months (95% CI, 8.4–15.4) versus 8.5 months (95% CI, 7.3–9.7) (log-rank p = 0.042; unadjusted HR 0.47, 95% CI, 0.23–0.98). Multivariable adjustment strengthened these estimates, whereas propensity score weighting and matching gave estimates of the same direction that did not reach significance. The objective response rate (ORR) was 26.9% (7/26) versus 14.8% (4/27) (p = 0.327) and the disease control rate (DCR) was 80.8% versus 77.8% (p = 1.000). Grade ≥ 3 adverse events (AEs) occurred in 11.5% versus 7.4% of patients (p = 0.669); leukopenia and neutropenia were more frequent with teniposide (26.9% vs. 3.7%; p = 0.024) but lost significance after Benjamini–Hochberg correction (q = 0.122). No unexpected toxicity types were observed, although any-grade leukopenia and neutropenia were more frequent with teniposide and should be anticipated in clinical use. Conclusions: In this exploratory real-world cohort, adding teniposide to TMZ plus Bev was associated with longer PFS and OS and a numerically higher ORR, without a significant increase in grade ≥ 3 toxicity, although any-grade leukopenia and neutropenia were more frequent and should be anticipated; however, treatment era could not be fully separated from treatment effect: in an era-matched analysis restricted to the concurrently treated cohorts, the direction of the effect was preserved but did not reach significance. The survival differences rested on a small number of events and were not robust to reclassification of individual patient outcomes. These findings warrant confirmation in prospective randomized studies.

Background: Patients presenting with concurrent lung and brain lesions pose a unique diagnostic and therapeutic challenge. The role of neurosurgical resection in the management of de novo non-small-cell lung cancer brain metastases (NSCLC-BM) remains poorly defined. Methods: Consecutive patients undergoing resection for NSCLC-BM between February 2018 and October 2025 were retrospectively analyzed. De novo NSCLC-BM was defined as radiographic detection of pulmonary and intracranial lesions concurrently or within 1 month during the initial diagnostic work-up. Clinical characteristics and outcomes were compared between de novo and metachronous brain metastases (BM). Multivariable Cox regression identified factors associated with overall survival (OS). Factors associated with long-term postoperative survival in the de novo subgroup were further explored using Firth logistic regression. Results: Among 248 surgically treated patients, 113 (45.6%) presented with de novo BM. Compared with metachronous BM, de novo patients more frequently presented with symptomatic and multifocal intracranial disease. Among 73 de novo patients with evaluable survival, median postoperative OS was 57.0 months (95% CI, 22.9–not reached). Postoperative OS and intracranial progression-free survival (iPFS) did not differ significantly between the two groups, and de novo presentation was not independently associated with postoperative survival. Driver-positive status and lower intracranial tumor burden were associated with durable postoperative survival in the de novo subgroup. Conclusions: Neurosurgical resection represents a reasonable option for appropriately selected patients with de novo NSCLC-BM. These findings provide real-world evidence to inform multidisciplinary, individualized decision-making in patients presenting with concurrent lung and brain lesions.

Background: Early postoperative pneumonia (POP) is a common and serious complication after brain tumor surgery, but early recognition is difficult because postoperative neurological dysfunction and respiratory symptoms are often non-specific. Existing models are mostly retrospective, not designed for neurosurgical patients, and rarely prospectively validated across centers. We aimed to develop an interpretable model for early POP risk stratification. Methods: We used routine perioperative data from 1,856 patients undergoing brain tumor surgery at multiple centers in China between 2022 and 2025. Ten machine learning algorithms were compared. From 41 candidate variables, 11 predictors were selected using correlation analysis and LASSO. The final locked model was prospectively tested in one internal temporal cohort and three external cohorts. Performance was assessed by AUC, calibration, and decision curve analysis. Interpretability was evaluated using SHAP, a nomogram, and a web calculator. Results: Logistic regression showed the best overall performance, with an AUC of 0.897 (95% CI, 0.842–0.952) in the internal cohort and a mean AUC of 0.876 ± 0.044 across the three external cohorts. Key predictors included chronic lung disease (CLD), diabetes mellitus (DM), body mass index (BMI), admission Karnofsky Performance Status (KPS), and preoperative albumin (Alb) and glucose (Glu). Conclusion: This interpretable 11-variable model enables early POP risk stratification after brain tumor surgery and may support timely preventive intervention in neurosurgical care.

Background/Objectives: Brain metastases (BMs) are a major cause of morbidity and mortality in non-small-cell lung cancer (NSCLC). In this setting, EGFR-mutant and ALK-rearranged tumors represent clinically actionable, CNS-relevant oncogenic subgroups for which matched TKIs are essential to management, yet lesion-level molecular profiling is not always feasible or immediately available. We aimed to develop and externally validate DriverNet, a clinical and MRI-based framework for noninvasive pre-treatment molecular triage of EGFR/ALK status in NSCLC-BM. Methods: In this multicenter study, we analyzed pretreatment clinical, T1CE and T2-FLAIR MRI data to develop unimodal radiomics, 2D/2.5D deep learning (DL), and multimodal fusion models. The final model used ImageNet-pretrained CNNs for feature extraction and a Transformer-based architecture for fusion. The primary cohort was split strictly at the patient level before slice extraction and model development, and two independent external cohorts were used for testing. Clinical-only, imaging-only, and clinical-imaging models were compared using discrimination, calibration, Brier score, and decision-curve analyses. Model interpretability and exploratory prognostic stratification were also assessed. Results: A total of 374 patients from three centers were included. Center 1 comprised 224 patients (Chinese) and was divided into training (n = 179, EGFR/ALK+ 55.3%) and internal validation (n = 45, EGFR/ALK+ 57.8%) sets. External cohorts included 54 patients from Center 2 (Chinese, test 1, EGFR/ALK+ 42.6%) and 96 from Center 3 (Western, test 2, EGFR/ALK+ 12.5%). Among all evaluated models, DriverNet achieved the best overall performance, with AUCs of 0.967, 0.947, 0.962, and 0.952 in the training, internal validation, and two external cohorts, respectively, outperforming the clinical-only and imaging-only models. Model-derived labels were also associated with overall survival in exploratory analyses. Conclusions: DriverNet is a clinical and MRI-based framework for noninvasive pre-treatment molecular triage in NSCLC-BM. It may provide complementary information for future molecular triage studies when lesion-level profiling is unavailable or delayed. Prospective validation in larger and more molecularly balanced cohorts remains necessary before any clinical implementation can be considered.

Brain metastases (BM) remain a major cause of morbidity and treatment failure in non-small cell lung cancer (NSCLC). Among actionable pathways, mesenchymal

Objective: This systematic review and meta-analysis evaluated surgical outcomes, complications, and survival in adult thalamic glioma patients to inform optimal surgical and adjuvant treatment strategies.Methods: We searched PubMed, Web of Science, and Embase up to July 10, 2025, analyzing 15 studies with 695 adults. Data included patient characteristics, surgical approaches (lateral, medial, posterior), extent of resection (EOR, gross total/subtotal resection [GTR/STR]), or partial resection [PR]), complications, and overall survival (OS). Cox proportional hazards models assessed survival factors (p<0.05).Results: High-grade gliomas (HGGs) accounted for the majority (77.8%), and GTR/STR was achieved in 86.1% of cases, primarily through a lateral-related surgical approach (51.8%). Common postoperative complications were movement disorders (29%), infection/fever (25%), and sensory disorders (13%). In the pooled cohort consisting of 103 patients, median OS was 16 months for HGGs and 23 months for low-grade gliomas (LGGs). Multivariate Cox analysis confirmed prolonged OS in LGGs (hazard ratios [HRs]: 0.34, p = 0.005) and with adjuvant therapies (chemotherapy: HR 0.19, p=0.025; radiotherapy: HR 0.10, p=0.002; radiochemotherapy: HR 0.13, p=0.003).Conclusion: Maximal safe resection with adjuvant therapies enhances survival in thalamic gliomas, despite high complication rates. Tailored surgical strategies and molecular profiling, are essential to optimize outcomes and guide targeted therapies.