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Purpose: Given the availability of TKIs with high central nervous system efficacy, the question arises as to whether upfront SRS provides additional clinical benefits. The goal of this study was to characterize the clinical outcomes of SRS as salvage therapy for TKI-uncontrolled BMs., Methods: This retrospective study included EGFR-mutant NSCLC patients presenting BMs at the time of primary tumor diagnosis. BMs were categorized into three subgroups, referred to as "Nature of TKI-treated BMs", "TKI-controlled brain metastases ± SRS", and "SRS salvage therapy". The first subgroup analysis characterized the effects of TKIs on tumor behavior. In the second subgroup, we compared outcomes of TKI-controlled BMs treated with TKI alone versus those treated with combined TKI-SRS therapy. The third subgroup characterized the outcomes of TKI-uncontrolled BMs treated with SRS as salvage therapy Clinical outcomes include local and distant tumor control., Results: This study included 106 patients with a total of 683 BMs. TKI treatment achieved control in 63% of local tumors at 24 months. Among the TKI-controlled BMs, local tumor control was significantly higher in the combined TKI-SRS group (93%) than in the TKI-alone group (65%) at 24 months (p < 0.001). No differences were observed between the two groups in terms of distant tumor control (p = 0.832). In dealing with TKI-uncontrolled BMs, salvage SRS achieved local tumor control in 58% of BMs at 24 months., Conclusions: While upfront TKI alone proved highly effective in BM control, this study also demonstrated the outcomes of SRS when implemented concurrently with TKI or as salvage therapy for TKI-uncontrolled BMs. This study also presents a strategy of the precise timing and targeting of SRS to lesions in progression., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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 (≧28cm 3 ; 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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Stereotactic radiosurgery (SRS) is an effective treatment for brain metastases (BMs) in patients with non-small cell lung cancer (NSCLC). However, factors associated with the development of post-SRS leptomeningeal metastasis (LM) remain unclear. The authors analyzed the incidence and risk factors of LM development in patients with NSCLC and BMs after SRS and examined the survival outcomes and prognostic factors after LM development., Methods: This retrospective study included patients with NSCLC treated with SRS for MRI-diagnosed BM from 2002 to 2021. The authors recorded various clinical and demographic data, including age, sex, tumor histology, molecular profile of tumors, extracranial disease status, previous craniotomy, Karnofsky Performance Status, systemic treatments, tumor volume, and number of BMs. The management and survival outcomes after LM diagnosis were also recorded., Results: LM developed in 13.7% of patients with NSCLC and BMs after SRS treatment. Large initial tumor volume and more than 5 BM lesions, but not EGFR mutation status and post-SRS treatment, were associated with LM development after SRS. Multivariate analysis revealed that chemotherapy and targeted therapy after LM were associated with better survival in patients with LM after SRS., Conclusions: This study is the first to evaluate the risk factors for LM in a relatively large cohort of patients with NSCLC after SRS. In patients with BMs harboring risk factors for subsequent LM, such as initial tumor volume and number of metastatic lesions, aggressive therapies with high CNS penetrating ability should be considered.

Objective: Tyrosine kinase inhibitors (TKIs) is the first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC); however, its applicability to patients with wild-type NSCLC remains an issue of contention. This study compared the effects of gamma knife radiosurgery (GKRS) alone versus combining GKRS and TKIs in treating two genetic forms of NSCLC., Methods: This retrospective study examined 479 NSCLC patients with 1982 brain metastases who underwent GKRS and for whom imaging follow-up data or death records were available. All our patients were consecutive. All gene mutations were confirmed by lung biopsy. The three main endpoints in this study were overall survival (OS), local intracranial tumor control (LC), and distal intracranial tumor control (DC)., Results: There were 296 NSCLC patients with EGFR positive: TKI treatment (n = 262) and without TKI treatment (n = 34). GKRS + TKIs was more effective than GKRS alone in terms of OS (HR 0.53, p = 0.085) and DC (HR 0.51, p < 0.001). There were 150 NSCLC patients with wild-type EGFR: TKI treatment (n = 50) and without TKI treatment (n = 100). GKRS + TKIs was less effective than GKRS alone in terms of OS (HR 1.82, p = 0.049) and DC (HR: 1.40, p = 0.011). We observed no difference in terms of LC in both genetic groups., Conclusions: Combining GKRS with TKIs proved effective in EGFR positive NSCLC patients; however, we do not observe the similar results when combining GKRS with TKIs for patients with wild-type NSCLC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

One of the eligible criteria for patients to receive boron neutron capture therapy (BNCT) is based on the tumour-to-normal ratio (T/N) measured by FBPA-PET. However, there is no standard protocol for normal region-of-interested delineation. With comparison of contralateral cerebrum, our study revealed the consistency (p < 0.05) and high feasibility using the cerebellum as an alternative normal tissue baseline because of its homogeneous uptake. Following RECIST version 1.1, the standard-operating-procedure (SOP) for the BNCT fulfilled the expected tumour response and tumour shrinkage rate (p < 0.05). Our modified procedure can provide more precise information for BNCT within a reasonable time., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in this study. The authors have no personal, financial or institutional interest in any drugs, materials or devices in this study., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Stereotactic radiosurgery (SRS) is a potential re-irradiation treatment for recurrent intracranial ependymoma after prior radiation therapy. The purpose of this study was to examine the efficacy and safety of repeated SRS in the treatment of recurrent intracranial ependymomas., Methods: This is a retrospective study of consecutive patients with residual or recurrent intracranial ependymomas who were treated with SRS between 1993 and 2018. Tumor progression was defined as a ≥ 10% increase in tumor volume. Tumor regression was defined as a ≥ 10% reduction in tumor volume. A tumor that remained within 10% of its original volume was defined as stable. Tumor control comprised tumor regression and stability. Time-dependent analyses were performed using two treatment failure endpoint definitions: (1) evidence of local tumor progression or distant metastasis (single SRS analysis), and (2) lack of tumor response to SRS (repeated SRS analysis). These analyses were adjusted for the competing risk of death., Results: The study comprised 37 patients (65 intracranial ependymomas) who underwent multiple SRS sessions (range: 1-7). Median age was 10.2 years (range: 0.8-53.8 years), and median tumor volume was 1.5 mL (range: 0.01-22.5 mL). The median radiation dose was 13.3 Gy (range: 7.9-22.0 Gy) at a median isodose line of 57% (range: 50-90%). Overall tumor control rates in the single SRS analysis adjusting for the competing risk of death were 53.6%, 30.5%, and 23.6% at 1, 3, and 5 years, respectively. Overall tumor control rates in the repeated SRS analysis adjusting for the competing risk of death were 70.6%, 50.4%, and 43.1% at 1, 3, and 5 years, respectively. Prior gross total resection was the only independent predictor of overall tumor control after SRS (aHR = 25.62 (1.55-422.1), p = 0.02)., Conclusions: Repeated GKRS appeared to be an effective treatment strategy for recurrent or residual intracranial ependymomas, with acceptable complication rates.

Objective: To study the expression and switching of Th1/Th2 cytokines gene in human gliomas and its effects on occurring and developing of human gliomas., Methods: Interleukin (IL)-2 and interferon-gamma represent Th1 type cytokines. IL-4, IL-6, IL-10, and IL-13 represent Th2 type cytokines. The gene expressions of Thl/Th2 cytokines in human glioma cells, glioma infiltrating lymphocytes, and glioma cell lines were detected by reverse transcription polymerase chain reaction (RT-PCR). The biological activity of cytokines in the supernatant of glioma cell lines was assayed by enzyme-linked immunosorbent assay (ELISA)., Results: The total positive rates of Th1 and Th2 type cytokines gene in human glioma cells were 14.77% and 75%. The total positive rates of Th1 and Th2 type cytokines gene in glioma infiltrating lymphocytes were 22.73% and 68.17%. There was obviously predominant expression of Th2 type cytokines in human glioma tissues, glioma infiltrating lymphocytes, and glioma cell lines. There was no unbalanced expression of Th1/Th2 cytokines in normal brain tissues., Conclusion: There is a predominant expression of Th2 type cytokines in human glioma cells. The switching of Thl/Th2 cytokines gene may play an important role in the occurring and developing of human gliomas.

In order to explore the new methods of biological treatment of human gliomas, this project is to study the biological properties of gliomas from four different aspects, the results show that there is a IL-6 autocrine loop in human gliomas and the growth of gliomas will be inhibited when the autocrine loop is broken. There is a magnificent predominant expression of Th2 cytokines in human gliomas and human glioma cells, the switching of Th2 to Th1 can inhibit the proliferation of glioma cells. The dosage of 100 micrograms/ml of erythromycin is the best of therapeutic effect. Angiostatin can not only inhibit the vascular endothelial growth, but also have the inhibitory role on the growth of glioma cells in vivo. The above studies have provided some new ideas and will be very helpful for the treatment of glioma patients.

Objective: To study the significance of the unbalanced expression of Th1/Th2 type cytokines in human glioma., Methods: The gene expressions of Th1/Th2 type cytokines in 62 specimens of human glioma tissues, 4 glioma cell lines, peripheral blood mononuclear cell (PBMC) of 15 glioma patients, 5 specimens of normal adult brain tissue and 5 brain meningioma tissues were detected by semiquantitative reverse transcription polymerase chain reaction. IFN-gamma and IL-2 represent Th1 type cytokines. IL-4, IL-6, IL-10 and IL-13 represent Th2 type cytokines., Results: There were obviously predominant expression of Th2 type cytokines in glioma cell lines (P < 0.01) and specimens of human glioma tissues (P < 0.01). The tendency of distinct expression of Th2 type cytokines in PBMC was also existent. There wasn't obvious discrepancy of the expression of two type cytokines in normal adult brain tissues and meningioma tissues., Conclusions: It is likely that the switching of Th1/Th2 type cytokines in gliomas as predominant expression of Th2 type cytokine genes is related to the origination of gliomas and the evasion of glioma cells from immune surveillance.

Objective: To study the influence of adjustment of balance of Th1/Th2 by external cytokines on proliferation of glioma cells., Methods: The gene expressions of Th1/Th2 type cytokines in C6, 9L, U251 and SHG44 glioma cells were detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). After the cells were induced with IFN-gamma + IL-4 McAb and IL-4 + IFN-gamma McAb respectively, we isolated the total RNA to proceed RT-PCR again. The evaluation of cell proliferation was proceeded by MTT assay method., Results: There was obviously predominant expression of Th2 type cytokines in glioma cell lines (P < 0.01). The expression intensity of IFN-gamma was improved in IFN-gamma + IL-4 McAb groups and Th2 type cytokines were enhanced in IL-4 + IFN-gamma McAb groups. IFN-gamma and IL-4 McAb could cause the switch from Th2 to Th1, and could remarkably inhibit the proliferation of glioma cells in a dose-dependent way (P < 0.01). On the other hand, IL-4 and IFN-gamma McAb could strengthen the switch of Th2, and might stimulate the glioma cell growth, also in a dose-dependent way (P < 0.01)., Conclusions: There is a Th2 preponderance in glioma cells. IFN-gamma and IL-4 McAb could regulate the switch from Th2 to Th0 or Th1, and inhibit the proliferation of glioma cells.