Journal of Neuro-Oncology最新文献

{"title":"MR perfusion characteristics of pseudoprogression in brain tumors treated with immunotherapy - a comparative study with chemo-radiation induced pseudoprogression and radiation necrosis.","authors":"Hongyan Chen, Guirong Tan, Lijuan Zhong, Yichuan Hu, Wenjing Han, Yi Huang, Qiong Liang, Denes Szekeres, Haihui Jiang, Rajnish Bharadwaj, Stephen M Smith, Henry Z Wang, Xiang Liu","doi":"10.1007/s11060-024-04910-0","DOIUrl":"https://doi.org/10.1007/s11060-024-04910-0","url":null,"abstract":"<p><strong>Purpose: </strong>Pseudoprogression is an atypical imaging pattern of response to immunotherapy in patients with brain tumors. MR perfusion studies in this field are limited. The purpose of our study is to compare the perfusion features between pseudoprogression lesions in malignant gliomas and brain metastases treated with immunotherapy (iPsP) and the pseudoprogression after chemo-radiation therapy and radiation necrosis after radiation treatment (ChR-PsP & RN).</p><p><strong>Methods: </strong>We retrospectively reviewed 25 iPsP lesions in 16 brain tumor patients and 48 ChR-PsP & RN lesions in 35 patients. The cerebral blood volume (CBV) of MR dynamic susceptibility contrast (DSC) perfusion weighted imaging (PWI) was analyzed, and the mean and maximal values of the ratio of CBV (rCBV_mean and rCBV_max) of iPsPs and ChR-PsP & RNs were calculated and compared between these two groups using the Mann-Whitney U test. A receiver operating characteristic curve analysis was conducted, and the optimal cutoff of perfusion parameters were determined using the area under the curve, sensitivity, and specificity.</p><p><strong>Results: </strong>The medians of rCBV_mean and rCBV_max in iPsP group were significantly higher (0.94 and 1.39 respectively) than ChR-PsP & RN group (0.67, p < 0.01 and 1.1, p = 0.01 respectively). The rCBV_mean value of 0.69 can differentiate the iPsP from ChR-PsP & RN with the area under the curve of 0.71, sensitivity of 0.72, and specificity of 0.56.</p><p><strong>Conclusion: </strong>These findings may suggest immunotherapy-induced higher perfusion in the iPsP lesions compared to ChR-PsP & RN lesions in primary and metastatic brain tumors.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health-related quality of life in 62 patients with diffuse low-grade glioma during a non-therapeutic and progression-free phase: a cross-sectional study.","authors":"Tiphaine Obara, Marie Blonski, Marie Forest-Dodelin, Fabien Rech, Luc Taillandier","doi":"10.1007/s11060-024-04888-9","DOIUrl":"10.1007/s11060-024-04888-9","url":null,"abstract":"<p><strong>Purpose: </strong>Few studies have evaluated the health-related quality of life (HRQoL) of patients with diffuse low-grade glioma (LGG) during a clinical and radiological monitoring period. We report a cross sectional cohort study of HRQoL in patients with LGG and compare the results with normative population data. We then explore factors associated with HRQoL.</p><p><strong>Methods: </strong>We used the European Organisation for Research and Treatment of Cancer QLQ-C30, BN-20 and the Hospital Anxiety and Depression Scale (HADS) to evaluate HRQoL. Averaged QLQC30 and HADS scores were compared with scores of a normative population. A general linear model multivariate analysis of variance was used to investigate the association between HRQoL and independent factors.</p><p><strong>Results: </strong>A total of 62 patients with LGG completed HRQoL questionnaires. Compared with a normative population, LGG patients reported statistical and clinically significant lower cognitive, emotional, role and social functioning. Fatigue, anxiety, depression and sleep disturbances were frequently reported. Awake surgery and preserved high Karnofsky Performance Status were found to be independent prognostic factors for better global HRQoL, while radiotherapy was associated with worsened HRQoL.</p><p><strong>Conclusion: </strong>Despite a non-therapeutic and progression free phase, LGG patients report noticeable limitations in several HRQoL subscales. Our study highlights the importance of HRQoL assessment not only at diagnosis or during active therapeutic stage. Further studies are needed to develop better adapted tools of HRQoL assessment.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine effects of MEK and BRAF inhibitor therapy in paediatric patients: a tertiary centre experience.","authors":"Arif Hanafi Bin Jalal, Harriet Gunn, Buddhi Gunasekara, Hoong-Wei Gan","doi":"10.1007/s11060-024-04896-9","DOIUrl":"https://doi.org/10.1007/s11060-024-04896-9","url":null,"abstract":"<p><strong>Purpose: </strong>BRAF and MEK inhibitors are used to treat a range of paediatric tumours including low-grade gliomas. The ubiquitous nature of the BRAF/MAPK/MEK pathway means such treatments are not without side effects such as renal tubulopathies and hyperglycaemia. This study aims to describe the endocrine dysfunction observed in a cohort of children treated with BRAF and MEK inhibitors at the largest paediatric centre in the UK utilising these treatments.</p><p><strong>Methods: </strong>Electronic data for patients treated with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) from January 2019 to May 2022 were retrospectively reviewed. Outcomes included diagnosis of glucose dysregulation, the presence of hyponatraemia (< 135 mmol/l) and sodium nadir during treatment.</p><p><strong>Results: </strong>A total of 55 patients were included for analysis. Nine patients had at least one hyponatraemic episode during treatment of whom three had coexisting central diabetes insipidus. A statistically significant difference (p-value = 0.037) with regards to the plasma sodium nadir during treatment was observed between patients with diabetes insipidus (median = 134 (132-137) mmol/l) and patients without (median = 137 (127-141 mmol/l). Six patients were diagnosed with a form of glucose dysregulation (e.g. insulin resistance, type 2 diabetes), of whom four were diagnosed during treatment with dabrafenib, all with hypothalamo-pituitary lesions.</p><p><strong>Conclusion: </strong>Clinicians using such treatments need to be aware of these potential effects, particularly the risk of hyponatraemia in patients with pre-existing central diabetes insipidus and monitor for these accordingly, including performing measurements of sodium and glucose prior to, during and after treatment.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating biomarkers in high-grade gliomas: current insights and future perspectives.","authors":"Suchet Taori, Ahmed Habib, Samuel Adida, Neslihan Nisa Gecici, Nikhil Sharma, Michael Calcaterra, Anthony Tang, Sumaarg Pandya, Arnav Mehra, Hansen Deng, Hayat Elidrissy, Yassine Alami Idrissi, Mohammadreza Amjadzadeh, Pascal O Zinn","doi":"10.1007/s11060-024-04903-z","DOIUrl":"https://doi.org/10.1007/s11060-024-04903-z","url":null,"abstract":"<p><strong>Purpose: </strong>High-grade gliomas (HGG) represent a challenging subset of brain tumors characterized by aggressive nature and poor prognosis. Histopathology remains to be the standard for diagnosis, however, it is invasive, prone to sampling errors, and may not capture the full tumor heterogeneity and evolution over time. In recent years, there has been a growing interest in the potential utility of circulating biomarkers, obtained through minimally-invasive liquid biopsies, providing an opportunity for diagnosis, prognostication, monitoring treatment response and developing targeted therapies.</p><p><strong>Methods: </strong>We have reviewed the literature on circulating biomarkers for HGG, including circulating tumor cells (CTCs), circulating tumor-derived exosomes/extracellular vesicles (ctEVs), circulating tumor-derived DNA (ctDNA), circulating tumor-derived miRNA (ctmiRNA), and circulating tumor-derived proteins.</p><p><strong>Results: </strong>CTCs provide real-time information about tumor characteristics for molecular profiling and monitoring treatment response, yet their low numbers in circulation makes detection challenging. ctEVs carry a range of biomolecules and are easily detectable. However, they are not exclusively released from tumor cells and heterogeneity in their content requires standardized isolation and analysis methods. ctDNA is another promising biomarker with its levels correlating with the disease stage. However, its low concentration in blood requires highly sensitive techniques for identification and differentiation from normal cell-free DNA. ctmiRNA and tumor-derived proteins show promise but are limited by their susceptibility to dilution and lack of specificity in current technology.</p><p><strong>Conclusion: </strong>This review highlights the transformative potential of circulating biomarkers in the management of HGG, with implications for improving patient outcomes, optimizing treatment strategies, and advancing precision oncology in neuro-oncology practice.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary diffuse leptomeningeal glioblastoma: a case report and literature review.","authors":"Mark Willy L Mondia, Rebekka E Hooks, Georgios A Maragkos, Vanessa L Smith, Matthew R McCord, Joseph H Donahue, Eli S Williams, M Beatriz Lopes, David Schiff, Ashok R Asthagiri","doi":"10.1007/s11060-024-04908-8","DOIUrl":"https://doi.org/10.1007/s11060-024-04908-8","url":null,"abstract":"<p><strong>Purpose: </strong>Glioblastoma (GBM) that presents as leptomeningeal disease (LMD) is extremely rare and fatal. Limited data are available regarding incidence, clinical presentation, and management. Prognosis is poor and no treatment is known to improve survival.</p><p><strong>Methods and results: </strong>We present a case report of a 72-year-old female who presented with depressed sensorium, ataxia, and myelopathy. Magnetic resonance imaging (MRI) showed diffuse supratentorial and spinal LMD. There was an absence of any detectable and distinct intraparenchymal lesion on neuroaxis imaging. Biopsy of the Sylvian fissure nodule revealed GBM. Steroid therapy was ineffective for symptom relief. She opted for palliative care and expired shortly after diagnosis.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first reported case of GBM presenting exclusively as LMD without a primary lesion. If systemic imaging techniques do not provide a biopsy target and cerebrospinal fluid (CSF) studies are non-diagnostic, tissue diagnosis from leptomeningeal biopsy is recommended. Palliative chemoradiation or best supportive care are reasonable treatment options.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of failure after stereotactic radiosurgery for brain metastases from small cell lung cancer: outcomes in the immunotherapy era.","authors":"Alexander S Marwaha, Yun Liang, Matthew J Shepard, Alexander Yu, Stephen M Karlovits, Rodney E Wegner","doi":"10.1007/s11060-024-04895-w","DOIUrl":"https://doi.org/10.1007/s11060-024-04895-w","url":null,"abstract":"<p><strong>Purpose/objective(s): </strong>Small cell lung cancer (SCLC) is known to have high rates of development of brain metastases. Standard treatment has been whole brain radiation therapy (WBRT) but the role for more focused treatment and hippocampal avoidance has arisen in the past decade. In addition, with possible penetration of the central nervous system by more modern immunotherapies, the risk of distant failure may be lower. As such, we reviewed patients at our institution treated with stereotactic radiosurgery (SRS) to look at patterns, locations, and predictors of failure in the brain.</p><p><strong>Materials/methods: </strong>A retrospective review and analysis of charts was done on 46 patients treated with SRS (no history of prior WBRT) for their brain metastases from SCLC. Multivariate analysis was used to determine significant prognostic factors influencing survival and local/distant failure. We tracked timing and type of immunotherapy, if any, as well as if patients failed in the hippocampus or required WBRT.</p><p><strong>Results: </strong>There were 46 patients with 97 total brain metastases treated with SRS in this study. Median number of metastases was 2 (1-5). The median dose of radiation was 20 Gy (20-30) in 3 fractions (1-5) for all 97 tumors. 11 patients did not receive immunotherapy, whereas 35 patients had immunotherapy of some sort. Median overall survival (OS) for the entire cohort was 13 months, with a 12 month OS of 59% and 2 year OS of 30%. Cox regression did not reveal any significant predictors of OS, including age, sex, total volume, extracranial disease, KPS, immunotherapy, or number of metastases. 12 month and 24 month local control of disease was 95% and 80%, respectively. There were no significant predictors of local failure including volume, dose, or immunotherapy. 25 of the patients had distant brain failure, with a rate of distant failure of 38% and 64% for 6 and 12 months, respectively. Immunotherapy, number of metastases, total target volume, nor presence of extracranial disease was predictive of distant brain failure. WBRT free survival was also measured and found to be 73% at 1 year. There were no significant predictors for this measure. Lastly, five patients in this cohort showed failure in the hippocampus, where the rate of failure at 6 and 12 months was 16%.</p><p><strong>Conclusion: </strong>Rates of distant brain failure in SCLC patients after SRS remain similar to those of NSCLC patients in the immunotherapy era. We did not show a decrease in distant failure rate based on immunotherapy use. The rate of hippocampal failure was quite low and should provide reassurance that SRS and techniques such as HA-IMRT can be reasonably used in these patients. Ongoing clinical trials will help provide more definitive answers in this arena.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of immunohistochemical staining for H3K27me3 and EZH2 in astrocytoma, IDH-mutant.","authors":"Shumpei Onishi, Fumiyuki Yamasaki, Vishwa Jeet Amatya, Ushio Yonezawa, Akira Taguchi, Iori Ozono, Novita Ikbar Khairunnisa, Yukari Go, Yukio Takeshima, Nobutaka Horie","doi":"10.1007/s11060-024-04897-8","DOIUrl":"https://doi.org/10.1007/s11060-024-04897-8","url":null,"abstract":"<p><strong>Background: </strong>H3 histone 27 lysine (H3K27) trimethylation (H3K27me3), which is catalyzed by enhancer of zeste homolog 2 (EZH2), regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a diagnostic marker for diffuse midline glioma and as a surrogate marker to distinguish posterior fossa ependymoma A and B. However, the clinical significance of the EZH2-H3K27me3 axis in astrocytoma, IDH-mutant has not been reported, prompting this investigation.</p><p><strong>Methods: </strong>Thirty-three patients with astrocytoma, IDH-mutant treated at our institute were included in this study. Immunohistochemistry (IHC) targeting H3K27me3, H3K27M, EZH2, EZH inhibitory protein, IDH1-R132H, p53, ATRX, Ki-67, and MTAP was performed. Kaplan-Meier analysis and Cox regression analysis were performed to analyze the correlations of overall survival (OS) and progression-free survival (PFS) with various factors, including age, World Health Organization (WHO) grade, the extent of resection, and immunohistochemical results.</p><p><strong>Results: </strong>The mean patient age was 40.6 ± 11.0 years. IHC for H3K27me3 was positive in 19 patients and negative in 14 patients. The WHO grade and Ki-67 index were significantly higher in the H3K27me3-positive group (p = 0.004 and p = 0.024, respectively). OS and PFS were significantly shorter in the H3K27me3-positive group (p = 0.002 and p = 0.026, respectively). Furthermore, the H3K27me3 and EZH2 double-positive group was associated with a higher WHO grade and higher Ki-67 index (p = 0.001 and p = 0.024, respectively). In the analysis of patients with WHO grade 2/3, double positivity for H3K27me3 and EZH2 was linked to significantly shorter OS and PFS (p = 0.0053 and p = 0.0048, respectively).</p><p><strong>Conclusion: </strong>Positivity for H3K27me3, especially double positivity for H3K27me3 and EZH2, could be a poor prognostic factor for astrocytoma, IDH-mutant. These results suggest the utility of H3K27me3 and EZH2 as candidate markers for estimating the malignancy of astrocytoma, IDH-mutant.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA-seq reveals diverse molecular signatures associated with Methotrexate resistance in primary central nervous system lymphoma cells.","authors":"Ryosuke Osako, Azusa Hayano, Atsushi Kawaguchi, Ryuya Yamanaka","doi":"10.1007/s11060-024-04893-y","DOIUrl":"10.1007/s11060-024-04893-y","url":null,"abstract":"<p><strong>Purpose: </strong>Methotrexate is one of the most essential single agents in patients with primary central nervous system lymphoma (PCNSL). However, 25-50% result in relapse with a poor prognosis. Therefore, studies on methotrexate resistance are warranted to explore salvage chemotherapy for recurrent PCNSL. Single-cell sequence analysis enables the characterization of novel cell types and provides a precise understanding of cancer biology.</p><p><strong>Methods: </strong>Single-cell sequence analysis of parental and methotrexate-resistant PCNSL cells was performed. We used a Weighted Gene Co-expression Network Analysis to identify groups of significantly connected genes.</p><p><strong>Results: </strong>We identified consensus modules in both the HKBML and TK datasets. HLA-DRβ1, HLA-DQβ1,and SNRPG were hub genes those detected in both datasets revealed by network analysis. Cyclosporine A was selected as the candidate drug for treating methotrexate-resistant cells.</p><p><strong>Conclusion: </strong>The results of the present study characterized the methotrexate resistance-related signaling pathways in cultured PCNSL cells. Overall, these results may account for variations in treatment responses and lead potential novel therapeutic strategies for patients with PCNSL.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TTF-1 negativity in synchronous M1b/M1c wildtype lung adenocarcinoma brain metastases predicts worse survival with increased risk of intracranial progression.","authors":"David Wasilewski, Tommaso Araceli, Philip Bischoff, Anton Früh, Rober Ates, Selin Murad, Niklas Jung, Jan Bukatz, Majd Samman, Katharina Faust, Julia Jünger, Martin Witzenrath, David Horst, Atik Baborie, Arend Koch, David Capper, Frank L Heppner, Helena Radbruch, Markus J Riemenschneider, Nils Ole Schmidt, Peter Vajkoczy, Martin Proescholdt, Julia Onken, Nikolaj Frost","doi":"10.1007/s11060-024-04885-y","DOIUrl":"https://doi.org/10.1007/s11060-024-04885-y","url":null,"abstract":"<p><strong>Background: </strong>Thyroid Transcription Factor-1 (TTF-1) expression in lung adenocarcinoma (LUAD) has been studied for its prognostic value in early-stage and metastatic disease. Its role in brain metastasis remains unexplored. This study investigates the predictive value and association of TTF-1 status with clinicopathological variables in patients with synchronous LUAD brain metastases.</p><p><strong>Material and methods: </strong>In this bicentric retrospective study, 245 patients with newly diagnosed, treatment-naïve brain metastasis undergoing resection were included. Patient data were retrieved from electronic records. Outcomes included overall and progression-free survival. Statistical analysis included Kaplan-Meier estimates and Cox proportional hazards regression.</p><p><strong>Results: </strong>Mean Ki67 index in TTF-1 negative patients was 43% [95% CI 38-48%] compared to 32% [95% CI 29-35%] in TTF-1 positive (TTF-1 +) patients (p < 0.001). Tumor volume was significantly larger in TTF-1 negative (TTF-1-) patients (mean volume 24 mL [95% CI 18-31 mL]) vs. 15 mL [95% CI 12-17 mL] in TTF-1 + patients (padjust = 0.003). Perifocal edema was smaller in TTF-1- patients (mean volume: 58 mL [95% CI 45-70 mL]) vs. 84 mL [95% CI 73-94 mL] in TTF-1 + patients (padjust = 0.077). Tumor and edema volume did not correlate. TTF-1- patients showed worse overall, intracranial, and extracranial progression-free survival. In a multivariable Cox model, positive TTF-1 status was independently associated with improved outcomes. Negative TTF-1 status was associated with increased hazard for intracranial disease progression compared to extracranial progression.</p><p><strong>Conclusion: </strong>In synchronous LUAD brain metastases, TTF-1 negativity reflects an aggressive phenotype with larger proliferation capacity and tumor volume. Future research should explore the underlying cellular and molecular alterations of this phenotype.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal treatment of glioblastoma with multiple lesions - a multi-center retrospective analysis.","authors":"Harald Krenzlin, Dragan Jankovic, Alice Dauth, Felipa Lange, Martin Wetzel, Leon Schmidt, Insa Janssen, Christoph Richter, Marcus Stockinger, Heinz Schmidberger, Marc A Brockmann, Clemens Sommer, Bernhard Meyer, Naureen Keric, Florian Ringel","doi":"10.1007/s11060-024-04810-3","DOIUrl":"10.1007/s11060-024-04810-3","url":null,"abstract":"<p><strong>Objective: </strong>The presence of multiple localizations (ML) in glioblastoma is rare and associated with perceived poor prognosis. The aim of this study is to evaluate the impact of a multimodal treatment on progression-free survival (PFS) and overall survival (OS) in ML glioblastoma.</p><p><strong>Methods: </strong>Patients presenting with CNS WHO grade 4 glioblastoma with ML to 2 major German Departments of Neurosurgery between January 1st, 2008, to December 31st, 2020 were included in this study. Primary outcome parameters were extent of resection (EOR) using the 2021 RANO criteria, progression free- and overall survival.</p><p><strong>Results: </strong>A total of 483 patients with newly diagnosed glioblastoma (CNS WHO grade 4) were assessed. 134 patients presented with ML (72 multifocal (MF), 62 multicentric (MC)). The median PFS and OS did not differ among MC and MF glioblastomas. The EOR was a significant predictor of PFS and OS in ML glioblastoma. complete-, near total-, and subtotal resection significantly prolonged PFS (p < 0.0001) and OS (p < 0.0001) compared to biopsy alone. Standard radiotherapy (p = 0.045) and hypofractionated (p < 0.0001) radiotherapy and adjuvant treatment (Stupp protocol) prolonged PFS (p = 0.0012) and OS (p < 0.0001). In multivariate analysis Karnfosky performance score, EOR, and concomitant adjuvant treatment remained significant factors influencing OS. Propensity score matching of patients with ML and solitary lesion tumors showed similar PFS and OS (p = 0.08).</p><p><strong>Conclusion: </strong>The presented data suggests that glioblastomas with multiple lesions treated with multimodal therapy equal survival rates compared to patients with solitary lesion tumors can be achieved. The results reflect the importance of an equally aggressive maximal treatment effort in this particular and often marginalized group of patients.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"555-566"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}