Neuro-oncology最新文献

{"title":"Expanding therapeutic options for people with NF2-related schwannomatosis: Encouraging results with brigatinib.","authors":"Scott R Plotkin, Jaishri O Blakeley","doi":"10.1093/neuonc/noae137","DOIUrl":"10.1093/neuonc/noae137","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1949-1950"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400869","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":"Risk factors for domain-specific neurocognitive outcome in pediatric survivors of a brain tumor in the posterior fossa-Results of the HIT 2000 trial.","authors":"Martin Mynarek, Anne Rossius, Anika Guiard, Holger Ottensmeier, Katja von Hoff, Denise Obrecht-Sturm, Lisa Bußenius, Carsten Friedrich, Andre O von Bueren, Nicolas U Gerber, Thomas Traunwieser, Rolf-Dieter Kortmann, Monika Warmuth-Metz, Brigitte Bison, Ulrich-W Thomale, Juergen Krauss, Torsten Pietsch, Steven C Clifford, Stefan M Pfister, Dominik Sturm, Felix Sahm, Tanja Tischler, Stefan Rutkowski","doi":"10.1093/neuonc/noae092","DOIUrl":"10.1093/neuonc/noae092","url":null,"abstract":"<p><strong>Background: </strong>Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization, and biology in pediatric survivors of a posterior fossa tumor.</p><p><strong>Methods: </strong>Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic tool based on Cattell-Horn-Carroll's model for intelligence were analyzed.</p><p><strong>Results: </strong>Cognitive performance 5.14 years (mean; range = 1.52-13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had a strong impact on most subtests. pCMS was associated with psychomotor abilities (β = -0.25 to -0.16) and processing speed (β = -0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β = -0.20) and short-term memory (β = -0.15), age with crystallized intelligence (β = 0.15) and psychomotor abilities (β = -0.16 and β = -0.17). Scores for fluid intelligence (β = -0.23), short-term memory (β = -0.17) and visual processing (β = -0.25) declined, and scores for selective attention improved (β = 0.29) with time after diagnosis.</p><p><strong>Conclusions: </strong>The dose of CSI was strongly associated with neurocognitive outcomes. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI dose and toxicity caused by other treatment modalities.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2113-2124"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248441","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":"Letter to the editor on \"The cochlear dose and the age at radiotherapy predict severe hearing loss after passive scattering proton therapy and cisplatin in children with medulloblastoma\".","authors":"Wenjue Tang, Huihong Dou","doi":"10.1093/neuonc/noae154","DOIUrl":"10.1093/neuonc/noae154","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2152-2153"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375768","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":"Development and validation of a clinical risk model for postoperative outcome in newly diagnosed glioblastoma: a report of the RANO resect group.","authors":"Philipp Karschnia, Jacob S Young, Gilbert C Youssef, Antonio Dono, Levin Häni, Tommaso Sciortino, Francesco Bruno, Stephanie T Juenger, Nico Teske, Jorg Dietrich, Michael Weller, Michael A Vogelbaum, Martin van den Bent, Juergen Beck, Niklas Thon, Jasper K W Gerritsen, Shawn Hervey-Jumper, Daniel P Cahill, Susan M Chang, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Raymond Y Huang, Patrick Y Wen, Mitchel S Berger, Annette M Molinaro, Joerg-Christian Tonn","doi":"10.1093/neuonc/noae231","DOIUrl":"https://doi.org/10.1093/neuonc/noae231","url":null,"abstract":"<p><strong>Background: </strong>Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.</p><p><strong>Methods: </strong>The RANO resect group retrospectively compiled an international, seven-center training cohort of patients with newly diagnosed glioblastoma. The combined associations of residual tumor with molecular or clinical factors and survival were analyzed, and recursive partitioning analysis was performed for risk modeling. The resulting model was prognostically verified in a separate external validation cohort.</p><p><strong>Results: </strong>Our training cohort compromised 1003 patients with newly diagnosed isocitrate dehydrogenase-wildtype glioblastoma. Residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, age, and postoperative KPS were prognostic for survival and incorporated into regression tree analysis. By individually weighting the prognostic factors, an additive score (range, 0-9 points) integrating these four variables distinguished patients with low (0-2 points), intermediate (3-5 points), and high risk (6-9 points) for inferior survival. The prognostic value of our risk model was retained in treatment-based subgroups and confirmed in an external validation cohort of 258 patients with glioblastoma. Compared to previously postulated models, goodness-of-fit measurements were superior for our model.</p><p><strong>Conclusions: </strong>The novel RANO risk model serves as an easy-to-use, yet highly prognostic tool for postoperative patient stratification prior to further therapy. The model may serve to guide patient management and reduce imbalances between study arms in prospective trials.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569113","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":"Multidisciplinary management strategies for recurrent brain metastasis after prior radiotherapy: An overview.","authors":"Rupesh Kotecha, Alonso La Rosa, Paul D Brown, Michael A Vogelbaum, Pierina Navarria, Raphael Bodensohn, Maximilian Niyazi, Philipp Karschnia, Giuseppe Minniti","doi":"10.1093/neuonc/noae220","DOIUrl":"https://doi.org/10.1093/neuonc/noae220","url":null,"abstract":"<p><p>As cancer patients with intracranial metastatic disease experience increasingly prolonged survival, the diagnosis and management of recurrent brain metastasis pose significant challenges in clinical practice. Prior to deciding upon a management strategy, it is necessary to ascertain whether patients have recurrent/progressive disease vs adverse radiation effect, classify the recurrence as local or distant in the brain, evaluate the extent of intracranial disease (size, number and location of lesions, and brain metastasis velocity), the status of extracranial disease, and enumerate the interval from the last intracranially directed intervention to disease recurrence. A spectrum of salvage local treatment options includes surgery (resection and laser interstitial thermal therapy [LITT]) with or without adjuvant radiotherapy in the forms of external beam radiotherapy, intraoperative radiotherapy, or brachytherapy. Nonoperative salvage local treatments also range from single fraction and fractionated stereotactic radiosurgery (SRS/FSRS) to whole brain radiation therapy (WBRT). Optimal integration of systemic therapies, preferably with central nervous system (CNS) activity, may also require reinterrogation of brain metastasis tissue to identify actionable molecular alterations specific to intracranial progressive disease. Ultimately, the selection of the appropriate management approach necessitates a sophisticated understanding of patient, tumor, and prior treatment-related factors and is often multimodal; hence, interdisciplinary evaluation for such patients is indispensable.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569115","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":"Outcomes and relapse patterns in primary central nervous system lymphoma: Longitudinal analysis of 559 patients diagnosed from 1983 to 2020.","authors":"Kathryn R Tringale, Michael Scordo, Joachim Yahalom, Charlie White, Zhigang Zhang, Behroze Vachha, Gustav Cederquist, Lauren Schaff, Lisa DeAngelis, Christian Grommes, Brandon S Imber","doi":"10.1093/neuonc/noae115","DOIUrl":"10.1093/neuonc/noae115","url":null,"abstract":"<p><strong>Background: </strong>Contemporary outcomes and relapse patterns in primary CNS lymphoma (PCNSL) are lacking. We analyzed factors associated with relapse in a large cohort with extensive follow-up.</p><p><strong>Methods: </strong>T1-post-contrast-enhancing disease was characterized in immunocompetent PCNSL (diffuse large B-cell) patients from 1983 to 2020. Patients were stratified by response to induction and consolidation (complete/unconfirmed [CR/CRu], partial, stable, progression [POD]). Refractory was POD during (or relapse ≤3 months of) induction. Initial relapse site was categorized as local (involving/adjacent to baseline), distant intraparenchymal, leptomeningeal, or other. Progression-free (PFS) and overall survival (OS) were assessed with proportional hazards. Cumulative incidence with competing risks was used to assess local relapse.</p><p><strong>Results: </strong>Median follow-up was 7.4 years (N = 559). Most (321, 57%) were recursive partitioning analysis class 2 (age ≥50, Karnosfky Performance Status [KPS] ≥70). Most had supratentorial (420, 81%), multifocal (274, 53%), bilateral (224, 43%), and deep structure involvement (314, 56%). Nearly all received methotrexate-based induction (532, 95%). There was no difference in PFS or OS from consolidation based on initial response to induction (CR/CRu vs PR) in patients who ultimately achieved a CR/CRu to consolidation. PFS at 1-, 5 years for 351 patients with CR/CRu to consolidation was 80% (95% confidence interval [95% CI]: 76%-84%) and 46% (95% CI: 41%-53%), respectively; 1-year cumulative incidence of local versus nonlocal relapse was 1.8% versus 15%, respectively. For 97 refractory patients, 1-year cumulative incidence of local versus nonlocal relapse was 57% versus 42%, respectively. Deep structure involvement (HR 1.89, 95% CI: 1.10%-3.27%) was associated with local relapse in refractory patients.</p><p><strong>Conclusions: </strong>We report the first comprehensive relapse patterns in a large PCNSL cohort. While relapses post-CR to consolidation are typically distant and unpredictable, refractory patients had a relatively high incidence of local relapse. These findings can help optimize multimodality therapy for this highest-risk population.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2061-2073"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446679","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":"Inhibition of PERK-mediated unfolded protein response acts as a switch for reversal of residual senescence and as senolytic therapy in glioblastoma.","authors":"Madhura Ketkar, Sanket Desai, Pranav Rana, Rahul Thorat, Sridhar Epari, Amit Dutt, Shilpee Dutt","doi":"10.1093/neuonc/noae134","DOIUrl":"10.1093/neuonc/noae134","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma due to recurrence is clinically challenging with 10-15 months overall survival. Previously we showed that therapy-induced senescence (TIS) in glioblastoma reverses causing recurrence. Here, we aim to delineate the TIS reversal mechanism for potential therapeutic intervention to prevent glioblastoma (GBM) recurrence.</p><p><strong>Methods: </strong>Residual senescent (RS) and end of residual senescence (ERS) cells were captured from GBM patient-derived primary-cultures and cell lines mimicking clinical scenarios. RNA-sequencing, transcript/protein validations, knock-down/inhibitor studies, ChIP RT-PCR, biochemical assays, and IHCs were performed for the mechanistics of TIS reversal. In vivo validations were conducted in GBM orthotopic mouse model.</p><p><strong>Results: </strong>Transcriptome analysis showed co-expression of endoplasmic reticulum (ER) stress-unfolded protein response (UPR) and senescence-associated secretory phenotype (SASP) with TIS induction and reversal. Robust SASP production and secretion by RS cells could induce senescence, Reactive oxygen specis (ROS), DNA damage, and ER stress in paracrine fashion independent of radiation. Neutralization of most significantly enriched cytokine from RS-secretome IL1β, suppressed SASP, and delayed senescence reversal. Mechanistically, with SASP and massive protein accumulation in ER, RS cells displayed stressed ER morphology, upregulated ER stress markers, and PERK pathway activation via peIF2α-ATF4-CHOP which was spontaneously resolved in ERS. ChIP RT-PCR showed CHOP occupancy at CXCL8/IL8, CDKN1A/p21, and BCL2L1/BCLXL aiding survival. PERK knockdown/inhibition with GSK2606414 in combination with radiation led to sustained ER stress and senescence without SASP. PERKi in RS functioned as senolytic via apoptosis and prevented recurrence in vitro and in vivo ameliorating overall survival.</p><p><strong>Conclusion: </strong>We demonstrate that PERK-mediated UPR regulates senescence reversal and its inhibition can be exploited as a potential seno-therapeutic option in glioblastoma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2027-2043"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634127","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":"Enhancing neuro-oncology care through equity-driven applications of artificial intelligence.","authors":"Mulki Mehari, Youssef Sibih, Abraham Dada, Susan M Chang, Patrick Y Wen, Annette M Molinaro, Ugonma N Chukwueke, Joshua A Budhu, Sadhana Jackson, J Ricardo McFaline-Figueroa, Alyx Porter, Shawn L Hervey-Jumper","doi":"10.1093/neuonc/noae127","DOIUrl":"10.1093/neuonc/noae127","url":null,"abstract":"<p><p>The disease course and clinical outcome for brain tumor patients depend not only on the molecular and histological features of the tumor but also on the patient's demographics and social determinants of health. While current investigations in neuro-oncology have broadly utilized artificial intelligence (AI) to enrich tumor diagnosis and more accurately predict treatment response, postoperative complications, and survival, equity-driven applications of AI have been limited. However, AI applications to advance health equity in the broader medical field have the potential to serve as practical blueprints to address known disparities in neuro-oncologic care. In this consensus review, we will describe current applications of AI in neuro-oncology, postulate viable AI solutions for the most pressing inequities in neuro-oncology based on broader literature, propose a framework for the effective integration of equity into AI-based neuro-oncology research, and close with the limitations of AI.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1951-1963"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004832","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":"Thrombosis, brain metastasis formation, and the perivascular metastatic niche-Novel insights from the tumor microvascular circulation.","authors":"Christopher Alvarez-Breckenridge, Priscilla K Brastianos, Daniel P Cahill","doi":"10.1093/neuonc/noae168","DOIUrl":"10.1093/neuonc/noae168","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2100-2101"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110032","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":"Raman-based machine-learning platform reveals unique metabolic differences between IDHmut and IDHwt glioma.","authors":"Adrian Lita, Joel Sjöberg, David Păcioianu, Nicoleta Siminea, Orieta Celiku, Tyrone Dowdy, Andrei Păun, Mark R Gilbert, Houtan Noushmehr, Ion Petre, Mioara Larion","doi":"10.1093/neuonc/noae101","DOIUrl":"10.1093/neuonc/noae101","url":null,"abstract":"<p><strong>Background: </strong>Formalin-fixed, paraffin-embedded (FFPE) tissue slides are routinely used in cancer diagnosis, clinical decision-making, and stored in biobanks, but their utilization in Raman spectroscopy-based studies has been limited due to the background coming from embedding media.</p><p><strong>Methods: </strong>Spontaneous Raman spectroscopy was used for molecular fingerprinting of FFPE tissue from 46 patient samples with known methylation subtypes. Spectra were used to construct tumor/non-tumor, IDH1WT/IDH1mut, and methylation-subtype classifiers. Support vector machine and random forest were used to identify the most discriminatory Raman frequencies. Stimulated Raman spectroscopy was used to validate the frequencies identified. Mass spectrometry of glioma cell lines and TCGA were used to validate the biological findings.</p><p><strong>Results: </strong>Here, we develop APOLLO (rAman-based PathOLogy of maLignant gliOma)-a computational workflow that predicts different subtypes of glioma from spontaneous Raman spectra of FFPE tissue slides. Our novel APOLLO platform distinguishes tumors from nontumor tissue and identifies novel Raman peaks corresponding to DNA and proteins that are more intense in the tumor. APOLLO differentiates isocitrate dehydrogenase 1 mutant (IDH1mut) from wild-type (IDH1WT) tumors and identifies cholesterol ester levels to be highly abundant in IDHmut glioma. Moreover, APOLLO achieves high discriminative power between finer, clinically relevant glioma methylation subtypes, distinguishing between the CpG island hypermethylated phenotype (G-CIMP)-high and G-CIMP-low molecular phenotypes within the IDH1mut types.</p><p><strong>Conclusions: </strong>Our results demonstrate the potential of label-free Raman spectroscopy to classify glioma subtypes from FFPE slides and to extract meaningful biological information thus opening the door for future applications on these archived tissues in other cancers.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1994-2009"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200397","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}