Neuro-oncologyPub Date : 2024-10-01DOI: 10.1093/neuonc/noae200
Francesco Cicone, Silvano Gnesin, Giulia Santo, Caroline Stokke, Mirco Bartolomei, Giuseppe Lucio Cascini, Giuseppe Minniti, Giovanni Paganelli, Antoine Verger, Marta Cremonesi
{"title":"Do we need dosimetry for 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":"https://doi.org/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, radiopharmaceuticals 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 explain dose-effect correlations and to individualize radiopharmaceutical treatments. The present article introduces the basic principles of internal dosimetry and provides an overview of available locoregional and systemic radiopharmaceutical treatments for 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":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuro-oncologyPub Date : 2024-10-01DOI: 10.1093/neuonc/noae205
Thomas Zeyen, Laura Böhm, Daniel Paech, Niklas Schäfer, Theophilos Tzaridis, Cathrina Duffy, Louisa Nitsch, Matthias Schneider, Anna-Laura Potthoff, Javen Lennard Schneider-Rothhaar, Joachim Peter Steinbach, Peter Hau, Thomas Kowalski, Clemens Seidel, Dietmar Krex, Oliver Grauer, Roland Goldbrunner, Pia Susan Zeiner, Ghazaleh Tabatabai, Norbert Galldiks, Walter Stummer, Elke Hattingen, Martin Glas, Eleni Gkika, Hartmut Vatter, Alexander Radbruch, Ulrich Herrlinger, Johannes Weller, Christina Schaub
{"title":"Quantitative assessment of residual tumor is a strong and independent predictor of survival in methylated glioblastoma following radiochemotherapy with CCNU/TMZ.","authors":"Thomas Zeyen, Laura Böhm, Daniel Paech, Niklas Schäfer, Theophilos Tzaridis, Cathrina Duffy, Louisa Nitsch, Matthias Schneider, Anna-Laura Potthoff, Javen Lennard Schneider-Rothhaar, Joachim Peter Steinbach, Peter Hau, Thomas Kowalski, Clemens Seidel, Dietmar Krex, Oliver Grauer, Roland Goldbrunner, Pia Susan Zeiner, Ghazaleh Tabatabai, Norbert Galldiks, Walter Stummer, Elke Hattingen, Martin Glas, Eleni Gkika, Hartmut Vatter, Alexander Radbruch, Ulrich Herrlinger, Johannes Weller, Christina Schaub","doi":"10.1093/neuonc/noae205","DOIUrl":"https://doi.org/10.1093/neuonc/noae205","url":null,"abstract":"<p><strong>Background: </strong>Maximum tumor resection improves overall survival (OS) in patients with glioblastoma. The extent of resection (EOR) is historically dichotomized. The RANO resect group recently proposed criteria for volumetry-based EOR assessment in patients that were treated according to Stupp´s protocol. The purpose of this study was (1) to investigate the prognostic value of EOR in patients receiving combined chemotherapy with lomustine (CCNU)/temozolomide (TMZ), and (2) to analyse the prognostic performance of binary EOR assessment compared to volumetric assessment.</p><p><strong>Methods: </strong>78 patients with newly diagnosed MGMT-methylated GBM undergoing tumor resection followed by radiochemotherapy with CCNU/TMZ were included in this study. Residual contrast-enhancing (CE) tumor volume after the first resection was measured and its influence on OS and PFS was analysed using uni- and multivariable Cox regression analysis as well as two-sided log rank test. Patients were divided into RTV ≤1 cm³, >1 cm³ - ≤5 cm³ and >5 cm³ following the proposed criteria of the RANO resect group.</p><p><strong>Results: </strong>Prolonged OS was associated with age <60 years, low RTV, and gross total resection (GTR). Residual tumor volume (RTV) had a superior prognostic value compared to binary EOR assessment. Patients with total or near total resection of CE tumor (≤1 cm³ RTV) showed prolonged OS (median 54.4 months, 95% CI 46.94-not reached), with a 5-year survival rate of 49%.</p><p><strong>Conclusion: </strong>Low RTV is associated with increased survival in glioblastoma patients undergoing radiochemotherapy with CCNU/TMZ. This study demonstrates the applicability of the recently proposed RANO resect criteria in this subgroup of patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351009","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}
Neuro-oncologyPub Date : 2024-10-01DOI: 10.1093/neuonc/noae192
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
{"title":"Targeted radionuclide therapy for patients with CNS 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":"https://doi.org/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 expression of a particular target (thera-nostics). This mode of treatment can also compete with or supplement conventional radiotherapy e.g., if MRI does not fully capture the extent of 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 (PSMA)-expressing prostate cancer are approved, and numerous approaches of targeted radionuclide therapy for patients with metastatic cancer are in development (e.g. using fibroblast activation protein (FAP) as a target). Although brain metastases are rare in the 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":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuro-oncologyPub Date : 2024-09-28DOI: 10.1093/neuonc/noae198
Minh P Nguyen, Ramin A Morshed, Mark W Youngblood, Haley K Perlow, Calixto-Hope G Lucas, Akash J Patel, Joshua D Palmer, Craig M Horbinski, Stephen T Magill, William C Chen, David R Raleigh
{"title":"A targeted gene expression biomarker predicts clinic low-risk meningioma recurrence.","authors":"Minh P Nguyen, Ramin A Morshed, Mark W Youngblood, Haley K Perlow, Calixto-Hope G Lucas, Akash J Patel, Joshua D Palmer, Craig M Horbinski, Stephen T Magill, William C Chen, David R Raleigh","doi":"10.1093/neuonc/noae198","DOIUrl":"https://doi.org/10.1093/neuonc/noae198","url":null,"abstract":"<p><strong>Background: </strong>Despite reassuring clinical and histological features, low grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood.</p><p><strong>Methods: </strong>This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression biomarker and gene expression risk score (continuous from 0 to 1) was evaluated in all samples.</p><p><strong>Results: </strong>The study cohort was comprised of 723 patients, none of which were used for discovery or training of the gene expression biomarker and 265 of which were previously unreported. There were 626 WHO grade 1 meningiomas, 490 with GTR and 126 with STR, and 97 WHO grade 2 meningiomas with GTR. Targeted gene expression profiling classified 51.3% of clinical low-risk meningiomas as molecular intermediate-risk and 9.5% as molecular high-risk. Combining the gene expression biomarker with extent of resection revealed 19.8% of clinical low-risk meningiomas had unfavorable local freedom from recurrence (LFFR) and overall survival (OS), including 7.1% of newly diagnosed WHO grade 1 meningiomas with GTR. The risk score was prognostic for LFFR (HR per 0.1 increase in risk score 1.89, 95% CI 1.58-2.25) across all WHO grades, extents of resection, and newly diagnosed or recurrent presentations.</p><p><strong>Conclusions: </strong>Targeted gene expression profiling can identify clinical low-risk meningiomas that are likely to recur after surgery.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351006","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}
Neuro-oncologyPub Date : 2024-09-28DOI: 10.1093/neuonc/noae201
Rami A El Shafie, Denise Bernhardt, Thomas Welzel, Annabella Schiele, Daniela Schmitt, Paul Thalmann, Sinem Erdem, Angela Paul, Simon Höne, Kristin Lang, Laila König, Fabian Weykamp, Sebastian Adeberg, Adriane Lentz-Hommertgen, Cornelia Jäkel, Farastuk Bozorgmehr, Ursula Nestle, Michael Thomas, Anja Sander, Meinhard Kieser, Jürgen Debus, Stefan Rieken
{"title":"Stereotactic Radiosurgery for 1-10 Brain Metastases to avoid Whole-Brain Radiotherapy - Results of the CYBER-SPACE Randomized Phase 2 Trial.","authors":"Rami A El Shafie, Denise Bernhardt, Thomas Welzel, Annabella Schiele, Daniela Schmitt, Paul Thalmann, Sinem Erdem, Angela Paul, Simon Höne, Kristin Lang, Laila König, Fabian Weykamp, Sebastian Adeberg, Adriane Lentz-Hommertgen, Cornelia Jäkel, Farastuk Bozorgmehr, Ursula Nestle, Michael Thomas, Anja Sander, Meinhard Kieser, Jürgen Debus, Stefan Rieken","doi":"10.1093/neuonc/noae201","DOIUrl":"https://doi.org/10.1093/neuonc/noae201","url":null,"abstract":"<p><strong>Background: </strong>Stereotactic Radiosurgery (SRS) is an emerging alternative to whole-brain radiotherapy (WBRT) for treating multiple brain metastases (BM), reducing toxicity and improving tumor control. The CYBER-SPACE trial compared SRS based on either SPACE or MPRAGE MRI sequence for avoiding or delaying WBRT in patients with 1-10 BM.</p><p><strong>Methods: </strong>Patients with 1-10 untreated BM were randomized 1:1 to receive SRS of all lesions based on either SPACE or MPRAGE MRI sequences. If subsequently new BM occurred, SRS was repeated. WBRT was indicated upon occurrence of >10 new BM, leptomeningeal disease or exhausted SRS-radiotolerance. The primary outcome was freedom from WBRT indication (WBRTi). Secondary outcomes included overall survival (OS), safety, and quality of life.</p><p><strong>Results: </strong>202 patients were randomized; SPACE n=99, MPRAGE n=103. 12-month WBRTi-free survival was 77.1% (95%-CI: 69.5%-83.1%) overall, 78.5% (95%-CI: 66.7%-86.5%) for SPACE, and 76.0% (95%-CI: 65.2%-83.9%) for MPRAGE (HR=0.84, 95%-CI: 0.43-1.63, p=0.590). Patients with 5-10 BM had shorter WBRTi-free survival (HR=3.13, 95%-CI: 1.53-6.40, p=0.002). Median OS was 13.1 months overall, 10.5 months for SPACE, and 15.2 months for MPRAGE (HR=1.10, 95%-CI: 0.78-1.56, p=0.585). Neurologic death rate was 10.1%. Predictors for longer OS included Karnofsky Performance Status >80% (HR=0.51, 95%-CI: 0.33-0.77, p=0.002) and concurrent immunotherapy (HR=0.34, 95%-CI: 0.23-0.52, p<0.001).</p><p><strong>Conclusions: </strong>The more sensitive SPACE sequence did not improve outcomes over MPRAGE. SRS with thorough monitoring and immediate re-treatment for new lesions decreases the need for WBRT and achieves low neurologic death rates. SRS should be considered a favorable alternative to WBRT for patients with 1-10 BM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351010","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}
Neuro-oncologyPub Date : 2024-09-27DOI: 10.1093/neuonc/noae189
Maura Massimino, Francesco Barretta, Chiara Dossena, Simone Minasi, Francesca Romana Buttarelli, Veronica Biassoni, Matilde Oriani, Elisabetta Schiavello, Marica Ficorilli, Olga Nigro, Bianca Pollo, Manila Antonelli, Vittoria Donofrio, Marco Maggioni, Marcel Kool, Emilia Pecori, Sabina Vennarini, Felice Giangaspero, Francesca Gianno, Alessandra Erbetta, Luisa Chiapparini, Roberto Luksch, Elena Barzanò, Cristina Meazza, Marta Podda, Filippo Spreafico, Monica Terenziani, Luca Bergamaschi, Andrea Ferrari, Michela Casanova, Stefano Chiaravalli, Giovanna Gattuso, Piergiorgio Modena, Simon Bailey, Loris De Cecco
{"title":"Long-term outcome of the Milano-HART strategy for high-risk medulloblastoma, including the impact of molecular subtype.","authors":"Maura Massimino, Francesco Barretta, Chiara Dossena, Simone Minasi, Francesca Romana Buttarelli, Veronica Biassoni, Matilde Oriani, Elisabetta Schiavello, Marica Ficorilli, Olga Nigro, Bianca Pollo, Manila Antonelli, Vittoria Donofrio, Marco Maggioni, Marcel Kool, Emilia Pecori, Sabina Vennarini, Felice Giangaspero, Francesca Gianno, Alessandra Erbetta, Luisa Chiapparini, Roberto Luksch, Elena Barzanò, Cristina Meazza, Marta Podda, Filippo Spreafico, Monica Terenziani, Luca Bergamaschi, Andrea Ferrari, Michela Casanova, Stefano Chiaravalli, Giovanna Gattuso, Piergiorgio Modena, Simon Bailey, Loris De Cecco","doi":"10.1093/neuonc/noae189","DOIUrl":"10.1093/neuonc/noae189","url":null,"abstract":"<p><strong>Background: </strong>We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC/A histology, TP53 mutations, MYC/MYCN amplification.</p><p><strong>Methods: </strong>Patients over 3-years-old received,after surgery,staging and histo-biological analysis,sequential high-dose-methotrexate(HD-MTX),high-dose-etoposide(HD-VP16),high-dose-cyclophosphamide(HD-Cyclo),high-dose-carboplatin(HD-Carbo).Hyperfractionated-accelerated-radiotherapy-craniospinal(HART-CSI),administered in twice daily 1.3 Gy-fractions reached a total dose tailored to the patients' age and pre-radiation response to chemotherapy(CT): 31.2 Gy if under 10-years-old and complete response(CR) or partial response(PR) obtained or absence of metastatic disease,39 Gy in other/older patients.Boosts to posterior fossa/residual metastatic(M+) deposits were given up to a total dose of 60 Gy/9 Gy,respectively,but avoided if metastatic nodules were very big or patients very young.Two courses of high-dose-thiotepa were delivered in case of not CR/PR after pre-radiotherapy(RT) phase and in all M0 patients either - pre/post HART.Subgrouping was performed where tissue was available.</p><p><strong>Results: </strong>Eighy-nine patients were enrolled,median age 8.8 years,median follow up 136 months.Overall-survival(OS) and event-free-survival(EFS) at 5/15 years were 75.9/66.5% and 68.2/65.3%, respectively;5/28 fatal events were not related to relapse(three developed secondary malignancies).Sex,age less than 10 years,histological subtype,presence of MYC/MYCN amplification,reduction in CSI dose,omission of RT-boosts,implementation of myeloablative therapy,presence/absence of metastases did not impact prognosis.Patients progressing after pre-HART CT(14/89) and stable-disease(SD)+PD after HART(10/89) negatively affected outcome(P<0.001).Subgrouping in 66/89 patients' samples demonstrated a significantly worse EFS for patients with Sonic Hedgehog(SHH)-tumors(#15, 2 with constitutional TP53-mutations) vs. group 3 and 4(15 and 29 patients, respectively, group3/4 in 7).Patients younger than 10 received lower CSI doses if stratified according to CT response.</p><p><strong>Conclusions: </strong>This strategy, partly adopted in the ongoing SIOPE protocol,confirmed improved EFS and OS over previously reported outcomes in all high-risk categories;SHH tumors appeared the most aggressive.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351008","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}
Neuro-oncologyPub Date : 2024-09-25DOI: 10.1093/neuonc/noae199
Jennifer Wu, Brian D Wishart, Stephanie E Cohen, Patricia Orme, Susan S Quinn, Donna Nimec
{"title":"The Pediatric Physiatric Posterior Fossa Symptoms scale (3PFSs): Impairments and outcome in pediatric inpatient rehabilitation for posterior fossa brain tumors.","authors":"Jennifer Wu, Brian D Wishart, Stephanie E Cohen, Patricia Orme, Susan S Quinn, Donna Nimec","doi":"10.1093/neuonc/noae199","DOIUrl":"https://doi.org/10.1093/neuonc/noae199","url":null,"abstract":"<p><strong>Background: </strong>Clinical recognition of the post-operative neurologic sequelae of posterior fossa tumors is inconsistent. This study aimed to characterize functional impairments and recovery trajectories in pediatric patients admitted to inpatient rehabilitation following surgical resection of posterior fossa brain tumors. This study also introduces the Pediatric Physiatric Posterior Fossa Symptom scale (3PFSs) for serial assessment of post-operative symptoms in pediatric posterior fossa brain tumors.</p><p><strong>Methods: </strong>This retrospective cohort study included 49 patients aged 1.1 to 19.9 years admitted to a pediatric unit of a free-standing rehabilitation hospital following resection of a posterior fossa brain tumor. Functional Independence Measure for Children (WeeFIM) and 3PFSs scores at admission and discharge were the primary outcome measures.</p><p><strong>Results: </strong>Across the group, WeeFIM score improved from 51.5±23.5 points at admission to 74.2±28.2 points at discharge (t=4.34, p<0.001). The 3PFSs score also showed improvement from 10[IQR=9-12] points at admission to 8[7-10] points at discharge (t=9.3, p<0.0001). While change in both the WeeFIM and 3PFSs captured statistically significant improvement in function, there was low inter-rating correlation (p>0.7). In addition, mortality was correlated with higher discharge 3PFSs score (p=0.007) but not discharge WeeFIM score.</p><p><strong>Conclusion: </strong>In pediatric patients with post-operative neurologic sequelae due to posterior fossa brain tumors, inpatient rehabilitation resulted in global and domain specific functional improvements. This initial application of the 3PFSs demonstrates potential applicability for stratifying patients to appropriate levels of rehabilitation, capturing functionally relevant response to rehabilitation treatment, and prognosticating long-term outcomes. These initial results are promising but require additional validation in a larger cohort.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351012","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}
Neuro-oncologyPub Date : 2024-09-21DOI: 10.1093/neuonc/noae197
{"title":"Corrigendum to: Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer.","authors":"","doi":"10.1093/neuonc/noae197","DOIUrl":"https://doi.org/10.1093/neuonc/noae197","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292328","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}
Neuro-oncologyPub Date : 2024-09-17DOI: 10.1093/neuonc/noae188
Lara S Fleischmann, Karolina Nemes, Selina Glaser, Alexandra G Kouroukli, Matej Boros, Susanne Bens, Sonja Dahlum, Helene Kretzmer, Florian Oyen, Joachim Gerss, Martin Hasselblatt, Michael C Frühwald, Reiner Siebert
{"title":"Constitutional mosaicism of pathogenic variants in SMARCB1 in a subset of patients with sporadic rhabdoid tumors","authors":"Lara S Fleischmann, Karolina Nemes, Selina Glaser, Alexandra G Kouroukli, Matej Boros, Susanne Bens, Sonja Dahlum, Helene Kretzmer, Florian Oyen, Joachim Gerss, Martin Hasselblatt, Michael C Frühwald, Reiner Siebert","doi":"10.1093/neuonc/noae188","DOIUrl":"https://doi.org/10.1093/neuonc/noae188","url":null,"abstract":"Background Malignant rhabdoid tumors are aggressive malignancies predominantly affecting very young children. The characteristic genetic alteration is biallelic inactivation of SMARCB1. In approximately 30% of patients one SMARCB1 allele is constitutionally altered conferring a particularly unfavourable prognosis. Constitutional mosaicism for pathogenic SMARCB1 mutations has recently been reported in distinct cases of allegedly sporadic rhabdoid tumors. We aimed to systematically investigate the frequency and clinical impact of constitutional mosaicism in patients with sporadic rhabdoid tumors included in the EU-RHAB registry. Methods We selected 29 patients with rhabdoid tumors displaying at least one pathogenic small variant in SMARCB1 in the tumor DNA and absence of a germline mutation. We re-screened blood-derived patient and control DNA for the respective small variant by PCR with unique molecular identifiers and ultra-deep next generation sequencing. Clinical data in patients with and without mosaicism and 174 EU-RHAB controls were compared. Results Employing an ultra-deep sequencing approach, we detected tumor-associated SMARCB1 variants in blood-derived DNA in 9/29 patients. In 6/29 patients (21%), whose variant allele frequency (VAF) exceeded 2%, constitutional mosaicism was assumed whereas tumor DNA contamination was documented in 1/3 patients with VAF below 1%. No significant differences were observed between 6 mosaic-positive and 20 -negative patients regarding age at diagnosis, presence of metastases, event-free or overall survival. Conclusion Constitutional mosaicism for pathogenic small SMARCB1 variants is recurrent in patients with allegedly sporadic rhabdoid tumors. The clinical implications of such variants need to be determined in larger, prospective cohorts also including detection of structural variants of SMARCB1.","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":"47 1","pages":""},"PeriodicalIF":15.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261617","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}
Neuro-oncologyPub Date : 2024-09-17DOI: 10.1093/neuonc/noae194
Kira Tosefsky,Stephen Yip
{"title":"\"Splice of Life: How RNA is Rewriting the Meningioma Story\".","authors":"Kira Tosefsky,Stephen Yip","doi":"10.1093/neuonc/noae194","DOIUrl":"https://doi.org/10.1093/neuonc/noae194","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":"1 1","pages":""},"PeriodicalIF":15.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261616","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}