Purpose: Chloroquine (CQ) has been studied for over 50 years as a potential adjuvant to cancer therapy. However, clinical studies investigating CQ combined with radiotherapy for brain tumors have yielded conflicting results. We aimed to synthesize existing evidence on the safety and efficacy of adjuvant CQ with radiotherapy for treatment of high-grade gliomas (HGG) and brain metastases.
Methods: We conducted a systematic review using the PubMed, Embase, Scopus, and Web of Science databases with no date restrictions. We included English-language clinical studies (n ≥ 5 patients) that evaluated the combination of CQ or its analogues with radiotherapy for HGG or brain metastases and reported overall survival (OS) outcomes. Pre-clinical studies and reviews were excluded.
Results: We identified 13 eligible studies with 789 patients. Across both HGG and brain metastases, the median CQ dose was 250 mg daily, with whole-brain radiotherapy as the most common radiotherapy modality. For HGG, 3 out of 8 controlled trials reported significant benefit from treatment, with median survival ranging from 7.9 to 36.6 months. By comparison, only a single study of brain metastases found significantly improved progression-free survival relative to control. The safety profile of adjuvant CQ was generally favorable, with mild adverse effects reported in both patient populations.
Conclusions: For HGG, CQ combined with radiotherapy shows promise but modest, inconsistent survival benefits. For brain metastases, evidence is limited and less favorable, with no consistent benefit across tumor types or study designs. Adverse events are generally mild, though most studies used low CQ doses and long‑term safety remains uncertain.
Purpose: Predicting future tumor growth from initial imaging of incidentally discovered meningioma (IDM) could inform treatment decisions. However, most factors identified in prior studies on meningioma growth are qualitative. The aim of this study is to identify factors associated with tumor growth using quantitative radiomics features from MRI data.
Methods: MRI T2 features from initial imaging of 24 tumor growth cases were compared with those of 25 cases without growth. An in-house program was developed to reduce the time required for data analysis. This program is based on the open-source software 3D Slicer 5.6.2 and PyRadiomics 3.1.0. It enables semi-automatic batch t-test analyses for each feature to compare tumor growth and non-growth groups. Regions of interest (ROIs) were placed in the tumor, outer tumor edge, whole brain, and white matter contralateral to the tumor. A total of 107 features were analyzed across seven classifications: First Order, Shape, Gray Level Co-occurrence Matrix, Gray Level Run Length Matrix, Gray Level Size Zone Matrix, Gray Level Dependence Matrix, and Neighboring Gray Tone Difference Matrix. A t-test was used to identify significant predictors.
Results: Ten features across five classifications showed significant differences (p < 0.05): 2 First Order statistics, 2 Shape features, 4 Gy Level Co-occurrence Matrices, 1 Gy Level Size Zone Matrix, and 1 Neighboring Gray Tone Difference Matrix.
Conclusions: Potential predictors of IDM growth were identified using radiomics features. Future studies with larger cohorts and validation will be essential to confirm the clinical utility and improve the predictive accuracy of these features.
Purpose: Resection of glioblastomas infiltrating the motor cortex and corticospinal tract (CST) is often linked to increased perioperative morbidity. Navigated transcranial magnetic stimulation (nTMS) motor mapping has been advocated to increase patient safety in these cases. The additional impact of patient frailty on overall outcome after resection of cases with increased risk for postoperative motor deficits as identified with nTMS needs to be investigated.
Methods: Patients with newly diagnosed motor eloquent glioblastomas were retrospectively evaluated. Patients underwent nTMS- and tractography-based neuronavigation. Demographic, imaging- and nTMS-derived data and the 11-item modified frailty index (mFI-11) were collected. Primary endpoint was discharge home after tumor resection. A 4-item score comprising preoperative motor deficit, mFI-11 ≥ 2 points, distance to the CST < 12 mm and infiltration of nTMS-positive cortex was established to predict overall outcome.
Results: N = 64 patients with a mean age of 64.8 ± 9.6 years (60.9% male) were included. 46 patients (71.9%) could be discharged to their homes. Risk factors for non-home discharge were greater mFI-11 (p = 0.027), surgery-related motor deficit (p < 0.001) and overall complications (p < 0.001 for non-surgical and p = 0.006 for surgical complications). In multiple regression analyses, mFI-11 and surgery-related deficit were statistically robust. The 4-item score predicted non-home discharge with an AUC = 0.745, 95%CI = 0.62-0.87, p < 0.001.
Conclusion: In patients with newly diagnosed motor-eloquent glioblastomas, nTMS-based planning helps to predict postoperative surgery-related motor deficits. Patient frailty needs to be respected in decision making in addition to nTMS- and tractography-based planning in order to avoid postsurgical motor deficits and to keep overall surgical morbidity on a low level.
Objective: This study aimed to compare and analyse the genomic features in cerebrospinal fluid (CSF) between patients with both brain parenchymal metastasis (BM) and meningeal metastasis (MM) of lung cancer and patients with MM only.
Methods: 34 patients with lung adenocarcinoma were included in this study, including 18 patients in the BM&MM group, 12 in the MM group and 4 in the BM group. The genomic characteristics were compared by circulating tumour DNA (ctDNA) detection in CSF and plasma samples.
Results: The positive rate of ctDNA detection in the CSF was significantly higher than that in plasma, and the variation detected in the CSF was more abundant, especially epidermal growth factor receptor (EGFR) mutation (p < 0.05). The consistency detected between the CSF and plasma was poor. There was no significant difference in the tumour mutation burden between the BM&MM and MM groups, and no significant differential mutations were found by mutation mapping and pathway enrichment analysis (p > 0.05). In the BM&MM group, there was a significant co-mutation relationship between RB1 and ERBB4, MTOR and ATM, MLH3 and CTNNB1 and TP53 and EGFR; in the MM group, there was a strong co-exclusion of EGFR and KRAS mutations. Chromosomal copy number variation analysis showed significant amplification in the MM group at the p15.33 bands on chromosome 5 and the 7p11.2 bands on chromosome 7. In the comparative analysis of tumour markers and CSF biochemical parameters between the two groups, no significant differences were found.
Conclusion: This study revealed significant differences in CSF genomic characteristics between patients with simultaneous BM and MM of lung cancer and patients with MM only. These differences provide potential biomarkers for the precise treatment of patients with brain metastases and help to distinguish patients with lung cancer brain metastases with different metastatic patterns.
Background: Brain metastases are a common and severe complication in patients with lung adenocarcinoma (ADC) harboring epidermal growth factor receptor (EGFR) mutations. Gamma Knife Radiosurgery (GKRS) is a standard treatment for brain metastases, and its efficacy may be influenced by the type of EGFR mutation and the generation of tyrosine kinase inhibitors (TKIs) used. This retrospective study evaluated the impact of EGFR mutation subtypes (exon 19 deletion vs. exon 21 L858R) and TKI generations on clinical outcomes in patients with lung ADC treated with GKRS.
Methods: A total of 55 patients and 136 brain metastases were analyzed from January 2017 to December 2023. Tumor response was assessed based on local failure and distant brain failure, defined as tumor progression at the treated site and new brain metastases outside the GKRS-treated regions, respectively. The Kaplan-Meier method and univariate and multivariate analyses using Cox proportional hazard regression models were used to identify prognostic factors for local failure, and distant brain failure.
Results: The study found that second- and third-generation TKIs, such as afatinib and osimertinib, provided significantly better local control compared to first-generation TKIs (hazard ratio [HR] = 0.12, p = 0.017). Furthermore, tumors with exon 19 deletion demonstrated improved distant brain control compared to those with exon 21 L858R substitution (HR = 2.18, p = 0.048). These findings suggest that mutation type and TKI generation are independent prognostic factors for clinical outcomes following GKRS.
Conclusion: This study suggests that both the generation of TKIs and the specific EGFR mutation subtype may influence clinical outcomes following GKRS in lung ADC patients with brain metastases. These findings may aid in stratifying patients and optimizing treatment strategies in clinical practice.

