Neuro-oncology最新文献

{"title":"Do we need dosimetry for the optimization of theranostics in CNS tumors?","authors":"Francesco Cicone, Silvano Gnesin, Giulia Santo, Caroline Stokke, Mirco Bartolomei, Giuseppe Lucio Cascini, Giuseppe Minniti, Giovanni Paganelli, Antoine Verger, Marta Cremonesi","doi":"10.1093/neuonc/noae200","DOIUrl":"10.1093/neuonc/noae200","url":null,"abstract":"<p><p>Radiopharmaceutical theranostic treatments have grown exponentially worldwide, and internal dosimetry has attracted attention and resources. Despite some similarities with chemotherapy, radiopharmaceutical treatments are essentially radiotherapy treatments, as the release of radiation into tissues is the determinant of the observed clinical effects. Therefore, absorbed dose calculations are key to explaining dose-effect correlations and individualizing radiopharmaceutical treatments. The present article introduces the basic principles of internal dosimetry and provides an overview of available loco-regional and systemic radiopharmaceutical treatments for central nervous system (CNS) tumors. The specific characteristics of dosimetry as applied to these treatments are highlighted, along with their limitations and most relevant results. Dosimetry is performed with higher precision and better reproducibility than in the past, and dosimetric data should be systematically collected, as treatment planning and verification may help exploit the full potential of theranostic of CNS tumors.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"S242-S258"},"PeriodicalIF":16.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and conduct of theranostic trials in neuro-oncology: Challenges and opportunities.","authors":"Patrick Y Wen, Matthias Preusser, Nathalie L Albert","doi":"10.1093/neuonc/noae162","DOIUrl":"10.1093/neuonc/noae162","url":null,"abstract":"<p><p>Theranostics is a new treatment modality integrating molecular imaging with targeted radionuclide therapy. Theranostic agents have received regulatory approval for some systemic cancers and have therapeutic potential in neuro-oncology. As clinical trials are developed to evaluate the efficacy of theranostic agents in brain tumors, specific considerations will have to be considered, taking into account lessons learned from previous studies examining other treatment modalities in neuro-oncology. These include the need for molecular imaging or surgical window-of-opportunity studies to confirm adequate passage across the blood-brain barrier, optimize eligibility criteria, and selection of the most appropriate response criteria and endpoints to address issues such as pseudoprogression. This review will discuss some of the issues that should be considered when designing clinical trials for theranostic agents.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"S199-S207"},"PeriodicalIF":16.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted radionuclide therapy for patients with central nervous system metastasis: Overlooked potential?","authors":"Emilie Le Rhun, Nathalie L Albert, Martin Hüllner, Enrico Franceschi, Norbert Galldiks, Philipp Karschnia, Giuseppe Minniti, Tobias Weiss, Matthias Preusser, Benjamin M Ellingson, Michael Weller","doi":"10.1093/neuonc/noae192","DOIUrl":"10.1093/neuonc/noae192","url":null,"abstract":"<p><p>Targeted radionuclide therapy is an emerging therapeutic concept for metastatic cancer that can be considered if a tumor can be delineated by nuclear medicine imaging and also targeted based on the expression of a particular target (thera-nostics). This mode of treatment can also compete with or supplement conventional radiotherapy, for example, if MRI does not fully capture the extent of the disease, including microscopic metastases. Targeted radionuclide therapy for patients with thyroid cancer, with certain somatostatin receptor 2-expressing tumors and with prostate-specific membrane antigen-expressing prostate cancer is approved, and numerous approaches of targeted radionuclide therapy for patients with metastatic cancer are in development (eg, using fibroblast activation protein as a target). Although brain metastases are rare in cancers with approved targeted radionuclide therapies, there is no a priori reason to assume that such treatments would not be effective against brain metastases if the targets are expressed and not shielded by the blood-brain barrier. Here, we discuss the current state of the art and opportunities of targeted radionuclide therapies for patients with brain and leptomeningeal metastases.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"S229-S241"},"PeriodicalIF":16.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted radionuclide therapy for gliomas: Emerging clinical trial landscape.","authors":"Michael Weller, Nathalie L Albert, Norbert Galldiks, Andrea Bink, Matthias Preusser, Erik P Sulman, Valerie Treyer, Patrick Y Wen, Joerg C Tonn, Emilie Le Rhun","doi":"10.1093/neuonc/noae125","DOIUrl":"10.1093/neuonc/noae125","url":null,"abstract":"<p><p>According to the new WHO classification of 2021, gliomas are a heterogeneous group of tumors with very different histology, molecular genetics, and prognoses. In addition to glioblastomas, the most common gliomas, there are also numerous less common gliomas, some of which have a very favorable prognosis. Targeted radionuclide therapy is a therapeutic option that can be attractive if a tumor can be targeted based on its molecular characteristics. It is particularly useful when tumors cannot be completely resected or when conventional imaging does not fully capture the extent of the tumor. Numerous approaches to radionuclide therapy for gliomas are in early development. The most advanced approaches for patients with gliomas in the clinic employ L-type amino acid transporter 1 as an uptake mechanism for radiolabeled amino acids or target somatostatin receptor 2 or gastrin-releasing peptide receptor. Here, we discuss the various target structures of radionuclide therapy in gliomas and provide an outlook for which glioma entities radionuclide therapy could most likely provide a therapeutic alternative.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"S208-S214"},"PeriodicalIF":16.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theranostics and molecular imaging in neuro-oncology: The beginning of a new era.","authors":"Nathalie L Albert, Matthias Preusser","doi":"10.1093/neuonc/noae191","DOIUrl":"10.1093/neuonc/noae191","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"S183-S184"},"PeriodicalIF":16.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical and statistical aspects of subgroup analyses in surgical neuro-oncology: A comprehensive review from the PIONEER Consortium.","authors":"Jasper K W Gerritsen, Philipp Karschnia, Jacob S Young, Martin J van den Bent, Susan M Chang, Timothy R Smith, Brian V Nahed, Jordina Rincon-Torroella, Chetan Bettegowda, Nader Sanai, Sandro M Krieg, Takashi Maruyama, Philippe Schucht, Marike L D Broekman, Joerg-Christian Tonn, Patrick Y Wen, Steven De Vleeschouwer, Arnaud J P E Vincent, Shawn Hervey-Jumper, Mitchel S Berger, Rania A Mekary, Annette M Molinaro","doi":"10.1093/neuonc/noae261","DOIUrl":"https://doi.org/10.1093/neuonc/noae261","url":null,"abstract":"<p><p>Subgroup analyses are essential to generate new hypotheses or to estimate treatment effects in clinically meaningful subgroups of patients. They play an important role in taking the next step towards personalized surgical treatment for brain tumor patients. However, subgroup analyses must be used with consideration and care because they have significant potential risks. Although some recommendations are available on the pearls and pitfalls of these analyses, a comprehensive guide is lacking, especially one focused on surgical neuro-oncology patients. This paper, therefore, reviews and summarizes for the first time comprehensively the practical and statistical considerations that are critical to this field. First, we evaluate the considerations when choosing a study design for surgical neuro-oncology studies and examine those unique to this field. Second, we give an overview of the relevant aspects to interpret subgroup analyses adequately. Third, we discuss the practical and statistical elements necessary to appropriately design and use subgroup analyses. The paper aims to provide an in-depth and complete guide to better understand risk modeling and assist the reader with practical examples of designing, using, and interpreting subgroup analyses.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuro-Oncological Superiority of Supratotal Resection in Lower-Grade Gliomas.","authors":"Alberto L Gallotti, Marco Rossi, Marco Conti Nibali, Tommaso Sciortino, Lorenzo G Gay, Guglielmo Puglisi, Antonella Leonetti, Francesco Bruno, Roberta Rudà, Riccardo Soffietti, Gabriella Cerri, Lorenzo Bello","doi":"10.1093/neuonc/noae264","DOIUrl":"https://doi.org/10.1093/neuonc/noae264","url":null,"abstract":"<p><strong>Background: </strong>Supratotal-Resection (SpTR) is a promising surgical strategy in Lower-grade gliomas (LGGs). SpTR assessment, feasibility and distinctive features, as well as clinical benefit at first and second surgery and on overall-survival must be better characterized. The critical percentage of resection exceeding FLAIR margins to obtain clinical benefit and its impact on long-term functional performance are also undefined.</p><p><strong>Methods: </strong>Included were 704 patients with primary and 439 with recurrent LGGs seen between 2010-2019, who underwent resection with Brain-Mapping-Technique (BMT) aimed at achieving a SpTR without any \"a-priori\" selection. Extent-Of-Resection, evaluated on 3D-FLAIR-MR and categorized according to residual tumor and cavity volume, was associated with Progression-Free-Survival (PFS) and Malignant(M)PFS at first and second surgery, and Overall-Survival by univariate, multivariate and propensity-score analysis. Functional performance was assessed by neuropsychological-NPS evaluation.</p><p><strong>Results: </strong>SpTR evaluation requires volumetric assessment enhanced by brain deformation measurement in parietal tumors; SpTR rate accounts on average for 50.2% and 35.7% at first and second surgery, is higher in grade-2, frontal and temporal locations (at expenses of Total-Resection-TR). Compared to TR, SpTR reduces and postpones first and second recurrences in all molecular subtypes and grades, delays MPFS without difference in rate and prolongs Overall-Survival. A degree of SpTR>120% associates with the lowest recurrence risk. SpTR associates with the best NPS longitudinal course.</p><p><strong>Conclusions: </strong>This study supports feasibility of SpTR in LGGs, its benefit at first and second surgery regardless of molecular subtypes, and on Overall-Survival, significantly reducing recurrence when SpTR>120%; SpTR also associates with the best patients' functional outcome.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to: Intracranial administration of anti-PD-1 and anti-CTLA-4 immune checkpoint-blocking monoclonal antibodies in patients with recurrent high-grade glioma.","authors":"","doi":"10.1093/neuonc/noae256","DOIUrl":"https://doi.org/10.1093/neuonc/noae256","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing a Time-Dependent Therapeutic Strategy using CDK4/6 Inhibitors in an Intracranial ATRT Model.","authors":"Brice Martin, Sergio W Guadix, Rekha Sathian, Madeline Laramee, Abhinav Pandey, Ishani Ray, Amy Wang, Ramana Davuluri, Craig J Thomas, Nadia Dahmane, Mark Souweidane","doi":"10.1093/neuonc/noae262","DOIUrl":"https://doi.org/10.1093/neuonc/noae262","url":null,"abstract":"<p><strong>Background: </strong>Inhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6), crucial for cell cycle regulation, have shown promise in early-stage studies for treating central nervous system (CNS) tumors. However, challenges such as limited CNS penetration, optimal treatment duration, and systemic side effects have impeded their clinical translation for pediatric brain tumors (PBTs).</p><p><strong>Methods: </strong>We evaluated the potency of CDK4/6 inhibitors across various PBTs cell lines, focusing particularly on palbociclib against atypical teratoid rhabdoid tumor (ATRT) with cell viability assays and gene expression analysis. Additionally, we assessed the efficacy and safety of intrathecal (IT) delivery of palbociclib through neurotoxicity and pharmacokinetic studies, along with survival assessments in murine leptomeningeal ATRT models.</p><p><strong>Results: </strong>Palbociclib showed the highest potency across various PBT cells, with extended treatments reducing growth inhibition 50 (GI50) values from the micromolar to nanomolar range. It suppressed critical cell cycle genes (CCNB1, CCNA2, CDK1) in BT-16 ATRT cells. Neurotoxicity (GFAP, CD45, NeuN, Iba1) and pharmacokinetic assays confirmed IT route as a feasible and effective method for delivering palbociclib to the cerebrospinal fluid (CSF), avoiding systemic toxicity and enhancing drug concentration to the brain. Finally, metronomic IT delivery using an osmotic pump (48mg/kg) increased survival in two murine leptomeningeal ATRT models, showcasing its potential as a novel therapy for leptomeningeal tumors.</p><p><strong>Conclusions: </strong>Metronomic IT delivery of palbociclib enhances drug efficacy and safety, improves survival, and offers a promising treatment strategy for PBTs with CSF dissemination.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: \"Ras-mediated modulation of pyruvate dehydrogenase activity regulates mitochondrial reserve capacity and contributes to glioblastoma tumorigenesis\".","authors":"","doi":"10.1093/neuonc/noae156","DOIUrl":"10.1093/neuonc/noae156","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2395"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}