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Background: Immunotherapy has revolutionized the treatment of various types of tumors, but there has been no breakthrough in the treatment of gliomas. The aim of this study is to discover valuable immunotherapy target in glioma, analyze its expression in glioma and the related microenvironment, explore potential immunotherapy strategies, and propose new possibilities for the treatment of gliomas., Methods: Immunohistochemistry (IHC) and multiplex fluorescence immunohistochemistry (mIHC) were used to analyze the expression of common immune markers and checkpoints in 187 glioma patients from Sun Yat-sen University Caner Center (SYSUCC). Bioinformatics analysis was used to examine the expression of TIM-3 in different macrophages using the Chinese Glioma Genome Atlas (CGGA) single-cell sequencing database. The Kaplan-Meier curve was used to predict the prognostic value of samples with high TIM-3 and CD68 expression. The R package was used to analyze the somatic mutation status and the sensitivity of small molecule inhibitors in TIM-3/CD68 double-high expression samples., Results: TIM-3 is a relatively highly expressed immune checkpoint in glioma. Unlike other tumors, TIM-3 is mainly expressed on macrophages in the glioma microenvironment. TIM-3/CD68 double-high expression suggests poor survival in glioma and may be a new upgrade marker in both IDH-mutant glioma and IDH-wildtype low-grade glioma (LGG) glioma (P < 0.01). Exploring the combination of TIM-3 inhibitors and p38 MAPK inhibitor may be a potential treatment direction for TIM-3/CD68 double high expression gliomas in the future., Conclusions: The combination of TIM-3 and CD68 holds significant importance as a potential target for both prognosis and therapeutic intervention in glioma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: IDH-mutant glioma is classified as oligodendroglioma or astrocytoma based on 1p19q-codeletion. Whether prognostic factors are similar between these tumor types is not well understood., Experimental Design: Retrospective cohort study. Molecular characterization was performed with targeted next-generation sequencing. Tumor volumes were calculated using semiautomatic 3D segmentation on all pre- and post-operative MRI scans. Overall survival was assessed with the Cox-proportional hazards model., Results: A total of 383 patients with newly diagnosed IDH-mutant glioma were followed up for a median of 7.2 years. Grades 3 and 4 patients had significantly lower Karnofsky performance, with tumors having more contrast enhancement. Patients also received more aggressive postsurgery treatment. Postoperative tumor volume is significantly and independently associated with survival (HR, per cm3 1.19; 95% CI, 1.03-1.39) in IDH-mutant glioma. A separate analysis of oligodendroglioma and astrocytoma showed a significant association of postoperative tumor volume in astrocytoma but not in oligodendroglioma. Higher age and histologic tumor grade were associated with worse survival in patients with oligodendroglioma but not with astrocytoma., Conclusions: Our data support an initial strategy of extensive resection in patients with oligodendroglioma and astrocytoma. Other important prognostic factors differ between these tumor types, urging researchers and clinicians to keep treating these tumors as separate entities., (©2024 American Association for Cancer Research.)

Background: For treating recurrent glioblastoma, for which there is no established treatment, the antiangiogenic antibody, bevacizumab, is used alone or with irinotecan. This study was aimed at comparing the survival of patients with recurrent glioblastoma receiving bevacizumab monotherapy and those receiving bevacizumab plus irinotecan combination therapy (B+I) by using a nationwide population-based dataset., Methods: Patients matching the International Classification of Diseases code C71.x were screened from the Health Insurance Review and Assessment Service database. From January 2008 to November 2021, patients who underwent surgery or biopsy and subsequent standard concurrent chemoradiation with temozolomide were included. Among them, those who received bevacizumab monotherapy or B+I were selected. Demographic characteristics, inpatient stay, prescription frequency, survival outcomes, and steroid prescription duration were compared between these two groups., Results: Eight hundred and forty-six patients who underwent surgery or biopsy and received concurrent chemoradiotherapy with temozolomide were included. Of these, 450 and 396 received bevacizumab monotherapy and B+I, respectively. The corresponding median overall survival from the initial surgery was 22.60 months (95% confidence interval [CI], 20.50-24.21) and 20.44 months (95% CI, 18.55-22.60; P = 0.508, log-rank test). The B+I group had significantly more bevacizumab prescriptions (median 5 times; BEV group: median 3 times). Cox analysis, based on the postsurgery period, revealed that male sex (hazard ratio [HR], 1.28; P = 0.002), older age (HR, 1.01; P = 0.042), and undergoing biopsy instead of surgery (HR, 1.79; P < 0.0001) were significantly associated with decreased survival. Fewer radiotherapy cycles correlated with improved survival outcomes (HR, 0.63; P = 0.001). Cox analysis, conducted from the start of chemotherapy including bevacizumab, showed that male sex was the only variable significantly associated with decreased survival (HR, 1.18; P = 0.044)., Conclusion: We found no significant difference in overall survival between the bevacizumab monotherapy and B+I groups. Considering the additional potential toxicity associated with irinotecan, bevacizumab monotherapy could be a suitable treatment option for treating recurrent glioblastoma., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

This study examined to evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients, a total of 76 patients diagnosed with glioma by pathology in Tengzhou Central People's Hospital were enrolled. The baseline data and follow ups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Ki-67 negative group showed of a longer OS survival time and a longer PFS survival time with log-rank test (x 2  = 16.101, P < 0.001 and x 2  = 16.961, P < 0.001). Age older than 50 years (HR = 2.074, 95% CI 1.097-3.923), abnormal treatment (HR = 2.932, 95% CI 1.343-6.403) and Ki-67 positive (HR = 2.722, 95% CI 1.097-6.755) were the independent predictive factors of death. High grade pathology (HR = 2.453, 95% CI 1.010-5.956) and Ki-67 positive (HR = 2.200, 95% CI 1.043-4.639) were the independent predictive factors of recurrence. The C-index for the nomogram of OS and PFS were 0.745 and 0.723, respectively. The calibration results showed that the nomogram could predict the overall and disease-free 1-year survival of glioma patients. In conclusion, the nomograms with Ki-67 as independent risk factor for OS and PFS could provide clinical consultation in the treatment and follow-up of malignant glioma., (© 2024. The Author(s).)

Glioma resection is associated with prolonged survival, but neuro-oncological trials have frequently refrained from quantifying the extent of resection. The Response Assessment in Neuro-Oncology (RANO) resect group is an international, multidisciplinary group that aims to standardise research practice by delineating the oncological role of surgery in diffuse adult-type gliomas as defined per WHO 2021 classification. Favourable survival effects of more extensive resection unfold over months to decades depending on the molecular tumour profile. In tumours with a more aggressive natural history, supramaximal resection might correlate with additional survival benefit. Weighing the expected survival benefits of resection as dictated by molecular tumour profiles against clinical factors, including the introduction of neurological deficits, we propose an algorithm to estimate the oncological effects of surgery for newly diagnosed gliomas. The algorithm serves to select patients who might benefit most from extensive resection and to emphasise the relevance of quantifying the extent of resection in clinical trials., Competing Interests: Declaration of interests DPC serves on advisory boards for Lilly, GlaxoSmithKline, Incephalo, Boston Pharmaceuticals, Servier, Boston Scientific, and Pyramid Biosciences; receives consultant fees from the USA National Institutes of Health and Department of Defense; and fees from lectures for Merck. MvdB receives consultant fees from Celgene, Bristol Myers Squibb, Agios, Boehringer, AbbVie, Bayer, Carthera, Nerviano, and Genenta. MW receives fees for honoraria or advisory board participation and consulting from Bayer, CureVac, Medac, Novartis, Novocure, Orbus, and Philogen; and research grants from Quercis and Versameb. MMK receives consultant fees from Blue Earth Diagnostics, and research grants from EpicentRx and Blue Earth Diagnostics. J-CT receives research grants from Novocure and Munich Surgical Imaging; serves on an advisory board for AAA Novartis; and receives royalties from Springer. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background/aim: In patients with recurrent glioblastoma, very little data are available regarding the prognostic value of platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte (NLR) ratios. This study investigated potential associations between PLR or NLR and treatment outcomes., Patients and Methods: PLR and NLR at diagnosis of recurrence plus 10 additional characteristics were retrospectively analyzed for associations with progression-free survival (PFS) and overall survival (OS) in 75 patients with recurrent glioblastoma., Results: On multivariate analyses, maximal cumulative diameter of recurrent lesion(s) <40 mm (p=0.015) and systemic therapy (p<0.001) were associated with improved PFS. On multivariate analysis of OS, improved outcomes were significantly associated with PLR ≤150 (p=0.029), maximal cumulative diameter <40 mm (p=0.030), and systemic therapy (p=0.010)., Conclusion: In addition to other characteristics, PLR at the time of recurrence was identified as an independent predictor of OS in patients with recurrent glioblastoma. PLR may be useful when designing personalized treatment approaches or clinical trials., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The prognostic value of scoring instruments was described for newly diagnosed glioblastoma. This study investigated five instruments in patients with recurrent tumors., Patients and Methods: Original Glasgow Prognostic Score (oGPS), modified GPS (mGPS), high-sensitivity mGPS (HS-mGPS), high-sensitivity oGPS (HS-oGPS), LabBM score, and 10 other factors were analyzed for progression-free survival (PFS) and overall survival (OS) in 51 patients., Results: On univariate analyses, oGPS 0-1, mGPS 0-1, and LabBM score 0-1.0 were significantly associated with improved OS and showed trends for improved PFS. On multivariate analysis, a trend was found for associations between LabBM score 0-1.0 and better OS. In addition, maximal cumulative diameter ≤40 mm and systemic therapy were independently associated with better PFS and OS, resection with PFS, and in-field recurrence with OS., Conclusion: Lower oGPS, mGPS, and LabBM scores were significantly associated with improved OS on univariate analyses. These instruments may be helpful when designing personalized treatment regimens for patients with recurrent glioblastoma., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Whether molecular glioblastomas (GBMs) identify with a similar dismal prognosis as a "classical" histological GBM is controversial. This study aimed to compare the clinical, molecular, imaging, surgical factors, and prognosis between molecular GBMs and histological GBMs., Methods: Retrospective chart and imaging review was performed in 983 IDH-wildtype GBM patients (52 molecular GBMs and 931 histological GBMs) from a single institution between 2005 and 2023. Propensity score-matched analysis was additionally performed to adjust for differences in baseline variables between molecular GBMs and histological GBMs., Results: Molecular GBM patients were substantially younger (58.1 vs. 62.4, P = 0.014) with higher rate of TERTp mutation (84.6% vs. 50.3%, P < 0.001) compared with histological GBM patients. Imaging showed higher incidence of gliomatosis cerebri pattern (32.7% vs. 9.2%, P < 0.001) in molecular GBM compared with histological GBM, which resulted in lesser extent of resection (P < 0.001) in these patients. The survival was significantly better in molecular GBM compared to histological GBM (median OS 30.2 vs. 18.4 months, P = 0.001). The superior outcome was confirmed in propensity score analyses by matching histological GBM to molecular GBM (P < 0.001)., Conclusion: There are distinct clinical, molecular, and imaging differences between molecular GBMs and histological GBMs. Our results suggest that molecular GBMs have a more favorable prognosis than histological GBMs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Glioblastoma, an aggressive brain tumor prevalent in adults, exhibits heterogeneity in its microstructures and vascular patterns. The delineation of its subregions could facilitate the development of region-targeted therapies. However, current unsupervised learning techniques for this task face challenges in reliability due to fluctuations of clustering algorithms, particularly when processing data from diverse patient cohorts. Furthermore, stable clustering results do not guarantee clinical meaningfulness. To establish the clinical relevance of these subregions, we will perform survival predictions using radiomic features extracted from them. Following this, achieving a balance between outcome stability and clinical relevance presents a significant challenge, further exacerbated by the extensive time required for hyper-parameter tuning. In this study, we introduce a multi-objective Bayesian optimization (MOBO) framework, which leverages a Feature-enhanced Auto-Encoder (FAE) and customized losses to assess both the reproducibility of clustering algorithms and the clinical relevance of their outcomes. Specifically, we embed the entirety of these processes within the MOBO framework, modeling both using distinct Gaussian Processes (GPs). The proposed MOBO framework can automatically balance the trade-off between the two criteria by employing bespoke stability and clinical significance losses. Our approach efficiently optimizes all hyper-parameters, including the FAE architecture and clustering parameters, within a few steps. This not only accelerates the process but also consistently yields robust MRI subregion delineations and provides survival predictions with strong statistical validation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Recent studies have investigated if the sodium fluorescein-guided (SFg) improves the extent of resection of BMs when compared to standard white light (sWL). Therefore, we aimed to assess the comparative efficacy and safety of SFg and sWL for resection of BMs., Methods: We searched Medline, Embase, and Cochrane Library databases following Cochrane and PRISMA guidelines for studies reporting comparative data of SFg and WL resection of BMs. We pooled odds ratios (OR) with 95% confidence intervals under random effects and applied I² statistics and leave-one-out sensitivity analysis to assess heterogeneity. I² > 40% was considered significant for heterogeneity., Results: Five studies involving 816 patients were included, of whom 390 underwent BMs resection with SFg and 426 with sWL, and ages ranging between 26 and 86.2 years old. Analysis revealed a statistically significant higher likelihood of complete resection in the SFg group when compared to the sWL group (OR = 2.15, 95%CI: 1.18-3.92, p = 0.01; I² = 47%). Sensitivity analysis revealed a consistent result in all five scenarios, with low heterogeneity in two of the five scenarios. Three studies reported significant improvement in OS in the SFg group, and the qualitative assessment of complications and procedure-related mortality did not provide sufficient information for conclusions., Conclusion: This systematic review and meta-analysis identified a higher likelihood of complete resection in the SFg group when compared to the standard sWL group. This study is the first to directly compare the impact of SFg and sWL on resection outcomes for BMs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

With increasing life expectancies and population aging, the incidence of elderly patients with grade 2 and 3 gliomas is increasing. However, there is a paucity of knowledge on factors affecting their treatment selection and overall survival (OS). Geriatric patients aged between 60 and 89 years with histologically proven grade 2 and 3 intracranial gliomas were identified from the National Cancer Database between 2010 and 2017. We analyzed patients' demographic data, tumor characteristics, treatment modality, and outcomes. The Kaplan-Meier method was used to analyze OS. Univariate and multivariate analyses were performed to assess the predictive factors of mortality and treatment selection. A total of 6257 patients were identified: 3533 (56.3 %) hexagenerians, 2063 (32.9 %) septuagenarians, and 679 (10.8 %) octogenarians. We identified predictors of lower OS in patients, including demographic factors (older age, non-zero Charlson-Deyo score, non-Hispanic ethnicity), socioeconomic factors (low income, treatment at non-academic centers, government insurance), and tumor-specific factors (higher grade, astrocytoma histology, multifocality). Receiving surgery and chemotherapy were associated with a lower risk of mortality, whereas receiving radiotherapy was not associated with better OS. Our findings provide valuable insights into the complex interplay of demographic, socioeconomic, and tumor-specific factors that influence treatment selection and OS in geriatric grade 2 and 3 gliomas. We found that advancing age correlates with a decrease in OS and a reduced likelihood of undergoing surgery, chemotherapy, or radiotherapy. While receiving surgery and chemotherapy were associated with improved OS, radiotherapy did not exhibit a similar association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Glioblastoma (GBM) is the most common primary brain cancer in adults with a very poor prognosis. Metabolic drivers of tumorigenesis are highly relevant within the central nervous system, where glucose is the critical source of energy. The impact of obesity on survival outcomes in patients with GBM is not well established. This study investigates the prognostic value of body mass index (BMI) in patients diagnosed with GBM., Methods: Adult patients with newly diagnosed GBM treated at Thomas Jefferson University Hospital between January 1, 2008, and December 31, 2022, were included in the study. BMI was calculated using the formula BMI = kg/m 2 . Patients BMI groups were underweight (BMI < 19.00), normal weight (BMI 19.00-24.99), overweight (BMI 25-29.99), and obese (BMI > 30.00). All patients received 60 Gy of radiation therapy with concurrent and adjuvant temozolomide following maximal safe resection. A difference in clinical outcomes of overall survival (OS) and progression-free survival (PFS) were evaluated between the groups using Kaplan-Meier and log-rank tests., Results: A total of 392 patients met inclusion criteria. The median age was 60.3 (range 18.9-86.7), with 144 females and 248 males. Median BMI was 27.0 (Range; 17.7-52.9). Non-overweight GBM patients (BMI < 25.00, OS 2.1 years, CI 1.7-2.4 years) had increased overall survival compared to overweight patients (BMI ≥ 25.00, OS 1.5 years, CI 1.4-1.6 years) (p < 0.001). Patients with MGMT-methylated GBM also had significantly greater OS and PFS compared to MGMT-unmethylated patients (p < 0.001). Non-overweight GBM patients (BMI < 25.00, median PFS 1.5 years, CI 1.3-2.0 years) also had increased progression-free survival compared to overweight patients (BMI ≥ 25.00, median PFS 1.1 years, CI 0.9-1.2 years) (p < 0.001)., Conclusions: Our study indicates normal BMI (19.00-24.99) at the time of GBM diagnosis is a favorable prognostic indicator for overall and progression-free survival. Additional studies are warranted for further analysis of BMI and survival outcomes in GBM patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No grants or outside funding was acquired for the completion of this study as well., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Acute Physiology and Chronic Health Evaluation II (APACHE II) is based on the data of intensive care unit (ICU) patients and often correlates with disease severity and prognosis. However, no prognostic predictors exist based on ICU admission data for patients with brain tumors, and no studies have reported an association between APACHE II and prognosis in patients with brain tumors. The Japanese Intensive Care Patients Database (JIPAD) was established to improve the quality of care delivered in intensive care medicine in Japan. We used JIPAD to examine factors associated with in-hospital mortality based on available data of postoperative patients with brain tumors admitted to the ICU., Methods: Patients aged ≥16 years enrolled in JIPAD between April 2015 and March 2018 after surgical brain tumor resection or biopsy of brain tumors. We examined factors related to outcomes at discharge based on blood tests and medical procedures performed during ICU admission, tumor type, and APACHE II score., Results: Among the 1454 patients (male:female ratio: 1:1.1, mean age: 62 years) in the study, 32 (2.2 %) died during hospital stay. In multivariate analysis, male sex (odds ratio [OR] 2.70, [95 % confidence interval, CI 1.22-6.00]), malignant tumor (OR 2.51 [95 % CI 1.13-5.55]), and APACHE II score ≥15 (OR 2.51 [95 % CI 3.08-14.3]) were significantly associated with in-hospital mortality., Conclusion: By picking up cases with a high risk of in-hospital death at an early stage, it is possible to improve methods of treatment and support for the patient's family., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Maximal-safe resection has been shown to improve overall survival in elderly patients with glioblastoma in observational studies, however, the only clinical trial comparing resection versus biopsy in elderly patients with surgically-accessible glioblastoma showed no improvements in overall survival. A meta-analysis is needed to assess whether surgical resection of glioblastoma in older patients improves surgical outcomes when compared to biopsy alone., Methods: A search was conducted until October 9th, 2023, to identify published studies reporting the clinical outcomes of glioblastoma patients > 65 years undergoing resection or biopsy (PubMed, MEDLINE, EMBASE, and COCHRANE). Primary outcomes were overall survival (OS), progression-free survival (PFS), and complications. We analyzed mean difference (MD) and hazard ratio (HR) for survival outcomes. Postoperative complications were analyzed as a dichotomic categorical variable with risk ratio (RR)., Results: From 784 articles, 20 cohort studies and 1 randomized controlled trial met our inclusion criteria, considering 20,523 patients for analysis. Patients undergoing surgical resection had an overall survival MD of 6.13 months (CI 95%=2.43-9.82, p = < 0.001) with a HR of 0.43 (95% CI = 0.35-0.52, p = < 0.00001). The progression-free survival MD was 2.34 months (95%CI = 0.79-3.89, p = 0.003) with a 0.50 h favoring resection (95%CI = 0.37-0.68, p = < 0.00001). The complication RR was higher in the resection group favoring biopsy (1.49, 95%CI = 1.06-2.10)., Conclusions: Our meta-analysis suggests that upfront resection is associated with improved overall survival and progression-free survival in elderly patients with newly diagnosed glioblastoma over biopsy. However, postoperative complications are more common with resection. Future clinical trials are essential to provide more robust evaluation in this challenging patient population., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Targeted treatment options for non-small cell lung cancer (NSCLC) brain metastases (BMs) may be combined with stereotactic radiosurgery (SRS) to optimize survival. We assessed patient outcomes after SRS for NSCLC BMs, identifying survival trajectories associated with targetable mutations., Methods: In this retrospective time-dependent analysis, we analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC from 2001 to 2021. We compared survival of patients with and without targetable mutations based on clinical variables and treatment., Results: Among the 213 patients included, 87 (40.8%) had targetable mutations-primarily EGFR (22.5%)-and 126 (59.2%) did not. Patients with targetable mutations were more often female (63.2%, p <.001) and nonsmokers (58.6%, p <.001); had higher initial lung-molGPA (2.0 vs. 1.5, p <.001) and lower cumulative tumor volume (3.7 vs. 10.6 cm 3 , p <.001); and received more concurrent (55.2% vs. 36.5%, p =.007) and total (median 3 vs. 2, p <.001) systemic therapies. These patients had lower mortality rates (74.7% vs. 91.3%, p <.001) and risk (HR 0.298 [95%CI 0.190-0.469], p <.001) and longer median overall survival (20.2 vs. 7.4 months, p <.001), including survival ≥ 3 years (p =.001). Survival was best predicted by SRS with tumor resection in patients with non-targetable mutations (HR 0.491 [95%CI 0.318-757], p =.001) and by systemic therapy with SRS for those with targetable mutations (HR 0.124 [95%CI 0.013-1.153], p =.067)., Conclusion: The presence of targetable mutations enhances survival in patients receiving SRS for NSCLC BM, particularly when used with systemic therapies. Survival for patients without targetable mutations was longest with SRS and surgical resection. These results inform best practices for managing patients with NSCLC BM based on driver mutation status., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In the era of personalized medicine, individualized prognostic models with tumor characteristics are needed to inform patients about survival. Before clinical use, external validation of such models by an independent group is needed. An updated version of the graded prognostic assessment (GPA) estimates survival in patients with brain metastases (BMs) of non-small cell lung cancer (NSCLC). This is the first external validation of the updated Lung-molGPA in patients treated with stereotactic radiotherapy (SRT) for one or more BMs., Materials and Methods: Patients treated with SRT for BMs from NSCLC adenocarcinoma were retrospectively included. GPA score was calculated for each patient based on six prognostic factors including age, Karnofsky Performance Status, number of BMs, extracranial metastases, EGFR/ALK status, and PD-L1 expression. Kaplan-Meier analysis evaluated survival probability. Impact of individual prognostic factors on survival was assessed by univariate and multivariate analyses using the Cox proportional hazard model. Predictive performance was evaluated using discrimination (C-statistic) and calibration (Brier test)., Results: The cohort (n = 241) was divided into four prognostic groups. Overall median survival was 15 months. Predicted and observed median survival were similar between the original and validation cohorts, apart from the most favorable prognostic group. With adequate C-statistics and Brier scores, the Lung-molGPA provided accurate survival predictions., Conclusion: The Lung-molGPA accurately predicted survival in our European population, except for an overestimation of survival in the small most favorable prognostic group. This prognostic model was externally validated and is therefore useful for counseling of patients with BMs of NSCLC adenocarcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: This study investigates the outcomes of microsurgical resection of multiple brain metastasis (BMs)., Methods: This retrospective, monocentric analysis included clinical data from all consecutive BM patients, who underwent simultaneous resection of ≥ 2 BMs between January 2018 and May 2023. Postoperative neurological and functional outcomes, along with perioperative complications, as well as survival data were evaluated., Results: A total of 47 patients, with a median age of 61 years (IQR 48-69), underwent 73 craniotomies (median 2; range 1-3) for resection of 104 BMs. Among patients, 80.8% presented with symptomatic BMs, causing focal neurological deficits in 53% of cases. Gross total resection was achieved in 87.2% of BMs. Karnofsky Performance Scale (KPS) scores improved in 42.6% of patients, remained unchanged in 46.8%, and worsened in 10.6% after surgery. Perioperative complications were observed in 29.8% of cases, with transient complications occurring in 19.2% and permanent deficits in 10.6%. The 30-days mortality rate was 2.1%. Logistic regression identified eloquent localization (p = 0.036) and infratentorial craniotomy (p = 0.018) as significant predictors of postoperative complications. Concerning overall prognosis, patients with permanent neurological deficits post-surgery (HR 11.34, p = 0.007) or progressive extracranial disease (HR: 4.649; p = 0.006) exhibited inferior survival., Conclusion: Microsurgical resection of multiple BMs leads to clinical stabilization or functional improvement in most patients. Although transient complications do not affect overall survival, the presence of persistent neurological deficits (> 3 months post-surgery) and progressive extracranial disease negatively impact overall survival. This highlights the importance of careful patient selection for resection of multiple BMs., (© 2024. The Author(s).)

Purpose: Glioblastoma (GBM) is the most common malignant primary brain tumor with a dismal prognosis of less than 2 years under maximal therapy. Despite the poor prognosis, small fractions of GBM patients seem to have a markedly longer survival than the vast majority of patients. Recently discovered intertumoral heterogeneity is thought to be responsible for this peculiarity, although the exact underlying mechanisms remain largely unknown. Here, we investigated the epigenetic contribution to survival., Methods: GBM treatment-naïve samples from 53 patients, consisting of 12 extremely long-term survivors (eLTS) patients and 41 median-term survivors (MTS) patients, were collected for DNA methylation analysis. 865 859 CpG sites were examined and processed for detection of differentially methylated CpG positions (DMP) and regions (DMR) between both survival groups. Gene Ontology (GO) and pathway functional annotations were used to identify associated biological processes. Verification of these findings was done using The Cancer Genome Atlas (TCGA) database., Results: We identified 67 DMPs and 5 DMRs that were associated with genes and pathways - namely reduced interferon beta signaling, in MAPK signaling and in NTRK signaling - which play a role in survival in GBM., Conclusion: In conclusion, baseline DNA methylation differences already present in treatment-naïve GBM samples are part of genes and pathways that play a role in the survival of these tumor types and therefore may explain part of the intrinsic heterogeneity that determines prognosis in GBM patients., (© 2024. The Author(s).)

Purpose: Sarcopenia may complicate treatment in cancer patients. Herein, we assessed whether sarcopenia measurements derived from radiation planning computed tomography (CT) were associated with complications and tumor progression during radiochemotherapy for glioblastoma., Methods: Consecutive patients undergoing radiotherapy planning for glioblastoma between 2010 and 2021 were analyzed. Retrocervical muscle cross-sectional area (CSA) was measured via threshold-based semi-automated radiation planning CT analysis. Patients in the lowest sex-specific quartile of muscle measurements were defined as sarcopenic. We abstracted treatment characteristics and tumor progression from the medical records and performed uni- and multivariable time-to-event analyses., Results: We included 363 patients in our cohort (41.6% female, median age 63 years, median time to progression 7.7 months). Sarcopenic patients were less likely to receive chemotherapy (p < 0.001) and more likely to be treated with hypofractionated radiotherapy (p = 0.005). Despite abbreviated treatment, they more often discontinued radiotherapy (p = 0.023) and were more frequently prescribed corticosteroids (p = 0.014). After treatment, they were more often transferred to inpatient palliative care treatment (p = 0.035). Finally, progression-free survival was substantially shorter in sarcopenic patients in univariable (median 5.1 vs. 8.4 months, p < 0.001) and multivariable modeling (hazard ratio 0.61 [confidence interval 0.46-0.81], p = 0.001)., Conclusion: Sarcopenia is a strong risk factor for treatment discontinuation and reduced progression-free survival in glioblastoma patients. We propose that sarcopenic patients should receive intensified supportive care during radiotherapy and during follow-up as well as expedited access to palliative care., (© 2024. The Author(s).)

Background and Objectives: Contrast enhancement in glioblastoma, IDH-wildtype is common but not systematic. In the era of the WHO 2021 Classification of CNS Tumors, the prognostic impact of a contrast enhancement and the pattern of contrast enhancement is not clearly elucidated., Methods: We performed an observational, retrospective, single-centre cohort study at a tertiary neurosurgical oncology centre (January 2006 - December 2022). We screened adult patients with a newly-diagnosed glioblastoma, IDH-wildtype in order to assess the prognosis role of the contrast enhancement and the pattern of contrast enhancement., Results: We included 1149 glioblastomas, IDH-wildtype: 26 (2.3%) had a no contrast enhancement, 45 (4.0%) had a faint and patchy contrast enhancement, 118 (10.5%) had a nodular contrast enhancement, and 960 (85.5%) had a ring-like contrast enhancement. Overall survival was longer in non-contrast enhanced glioblastomas (26.7 months) than in contrast enhanced glioblastomas (10.9 months) (p < 0.001). In contrast enhanced glioblastomas, a ring-like pattern was associated with shorter overall survival than in faint and patchy and nodular patterns (10.0 months versus 13.0 months, respectively) (p = 0.033). Whatever the presence of a contrast enhancement and the pattern of contrast enhancement, surgical resection was an independent predictor of longer overall survival, while age ≥ 70 years, preoperative KPS score < 70, tumour volume ≥ 30cm 3 , and postoperative residual contrast enhancement were independent predictors of shorter overall survival., Conclusion: A contrast enhancement is present in the majority (97.7%) of glioblastomas, IDH-wildtype and, regardless of the pattern, is associated with a shorter overall survival. The ring-like pattern of contrast enhancement is typical in glioblastomas, IDH-wildtype (85.5%) and remains an independent predictor of shorter overall survival compared to other patterns (faint and patchy and nodular)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The introduction of molecular markers in to the diagnosis of gliomas has changed the therapeutic approach to this tumors. The aim of this study was to examine the impact of surgery on anaplastic astrocytomas (AA), which has not previously been fully elucidated., Methods: This was a retrospective study involving a total of 143 patients who underwent surgery for primary AA in our department between 1995 and 2020., Results: Total tumor resection was achieved more often in patients with IDH-mutant tumors (41.09%) than in patients with IDH-wildtype tumors (30.76%). The median PFS was 1876 days for patients with IDH1 mutations and 238 days for patients with IDH-wildtype tumors. The 1-, 3-, 5- and 10-year PFS were longer in patients with total tumor resection and IDH-mutant AA (86.2%, 69%, 65.5% and 44.8%, respectively) than in patients with subtotal tumor resection and IDH-mutant AA (83.3%, 55.6%, 41.7% and 25%, respectively) and even longer compared to all IDH-wildtype tumors. The median OS was 2472 days for patients with IDH1 mutations and 434 days for patients with IDH-wildtype tumors. The 3-, 5- and 10-year OS times were longer in patients with total tumor resection and IDH-mutant AA (89.2%, 85.2% and 72.6%, respectively) than in patients with subtotal tumor resection and IDH-mutant AA (85.9%, 73.7% and 52.6%, respectively) and were even longer compared to all IDH-wildtype tumors., Conclusion: Total tumor resection is more common with IDH-mutant AA than with IDH-wildtype tumors. Patients with IDH-mutant AA had significantly better PFS and OS after total tumor resection than after subtotal tumor resection and biopsy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/purpose: Radiation is a key component in the treatment of central nervous system pure germinoma (PG) in children and adolescents. Proton therapy (PT) improves normal tissue sparing and potentially reduces adverse effects (AE). The aim of this study was to present the largest single institution experience utilizing PT for the management of PG., Materials Methods: We enrolled 35 non-metastatic patients with PG that were treated with PT at our institution between July 2007 - September 2021. Most received induction chemotherapy (n = 31, 89 %) and whole ventricular irradiation with an involved field boost (n = 29, 83 %). The most common total dose was 30 CGE (n = 18, 51.4 %). We utilized the cumulative incidence method to estimate local control (LC), freedom from distant metastases (FFDM), freedom from progression (FFP), and overall survival (OS). Treatment related toxicity was assessed per CTCAE version 5., Results: Median follow-up was 6.2 years (range, 0.9---15.2). The 10-year Kaplan-Meier estimates for LC, FFDM, FFP, and OS were 100 %, 100 %, 100 %, and 94 % respectively. The most common AE were hearing impairment requiring hearing aids (n = 3), transient hypersomnia requiring medication (n = 3), and new onset endocrinopathy (n = 1). Of the 23 evaluable patients ≥ 18 years old at last follow-up, 8 were high school graduates/in college, 8 college graduates, and 7 others gainfully employed., Conclusions: When utilized in modern multimodality treatment of non-metastatic PG, the precise dosimetry of PT does not compromise disease control. Although serious radiation side effects are rare, the 100% cure rate supports further investigation into selective radiation dose and volume de-escalation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The incidence of brain tumors has increased in elderly population overtime. Their eligibility to a major surgery remains a questionable subject. This study evaluated prognostic factors and 30-days morbidity and mortality in octogenarian population who underwent craniotomy for resection of brain tumor., Materials and Methods: A total of 154 patients were divided into two different groups: patients above 80 years old and patients below 65 years old. In both groups, patients were stratified based on diagnosis with benign tumors [meningioma] and malignant tumors [high-grade gliomas and metastases]. Multivariable logistic regression model with backward elimination method was utilized to identify the independent risk factors for 30-days readmission and post-operative complications., Results: The analysis revealed no significant difference in 30-day readmission ( p  = 0.7329), 30-day mortality (0.6854) or in post-operative complication ( p  = 0.3291) between age ≥ 80 and age ≤ 65 groups. A longer length of stay (LOS) was observed in the older patients ( p  = 0.0479). There was a significant difference in the pre-post KPS between the two groups ( p  < 0.0001). ASA ( p  = 0.0315) and KPS ( p  = 0.071) were found as important prognostic factors associated with post-operative mortality in both groups., Conclusion: Octogenarians can withstand craniotomy without any significant increase in 30-day readmission, 30-day mortality and post-operative complications as compared to patients younger than age 65. The ASA score (>3) and/or KPS (<70) were the most important prognostic factors for 30-days readmission and mortality.

Background: Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches., Methods: Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model., Results: 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm 3 , reduced to 3 cm 3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS., Conclusions: Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases., (© 2024. The Author(s).)

Patients with high-grade glioma (HGG) have an extremely poor prognosis compounded by a lack of advancement in clinical care over the past few decades. Regardless of classification, most newly diagnosed patients receive the same treatment, radiation and temozolomide (RT/TMZ). We developed a functional precision oncology test that prospectively identifies individual patient's response to this treatment regimen. Tumor tissues isolated from patients with newly diagnosed HGG enrolled in 3D PREDICT REGISTRY were evaluated for response to chemotherapeutic agents using the 3D Predict™ Glioma test. Patients receiving RT/TMZ were followed for 2 years. Clinical outcomes including imaging, assessments, and biomarker measurements were compared to patient matched test-predicted therapy response. Median survival between test-predicted temozolomide responders and test-predicted temozolomide non-responders revealed a statistically significant increase in progression-free survival when using the test to predict response across multiple subgroups including HGG (5.8 months), glioblastoma (4.7 months), and MGMT unmethylated glioblastoma (4.7 months). Overall survival was also positively separated across the subgroups at 7.6, 5.1, and 6.3 months respectively. The strong correlation of 3D Predict Glioma test results with clinical outcomes demonstrates that this functional test is prognostic in patients treated with RT/TMZ and supports aligning clinical treatment to test-predicted response across varying HGG subgroups., (© 2024. The Author(s).)

High-grade glioma (HGG) is an aggressive brain tumor. Sex is an important factor that differentially affects survival outcomes in HGG. We used an end-to-end deep learning approach on hematoxylin and eosin (H&E) scans to (i) identify sex-specific histopathological attributes of the tumor microenvironment (TME), and (ii) create sex-specific risk profiles to prognosticate overall survival. Surgically resected H&E-stained tissue slides were analyzed in a two-stage approach using ResNet18 deep learning models, first, to segment the viable tumor regions and second, to build sex-specific prognostic models for prediction of overall survival. Our mResNet-Cox model yielded C-index (0.696, 0.736, 0.731, and 0.729) for the female cohort and C-index (0.729, 0.738, 0.724, and 0.696) for the male cohort across training and three independent validation cohorts, respectively. End-to-end deep learning approaches using routine H&E-stained slides, trained separately on male and female patients with HGG, may allow for identifying sex-specific histopathological attributes of the TME associated with survival and, ultimately, build patient-centric prognostic risk assessment models.

Background: Brain metastasis (BrM) is prevalent among patients with NSCLC, and surgical resection of BrM constitutes a promising treatment strategy for local management and histopathological diagnosis, although it is offered for a select group of patients. Limited information exists concerning the improvement in performance status (PS) following BrM resection or the outcomes stratified by subsequent systemic therapy., Methods: We conducted a retrospective single-center cohort study including NSCLC patients with surgically resected BrM and focused on the improvement in PS and subsequent therapy after BrM resection., Results: 71 patients were included, and the median overall survival was 18.3 months (95% confidence interval [95% CI]: 8.7, not reached). Patients with NSCLC who underwent surgical resection of BrM showed significant improvement in PS (18% and 39% showed ECOG PS of 0-1, before and after BrM resection, respectively [p = 0.006]), and patients with PS improvement were younger than those with PS unimprovement (median, 62 years versus 66 years; p = 0.041). Regarding subsequent systemic therapy after BrM resection, 21 patients (30%) received cytotoxic chemotherapy, 14 patients (20%) received tyrosine kinase inhibitors (TKIs), 3 patients (4%) received immune checkpoint inhibitors (ICIs), and 21 patients (30%) received no subsequent therapy. The survival outcomes of patients stratified by subsequent systemic treatments suggested the tendency that those who received TKI or ICI showed better survival outcomes, although a small number of patients hindered statistical comparisons., Conclusions: We describe the outcomes of patients with NSCLC who underwent surgical resection of BrM, revealing that younger patients were more likely to anticipate improvement in PS, and patients who received TKI or ICI after BrM resection tended to exhibit a more preferable prognosis., (© 2024. The Author(s).)

Background: There is ongoing uncertainty about the effectiveness of various adjuvant treatments for low-grade gliomas (LGGs). Machine learning (ML) models that predict individual treatment effects (ITE) and provide treatment recommendations could help tailor treatments to each patient's needs., Objective: We sought to discern the individual suitability of radiotherapy (RT) or chemoradiotherapy (CRT) in LGG patients using ML models., Methods: Ten ML models, trained to infer ITE in 4,042 LGG patients, were assessed. We compared patients who followed treatment recommendations provided by the models with those who did not. To mitigate the risk of treatment selection bias, we employed inverse probability treatment weighting (IPTW)., Results: The Balanced Survival Lasso-Network (BSL) model showed the most significant protective effect among all the models we tested (hazard ratio (HR): 0.52, 95% CI, 0.41-0.64; IPTW-adjusted HR: 0.58, 95% CI, 0.45-0.74; the difference in restricted mean survival time (DRMST): 9.11, 95% CI, 6.19-12.03; IPTW-adjusted DRMST: 9.17, 95% CI, 6.30-11.83). CRT presented a protective effect in the 'recommend for CRT' group (IPTW-adjusted HR: 0.60, 95% CI, 0.39-0.93) yet presented an adverse effect in the 'recommend for RT' group (IPTW-adjusted HR: 1.64, 95% CI, 1.19-2.25). Moreover, the models predict that younger patients and patients with overlapping lesions or tumors crossing the midline are better suited for CRT (HR: 0.62, 95% CI, 0.42-0.91; IPTW-adjusted HR: 0.59, 95% CI, 0.36-0.97)., Conclusion: Our findings underscore the potential of the BSL model in guiding the choice of adjuvant treatment for LGGs patients, potentially improving survival time. This study emphasizes the importance of ML in customizing patient care, understanding the nuances of treatment selection, and advancing personalized medicine., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Glioma is the most common malignant tumor of the adult central nervous system. In this study, we aimed to identify a novel model for predicting glioma prognosis and a potential therapeutic target. Here, lncRNAs related to prognosis and ferroptosis were analyzed and screened through R software and online websites. A nomogram model was established and evaluated with calibration curve, receiver operating characteristic curve and decision curve analysis. Further, an enrichment analysis and immune infiltration analysis were performed. In addition, the expression level and biological function of ITGA6-AS1 were verified in vitro. We obtained a ferroptosis-related 7-lncRNA signature, and constructed a nomogram prognostic model with good predictability for 1-, 3- and 5-year overall survival of glioma patients. The enrichment analysis indicated potential involvement of certain pathways and suggested a correlation between the high-risk group and infiltration of M2 macrophages and MDSCs. Furthermore, the expression level of ITGA6-AS1 in the U118, U87, and LN229 cells was upregulated compared to the H1800 cell. Interestingly, knockdown of ITGA6-AS1 may inhibit U118 cells' proliferation, migration and invasion in vitro. while overexpression of ITGA6-AS1 in LN229 cells plays a promoting role. This study implies that the 7-lncRNA signature may contribute to the stratification of glioma prognosis, and the immune suppressive microenvironment may be associated with macrophage-ferroptosis crosstalk. Furthermore, ITGA6-AS1 may be a potential therapeutic target for patients with glioma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to investigate the intra- and inter-observer consistency of the Visually Accessible Rembrandt Images (VASARI) feature set before and after dichotomization, and the association between dichotomous VASARI features and the overall survival (OS) in glioblastoma (GBM) patients., Methods: This retrospective study included 351 patients with pathologically confirmed IDH1 wild-type GBM between January 2016 and June 2022. Firstly, VASARI features were assessed by four radiologists with varying levels of experience before and after dichotomization. Cohen's kappa coefficient (κ) was calculated to measure the intra- and inter-observer consistency. Then, after adjustment for confounders using propensity score matching, Kaplan-Meier curves were used to compare OS differences for each dichotomous VASARI feature. Next, patients were randomly stratified into a training set (n = 211) and a test set (n = 140) in a 3:2 ratio. Based on the training set, Cox proportional hazards regression analysis was adopted to develop combined and clinical models to predict OS, and the performance of the models was evaluated with the test set., Results: Eleven VASARI features with κ value of 0.61-0.8 demonstrated almost perfect agreement after dichotomization, with the range of κ values across all readers being 0.874-1.000. Seven VASARI features were correlated with GBM patient OS. For OS prediction, the combined model outperformed the clinical model in both training set (C-index, 0.762 vs. 0.723) and test set (C-index, 0.812 vs. 0.702)., Conclusion: The dichotomous VASARI features exhibited excellent inter- and intra-observer consistency. The combined model outperformed the clinical model for OS prediction., (© 2024. The Author(s).)

Introduction: Gliomas are the most common primary intracranial tumors, known for their high invasiveness and destructiveness. Sialic acid-binding immunoglobulin-like lectin 7 (SIGLEC7) is present in various immune cells, especially macrophages, and significantly affects immune homeostasis and cancer cell response. However, research on the role and prognostic impact of SIGLEC7 in glioma patients is currently limited., Methods: We utilized transcriptomic data from 702 glioma patients in The Cancer Genome Atlas (TCGA) and 693 glioma patients in the Chinese Glioma Genome Atlas (CGGA), along with clinical samples we collected, to comprehensively investigate the impact of SIGLEC7 on glioma expression patterns, biological functions, and prognostic value. We focused on its role in glioma-related immune responses and immune cell infiltration and analyzed its expression at the single-cell level. Finally, we validated the role of SIGLEC7 in gliomas through tissue and cell experiments., Results: SIGLEC7 expression was significantly increased in glioma patients with malignant characteristics. Survival analysis indicated that glioma patients with high SIGLEC7 expression had significantly lower survival rates. Gene function analysis revealed that SIGLEC7 is primarily involved in immune and inflammatory responses and is strongly negatively correlated with tumor-associated immune regulation. Additionally, the expression of most immune checkpoints was positively correlated with SIGLEC7, and immune cell infiltration analysis clearly demonstrated a significant positive correlation between SIGLEC7 expression and M2 macrophage infiltration levels. Single-cell analysis, along with tissue and cell experiments, confirmed that SIGLEC7 enhances macrophage polarization towards the M2 phenotype, thereby promoting glioma invasiveness through the immunosuppressive effects of M2 macrophages. Cox regression analysis and the establishment of survival prediction models indicated that high SIGLEC7 expression is an unfavorable prognostic factor for glioma patients., Discussion: High SIGLEC7 expression predicts poor prognosis in glioma patients and is closely associated with M2 macrophages in the tumor environment. In the future, SIGLEC7 may become a promising target for glioma immunotherapy., Competing Interests: Author PW, YC, ZH and XH are employed by the company Beijing Yihua Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 An, Ren, Yuan, Qiu, Wang, Cheng, He, Han, Li and An.)

Purpose: DNA methylation profiling stratifies isocitrate dehydrogenase (IDH)-mutant astrocytomas into methylation low- and high-grade groups. We investigated the utility of the T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign for predicting DNA methylation grade and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion, a molecular biomarker for grade 4 IDH-mutant astrocytomas, according to the 2021 World Health Organization classification., Experimental Design: Preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n = 71) were independently evaluated by two radiologists for the T2-FLAIR mismatch sign. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed., Results: The T2-FLAIR mismatch sign was present in 21 of 45 (46.7%) methylation low-grade and 1 of 26 (3.9%) methylation high-grade cases (P < 0.001), resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status (P = 0.028) with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for progression-free survival (P = 0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, copy number variation, and methylation grade, showed trends toward significance for DNA methylation grade with overall survival (P = 0.045) and CDKN2A/B status with progression-free survival (P = 0.052)., Conclusions: The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas., (©2024 American Association for Cancer Research.)

Background: Glioblastoma (GBM) is a poor prognosis grade 4 glioma. After surgical resection, the standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Our previous data on melanoma patients showed that Dendritic Cell vaccination (DCvax) could increase the amount of intratumoral-activated cytotoxic T lymphocytes., Methods: This is a single-arm, monocentric, phase II trial in two steps according to Simon's design. The trial aims to evaluate progression-free survival (PFS) at three months and the safety of a DCvax integrated with standard therapy in resected GBM patients. DCvax administration begins after completion of RT-CTwith weekly administrations for 4 weeks, then is alternated monthly with TMZ cycles. The primary endpoints are PFS at three months and safety. One of the secondary objectives is to evaluate the immune response both in vitro and in vivo (DTH skin test)., Results: By December 2022, the first pre-planned step of the study was concluded with the enrollment, treatment and follow up of 9 evaluable patients. Two patients had progressed within three months after leukapheresis, but none had experienced DCvax-related G3-4 toxicities Five patients experienced a positive DTH test towards KLH and one of these also towards autologous tumor homogenate. The median PFS from leukapheresis was 11.3 months and 12.2 months from surgery., Conclusions: This combination therapy is well-tolerated, and the two endpoints required for the first step have been achieved. Therefore, the study will proceed to enroll the remaining 19 patients. (Eudract number: 2020-003755-15 https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003755-15/IT)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ridolfi, Gurrieri, Riva, Bulgarelli, De Rosa, Guidoboni, Fausti, Ranallo, Calpona, Tazzari, Petrini, Granato, Pancisi, Foca, D'Allagata, Bondi, Amadori, Cortesi, Zani, Ancarani, Gamboni, Polselli, Pasini, Bartolini, Maimone, Arpa and Tosatto.)

Background: Differences in radiation-induced lymphopenia and prognosis between methods of radiotherapy (RT) for brain metastases remain unclear., Methods: In this retrospective analysis of patients who underwent whole-brain radiotherapy (WBRT) or stereotactic radiosurgery/radiotherapy (SRS/SRT) for brain metastases, baseline total lymphocyte count (TLC) data were obtained within 2 weeks before RT initiation. Follow-up TLC data were evaluated at 0-2, 2-4, and 4-8 weeks after RT completion. Persistent lymphopenia was defined as <800/μL at any time point., Results: Overall, 138 RT courses in 128 patients were eligible (94 WBRT; 44 SRS/SRT). In the WBRT courses, the median baseline TLC was 1325/μL (IQR: 923-1799). Follow-up TLC decreased significantly to 946/μL (626-1316), 992/μL (675-1291), and 1075/μL (762-1435) ( p < 0.001). SRS/SRT courses showed no significant TLC decrease. Multivariate analysis revealed female sex, prior RT, baseline TLC < 800/μL, and WBRT use were significantly associated with persistent lymphopenia. In the WBRT group, overall survival was significantly different between those with and without persistent lymphopenia (median, 2.6 and 6.1 months; p < 0.001). However, there was no significant difference in survival in the SRS/SRT group ( p = 0.60)., Conclusion: This study suggests SRS/SRT might be preferable for lymphocyte preservation in brain metastasis patients.

Background: Visually Accessible Rembrandt (Repository for Molecular Brain Neoplasia Data) Images (VASARI) features, a vocabulary to establish reproducible terminology for glioma reporting, have been applied for a decade, but a systematic performance evaluation is lacking., Purpose: Our aim was to conduct a systematic review and meta-analysis of the performance of the VASARI features set for glioma assessment., Data Sources: MEDLINE, Web of Science, EMBASE, and the Cochrane Library were systematically searched until September 26, 2023., Study Selection: Original articles predicting diagnosis, progression, and survival in patients with glioma were included., Data Analysis: The modified Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to evaluate the risk-of-bias. The meta-analysis used a random effects model and forest plot visualizations, if ≥5 comparable studies with a low or medium risk of bias were provided., Data Synthesis: Thirty-five studies (3304 patients) were included. Risk-of-bias scores were medium ( n  = 33) and low ( n  = 2). Recurring objectives were overall survival ( n  = 18) and isocitrate dehydrogenase mutation ( IDH ; n  = 12) prediction. Progression-free survival was examined in 7 studies. In 4 studies (glioblastoma n  = 2, grade 2/3 glioma n  = 1, grade 3 glioma n  = 1), a significant association was found between progression-free survival and single VASARI features. The single features predicting overall survival with the highest pooled hazard ratios were multifocality (hazard ratio = 1.80; 95%-CI, 1.21-2.67; I 2 = 53%), ependymal invasion (hazard ratio = 1.73; 95% CI, 1.45-2.05; I 2 = 0%), and enhancing tumor crossing the midline (hazard ratio = 2.08; 95% CI, 1.35-3.18; I 2 = 52%). IDH mutation-predicting models combining VASARI features rendered a pooled area under the receiver operating characteristic curve of 0.82 (95% CI, 0.76-0.88) at considerable heterogeneity (I 2 = 100%). Combined input models using VASARI plus clinical and/or radiomics features outperformed single data-type models in all relevant studies ( n  = 17)., Limitations: Studies were heterogeneously designed and often with a small sample size. Several studies used The Cancer Imaging Archive database, with likely overlapping cohorts. The meta-analysis for IDH was limited due to a high study heterogeneity., Conclusions: Some VASARI features perform well in predicting overall survival and IDH mutation status, but combined models outperform single features. More studies with less heterogeneity are needed to increase the evidence level., (© 2024 by American Journal of Neuroradiology.)

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations also have expression associations with patient survival, including BCOR, TERT, RCOR2, and PDLIM4. DNA methylation changes in recurrent or progressive tumors compared to the initial tumor within the same patient can predict survival in pediatric and adult cancers. Our comprehensive and pan-histology genomic analyses reveal mechanisms of noncoding alterations impacting cancer genes., (© 2024. The Author(s).)

Background and Purpose: In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC)., Methods: This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI., Results: 120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group., Conclusion: The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy., (© 2024. The Author(s).)

Background: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 World Health Organization classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults., Methods: We included molecularly confirmed H3 K27M-mutated glioma cases in patients ≥ 18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors., Results: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 ± 14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy. Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, P = .007). Preoperative Karnofsky-Performance Score (KPS) ≤ 80 showed a reduced OS (4.2 vs. 18 months, P = .02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, P = .0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, P = .4006)., Conclusions: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Stereotactic irradiation has become the mainstay treatment for brain metastases (BM), and whole-brain radiotherapy (WBRT) is often used for symptom palliation. However, the survival time of patients with BM undergoing palliative WBRT (pWBRT) is limited, making it difficult to select patients who should receive treatment., Methods: We collected patient data from 2016 to 2022 at the Shizuoka Cancer Center and retrospectively analyzed the factors related to survival time. Overall survival (OS) was defined as the survival time after WBRT., Results: A total of 301 patients (median age, 66 years) who underwent pWBRT were included. The primary cancers were lung, breast, gastrointestinal tract, and other cancers in 203 (67%), 38 (13%), 33 (11%), and 27 (9%) patients, respectively. Median OS of all patients was 4.1 months. In the multivariate analysis, male sex (hazard ratio [HR]:1.4), Karnofsky Performance Status (KPS) ≤ 60 (HR:1.7), presence of extracranial metastasis (ECM) (HR:1.6), neutrophil-lymphocyte ratio (NLR) ≥ 5 (HR:1.6), and lactate dehydrogenase (LDH) ≥ upper limit of normal (ULN) (HR:1.3) were significantly associated with shorter OS (all P < 0.05). To predict the OS, we created a prognostic scoring system (PSS). We gave one point to each independent prognostic factor. Median OS for patients with scores of 0-2, 3, and 4-5 were 9.0, 3.5 and 1.7 months, respectively (P < 0.001)., Conclusions: Male sex, KPS ≤ 60, presence of ECM, NLR ≥ 5, and LDH ≥ ULN were poor prognostic factors for patients with BM undergoing pWBRT. By PSS combining these factors, it may be possible to select patients who should undergo pWBRT., (© 2024. The Author(s).)

TNFAIP8 family molecules have been recognized for their involvement in the progression of tumors across a range of cancer types. Emerging experimental data suggests a role for certain TNFAIP8 family molecules in the development of glioma. Nonetheless, the comprehensive understanding of the genomic alterations, prognostic significance, and immunological profiles of TNFAIP8 family molecules in glioma remains incomplete. In the study, using the comprehensive bioinformatics tools, we explored the unique functions of 4 TNFAIP8 members including TNFAIP8, TNFAIP8L1, TNFAIP8L2 and TNFAIP8L3 in glioma. The expressions of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were notably upregulated in glioma tissues compared to normal tissues. Furthermore, survival analysis indicated that elevated expression levels of TNFAIP8, TNFAIP8L1 and TNFAIP8L2 were correlated with unfavorable outcomes in terms of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) among glioma patients. Genetic modifications, such as mutations and copy number alterations, within the TNFAIP8 family exhibited a significant association with extended OS, DSS and PFS in individuals diagnosed with glioma. The findings suggest a noteworthy correlation between TNFAIP8 family members and the age and 1p/19q codeletion status of glioma patients. We also found that there were significant relationships between TNFAIP8 family expression and tumor immunity in glioma. Furthermore, functional annotation of TNFAIP8 family members and their co-expressed genes in gliomas was carried out using GO and KEGG pathway analysis. The GO analysis revealed that the primary biological processes influenced by the TNFAIP8 family co-expressed genes included cell chemotaxis, temperature homeostasis, and endocytic vesicle formation. Additionally, the KEGG analysis demonstrated that TNFAIP8 family co-expressed genes are involved in regulating various pathways such as inflammatory mediator regulation of TRP channels, pathways in cancer, prolactin signaling pathway, and Fc gamma R-mediated phagocytosis. Overall, the findings suggest that TNFAIP8 family members may play a significant role in the development of glioma and have the potential to serve as prognostic indicators and therapeutic targets for individuals with glioma., (© 2024. The Author(s).)

Objective: This retrospective study is to explore the risk factors and prognostic factors of brain metastases of triple-negative breast cancer (TNBC) in a single center., Methods: Clinical data of patients with stages I-III TNBC were collected. The Kaplan-Meier method, log-rank test, and stepwise COX regression were performed., Results: The 437 patients with stages I-III TNBC were followed up for five years. Among them, 89 cases (20.4%) developed brain metastases, and they were followed up for 2 years after brain metastasis. The cumulative brain metastasis rates of TNBC patients at six months, one year, two years, three years, and five years were 1.38%, 5.75%, 12.94%, 17.63%, and 21.26%, respectively. Multivariate analysis suggested that the first diagnosis age ≤35 years old, advanced pathological stage, lymph node metastasis, and Ki-67 ≥30% represented the risk factors for brain metastasis. In contrast, the surgical method was a protective factor for brain metastasis. The median survival time after brain metastasis was 4.87 months. The survival rates at one, three, six, 12, and 24 months were 84.27%, 60.67%, 34.83%, 15.69%, and 6.64%, respectively. The age >60 years at first diagnosis, Ki-67 ≥30%, local recurrence, and distant metastasis were closely related to the poor prognosis of TNBC patients with brain metastases, while radiotherapy alone, systemic therapy, and combined chemotherapy and radiotherapy represented the prognostic protective factors., Conclusions: Patient age, Ki-67 level, metastasis, and treatment methods are the risk factors and prognostic factors for brain metastasis of TNBC. Surgical resection of the primary lesion during the first treatment is essential to reduce the incidence of brain metastases. Close postoperative follow-up (such as brain magnetic resonance imaging [MRI]) within 2-3 years after surgery is recommended to improve the prognosis., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Objectives: High-grade gliomas (HGGs) are highly malignant, aggressive, and have a high incidence and mortality rate. The aim of this study was to investigate survival outcomes and prognostic factors in patients with HGGs., Methods: In this retrospective study, a total of 159 patients with histologically confirmed HGGs were included. The recruitment period was from January 2011 to December 2019. We evaluated patient demographic data, tumor characteristics, treatment methods, immunocytochemistry results, overall survival (OS) time, and progression-free survival (PFS) time using Kaplan-<>Meier survival analysis with log-rank testing. Additionally, we employed Cox regression analysis to identify independent factors associated with survival outcomes., Results: Kaplan-Meier survival analysis revealed that the 1-, 2-, and 5-years OS rates were 81.8%, 50.3%, and 12.6%, respectively. Similarly, the 1-, 2-, and 5-years PFS rates were 50.9%, 22.4%, and 3.1%, respectively. The median OS duration was 35.0 months. The univariate analysis indicated that postoperative pathological classification, grade, and age were significantly associated with patient outcomes (p < 0.01). Among the patients, 147 received concurrent chemoradiotherapy, while 12 did not. The immunohistochemical markers of ki-67, MGMT, IDH1R132H, and p53 demonstrated statistically significant differences in their prognostic impact (p = 0.001, p = 0.020, p = 0.003, and p = 0.021, respectively). In conclusion, we found that grades, age, pathological classification, ki-67, MGMT, and IDH1R132H expression were statistically significantly associated with PFS (p < 0.01, p = 0.004, p = 0.003, p = 0.001, p = 0.036, and p = 0.028). Additionally, immunohistochemical expressions of TRIB3 and AURKA were significantly higher in patients with shorter survival (p = 0.015 and p = 0.023)., Conclusions: Tumor grade and the use of concurrent chemoradiotherapy after surgery were independent prognostic factors that significantly influenced patient survival. Additionally, tumor grade and MGMT expression were found to be independent factors affecting progression-free survival (PFS). Notably, the expression of TRIB3 and AURKA was higher in patients with poor survival outcomes., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Neurocytomas represent 0.25 to 0.5% of primary brain tumours and are mainly found in young adults. These tumours have neuronal differentiation. The cornerstone treatment is neurosurgery. The efficacy of other therapies, including radiotherapy, is still unclear. The objective of this study was to evaluate the management of central neurocytomas and the role of radiotherapy., Materials and Methods: All adult patients (age 18 years or older) newly diagnosed with a histologically confirmed neurocytoma between 2006 and 2015 in France were included., Results: One hundred and sixteen patients were diagnosed with a central neurocytoma during the study period. All patients underwent surgical resection, and six received adjuvant radiotherapy. Eleven patients received radiotherapy due to progression. After a median follow-up of 68.7 months, local failure occurred in 29 patients. The 5-year local control rate was 73.4%. According to univariate analysis, marker of proliferation Ki67 index greater than 2% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.40-1.57; P=0.027) and subtotal resection (HR: 8.48; CI: 8.01-8.99; P<0.001) were associated with an increase in local failure. Gross total resection was associated with a higher risk of sequelae epilepsy (HR: 3.62; CI: 3.42-3.83; P<0.01) and memory disorders (HR: 1.35; CI: 1.07-1.20; P<0.01). Ten patients (8.6%) died during the follow-up. The 10-year overall survival rate was 89.0%. No prognostic factors for overall survival were found., Conclusion: The analysis showed that patients who underwent subtotal surgical resection, particularly when the tumour had a Ki67 index greater than 2%, had an increased risk of local recurrence. These patients could benefit from adjuvant radiotherapy., (Copyright © 2024 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background/aim: Resection of brain metastases is a well-established treatment modality that can prolong the survival of patients for whom surgery is indicated. Whole-brain radiotherapy (WBRT) has been the standard postoperative therapy. In recent years, however, clinicians have increasingly avoided WBRT due to its associated adverse events. This study investigated the impact of postoperative WBRT and systemic chemotherapy as prognostic factors on the survival of patients who had undergone resection of brain metastases., Patients and Methods: The study subjects were 172 patients who underwent surgical resection for brain metastases. Comparative analyses of survival after WBRT and systemic chemotherapy were performed., Results: Postoperative WBRT had no survival-prolonging effect, whereas postoperative systemic chemotherapy prolonged survival. A comparison based on the number of systemic chemotherapy regimens administered prior to surgery showed that fewer regimens correlated with a better prognosis., Conclusion: The addition of WBRT after surgical resection of brain metastases is no longer a standard treatment strategy and systemic chemotherapy after surgery is a positive prognostic factor., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram., Methods: Data from elderly individuals (age ≥65 years) histologically diagnosed with brain glioma were sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio. Additionally, data obtained from Tangdu Hospital constituted an external validation cohort for the study. The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis, enabling the construction of a nomogram. Model performance was evaluated using C-index, ROC curves, calibration plot and decision curve analysis (DCA)., Results: A cohort of 20 483 elderly glioma patients was selected from the SEER database. Five prognostic factors (age, marital status, histological type, stage, and treatment) were found to significantly impact overall survival (OS) and cancer-specific survival (CSS), with tumor location emerging as a sixth variable independently linked to CSS. Subsequently, nomogram models were developed to predict the probabilities of survival at 6, 12, and 24 months. The assessment findings from the validation queue indicate a that the model exhibited strong performance., Conclusion: Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients. They can potentially assist in risk stratification and clinical decision-making., (© 2024. Huazhong University of Science and Technology.)

Background and Purpose: Evidence and clinical guidelines support the use of adjuvant RT in high-risk low-grade gliomas. However, patients with oligodendroglioma have a more indolent disease course and delaying or avoiding RT is often considered to reduce treatment-related toxicities. As the optimal adjuvant management for oligodendroglioma is unclear, we aimed to assess the effect of adjuvant RT on overall survival (OS) and progression-free survival (PFS)., Methods: MEDLINE, EMBASE, CENTRAL and CINAHL were searched from January 1990 to February 2023 for studies comparing adjuvant RT versus no adjuvant RT for patients with oligodendroglioma., Results: This review found 17 eligible studies including 14 comparative retrospective studies and 3 randomized controlled trials. Using random-effects model, the results suggested that adjuvant RT improved OS by 28 % (HR 0.72, 95 % CI (0.56-0.93), I 2  = 86 %), and PFS by 48 % (HR 0.52, (95 % CI 0.40-0.66), I 2  = 48 %) compared to patients without adjuvant RT. Subgroup analysis showed that upfront adjuvant RT improved OS and PFS compared to salvage RT. There were no significant differences in OS and PFS between adjuvant RT versus adjuvant chemotherapy. There was improvement in PFS but not OS for adjuvant chemoradiotherapy versus adjuvant chemotherapy alone. Adjuvant RT improved OS in WHO Grade 3 but not WHO Grade 2 oligodendroglioma., Conclusion: Overall, adjuvant RT improved OS and PFS in patients with oligodendroglioma. In patients with low-risk features (e.g. Grade 2, gross total resection), alternative approaches and individualization of management such as adjuvant chemotherapy alone may be reasonable considering the lack of survival benefit. Future efforts should prospectively investigate these treatment regimens on molecularly-classified oligodendroglioma patients (defined by presence of IDH mutation and 1p/19q co-deletion), balancing between maximizing survival outcomes and reducing RT-related toxicities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The author (AW) would like to acknowledge financial support for her research work and contribution writing this paper from the National University Health System (NUHS) Seed Fund (NUHSRO/2021/052/RO5+6/Seed-Mar/01). AW has advisory roles at Astra Zeneca, Pfizer, Eisai, DKSH, Novartis. AW receives research funding from Otsuka Pharmaceuticals. The rest of the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Patients with glioblastoma (GBM) have a dismal prognosis. Although the DNA alkylating agent temozolomide (TMZ) is the mainstay of chemotherapy, therapeutic resistance rapidly develops in patients. Base excision repair inhibitor TRC102 (methoxyamine) reverses TMZ resistance in preclinical glioma models. We aimed to investigate the efficacy and safety of oral TRC102+TMZ in recurrent GBM (rGBM)., Patients and Methods: A preregistered (NCT02395692), nonrandomized, multicenter, phase 2 clinical trial (BERT) was planned and conducted through the Adult Brain Tumor Consortium (ABTC-1402). Arm 1 included patients with bevacizumab-naïve GBM at the first recurrence, with the primary endpoint of response rates. If sufficient activity was identified, a second arm was planned for the bevacizumab-refractory patients. The secondary endpoints were overall survival (OS), progression-free survival (PFS), PFS at 6 months (PFS6), and toxicity., Results: Arm 1 enrolled 19 patients with a median of two treatment cycles. Objective responses were not observed; hence, arm 2 did not open. The median OS was 11.1 months [95% confidence interval (CI), 8.2-17.9]. The median PFS was 1.9 months (95% CI, 1.8-3.7). The PFS6 was 10.5% (95% CI, 1.3%-33.1%). Most toxicities were grades 1 and 2, with two grade 3 lymphopenias and one grade 4 thrombocytopenia. Two patients with PFS ≥ 17 months and OS > 32 months were deemed "extended survivors." RNA sequencing of tumor tissue, obtained at diagnosis, demonstrated significantly enriched signatures of DNA damage response (DDR), chromosomal instability (CIN70, CIN25), and cellular proliferation (PCNA25) in "extended survivors.", Conclusions: These findings confirm the safety and feasibility of TRC102+TMZ in patients with rGBM. They also warrant further evaluation of combination therapy in biomarker-enriched trials enrolling GBM patients with baseline hyperactivated DDR pathways., (©2024 American Association for Cancer Research.)

Introduction: Central Neurocytoma (CN) is a rare, WHO grade 2 brain tumor that predominantly affects young adults. Gross total resection (GTR) is often curative for CNs, but the optimal treatment paradigm including incorporation of RT, following subtotal resection (STR) and for scarcer pediatric cases has yet to be established., Methods: Patients between 2001 and 2021 with a pathologic diagnosis of CN were reviewed. Demographic, treatment, and tumor characteristics were recorded. Recurrence free survival (RFS) and overall survival (OS) were calculated according to the Kaplan Meier-method. Post-RT tumor volumetric regression analysis was performed., Results: Seventeen adults (≥ 18 years old) and 5 children (< 18 years old) met the criteria for data analysis (n = 22). With a median follow-up of 6.9 years, there was no tumor-related mortality. Patients who received STR and/or had atypical tumors (using a cut-off of Ki-67 > 4%) experienced decreased RFS compared to those who received GTR and/or were without atypical tumors. RFS at 5 years for typical CNs was 67% compared to 22% for atypical CNs. Every pediatric tumor was atypical and 3/5 recurred within 5 years. Salvage RT following tumor recurrence led to no further recurrences within the timeframe of continued follow-up; volumetric analysis for 3 recurrent tumors revealed an approximately 80% reduction in tumor size., Conclusion: We provide encouraging evidence that CNs treated with GTR or with RT after tumor recurrence demonstrate good long-term tumor control., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We aimed to study whether the Bruton's tyrosine kinase (BTK) expression is correlated with the prognosis of patients with high-grade gliomas (HGGs) and predict its expression level prior to surgery, by constructing radiomic models. Clinical and gene expression data of 310 patients from The Cancer Genome Atlas (TCGA) were included for gene-based prognostic analysis. Among them, contrast-enhanced T1-weighted imaging (T1WI + C) from The Cancer Imaging Archive (TCIA) with genomic data was selected from 82 patients for radiomic models, including support vector machine (SVM) and logistic regression (LR) models. Furthermore, the nomogram incorporating radiomic signatures was constructed to evaluate its clinical efficacy. BTK was identified as an independent risk factor for HGGs through univariate and multivariate Cox regression analyses. Three radiomic features were selected to construct the SVM and LR models, and the validation set showed area under curve (AUCs) values of 0.711 (95% CI, 0.598-0.824) and 0.736 (95% CI, 0.627-0.844), respectively. The median survival times of the high Rad&#95;score and low-Rad&#95;score groups based on LR model were 15.53 and 23.03 months, respectively. In addition, the total risk score of each patient was used to construct a predictive nomogram, and the AUCs calculated from the corresponding time-dependent ROC curves were 0.533, 0.659, and 0.767 for 1, 3, and 5 years, respectively. BTK is an independent risk factor associated with poor prognosis in patients, and the radiomic model constructed in this study can effectively and non-invasively predict preoperative BTK expression levels and patient prognosis based on T1WI + C., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)