Neuro-oncology最新文献

{"title":"Corrigendum to: Reevaluating the imaging definition of tumor progression: perfusion MRI quantifies recurrent glioblastoma tumor fraction, pseudoprogression, and radiation necrosis to predict survival.","authors":"","doi":"10.1093/neuonc/noae244","DOIUrl":"https://doi.org/10.1093/neuonc/noae244","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807573","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":"The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma.","authors":"Matthew McCord, Thomas Sears, Wenxia Wang, Rahul Chaliparambil, Shejuan An, Jann Sarkaria, C David James, Bruce Ruggeri, Susan Gueble, Ranjit Bindra, Craig Horbinski","doi":"10.1093/neuonc/noae257","DOIUrl":"https://doi.org/10.1093/neuonc/noae257","url":null,"abstract":"<p><strong>Background: </strong>Acquired resistance to temozolomide (TMZ) chemotherapy due to DNA mismatch repair (MMR) enzyme deficiency is a barrier to improving outcomes for IDH wild-type glioblastoma (GBM) patients. KL-50 is a new imidazotetrazine-based therapeutic designed to induce DNA interstrand cross links, and subsequent double-stranded breaks, in an MMR-independent manner in cells with O-6-Methylguanine-DNA Methyltransferase (MGMT) deficiency. Previous research showed its efficacy against LN229 glioma cells with MMR and MGMT knockdown. Its activity against patient-derived GBM that model post-TMZ recurrent tumors is unclear.</p><p><strong>Methods: </strong>We created MMR-deficient GBM patient-derived xenografts through exposure to TMZ, followed by treatment with additional TMZ or KL-50. We also generated isogenic, MSH6 knockout patient-derived GBM and tested them for sensitivity to TMZ and KL-50.</p><p><strong>Results: </strong>KL-50 extended the median survival of mice intracranially engrafted with either patient-derived TMZ-naïve GBM6 or TMZ-naïve GBM12 by 1.75-fold and 2.15-fold, respectively (p<0.0001). A low dose (4 Gy) of fractionated RT further extended the survival of KL-50 treated GBM12 mice (median survival=80 days for RT+ KL-50 vs. 71 days KL-50 alone, P=0.018). KL-50 also extended the median survival of mice engrafted with post-TMZ, MMR-deficient GBM6R-m185 (140 days for KL-50 vs. 37 days for vehicle, p<0.0001). MSH6-KO increased TMZ IC50 for GBM6 and GBM12 cultures by >5-fold and >12-fold for cell death and live cell count outputs, respectively. In contrast, MSH6-KO actually decreased KL-50 IC50 by 10-80%.</p><p><strong>Conclusion: </strong>KL-50-based compounds are a promising new strategy for the treatment of MGMT-deficient, MMR-deficient GBM that recurs after frontline TMZ.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807669","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":"PET imaging of gliomas: Status quo and quo vadis?","authors":"Norbert Galldiks, Philipp Lohmann, Michel Friedrich, Jan-Michael Werner, Isabelle Stetter, Michael M Wollring, Garry Ceccon, Carina Stegmayr, Sandra Krause, Gereon R Fink, Ian Law, Karl-Josef Langen, Joerg-Christian Tonn","doi":"10.1093/neuonc/noae078","DOIUrl":"10.1093/neuonc/noae078","url":null,"abstract":"<p><p>PET imaging, particularly using amino acid tracers, has become a valuable adjunct to anatomical MRI in the clinical management of patients with glioma. Collaborative international efforts have led to the development of clinical and technical guidelines for PET imaging in gliomas. The increasing readiness of statutory health insurance agencies, especially in European countries, to reimburse amino acid PET underscores its growing importance in clinical practice. Integrating artificial intelligence and radiomics in PET imaging of patients with glioma may significantly improve tumor detection, segmentation, and response assessment. Efforts are ongoing to facilitate the clinical translation of these techniques. Considerable progress in computer technology developments (eg quantum computers) may be helpful to accelerate these efforts. Next-generation PET scanners, such as long-axial field-of-view PET/CT scanners, have improved image quality and body coverage and therefore expanded the spectrum of indications for PET imaging in Neuro-Oncology (eg PET imaging of the whole spine). Encouraging results of clinical trials in patients with glioma have prompted the development of PET tracers directing therapeutically relevant targets (eg the mutant isocitrate dehydrogenase) for novel anticancer agents in gliomas to improve response assessment. In addition, the success of theranostics for the treatment of extracranial neoplasms such as neuroendocrine tumors and prostate cancer has currently prompted efforts to translate this approach to patients with glioma. These advancements highlight the evolving role of PET imaging in Neuro-Oncology, offering insights into tumor biology and treatment response, thereby informing personalized patient care. Nevertheless, these innovations warrant further validation in the near future.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"S185-S198"},"PeriodicalIF":16.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545118","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":"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}