Journal of Neuro-Oncology最新文献

{"title":"Focused ultrasound-mediated enhancement of blood-brain barrier permeability for brain tumor treatment: a systematic review of clinical trials.","authors":"Honglin Zhu, Caitlin Allwin, Monica G Bassous, Antonios N Pouliopoulos","doi":"10.1007/s11060-024-04795-z","DOIUrl":"https://doi.org/10.1007/s11060-024-04795-z","url":null,"abstract":"<p><strong>Purpose: </strong>Brain tumors, particularly glioblastoma multiforme (GBM), present significant prognostic challenges despite multimodal therapies, including surgical resection, chemotherapy, and radiotherapy. One major obstacle is the limited drug delivery across the blood-brain barrier (BBB). Focused ultrasound (FUS) combined with systemically administered microbubbles has emerged as a non-invasive, targeted, and reversible approach to transiently open the BBB, thus enhancing drug delivery. This review examines clinical trials employing BBB opening techniques to optimise pharmacotherapy for brain tumors, evaluates current challenges, and proposes directions for further research.</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed and ClinicalTrials.gov up to November 2023, searching for \"ultrasound\" AND \"brain tumor\". The search yielded 1446 results. After screening by title and abstract, followed by full-text screening (n = 48), 35 studies were included in the analysis.</p><p><strong>Results: </strong>Our analysis includes data from 11 published studies and 24 ongoing trials. The predominant focus of these studies is on glioma, including GMB and astrocytoma. One paper investigated brain metastasis from breast cancer. Evidence indicates that FUS facilitates BBB opening and enhances drug uptake following sonication. Exploration of FUS in the pediatric population is limited, with no published studies and only three ongoing trials dedicated to this demographic.</p><p><strong>Conclusion: </strong>FUS is a promising strategy to safely disrupt the BBB, enabling precise and non-invasive lesion targeting, and enhance drug delivery. However, pharmacokinetic studies are required to quantitatively assess improvements in drug uptake. Most studies are phase I clinical trials, and long-term follow-up investigating patient outcomes is essential to evaluate the clinical benefit of this treatment approach. Further studies involving diverse populations and pathologies will be beneficial.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108296","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":"Initial management of newly diagnosed WHO grade 2-3 adult meningioma following surgery: results from the Dutch Brain Tumour Registry (2016-2021).","authors":"Vincent K Y Ho, Monique M Anten, Anniek Garst, Eelke M Bos, Tom J Snijders, Daniëlle B P Eekers, Tatjana Seute","doi":"10.1007/s11060-024-04730-2","DOIUrl":"https://doi.org/10.1007/s11060-024-04730-2","url":null,"abstract":"<p><strong>Purpose: </strong>Meningiomas classified as grade 2-3 according to the World Health Organisation (WHO) require combined surgery and in most cases radiotherapy (RT). Their initial management was evaluated using the Dutch Brain Tumour Registry.</p><p><strong>Methods: </strong>The study included 393 patients aged ≥ 18 years with newly diagnosed meningioma WHO grade 2-3 between 2016 and 2021. Factors associated with adjuvant RT < 6 months following surgery were identified using logistic regression analyses, thereby accounting for variation between CNS regional tumour boards through mixed-effect modelling. This variation was further assessed by funnel plots for case-mix adjusted ratios of RT across tumour boards. The association with patients' survival at 5 years was evaluated with inverse probability-weighted accelerated failure (Weibull) models. Analyses were performed on multiple imputed datasets (m = 10) to account for missing data.</p><p><strong>Results: </strong>Adjuvant RT was administered to 22.2% (59/266) of patients with WHO grade 2 meningioma following a total resection, to 61.1% (58/95) following a partial resection, and to 68.8% (22/32) of patients with WHO grade 3 meningioma (61.5% after partial and 73.7% after total resection). RT was associated with grade 3, partial resection, bone invasion, and absence of multiple lesions. Management varied across tumour boards for grade 2 meningioma following total resection. Adjuvant RT was associated with survival benefit in case of grade 3 disease (hazard ratio: 0.40, 95%-confidence interval: 0.16-0.95, p = 0.04).</p><p><strong>Conclusion: </strong>This national review revealed variation across CNS regional tumour boards in the management of grade 2 meningioma following total resection, and demonstrated survival benefit of adjuvant RT in grade 3 meningioma.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108297","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":"Blood-tumor barrier in focus - investigation of glioblastoma-induced effects on the blood-brain barrier.","authors":"Sanjana Mathew-Schmitt, Matthias Peindl, Philipp Neundorf, Gudrun Dandekar, Marco Metzger, Vera Nickl, Antje Appelt-Menzel","doi":"10.1007/s11060-024-04760-w","DOIUrl":"https://doi.org/10.1007/s11060-024-04760-w","url":null,"abstract":"<p><strong>Purpose: </strong>Glioblastoma (GBM) is the most prevalent, malignant, primary brain tumor in adults, characterized by limited treatment options, frequent relapse, and short survival after diagnosis. Until now, none of the existing therapy and treatment approaches have proven to be an effective cure. The availability of predictive human blood-tumor barrier (BTB) test systems that can mimic in-vivo pathophysiology of GBM would be of great interest in preclinical research. Here, we present the establishment of a new BTB in-vitro test system combining GBM spheroids and BBB models derived from human induced pluripotent stem cells (hiPSCs).</p><p><strong>Methods: </strong>We co-cultured hiPSC-derived brain capillary endothelial-like cells (iBCECs) with GBM spheroids derived from U87-MG and U373-MG cell lines in a cell culture insert-based format. Spheroids were monitored over 168 hours (h) of culture, characterized for GBM-specific marker expression and treated with standard chemotherapeutics to distinguish inhibitory effects between 2D mono-culture and 3D spheroids. GBM-induced changes on iBCECs barrier integrity were verified via measurement of transendothelial electrical resistance (TEER), immunocytochemical staining of tight junction (TJ) proteins claudin-5 and occludin as well as the glucose transporter-1 (Glut-1). GBM-induced secretion of vascular endothelial growth factor (VEGF) was additionally quantified.</p><p><strong>Results: </strong>Our hypothesis was validated by reduced expression of TJ proteins, occludin and claudin-5 together with significant barrier breakdown in iBCECs after only 24 h of co-culture, demonstrated by reduction in TEER from 1313 ± 265 Ω*cm² to 712 ± 299 Ω*cm² (iBCECs + U87-MG) and 762 ± 316 Ω*cm² (iBCECs + U373-MG). Furthermore, 3D spheroids show more resistance to standard GBM chemotherapeutics in-vitro compared to 2D cultures.</p><p><strong>Conclusions: </strong>We demonstrate the establishment of a simplified, robust in-vitro BTB test system, with potential application in preclinical therapeutic screening and in studying GBM-induced pathological changes at the BBB.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080619","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":"Radiotherapy dosing in intracranial ependymoma using the national cancer database.","authors":"Melanie L Rose, Erika Moen, Bryan Ager, Benjamin Bajaj, Matthew Poppe, Gregory Russo, Torunn I Yock","doi":"10.1007/s11060-024-04805-0","DOIUrl":"https://doi.org/10.1007/s11060-024-04805-0","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the dose-dependent effect of adjuvant radiotherapy on survival for pediatric intracranial ependymomas and explore patient and disease characteristics that experience survival benefit from higher doses.</p><p><strong>Methods: </strong>Data was accessed from the National Cancer Database. Inclusion criteria was comprised of a diagnosis of non-metastatic intracranial ependymoma, World Health Organization (WHO) grade 2 or 3, surgical resection, adjuvant radiotherapy between 4500-6300 cGy, and non-missing survivorship data. Crude and adjusted Cox proportional hazard ratios (HRs) were calculated to estimate the associations of patient, tumor, and treatment characteristics with overall survival (OS). Kaplan-Meier (KM) estimations were used to visualize survival curves for dosing for the general cohort and by subgroups (age, resection extent, and grade).</p><p><strong>Results: </strong>Of the 1154 patients who met inclusion criteria, 405 received ≤ 5400 cGy and 749 received > 5400 cGy. We found no difference in OS crude (0.95, 95% CI 0.72-1.06) or adjusted (0.88, 95% CI 0.46-1.69) HR for those receiving ≤ 5400 cGy. KM curves showed no difference in OS for dosing for the general cohort based on age, surgical extent, and grade. However, there was better OS in those with WHO grade 2 tumors compared to grade 3 regardless of dose received.</p><p><strong>Conclusions: </strong>There was no difference in OS between patients who received ≤ 5400 cGy compared to > 5400 cGy. We found improved OS in those with grade 2 tumors compared to grade 3, however there was no difference in OS based on dose received by tumor grade, age, or resection extent. Limitations in data available prevent exploring other outcomes or toxicity.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080621","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":"Raman and autofluorescence spectroscopy for in situ identification of neoplastic tissue during surgical treatment of brain tumors.","authors":"Ortrud Uckermann, Jonathan Ziegler, Matthias Meinhardt, Sven Richter, Gabriele Schackert, Ilker Y Eyüpoglu, Mido M Hijazi, Dietmar Krex, Tareq A Juratli, Stephan B Sobottka, Roberta Galli","doi":"10.1007/s11060-024-04809-w","DOIUrl":"https://doi.org/10.1007/s11060-024-04809-w","url":null,"abstract":"<p><strong>Purpose: </strong>Raman spectroscopy (RS) is a promising method for brain tumor detection. Near-infrared autofluorescence (AF) acquired during RS provides additional useful information for tumor identification and was investigated in comparison with RS for delineating brain tumors in situ.</p><p><strong>Methods: </strong>Raman spectra were acquired together with AF in situ within the solid tumor and at the tumor border during routine brain tumor surgeries (218 spectra; glioma WHO II-III, n = 6; GBM, n = 10; metastases, n = 10; meningioma, n = 3). Tissue classification for tumor identification in situ was trained on ex vivo data (375 spectra; glioma/GBM patients, n = 20; metastases, n = 11; meningioma, n = 13; and epileptic hippocampi, n = 4).</p><p><strong>Results: </strong>Both in situ and ex vivo data showed that AF intensity in brain tumors was lower than that in border regions and normal brain tissue. Moreover, a positive correlation was observed between the AF intensity and the intensity of the Raman band corresponding to lipids at 1437 cm^- 1, while a negative correlation was found with the intensity of the protein band at 1260 cm^- 1. The classification of in situ AF and RS datasets matched the surgeon's evaluation of tissue type, with correct rates of 0.83 and 0.84, respectively. Similar correct rates were achieved in comparison to histopathology of tissue biopsies resected in selected measurement positions (AF: 0.80, RS: 0.83).</p><p><strong>Conclusions: </strong>Spectroscopy was successfully integrated into existing neurosurgical workflows, and in situ spectroscopic data could be classified based on ex vivo data. RS confirmed its ability to detect brain tumors, while AF emerged as a competitive method for intraoperative tumor delineation.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080622","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":"Amino acid metabolism in glioma: in vivo MR-spectroscopic detection of alanine as a potential biomarker of poor survival in glioma patients.","authors":"Seyma Alcicek, Ulrich Pilatus, Andrei Manzhurtsev, Katharina J Weber, Michael W Ronellenfitsch, Joachim P Steinbach, Elke Hattingen, Katharina J Wenger","doi":"10.1007/s11060-024-04803-2","DOIUrl":"https://doi.org/10.1007/s11060-024-04803-2","url":null,"abstract":"<p><strong>Purpose: </strong>Reprogramming of amino acid metabolism is relevant for initiating and fueling tumor formation and growth. Therefore, there has been growing interest in anticancer therapies targeting amino acid metabolism. While developing personalized therapeutic approaches to glioma, in vivo proton magnetic resonance spectroscopy (MRS) is a valuable tool for non-invasive monitoring of tumor metabolism. Here, we evaluated MRS-detected brain amino acids and myo-inositol as potential diagnostic and prognostic biomarkers in glioma.</p><p><strong>Method: </strong>We measured alanine, glycine, glutamate, glutamine, and myo-inositol in 38 patients with MRI-suspected glioma using short and long echo-time single-voxel PRESS MRS sequences. The detectability of alanine, glycine, and myo-inositol and the (glutamate + glutamine)/total creatine ratio were evaluated against the patients' IDH mutation status, CNS WHO grade, and overall survival.</p><p><strong>Results: </strong>While the detection of alanine and non-detection of myo-inositol significantly correlated with IDH wildtype (p = 0.0008, p = 0.007, respectively) and WHO grade 4 (p = 0.01, p = 0.04, respectively), glycine detection was not significantly associated with either. The ratio of (glutamate + glutamine)/total creatine was significantly higher in WHO grade 4 than in 2 and 3. We found that the overall survival was significantly shorter in glioma patients with alanine detection (p = 0.00002).</p><p><strong>Conclusion: </strong>Focusing on amino acids in MRS can improve its diagnostic and prognostic value in glioma. Alanine, which is visible at long TE even in the presence of lipids, could be a relevant indicator for overall survival.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080618","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":"Biological effective dose as a predictor of local tumor control in stereotactic radiosurgery treated parasellar meningioma patients.","authors":"Ahmed Shaaban, Duy Pham, Salem M Tos, Georgios Mantziaris, David Schlesinger, Jason P Sheehan","doi":"10.1007/s11060-024-04804-1","DOIUrl":"https://doi.org/10.1007/s11060-024-04804-1","url":null,"abstract":"<p><strong>Introduction: </strong>The radio-surgical literature increasingly uses biological effective dose (BED) as a replacement for absorbed dose to analyze outcome of stereotactic radiosurgery (SRS). There are as yet no studies which specifically investigate the association of BED to local tumor control in para-sellar meningioma.</p><p><strong>Methods: </strong>we did a retrospective analysis of patients underwent stereotactic radiosurgery (SRS) for para-sellar meningioma during the period of 1995-2022. Demographic, clinical, SRS parameters, and outcome data were collected. The target margin BED with and without a model for sub-lethal repair was calculated, as well as a ratio of BED at the target margin to the absorbed dose at the target margin. Factors related to local control were further analyzed.</p><p><strong>Results: </strong>The study was comprised of 91 patients, 20 (22.0%) and 71 (78.0%) of whom were male and female, respectively. The median age was 55.0 (interquartile range Q1, Q3:47.5,65.5years). 34 (37%) patients had a resection of their meningioma prior to SRS. The median interval from SRS to last clinical follow up or progression was 89 months. 13 (14.3%) patients were found to have progression. 3-, 5- and 10-years local tumor control were 98%, 92% and 77%, respectively. In cox univariate analysis, the following factors were significant: Number of prior surgical resections (Hazard Ratio [HR] = 1.82, 95% CI = 1.08-3.05, p = 0.024), BED (HR = 0.96, 95% CI = 0.92-1.00, p = 0.03), and BED/margin (HR = 0.44, 95% CI = 0.21-0.92, p = 0.028). A BED threshold above 68 Gy was associated significantly with tumor control (P = 0.04).</p><p><strong>Conclusion: </strong>BED and BED /margin absorbed dose ratio can be predictors of local control after SRS in parasellar meningioma. Optimizing the BED above 68Gy_2.47 may afford better long-term tumor control.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073049","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":"Glioblastoma in the real-world setting: patterns of care and outcome in the Austrian population.","authors":"Andreas Hainfellner, Martin Borkovec, Lukas Seebrecht, Magdalena Neuhauser, Thomas Roetzer-Pejrimovsky, Lisa Greutter, Birgit Surböck, Andrea Hager-Seifert, Doris Gorka-Vom Hof, Tadeja Urbanic-Purkart, Martin Stultschnig, Clemens Cijan, Franz Würtz, Bernadette Calabek-Wohinz, Josef Pichler, Isolde Höllmüller, Annette Leibetseder, Serge Weis, Waltraud Kleindienst, Michael Seiberl, Lara Bieler, Constantin Hecker, Christoph Schwartz, Sarah Iglseder, Johanna Heugenhauser, Martha Nowosielski, Claudius Thomé, Patrizia Moser, Markus Hoffermann, Karin Loibnegger, Karin Dieckmann, Matthias Tomschik, Georg Widhalm, Karl Rössler, Christine Marosi, Adelheid Wöhrer, Johannes A Hainfellner, Stefan Oberndorfer","doi":"10.1007/s11060-024-04808-x","DOIUrl":"https://doi.org/10.1007/s11060-024-04808-x","url":null,"abstract":"<p><strong>Purpose: </strong>We present results of a retrospective population-based investigation of patterns of care and outcome of glioblastoma patients in Austria.</p><p><strong>Patients and methods: </strong>In this nation-wide cooperative project, all Austrian glioblastoma patients newly diagnosed between 2014 and 2018 and registered in the ABTR-SANOnet database were included. Histological typing used criteria of the WHO classification of CNS tumors, 4th edition 2016. Patterns of care were assessed, and all patients were followed until the end of 2019.</p><p><strong>Results: </strong>1,420 adult glioblastoma cases were identified. 813 (57.3%) patients were male and 607 (42.7%) female. Median age at diagnosis was 64 years (range: 18-88). Median overall survival (OS) was 11.6 months in the total cohort and 10.9 months in patients with proven IDH-wildtype. Median OS in the patient group ≤ 65 years receiving postoperative standard of care therapy was 16.1 months. In the patient group > 65 years with postoperative therapy, median OS was 11.2 months. Follow-up ≥ 5 years identified 13/264 (4.9%) long-term survivors. Brain tumor surgery frequently was assisted by 5-aminolevulinic acid (5-ALA) fluorescence (up to 55%). Postoperative treatment was initiated around one month after surgery (median: 31 days) following standardized protocols in 1,041/1,420 (73.3%) cases. In 830 patients (58.5%), concomitant radiochemotherapy was started according to the established standard of care. Treatment in case of progressive disease was considerably variable. 170/1,420 patients (12.0%) underwent a second surgical procedure, 467 (33.0%) received systemic treatment after progression, and 173 (12.2%) were re-irradiated.</p><p><strong>Conclusion: </strong>Our data illustrate and confirm nation-wide translation of effective standard of care to Austrian glioblastoma patients in the recent past. In the case of progressive disease, highly variable therapeutic approaches were used, most frequently accompanied by anti-angiogenic therapy. Long-term survival was observed in a minor proportion of mostly younger patients who typically had gross total tumor resection, a favorable postoperative ECOG score, and standard of care therapy.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080620","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":"Stereotactic radiosurgery for brain metastases from human epidermal receptor 2 positive breast Cancer: an international, multi-center study.","authors":"Stylianos Pikis, Georgios Mantziaris, Maria Protopapa, Salem M Tos, Roman O Kowalchuk, Richard Blake Ross, Chad G Rusthoven, Manjul Tripathi, Anne-Marie Langlois, David Mathieu, Cheng-Chia Lee, Huai-Che Yang, Selcuk Peker, Yavuz Samanci, Michael Yu Zhang, Steve E Braunstein, Zhishuo Wei, Ajay Niranjan, Dade L Lunsford, Jason Sheehan","doi":"10.1007/s11060-024-04775-3","DOIUrl":"https://doi.org/10.1007/s11060-024-04775-3","url":null,"abstract":"<p><strong>Purpose: </strong>To report patient outcomes and local tumor control rates in a cohort of patients with biopsy-proven HER-2 positive breast cancer treated with stereotactic radiosurgery (SRS) for brain metastases (BM).</p><p><strong>Methods: </strong>This international, retrospective, multicenter study, included 195 female patients with 1706 SRS-treated BM. Radiologic and clinical outcomes after SRS were determined and prognostic factors identified.</p><p><strong>Results: </strong>At SRS, median patient age was 55 years [interquartile range (IQR) 47.6-62.0], and 156 (80%) patients had KPS ≥ 80. The median tumor volume was 0.1 cm³ (IQR 0.1-0.5) and the median prescription dose was 16 Gy (IQR 16-18). Local tumor control (LTC) rate was 98%, 94%, 93%, 90%, and 88% at six-, 12-, 24-, 36- and 60-months post-SRS, respectively. On multivariate analysis, tumor volume (p = < 0.001) and concurrent pertuzumab (p = 0.02) improved LTC. Overall survival (OS) rates at six-, 12-, 24-, 36-, 48-, and 60-months were 90%, 69%, 46%, 27%, 22%, and 18%, respectively. Concurrent pertuzumab improved OS (p = 0.032). In this patient subgroup, GPA scores ≥ 2.5 (p = 0.038 and p = 0.003) and rare primary tumor histologies (p = 0.01) were associated with increased and decreased OS, respectively. Asymptomatic adverse radiation events (ARE) occurred in 27 (14.0%) and symptomatic ARE in five (2.6%) patients. Invasive lobular carcinoma primary (p = 0.042) and concurrent pertuzumab (p < 0.001) conferred an increased risk for overall but not for symptomatic ARE.</p><p><strong>Conclusion: </strong>SRS affords effective LTC for selected patients with BM from HER-2 positive breast cancer. Concurrent pertuzumab improved LTC and OS but at the same time increased the risk for overall, but not symptomatic, ARE.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080623","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":"Pulsed focused ultrasound alters the proteomic profile of the tumor microenvironment in a syngeneic mouse model of glioblastoma.","authors":"Hui Chen, Dimpy Koul, Yanrong Zhang, Sara Natasha Ghobadi, Yayu Zhu, Qingyi Hou, Edwin Chang, Frezghi G Habte, Ramasamy Paulmurugan, Sabbir Khan, Yuqi Zheng, Manuel B Graeber, Iris Herschmann, Kevin S Lee, Max Wintermark","doi":"10.1007/s11060-024-04801-4","DOIUrl":"https://doi.org/10.1007/s11060-024-04801-4","url":null,"abstract":"<p><strong>Purpose: </strong>Glioblastoma (GBM), a lethal primary adult malignancy, is difficult to treat because of the restrictive nature of the blood-brain barrier (BBB), blood-tumor barrier (BTB), and the immunosuppressive tumor microenvironment (TME). Since pulsed focused ultrasound (pFUS) is currently used to improve therapeutic deliveries across these barriers, this study aims to characterize the impact of pFUS on the TME proteomics upon opening the BBB and BTB.</p><p><strong>Methods: </strong>We utilized MRI-guided, pFUS with ultrasound contrast microbubbles (termed 'pFUS' herein) to selectively and transiently open the BBB and BTB investigating proteomic modifications in the TME. Utilizing an orthotopically-allografted mouse GL26 GBM model (Ccr2RFP/wt - Cx3cr1GFP/wt), pFUS's effect on glioma proteomics was evaluated using a Luminex 48-plex assay.</p><p><strong>Results: </strong>pFUS treated tumors exhibited increases in pro-inflammatory cytokines, chemokines, and trophic factors (CCTFs). Proteomic changes in tumors tend to peak at 24 h after single pFUS session (1x), with levels then plateauing or declining over the subsequent 24 h. Tumors receiving three pFUS sessions (3x) showed elevated CCTFs levels peaking as early as 6 h after the third session.</p><p><strong>Conclusions: </strong>pFUS together with microbubbles induces a sterile inflammatory response in the TME of a mouse GBM tumor. Moreover, this proinflammatory shift can be sustained and perhaps primed for more rapid responses upon multiple sessions of pFUS. These findings raise the intriguing potential that pFUS-induced BBB and BTB opening may not only be effective in facilitating the therapeutic agent delivery, but also be harnessed to modify the TME to assist immunotherapies in overcoming immune evasion in GBM.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046823","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}