GRIK1 promotes glioblastoma malignancy and is a novel prognostic factor of poor prognosis.

Primary tumors of the central nervous system (CNS) are classified into over 100 different histological types. The most common type of glioma is derived from astrocytes, and the most invasive glioblastoma (WHO IV) accounts for over 57% of these tumors. Glioblastoma (GBM) is the most common and fatal tumor of the CNS, with strong growth and invasion capabilities, which makes complete surgical resection almost impossible. Despite various treatment methods such as surgery, radiotherapy, and chemotherapy, glioma is still an incurable disease, and the median survival time of patients with GBM is shorter than 15 months. Thus, molecular mechanisms of GBM characteristic invasive growth need to be clarified to improve the poor prognosis. Glutamate ionotropic receptor kainate type subunit 1 (GRIK1) is essential for brain function and is involved in many mental and neurological diseases. However, GRIK1's pathogenic roles and mechanisms in GBM are still unknown. Single-nuclear RNA sequencing of primary and recurrent GBM samples revealed that GRIK1 expression was noticeably higher in the recurrent samples. Moreover, immunohistochemical staining of an array of GBM samples showed that high levels of GRIK1 correlated with poor prognosis of GBM, consistent with The Cancer Genome Atlas database. Knockdown of GRIK1 retarded GBM cells growth, migration, and invasion. Taken together, these findings show that GRIK1 is a unique and important component in the development of GBM and may be considered as a biomarker for the diagnosis and therapy in individuals with GBM.

Evolution of RANO in Assessing Brain Tumour Outcomes.

Assessing treatment response is extremely important in management of brain tumours. Response assessment in neuro-oncology (RANO) was introduced in 2008 for the purpose of making recommendations for it by addressing and countering the limitations in previously reported response criteriae. Subsequently, multiple RANO working groups have been formed to cater to different tumour types and to update their previous recommendations to counter the limitations in their criteria. Herein we have a summarized list of RANO criteria for adult brain tumours.

Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases.

Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.

Identification of genetic modifiers enhancing B7-H3-targeting CAR T cell therapy against glioblastoma through large-scale CRISPRi screening.

BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Current treatment options are limited and often ineffective. CAR T cell therapy has shown success in treating hematologic malignancies, and there is growing interest in its potential application in solid tumors, including GBM. However, current CAR T therapy lacks clinical efficacy against GBM due to tumor-related resistance mechanisms and CAR T cell deficiencies. Therefore, there is a need to improve CAR T cell therapy efficacy in GBM. METHODS: We conducted large-scale CRISPR interference (CRISPRi) screens in GBM cell line U87 MG cells co-cultured with B7-H3 targeting CAR T cells to identify genetic modifiers that can enhance CAR T cell-mediated tumor killing. Flow cytometry-based tumor killing assay and CAR T cell activation assay were performed to validate screening hits. Bioinformatic analyses on bulk and single-cell RNA sequencing data and the TCGA database were employed to elucidate the mechanism underlying enhanced CAR T efficacy upon knocking down the selected screening hits in U87 MG cells. RESULTS: We established B7-H3 as a targetable antigen for CAR T therapy in GBM. Through large-scale CRISPRi screening, we discovered genetic modifiers in GBM cells, including ARPC4, PI4KA, ATP6V1A, UBA1, and NDUFV1, that regulated the efficacy of CAR T cell-mediated tumor killing. Furthermore, we discovered that TNFSF15 was upregulated in both ARPC4 and NDUFV1 knockdown GBM cells and revealed an immunostimulatory role of TNFSF15 in modulating tumor-CAR T interaction to enhance CAR T cell efficacy. CONCLUSIONS: Our study highlights the power of CRISPR-based genetic screening in investigating tumor-CAR T interaction and identifies potential druggable targets in tumor cells that confer resistance to CAR T cell killing. Furthermore, we devised targeted strategies that synergize with CAR T therapy against GBM. These findings shed light on the development of novel combinatorial strategies for effective immunotherapy of GBM and other solid tumors.

[A Case of Five Years Recurrence-Free Survival after Successful Multidisciplinary Treatment for Simultaneous Brain Metastasis and Heterochronic Small Intestinal Metastasis from Lung Cancer].

The patient was a 54-year-old male at the time of initial examination. He was aware of numbness and weakness in the left hemisphere of his body and came to see the hospital. He was diagnosed with brain metastasis of lung cancer and started treatment(cT2N0M1[Brain]). He underwent gamma knife for the head lesion and nivolumab for the lung lesion. The patient's lesions shrank with the success of the medical treatment, but recurred with small intestinal metastasis. He underwent a partial resection of the small intestine and was treated again with nivolumab, which resulted in a complete response. He is currently alive without recurrence. We have experienced a very rare case of recurrence-free survival after treatment for brain metastasis and small intestinal metastasis of lung cancer.

NOP14 as a Potential Predictor of Adult-Type Diffuse Glioma Prognosis and Immunotherapy, is Related to Cell Migration, Proliferation, and CD8+T Cell Infiltration.

BACKGROUND: World Health Organization (WHO) grade 4 adult-type diffuse glioma is the most malignant primary tumor of the brain. Nucleolar protein 14 (NOP14) is recognized to contribute significantly to the assembly of small ribosomal subunits. However, the specific involvement of NOP14 in diverse cancers remains poorly understood, particularly its role in adult-type diffuse glioma, which has yet to be elucidated. METHODS: A total of 20 adult-type diffuse glioma samples with varying WHO stages were collected. The protein level of NOP14 was detected using immunohistochemistry. Additionally, NOP14 expression in LN229 and U251 cell lines and collected clinical tissue samples was quantified using the Western blot technique. Furthermore, the correlation between NOP14 and clinicopathological features, survival rates, matrix and immune scores, and immune components was investigated using data from the Cancer Gene Atlas database. RESULTS: NOP14 exhibited high expression in adult-type diffuse glioma patients, with the highest expression observed in the LN229 cell line. Moreover, elevated NOP14 expression was significantly correlated with poorer overall survival and demonstrated an association with unfavorable pathological features in a cohort of 703 glioblastoma (GBM) patients. Evidence of a connection between NOP14 and the tumor microenvironment was presented. Elevated NOP14 was linked to the infiltration of CD8+T cell and factors related to epithelial-mesenchymal transition. In in vitro assay, NOP14 was capable of suppressing adult-type diffuse glioma cell invasion and metastasis. CONCLUSIONS: NOP14 holds great promise as a candidate biomarker for detecting prognostic, molecular, and immune signatures of adult-type diffuse glioma.

Chat-GPT on brain tumors: An examination of Artificial Intelligence/Machine Learning's ability to provide diagnoses and treatment plans for example neuro-oncology cases.

OBJECTIVE: Assess the capabilities of ChatGPT-3.5 and 4 to provide accurate diagnoses, treatment options, and treatment plans for brain tumors in example neuro-oncology cases. METHODS: ChatGPT-3.5 and 4 were provided with twenty example neuro-oncology cases of brain tumors, all selected from medical textbooks. The artificial intelligence programs were asked to give a diagnosis, treatment option, and treatment plan for each of these twenty example cases. Team members first determined in which cases ChatGPT-3.5 and 4 provided the correct diagnosis or treatment plan. Twenty neurosurgeons from the researchers' institution then independently rated the diagnoses, treatment options, and treatment plans provided by both artificial intelligence programs for each of the twenty example cases, on a scale of one to ten, with ten being the highest score. To determine whether the difference between the scores of ChatGPT-3.5 and 4 was statistically significant, a paired t-test was conducted for the average scores given to the programs for each example case. RESULTS: In the initial analysis of correct responses, ChatGPT-4 had an accuracy of 85% for its diagnoses of example brain tumors and an accuracy of 75% for its provided treatment plans, while ChatGPT-3.5 only had an accuracy of 65% and 10%, respectively. The average scores given by the twenty independent neurosurgeons to ChatGPT-4 for its accuracy of diagnosis, provided treatment options, and provided treatment plan were 8.3, 8.4, and 8.5 out of 10, respectively, while ChatGPT-3.5's average scores for these categories of assessment were 5.9, 5.7, and 5.7. These differences in average score are statistically significant on a paired t-test, with a p-value of less than 0.001 for each difference. CONCLUSIONS: ChatGPT-4 demonstrates great promise as a diagnostic tool for brain tumors in neuro-oncology, as attested to by the program's performance in this study and its assessment by surveyed neurosurgeon reviewers.

Clinical diagnosis and management of multiple cerebral ring-enhancing lesions-study of 50 patients at a tertiary healthcare center.

AIM OF THE STUDY: Multiple ring-enhancing lesions are commonly experienced group of brain pathologies which we come across in day-to-day practice. Clinical symptoms in these lesions are quite non-specific, and hence, it is difficult to reach a final diagnosis. However, these lesions have a varied group of differential diagnosis and it is sometimes difficult to have an accurate diagnosis on conventional MRI. This article was written with the objective of discussing the demographical study and etiology, clinical diagnosis and management for these patients. MATERIALS AND METHODS: It is a prospective study carried out at the Department of Neurosurgery, Dr. D Y Patil Medical College and Hospital, Pune, from September 2019 to August 2022 and included 50 patients who presented to us multiple ring-enhancing brain lesions. RESULTS: In our study, 50 patients between age (1-70 years) with multiple ring-enhancing lesions were analyzed. Majority of the patients were between age group 30-39 years. Males (76%) were majority in our study than females (24%). Most common pathology was primary neoplasm (glioma) and metastasis, followed by nine patients of pyogenic abscess and tuberculosis each. Neurocysticercosis was seen in eight patients and three patients were diagnosed with CNS lymphoma. Most of our patients presented with headache (38 patients) and a subset of patients had associated seizures (28 patients). Two patients with primary neoplasm were diagnosed to have WHO grade 3 glioma and seven patients were diagnosed to have WHO grade 4 glioma. Glioblastoma multiforme presented as multifocal and multicentric lesions. Among the patients with primary neoplasm, three patients underwent stereotactic biopsy for diagnosis and the rest of seven patients underwent maximum safe resection followed by chemotherapy and radiotherapy. Ten patients were diagnosed with metastatic lesions, among them six patients underwent stereotactic biopsy for histopathological diagnosis and immunohistochemistry, and rest of the patients were managed on the basis of the primary lesion. Five patients were immune-compromised, among them two patients presented with abscess and three patients presented with primary neoplastic lesion. Thirty-six patients underwent biopsy, among them seven patients underwent frameless, seven patients underwent frame stereotactic biopsy, and the rest 22 patients underwent excision biopsy. CONCLUSION: Multiple ring-enhancing lesions of brain pose a challenge in terms of achieving an accurate diagnosis and planning further treatment. It is of utmost importance to have a diagnosis in mind based on radiological investigations, so that surgical intervention can be planned accordingly be it by invasive or minimal invasive techniques. An idea toward the diagnosis also helps in prognosticating these patients which could avoid costly whole-body scans and unnecessary surgical intervention.

Methods behind oncolytic virus-based DC vaccines in cancer: Toward a multiphase combined treatment strategy for Glioblastoma (GBM) patients.

Glioblastoma (GBM) remains an orphan cancer disease with poor outcome. Novel treatment strategies are needed. Immunotherapy has several modes of action. The addition of active specific immunotherapy with dendritic cell vaccines resulted in improved overall survival of patients. Integration of DC vaccination within the first-line combined treatment became a challenge, and immunogenic cell death immunotherapy during chemotherapy was introduced. We used a retrospective analysis using real world data to evaluate the complex combined treatment, which included individualized multimodal immunotherapy during and after standard of care, and which required adaptations during treatment, and found a further improvement of overall survival. We also discuss the use of real world data as evidence. Novel strategies to move the field of individualized multimodal immunotherapy forward for GBM patients are reviewed.

Novel prognostic biomarker TBC1D1 is associated with immunotherapy resistance in gliomas.

Background: Glioma, an aggressive brain tumor, poses a challenge in understanding the mechanisms of treatment resistance, despite promising results from immunotherapy. Methods: We identified genes associated with immunotherapy resistance through an analysis of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. Subsequently, qRT-PCR and western blot analyses were conducted to measure the mRNA and protein levels of TBC1 Domain Family Member 1 (TBC1D1), respectively. Additionally, Gene Set Enrichment Analysis (GSEA) was employed to reveal relevant signaling pathways, and the expression of TBC1D1 in immune cells was analyzed using single-cell RNA sequencing (scRNA-seq) data from GEO database. Tumor Immune Dysfunction and Exclusion (TIDE) database was utilized to assess T-cell function, while Tumor Immunotherapy Gene Expression Resource (TIGER) database was employed to evaluate immunotherapy resistance in relation to TBC1D1. Furthermore, the predictive performance of molecules on prognosis was assessed using Kaplan-Meier plots, nomograms, and ROC curves. Results: The levels of TBC1D1 were significantly elevated in tumor tissue from glioma patients. Furthermore, high TBC1D1 expression was observed in macrophages compared to other cells, which negatively impacted T cell function, impaired immunotherapy response, promoted treatment tolerance, and led to poor prognosis. Inhibition of TBC1D1 was found to potentially synergistically enhance the efficacy of immunotherapy and prolong the survival of cancer patients with gliomas. Conclusion: Heightened expression of TBC1D1 may facilitate an immunosuppressive microenvironment and predict a poor prognosis. Blocking TBC1D1 could minimize immunotherapy resistance in cancer patients with gliomas.

OH2 oncolytic virus: A novel approach to glioblastoma intervention through direct targeting of tumor cells and augmentation of anti-tumor immune responses.

Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4+ and CD8+ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.

Comparison of ASL and DSC perfusion methods in the evaluation of response to treatment in patients with a history of treatment for malignant brain tumor.

OBJECTIVE: Perfusion MRI is of great benefit in the post-treatment evaluation of brain tumors. Interestingly, dynamic susceptibility contrast-enhanced (DSC) perfusion has taken its place in routine examination for this purpose. The use of arterial spin labeling (ASL), a perfusion technique that does not require exogenous contrast material injection, has gained popularity in recent years. The aim of the study was to compare two different perfusion techniques, ASL and DSC, using qualitative and quantitative measurements and to investigate the diagnostic effectiveness of both. The fact that the number of patients is higher than in studies conducted with 3D pseudo-continious ASL (pCASL), the study group is heterogeneous as it consists of patients with both metastases and glial tumors, the use of 3D Turbo Gradient Spin Echo (TGSE), and the inclusion of visual (qualitative) assessment make our study unique. METHODS: Ninety patients, who were treated for malignant brain tumor, were enrolled in the retrospective study. DSC Cerebral Blood Volume (CBV), Cerebral Blood Flow (CBF) and ASL CBF maps of each case were obtained. In qualitative analysis, the lesions of the cases were visually classified as treatment-related changes (TRC) and relapse/residual mass (RRT). In the quantitative analysis, three regions of interest (ROI) measurements were taken from each case. The average of these measurements was compared with the ROI taken from the contralateral white matter and normalized values (n) were obtained. These normalized values were compared across events. RESULTS: Uncorrected DSC normalized CBV (nCBV), DSC normalized CBF (nCBF) and ASL nCBF values of RRT cases were higher than those of TRC cases (p < 0.001). DSC nCBV values were correlated with DSC nCBF (r: 0.94, p < 0.001) and correlated with ASL nCBF (r: 0.75, p < 0.001). Similarly, ASL nCBF was positively correlated with DSC nCBF (r: 0.79 p < 0.01). When the ROC curve parameters were evaluated, the cut-off values were determined as 1.211 for DSC nCBV (AUC: 0.95, 93% sensitivity, 82% specificity), 0.896 for DSC nCBF (AUC; 0.95, 93% sensitivity, 82% specificity), and 0.829 for ASL nCBF (AUC: 0.84, 78% sensitivity, 75% specificity). For qualitative evaluation (visual evaluation), inter-observer agreement was found to be good for ASL CBF (0.714), good for DSC CBF (0.790), and excellent for DSC CBV (0.822). Intra-observer agreement was also evaluated. For the first observer, good agreement was found in ASL CBF (0.626, 70% sensitive, 93% specific), in DSC CBF (0.713, 76% sensitive, 95% specific), and in DSC CBV (0.755, 87% sensitive - 88% specific). In the second observer, moderate agreement was found in ASL CBF (0.584, 61% sensitive, 97% specific) and DSC CBF (0.649, 65% sensitive, 100% specific), and excellent agreement in DSC CBV (0.800, 89% sensitive, 90% specific). CONCLUSION: It was observed that uncorrected DSC nCBV, DSC nCBF and ASL nCBF values were well correlated with each other. In qualitative evaluation, inter-observer and intra-observer agreement was higher in DSC CBV than DSC CBF and ASL CBF. In addition, DSC CBV is found more sensitive, ASL CBF and DSC CBF are found more specific for both observers. From a diagnostic perspective, all three parameters DSC CBV, DSC CBF and ASL CBF can be used, but it was observed that the highest rate belonged to DSC CBV.

Local and Systemic Management Options for Melanoma Brain Metastases.

ABSTRACT: Development of brain metastasis is one of the most serious complications of advanced melanoma, carrying a significant burden of morbidity and mortality. Although advances in local treatment modalities such as stereotactic radiosurgery and breakthrough systemic therapies including immunotherapy and targeted therapies have improved the outcomes of patients with metastatic melanoma, management of patients with melanoma brain metastases (MBMs) remains challenging. Notably, patients with MBMs have historically been excluded from clinical trials, limiting insights into their specific treatment responses. Encouragingly, a growing body of evidence shows the potential of systemic therapies to yield durable intracranial responses in these patients, highlighting the need for inclusion of patients with MBMs in future clinical trials. This is pivotal for expediting the advancement of novel therapies tailored to this distinct patient population. In this review, we will highlight the evolving landscape of MBM management, focusing on local and systemic treatment strategies.

[The importance and areas of modern supportive and early integrated palliative care in the treatment of brain tumor patients]. / A korszeru szupportív ellátás és az integrált korai palliatív gondozás jelentosége és fontosabb területei agydaganatos betegek kezelése során.

During the care of brain tumor patients, supportive care and palliation are carried out in an individualized manner, accompanied by adequate communication, in a multidisciplinary professional environment. In the case of brain tumor patients, the burden of symptoms resulting from the progression of the disease and the complications of treatments occur in a particularly high proportion. The supportive care of patients in a modern approach covers the targeted treatment of physical and psychosocial problems and also includes integrated palliation. Palliative care is a form of care that can be used in addition to curative therapies, and it is advisable and necessary to introduce it as early as possible among brain tumor patients due to the significant deterioration of the quality of life. Dealing with seriously ill patients on a daily basis is also an emotional burden for the professional staff, and carries the risk of burnout. The support of the staff and family members, as well as the issues of adequate communication, are also part of the scope of the supportive care approach.

Advancing glioblastoma treatment by targeting metabolism.

Alterations in cellular metabolism are important hallmarks of glioblastoma(GBM). Metabolic reprogramming is a critical feature as it meets the higher nutritional demand of tumor cells, including proliferation, growth, and survival. Many genes, proteins, and metabolites associated with GBM metabolism reprogramming have been found to be aberrantly expressed, which may provide potential targets for cancer treatment. Therefore, it is becoming increasingly important to explore the role of internal and external factors in metabolic regulation in order to identify more precise therapeutic targets and diagnostic markers for GBM. In this review, we define the metabolic characteristics of GBM, investigate metabolic specificities such as targetable vulnerabilities and therapeutic resistance, as well as present current efforts to target GBM metabolism to improve the standard of care.

Prognosis of glioblastoma patients improves significantly over time interrogating historical controls.

BACKGROUND: Glioblastoma (GBM) is the most common devastating primary brain cancer in adults. In our clinical practice, median overall survival (mOS) of GBM patients seems increasing over time. METHODS: To address this observation, we have retrospectively analyzed the prognosis of 722 newly diagnosed GBM patients, aged below 70, in good clinical conditions (i.e. Karnofsky Performance Status -KPS- above 70%) and treated in our department according to the standard of care (SOC) between 2005 and 2018. Patients were divided into two groups according to the year of diagnosis (group 1: from 2005 to 2012; group 2: from 2013 to 2018). RESULTS: Characteristics of patients and tumors of both groups were very similar regarding confounding factors (age, KPS, MGMT promoter methylation status and treatments). Follow-up time was fixed at 24 months to ensure comparable survival times between both groups. Group 1 patients had a mOS of 19 months ([17.3-21.3]) while mOS of group 2 patients was not reached. The recent period of diagnosis was significantly associated with a longer mOS in univariate analysis (HR=0.64, 95% CI [0.51 - 0.81]), p < 0.001). Multivariate Cox analysis showed that the period of diagnosis remained significantly prognostic after adjustment on confounding factors (adjusted Hazard Ratio (aHR) 0.49, 95% CI [0.36-0.67], p < 0.001). CONCLUSION: This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.

Palliative care for children with central nervous system tumors: results of a Spanish multicenter study

Background Brain tumors represent the most common cause of cancer-related death in children. Few studies concerning the palliative phase in children with brain tumors are available. Objectives (i) To describe the palliative phase in children with brain tumors; (ii) to determine whether the use of palliative sedation (PS) depends on the place of death, the age of the patient, or if they received specific palliative care (PC). Methods Retrospective multicenter study between 2010 and 2021, including children from one month to 18 years, who had died of a brain tumor. Results 228 patients (59.2% male) from 10 Spanish institutions were included. Median age at diagnosis was 5 years (IQR 2–9) and median age at death was 7 years (IQR 4–11). The most frequent tumors were medulloblastoma (25.4%) and diffuse intrinsic pontine glioma (DIPG) (24.1%). Median number of antineoplastic regimens were 2 (range 0–5 regimens). During palliative phase, 52.2% of the patients were attended by PC teams, while 47.8% were cared exclusively by pediatric oncology teams. Most common concerns included motor deficit (93.4%) and asthenia (87.5%) and communication disorders (89.8%). Most frequently prescribed supportive drugs were antiemetics (83.6%), opioids (81.6%), and dexamethasone (78.5%). PS was administered to 48.7% patients. Most of them died in the hospital (85.6%), while patients who died at home required PS less frequently (14.4%) (p = .01). Conclusion Children dying from CNS tumors have specific needs during palliative phase. The optimal indication of PS depended on the center experience although, in our series, it was also influenced by the place of death (AU)