Cerebellar glioblastoma in adults: a comparative single-center matched pair analysis and systematic review of the literature

Cerebellar glioblastoma in adults: a comparative single-center matched pair analysis and systematic review of the literature | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cerebellar glioblastoma in adults: a comparative single-center matched pair analysis and systematic review of the literature Yauhen Lizunou, Anna-Laura Potthoff, Niklas Schäfer, Andreas Waha, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4590644/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Sep, 2024 Read the published version in Journal of Cancer Research and Clinical Oncology → Version 1 posted 18 You are reading this latest preprint version Abstract Purpose The rarity of cerebellar glioblastoma presents a significant challenge in clinical practice due to the lack of extensive prognostic data on long-term survival rates, rendering it an underrepresented entity compared to its supratentorial counterpart. This study aims to analyze potential differences in survival outcome between patients with cerebellar and supratentorial glioblastomas. Methods From 2009 to 2020, 8 patients underwent surgical treatment for cerebellar glioblastoma at the authors’ institution. These patients were individually matched with a cohort of 205 consecutive patients from our institutional database with supratentorial glioblastoma, taking into account key prognostic parameters. We compared progression-free survival (PFS) and overall survival (OS) rates and performed a systematic literature review to compile additional survival data on cerebellar glioblastoma. Results The median OS for cerebellar glioblastoma patients was 18 months (95% CI 11–25). The balanced matched-pair analysis showed no significant difference in survival when compared to patients with supratentorial glioblastoma, exhibiting a median OS of 23 months (95% CI 0–62) (p = 0.63). Respective values for PFS were 8 months (95% CI 4–12) for cerebellar and 7 months (95% CI 0–16) for supratentorial glioblastoma (p = 0.2). The systematic review revealed that median OS for cerebellar glioblastoma in current literature ranges from 7 to 21 months. Conclusions The present findings indicate that patients with supra- and infratentorial glioblastoma do not significantly differ in regard to survival outcome parameters. This similarity in prognosis might encourage clinicians to consider surgical interventions for both supra- and infratentorial BMs in a similar manner. cerebellar glioblastoma supratentorial glioblastoma matched pair analysis overall survival propensity score matching Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Glioblastoma ranks among the most aggressive primary malignant brain tumors in adults (Ostrom et al. 2020 ). Numerous studies have been undertaken to hasten the development of more advanced treatment strategies through diverse therapeutic and surgical methods (Potthoff et al. 2019 , Schneider et al. 2019, Venkataramani et al. 2022 , Dejonckheere et al. 2023 ). Glioblastomas are most commonly found in the supratentorial region, with less than 1% occurring in the cerebellum (Tsung et al. 2011 ). Previous research has highlighted distinct molecular and clinical profiles between supratentorial and cerebellar glioblastomas, suggesting that cerebellar glioblastoma may represent a distinct subgroup (Adams et al. 2013 , Hong et al. 2018 ). Nonetheless, survival data on cerebellar glioblastoma remain sparse, and existing reports often rely on extended historical data sets and varied therapeutic approaches, which may affect consistency (Adams et al. 2013 , Levine et al. 1987 ). In response to this gap, we analyzed institutional data on adult cerebellar glioblastoma and conducted a matched-pair analysis to draw comparisons with supratentorial glioblastoma patients treated at our facility. Additionally, we performed a systematic review of the literature, extracting individual participant data to juxtapose our findings with the broader corpus of clinical research on this rare form of glioblastoma. Methods Patients Patients aged 18 years or older with newly diagnosed glioblastoma who underwent surgical intervention at our institution between 2009 and 2020 were systematically entered into a computerized database (SPSS, version 27, IBM Corp., Armonk, NY). We excluded patients with cerebellar glioblastoma who only had a biopsy and those with additional tumor infiltration into the brainstem. Our study adhered to the principles of the Helsinki Declaration and received approval from the institutional ethics committee (228/19). Informed consent was not sought in regard of the retrospective study design. We meticulously recorded data, including patient demographics, radiological findings, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and functional neurological status objectified by the Karnofsky performance scale (KPS) at both admission and throughout the course of treatment as previously described (Schneider et al. 2020, Borger et al. 2021 , Schneider et al. 2021 , Schneider et al. 2020). The institutional interdisciplinary tumor board made treatment decisions, encompassing the extent of neurosurgical intervention and postoperative care (Schäfer et al. 2021 ). The extent of resection (EOR) was determined based on early postoperative 3.0-Tesla MRI scans conducted within 72 hours following surgery. Definitions of gross-total resection (GTR) and subtotal resection (STR) corresponded to the removal of more than 95% and less than 95% of the initial contrast-enhancing tumor tissue, respectively (Shonka and Aizenberg 2017 , (Schneider et al. 2019). Following histopathological confirmation of glioblastoma, MGMT promoter methylation status was ascertained using pyrosequencing and combined bisulfite restriction analysis (Mikeska et al. 2007 ). Tumor classification followed the 2016 WHO classification criteria. Progression-free survival (PFS) was defined as the interval from glioblastoma surgery to the date of radiological progression, as previously outlined (Zeyen et al. 2023 ). Tumor progression criteria followed the Response Assessment in Neuro-Oncology (RANO) guidelines with certain modifications (Herrlinger et al. 2019 ). Overall survival (OS) was calculated from the date of glioblastoma surgery until the patient's death. Post-surgical treatment for all patients included adjuvant therapies according to the Stupp- (Stupp et al. 2005 ) or CeTeG-protocol (Herrlinger et al. 2019 ) in line with the institutional interdisciplinary tumor board's recommendations (Schäfer et al. 2021 ). Matching procedure For the purpose of conducting a matched-pair analysis, the statistical computing software R was used (version 4.2.3; The R Foundation for Statistical Computing, available at [ https://www.r-project.org/ ]). The initial patient cohort comprised 205 consecutive individuals who had undergone surgery for supratentorial glioblastoma and 8 patients with cerebellar glioblastoma. We applied a multivariate approach and propensity score matching with an aim for balance optimization, setting a matching ratio of 1:4 as previously described (Hamed et al. 2022 , Layer et al. 2023 , Hamed et al. 2023 ). In our effort to enhance the balance between the matched pairs, we selected several generally-known prognostic factors for matching. These factors included age, Karnofsky Performance Scale (KPS) at admission, the extent of resection (EOR) categorized as either gross-total resection (GTR) or subtotal resection (STR), and MGMT promoter methylation status, as these have been identified as predictors on patient outcomes (Li et al. 2016 , McGirt et al. 2009 , Radke et al. 2019 , Smrdel et al. 2016 ). Subsequently, from the pool of patients with supratentorial glioblastoma, we selected 32 individuals as a control group (depicted in Fig. 1 ), with the selection process conducted using the R software. Systematic review of the literature Search methods A systematic literature review was undertaken to gather current published data on survival outcome for cerebellar glioblastoma. We conducted a search on PubMed, covering publications from the years 2005 to 2023 as previously described (Schneider et al. 2019). The search utilized specific keywords: "cerebellar glioblastoma," "posterior fossa glioblastoma," and "infratentorial glioblastoma," with the latest access on 31 December 2023. The initial phase involved scrutinizing titles and abstracts to determine their relevance to our research query. Subsequent to this preliminary assessment, we retrieved the full-text versions of all studies deemed pertinent for further evaluation. Two authors (PS and MS) independently reviewed the selected articles to ensure the thoroughness of the analysis. Any inconsistencies or discrepancies in their assessments were addressed in a consensus meeting that included the senior author (MS), ensuring a unified and conclusive selection. Moreover, we extended our search to include the reference lists of the identified articles, aiming to uncover any additional studies published within the specified timeframe that could contribute to the literature review. Selection criteria Articles were included if they reported individual patient data on treatment in at least 4 patients with cerebellar glioblastoma. Studies reporting exclusively on pediatric patients were excluded. Furthermore, studies describing treatment of cerebellar glioblastoma with supratentorial fraction and/or brainstem involvement were excluded. Only articles written in English or German language were considered. Data collection and extraction If reported the following data was extracted from qualifying articles: study design, number of patients with cerebellar glioblastoma, preoperative KPS, extent of resection, histopathological features, PFS, and OS. Not all studies provided data or information on each subset of patients. If by far included studies reported only insufficient data on the above-mentioned factors, these were excluded from further analysis. Therefore, comparative analysis was limited by the nature of the data source. If available, data was independently extracted and verified by two authors (PS and MS). No disagreements were found. Statistics Data analyses were performed using the computer software package SPSS (version 27, IBM Corp., Armonk, NY). Mann-Whitney U test was used for parametric statistics. Categorical variables were analyzed in contingency tables using Fisher’s exact test. Results with p < 0.05 were considered statistically significant. OS and PFS were analyzed by the Kaplan-Meier method. Events in survival curves were defined as radiographic tumor progression and death and compared by using the Gehan-Breslow-Wilcoxon test. Results Patient characteristics Between 2009 and 2020, 8 patients underwent surgical therapy for cerebellar glioblastoma at the authors’ institution. Median age at the day of surgery was 70 years (IQR 64–76) and GTR was performed in 7 out of 8 patients (88%). Molecular analysis revealed methylated and unmethylated MGMT-promoter status in 5 (63%) and 3 (37%) patients. The median OS rate was 18 months (95% CI 11–25). For further details see Table 1 . Comparative matched pair analysis reveals comparable survival rates for cerebellar and supratentorial glioblastoma In order to compare median survival rates of the cohort of cerebellar glioblastoma patients and corresponding patients with supratentorial glioblastoma, we perfomred a multivariate and propensity score matching with additional balance optimization. Therefore, cerebellar glioblastoma patients were individually matched at a ratio of 1:4 to a cohort of 205 consecutive patients that had undergone resection of supratentorial glioblastoma at our university hospital between 2013 and 2018 (Fig. 1 ). Patient age and KPS at admission, EOR as well as MGMT promoter methylation status as the main known clinical and molecular predictors for survival of glioblastoma patients were chosen as matching parameters. Hence, matched pair analysis yielded two individually matched cohorts of 8 cerebellar and 32 supratentorial glioblastoma patients that did not significantly differ with regard to above mentioned prognostic parameters (Table 1 ). Analysis of median OS rates revealed no statistically significant differences depending on the tumor localization: patients with cerebellar glioblastoma revealed an OS rate of 18 months (95% CI 11–25) compared to 23 months (95% CI 0–62) for individually matched supratentorial glioblastoma patients (p = 0.63) (Table 1 , Fig. 2 ). PFS did also not significantly differ between the cerebellar cohort (8 months, 95% CI 4–12) and the supratentorial cohort (7 months, 95% CI 0–16), with p = 0.2 (Table 1 , Fig. 3 ). For the total group of 205 patients with supratentorial glioblastoma, analysis of median OS rates yielded 17 months (95% CI 14,4–18,6). Systematic review of the literature concerning survival rates of patients with cerebellar glioblastoma The PubMed search of the literature on cerebellar glioblastoma from 2005 to 2023 yielded 652 articles (Fig. 4 ). In consideration of a clear assignment of PFS and/or OS to the particular patient cohort as a further inclusion criterion beyond those mentioned in the methodological section, ultimately 7 studies were identified for further data analysis (Hong et al. 2018 , Cho et al. 2019 , Picart et al. 2018 , Takahashi et al. 2014 , Milinkovic et al. 2014 , Gopalakrishnan et al. 2012 , Utsuki et al. 2012 ). Median OS rates ranged from 7 up to 21 months. Discussion Cerebellar-located glioblastoma is a rare entity, occurring only in 0.4–3.4% of all cases of glioblastoma in adults (Babu et al. 2013 ). The scarcity of data concerning this patient group leads to a significant deficiency in available information. This deficit impedes the attainment of a comprehensive understanding of both clinical and biological characteristics inherent to this highly selective tumor entity. Recent published data suggest cerebellar and supratentorial glioblastoma to be characterized by significantly different frequencies of molecular subclasses (Schulte et al. 2020 ). Zhou et al., for example, revealed an independent role as prognostic factor of OLIG2 expression for patients with cerebellar glioblastoma (Zhou et al.2023). Further molecular analysis revealed that cerebellar glioblastoma themselves comprised a quite heterogen, methylation profile-based tumor entity with the so-called AAP subclass (anaplastic astrocytoma with piloid features) among the most frequent (Reinhardt et al. 2019 ). With regard to topographical, molecular and histopathological characteristics among others, cerebellar glioblastoma might imply quite different long-term outcome pattern than in case of their supratentorial counterparts. Unfortunately, due to the rare incidence of a cerebellar tumor localization of high-grade astrocytoma, existing literature on survival rates of cerebellar glioblastoma fails to present any sort of homogenous data pool. Referred to data collected from 3 up to 14 patients with cerebellar glioblastoma between 1975 and 2011, several previous retrospective studies have reported worse OS for cerebellar glioblastoma compared to supratentorial located glioblastoma (Babu et al. 2013 , Gopalakrishnan et al. 2012 ). In contrast, analyzing a more contemporary single-center experience with 5 patients between 2002 and 2012, Milinkovic et al. in turn described a significant survival advantage of cerebellar glioblastoma patients compared to a pooled cohort of patients with supratentorial glioblastoma with an OS of 18 months (Milinkovic et al. 2014 ). Such inconsistent outcome data might partly be ascribed to molecular, histopathological as well as clinical and surgical intrinsic individual features that might lead to a selection bias in a vanishingly low number of patients with cerebellar glioblastoma. Key factors influencing glioblastoma prognosis include patient age at surgery, KPS at admission, the extent of tumor resection in terms of STR and GTR, and MGMT promoter methylation status (Li et al. 2016 , McGirt et al. 2009 , Radke et al. 2019 , Smrdel et al. 2016 ). Furthermore, advancements in microsurgical techniques and more tailored chemotherapeutic strategies based on MGMT-promoter methylation status over the past 10 to 20 years have influenced survival outcomes. This progress, coupled with the implementation of the Stupp protocol since 2005 (Stupp et al. 2005 ) as the standard care, has markedly improved survival rates. Therefore, comparing current survival data with those from earlier periods (up to 30–50 years ago) may not accurately reflect the outcomes of patients treated under contemporary standards (Jeswani et al. 2013 , Takahashi et al. 2014 ). To the best of our knowledge, the present study is the first to apply propensity score matching using established prognostic factors to facilitate a more robust comparative survival analysis between cerebellar and supratentorial glioblastoma patients that had undergone surgical resection starting in 2005. Our findings suggest, that survival rates for patients with cerebellar glioblastoma do not significantly differ from those with supratentorial glioblastoma. In particular, the OS rate of our patient cohort with cerebellar glioblastoma was comparable to the latest available data from other institutions (Milinkovic et al. 2014 , Cho et al. 2019 , Utsuki et al. 2012 ). Further, PFS rates did not significantly differ between these entities of different glioblastoma localizations. Although there are only few publications reporting data on PFS of patient with cerebellar glioblastoma, the acknowledged data appears to be similar to our population (Hong et al. 2018 , Picart et al. 2018 , Milinkovic et al. 2014 , Gopalakrishnan et al. 2012 , Utsuki et al. 2012 ). However, there is a lack of sufficient data from multi-center studies that allows a valid assessment of survival of cerebellar glioblastoma patients especially taking into account possible histological or histochemical heterogeneity. Further multicenter-based studies are instantly needed in order to become able to sufficiently cope with the challenges during interdisciplinary modern treatment and aftercare of patients suffering from cerebellar glioblastoma. Limitations The present study has several limitations. Statistical analysis and data collection of the institutional data was retrospective and comprised only a small cohort. Additionally, the diagnoses followed the 2016 WHO classification. A subsequent reclassification according to the 2021 WHO classification was not possible, as some tumor samples were no longer available. Furthermore, all extracted individual data within the systematic review of the literature was also previously collected in a retrospective manner. Given the rarity of cerebellar glioblastoma, provisioning of Level I evidence with a Grade A recommendation is highly uncertain. Nevertheless, the use of a matched pair approach might outweigh some confounding factors regarding the comparison to supratentorial glioblastoma. This could provide sufficient support in order to justify the conception and establishment of a large-scale, cross-regional database for further analysis of the rare entity of cerebellar glioblastoma. Conclusions The present findings indicate no significant difference in the prognosis between patients with supratentorial and infratentorial glioblastomas. Current data on cerebellar glioblastomas is notably scarce and predominantly derives from single center series encompassing only a small cohort of patients. The establishment of large-scale, multicenter databases will be instantly needed in order to be capable to sufficiently cope with this inadequately represented subpopulation of glioblastoma patients. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: Conceptualization: P.S. and M.S.; methodology: Y.L. and A.-L.P.; software: A.-L.P.; validation: Y.L., P.S. and M.S.; writing – original draft preparation: P.S. and M.S.; writing – review and editing: Y.L., A.-L.P., N.S., A.W., V.B., U.H., H.V., P.S. and M.S.; visualization: Y.L. and A.-L.P.; supervision: P.S. and M.S.. Ethical approval: The present study was approved by the local ethics committee of the University of Bonn (228/19). Consent to participate: Informed consent was not sought in regard of the retrospective design. Consent for publication: All authors have read and approved the final manuscript. Availability of data and material: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. 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Cerebellar localization n=8 Supratentorial localization n= 32 p-value Matching parameters Median age (years, IQR) 70 (64-76) 66 (55-74) 0.22 Median KPS at admission (IQR) 65 (60-70) 70 (60-80) 0.33 EOR (STR/GTR) 1/7 8/24 0.45 IDH-Status (wt/-) 7/- Ω 32/0 - MGMT-promoter methylation 5 26 0.26 Outcome parameters Median PFS (mo, 95% CI) 8 (4-12) 7 (0-16) 0.2 Median OS (mo, 95% CI) 18 (11-25) 23 (0-62) 0.63 Ω 7 patients due to 1 patient with missing IDH status EOR, extent of resection; IDH, isocitrate dehydrogenase; GTR, gross total resection; KPS, Karnofsky performance scale; mo, months; MGMT, O-6-methylguanine-DNA methyltransferase; OS, overall survival; PFS, progression-free survival; STR, subtotal resection; wt, Wild-type; yrs, years. Table 2: Contemporary systematic review of the literature for cerebellar glioblastoma First author (year) Number of Patients included in further analysis Mean age (years) Mean KPS pre EOR (STR/GTR) MGMT Median PFS (m) Median OS (m) Hong B. et al. (2018) 6 48 na 3 / 3 5 3 7 Cho HJ. et al. (2019) 19 57 na na na na 21 Picart T. et al. (2018) 14 53 na na/8 3 4 8 Takahashi Y. et al. (2014) 9 56 68 na/2 na na 9 Milinkovic VP. et al. (2014) 5 46 na na/2 na 8 18 Gopalakrishnan C. et al. (2012) 4 50 92 0/4 na 10,4 9 Utsuki S. et al. (2012) 4 49 na 2 / 2 na 8 20.5 Present series (2023) 8 68.5 65 1/7 5 8 18 Total 69 53.4 75 - - 8 13.5 EOR, extent of resection; IDH, isocitrate dehydrogenase; GTR, gross total resection; KPS, Karnofsky performance scale; mo, months; MGMT, O-6-methylguanine-DNA methyltransferase; OS, overall survival; PFS, progression-free survival; STR, subtotal resection. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 28 Sep, 2024 Read the published version in Journal of Cancer Research and Clinical Oncology → Version 1 posted Editorial decision: Revision requested 16 Jul, 2024 Reviews received at journal 03 Jul, 2024 Reviews received at journal 02 Jul, 2024 Reviews received at journal 01 Jul, 2024 Reviews received at journal 30 Jun, 2024 Reviewers agreed at journal 28 Jun, 2024 Reviewers agreed at journal 25 Jun, 2024 Reviewers agreed at journal 23 Jun, 2024 Reviews received at journal 21 Jun, 2024 Reviewers agreed at journal 21 Jun, 2024 Reviewers agreed at journal 20 Jun, 2024 Reviewers agreed at journal 20 Jun, 2024 Reviews received at journal 20 Jun, 2024 Reviewers agreed at journal 20 Jun, 2024 Reviewers invited by journal 18 Jun, 2024 Editor assigned by journal 18 Jun, 2024 Submission checks completed at journal 18 Jun, 2024 First submitted to journal 16 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4590644","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":322366135,"identity":"5d10c967-f278-42b5-9626-6b2f61401751","order_by":0,"name":"Yauhen Lizunou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYHACNhAhwwbh2DBISIAZzAS18EC1pJGgBco5TFiLwfEzZg8+7mDg4eMHMdrOJ86c3XzscQGDtRxOLWdyzA1nngE57AyQ0XY7cbbMsXTjGQzpxji1HMgxk+ZtA2ph7AExbifOkwCK8DAcTmzApeX8GzPpvyAtzDwgLefgWupxarkBVMAI0sIG1nIgcTZUSwIuh0neeFYm2dsmwcPGw1YmOeNcsvHMOcfSpHkM0g1x2cJ3PnmbxM82Gzn5/sPbJD6U2cnOuN18TJqnwloely0KB8CUBIaDcWlgYJDHZf0oGAWjYBSMAjgAALukSaoC48nkAAAAAElFTkSuQmCC","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":true,"prefix":"","firstName":"Yauhen","middleName":"","lastName":"Lizunou","suffix":""},{"id":322366136,"identity":"02997ca9-a2d0-4f23-b71d-8c4a6cd49669","order_by":1,"name":"Anna-Laura Potthoff","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"Anna-Laura","middleName":"","lastName":"Potthoff","suffix":""},{"id":322366138,"identity":"b247c81c-5ad6-4d8f-bc42-46020c49be92","order_by":2,"name":"Niklas Schäfer","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"Niklas","middleName":"","lastName":"Schäfer","suffix":""},{"id":322366139,"identity":"d95c002a-896d-4fa9-a588-54c9b54a21f7","order_by":3,"name":"Andreas Waha","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Waha","suffix":""},{"id":322366140,"identity":"1d9b0a86-7522-49b8-8e86-83014e4cddc1","order_by":4,"name":"Valeri Borger","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"Valeri","middleName":"","lastName":"Borger","suffix":""},{"id":322366141,"identity":"4ca865b0-54cc-4a53-b142-6e077b1e4e91","order_by":5,"name":"Ulrich Herrlinger","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"Ulrich","middleName":"","lastName":"Herrlinger","suffix":""},{"id":322366142,"identity":"818bd4f3-c979-4990-b6ba-2b776542c55d","order_by":6,"name":"Hartmut Vatter","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"Hartmut","middleName":"","lastName":"Vatter","suffix":""},{"id":322366143,"identity":"cceaa36d-903c-4ce7-95f3-d685aac414e4","order_by":7,"name":"Patrick Schuss","email":"","orcid":"","institution":"BG Klinikum Unfallkrankenhaus Berlin gGmbH","correspondingAuthor":false,"prefix":"","firstName":"Patrick","middleName":"","lastName":"Schuss","suffix":""},{"id":322366144,"identity":"49ebea17-e138-4856-8156-930977ecd28d","order_by":8,"name":"Matthias Schneider","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"Matthias","middleName":"","lastName":"Schneider","suffix":""}],"badges":[],"createdAt":"2024-06-16 18:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4590644/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4590644/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00432-024-05959-0","type":"published","date":"2024-09-28T15:57:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60446567,"identity":"d3718a03-93f9-4501-8852-e61a2453e8ba","added_by":"auto","created_at":"2024-07-16 21:55:40","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":351955,"visible":true,"origin":"","legend":"\u003cp\u003eIllustration of matching procedure between cerebellar and supratentorial glioblastoma patients.\u003c/p\u003e\n\u003cp\u003e(A) Comparative matched pair analysis at a ratio of 1:4 identifies 32 out of 205 patients with supratentorial glioblastoma that individually correspond to the present series of 8 patients with cerebellar glioblastoma. Heat map as color-coded illustration of the matching strategy of supratentorial glioblastoma to individually-matched cerebellar glioblastoma cases by means of age at admission, KPS at admission, EOR as well as MGMT promoter methylation status as matching parameters. Red frames depict individually-matched supratentorial glioblastoma patients. (B) Visualization of mean difference between patients with supratentorial glioblastoma (purple stands for all patients and black - for patients after matching). (C) Visualization of obtained propensity scores for matched and unmatched glioblastoma patients. EOR, extent of resection; KPS, Karnofsky performance scale; MGMT, O6-methylguanine-DNA methyltransferase.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4590644/v1/0d29df77cedb07a4b153a860.jpeg"},{"id":60447496,"identity":"3aa0d2b5-4f5a-4bf1-b31c-be9bff658bae","added_by":"auto","created_at":"2024-07-16 22:03:40","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":255510,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival analysis for cerebellar and individual matched supratentorial glioblastoma patients\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4590644/v1/56cc62aa8c7ae5593d94ebec.jpeg"},{"id":60447497,"identity":"fdcebce4-6b6f-4bc1-bdeb-2ed0bd7771dc","added_by":"auto","created_at":"2024-07-16 22:03:40","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":219583,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-free survival analysis for cerebellar and individual matched supratentorial glioblastoma patients\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4590644/v1/5f00b45c94e67d59410769ae.jpeg"},{"id":60446569,"identity":"116f6709-fe27-4880-aa56-83fd56b6bcda","added_by":"auto","created_at":"2024-07-16 21:55:40","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":381308,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart depicting the search strategy for contemporary review of the literature regarding survival in cerebellar glioblastoma patients.\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4590644/v1/57961d7d961209491a1a4104.jpeg"},{"id":65627161,"identity":"51fd357a-03b5-4e95-ab13-b2cc6e710796","added_by":"auto","created_at":"2024-09-30 16:12:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1749573,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4590644/v1/61754273-621a-443e-836b-f35c5f59fdab.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cerebellar glioblastoma in adults: a comparative single-center matched pair analysis and systematic review of the literature","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlioblastoma ranks among the most aggressive primary malignant brain tumors in adults (Ostrom et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Numerous studies have been undertaken to hasten the development of more advanced treatment strategies through diverse therapeutic and surgical methods (Potthoff et al. \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2019\u003c/span\u003e, Schneider et al. 2019, Venkataramani et al. \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2022\u003c/span\u003e, Dejonckheere et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Glioblastomas are most commonly found in the supratentorial region, with less than 1% occurring in the cerebellum (Tsung et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Previous research has highlighted distinct molecular and clinical profiles between supratentorial and cerebellar glioblastomas, suggesting that cerebellar glioblastoma may represent a distinct subgroup (Adams et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2013\u003c/span\u003e, Hong et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Nonetheless, survival data on cerebellar glioblastoma remain sparse, and existing reports often rely on extended historical data sets and varied therapeutic approaches, which may affect consistency (Adams et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2013\u003c/span\u003e, Levine et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e1987\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn response to this gap, we analyzed institutional data on adult cerebellar glioblastoma and conducted a matched-pair analysis to draw comparisons with supratentorial glioblastoma patients treated at our facility. Additionally, we performed a systematic review of the literature, extracting individual participant data to juxtapose our findings with the broader corpus of clinical research on this rare form of glioblastoma.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003ePatients aged 18 years or older with newly diagnosed glioblastoma who underwent surgical intervention at our institution between 2009 and 2020 were systematically entered into a computerized database (SPSS, version 27, IBM Corp., Armonk, NY). We excluded patients with cerebellar glioblastoma who only had a biopsy and those with additional tumor infiltration into the brainstem. Our study adhered to the principles of the Helsinki Declaration and received approval from the institutional ethics committee (228/19). Informed consent was not sought in regard of the retrospective study design.\u003c/p\u003e \u003cp\u003eWe meticulously recorded data, including patient demographics, radiological findings, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and functional neurological status objectified by the Karnofsky performance scale (KPS) at both admission and throughout the course of treatment as previously described (Schneider et al. 2020, Borger et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2021\u003c/span\u003e, Schneider et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2021\u003c/span\u003e, Schneider et al. 2020). The institutional interdisciplinary tumor board made treatment decisions, encompassing the extent of neurosurgical intervention and postoperative care (Sch\u0026auml;fer et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe extent of resection (EOR) was determined based on early postoperative 3.0-Tesla MRI scans conducted within 72 hours following surgery. Definitions of gross-total resection (GTR) and subtotal resection (STR) corresponded to the removal of more than 95% and less than 95% of the initial contrast-enhancing tumor tissue, respectively (Shonka and Aizenberg \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2017\u003c/span\u003e, (Schneider et al. 2019).\u003c/p\u003e \u003cp\u003eFollowing histopathological confirmation of glioblastoma, MGMT promoter methylation status was ascertained using pyrosequencing and combined bisulfite restriction analysis (Mikeska et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). Tumor classification followed the 2016 WHO classification criteria.\u003c/p\u003e \u003cp\u003eProgression-free survival (PFS) was defined as the interval from glioblastoma surgery to the date of radiological progression, as previously outlined (Zeyen et al. \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Tumor progression criteria followed the Response Assessment in Neuro-Oncology (RANO) guidelines with certain modifications (Herrlinger et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOverall survival (OS) was calculated from the date of glioblastoma surgery until the patient's death. Post-surgical treatment for all patients included adjuvant therapies according to the Stupp- (Stupp et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2005\u003c/span\u003e) or CeTeG-protocol (Herrlinger et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) in line with the institutional interdisciplinary tumor board's recommendations (Sch\u0026auml;fer et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMatching procedure\u003c/h2\u003e \u003cp\u003eFor the purpose of conducting a matched-pair analysis, the statistical computing software R was used (version 4.2.3; The R Foundation for Statistical Computing, available at [\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.r-project.org/\u003c/span\u003e\u003cspan address=\"https://www.r-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e]). The initial patient cohort comprised 205 consecutive individuals who had undergone surgery for supratentorial glioblastoma and 8 patients with cerebellar glioblastoma. We applied a multivariate approach and propensity score matching with an aim for balance optimization, setting a matching ratio of 1:4 as previously described (Hamed et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2022\u003c/span\u003e, Layer et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2023\u003c/span\u003e, Hamed et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our effort to enhance the balance between the matched pairs, we selected several generally-known prognostic factors for matching. These factors included age, Karnofsky Performance Scale (KPS) at admission, the extent of resection (EOR) categorized as either gross-total resection (GTR) or subtotal resection (STR), and MGMT promoter methylation status, as these have been identified as predictors on patient outcomes (Li et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2016\u003c/span\u003e, McGirt et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2009\u003c/span\u003e, Radke et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2019\u003c/span\u003e, Smrdel et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Subsequently, from the pool of patients with supratentorial glioblastoma, we selected 32 individuals as a control group (depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e), with the selection process conducted using the R software.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSystematic review of the literature\u003c/h2\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eSearch methods\u003c/h2\u003e \u003cp\u003eA systematic literature review was undertaken to gather current published data on survival outcome for cerebellar glioblastoma. We conducted a search on PubMed, covering publications from the years 2005 to 2023 as previously described (Schneider et al. 2019). The search utilized specific keywords: \"cerebellar glioblastoma,\" \"posterior fossa glioblastoma,\" and \"infratentorial glioblastoma,\" with the latest access on 31 December 2023. The initial phase involved scrutinizing titles and abstracts to determine their relevance to our research query. Subsequent to this preliminary assessment, we retrieved the full-text versions of all studies deemed pertinent for further evaluation.\u003c/p\u003e \u003cp\u003eTwo authors (PS and MS) independently reviewed the selected articles to ensure the thoroughness of the analysis. Any inconsistencies or discrepancies in their assessments were addressed in a consensus meeting that included the senior author (MS), ensuring a unified and conclusive selection. Moreover, we extended our search to include the reference lists of the identified articles, aiming to uncover any additional studies published within the specified timeframe that could contribute to the literature review.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSelection criteria\u003c/h2\u003e \u003cp\u003eArticles were included if they reported individual patient data on treatment in at least 4 patients with cerebellar glioblastoma. Studies reporting exclusively on pediatric patients were excluded. Furthermore, studies describing treatment of cerebellar glioblastoma with supratentorial fraction and/or brainstem involvement were excluded. Only articles written in English or German language were considered.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData collection and extraction\u003c/h2\u003e \u003cp\u003eIf reported the following data was extracted from qualifying articles: study design, number of patients with cerebellar glioblastoma, preoperative KPS, extent of resection, histopathological features, PFS, and OS. Not all studies provided data or information on each subset of patients. If by far included studies reported only insufficient data on the above-mentioned factors, these were excluded from further analysis. Therefore, comparative analysis was limited by the nature of the data source. If available, data was independently extracted and verified by two authors (PS and MS). No disagreements were found.\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eStatistics\u003c/h2\u003e \u003cp\u003eData analyses were performed using the computer software package SPSS (version 27, IBM Corp., Armonk, NY). Mann-Whitney U test was used for parametric statistics. Categorical variables were analyzed in contingency tables using Fisher\u0026rsquo;s exact test. Results with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. OS and PFS were analyzed by the Kaplan-Meier method. Events in survival curves were defined as radiographic tumor progression and death and compared by using the Gehan-Breslow-Wilcoxon test.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eBetween 2009 and 2020, 8 patients underwent surgical therapy for cerebellar glioblastoma at the authors\u0026rsquo; institution. Median age at the day of surgery was 70 years (IQR 64\u0026ndash;76) and GTR was performed in 7 out of 8 patients (88%). Molecular analysis revealed methylated and unmethylated MGMT-promoter status in 5 (63%) and 3 (37%) patients. The median OS rate was 18 months (95% CI 11\u0026ndash;25). For further details see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eComparative matched pair analysis reveals comparable survival rates for cerebellar and supratentorial glioblastoma\u003c/h2\u003e \u003cp\u003eIn order to compare median survival rates of the cohort of cerebellar glioblastoma patients and corresponding patients with supratentorial glioblastoma, we perfomred a multivariate and propensity score matching with additional balance optimization. Therefore, cerebellar glioblastoma patients were individually matched at a ratio of 1:4 to a cohort of 205 consecutive patients that had undergone resection of supratentorial glioblastoma at our university hospital between 2013 and 2018 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Patient age and KPS at admission, EOR as well as MGMT promoter methylation status as the main known clinical and molecular predictors for survival of glioblastoma patients were chosen as matching parameters. Hence, matched pair analysis yielded two individually matched cohorts of 8 cerebellar and 32 supratentorial glioblastoma patients that did not significantly differ with regard to above mentioned prognostic parameters (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Analysis of median OS rates revealed no statistically significant differences depending on the tumor localization: patients with cerebellar glioblastoma revealed an OS rate of 18 months (95% CI 11\u0026ndash;25) compared to 23 months (95% CI 0\u0026ndash;62) for individually matched supratentorial glioblastoma patients (p\u0026thinsp;=\u0026thinsp;0.63) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). PFS did also not significantly differ between the cerebellar cohort (8 months, 95% CI 4\u0026ndash;12) and the supratentorial cohort (7 months, 95% CI 0\u0026ndash;16), with p\u0026thinsp;=\u0026thinsp;0.2 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). For the total group of 205 patients with supratentorial glioblastoma, analysis of median OS rates yielded 17 months (95% CI 14,4\u0026ndash;18,6).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSystematic review of the literature concerning survival rates of patients with cerebellar glioblastoma\u003c/h2\u003e \u003cp\u003eThe PubMed search of the literature on cerebellar glioblastoma from 2005 to 2023 yielded 652 articles (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In consideration of a clear assignment of PFS and/or OS to the particular patient cohort as a further inclusion criterion beyond those mentioned in the methodological section, ultimately 7 studies were identified for further data analysis (Hong et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2018\u003c/span\u003e, Cho et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e, Picart et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2018\u003c/span\u003e, Takahashi et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2014\u003c/span\u003e, Milinkovic et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2014\u003c/span\u003e, Gopalakrishnan et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2012\u003c/span\u003e, Utsuki et al. \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Median OS rates ranged from 7 up to 21 months.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eCerebellar-located glioblastoma is a rare entity, occurring only in 0.4\u0026ndash;3.4% of all cases of glioblastoma in adults (Babu et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). The scarcity of data concerning this patient group leads to a significant deficiency in available information. This deficit impedes the attainment of a comprehensive understanding of both clinical and biological characteristics inherent to this highly selective tumor entity. Recent published data suggest cerebellar and supratentorial glioblastoma to be characterized by significantly different frequencies of molecular subclasses (Schulte et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Zhou et al., for example, revealed an independent role as prognostic factor of OLIG2 expression for patients with cerebellar glioblastoma (Zhou et al.2023).\u003c/p\u003e \u003cp\u003eFurther molecular analysis revealed that cerebellar glioblastoma themselves comprised a quite heterogen, methylation profile-based tumor entity with the so-called AAP subclass (anaplastic astrocytoma with piloid features) among the most frequent (Reinhardt et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). With regard to topographical, molecular and histopathological characteristics among others, cerebellar glioblastoma might imply quite different long-term outcome pattern than in case of their supratentorial counterparts.\u003c/p\u003e \u003cp\u003eUnfortunately, due to the rare incidence of a cerebellar tumor localization of high-grade astrocytoma, existing literature on survival rates of cerebellar glioblastoma fails to present any sort of homogenous data pool. Referred to data collected from 3 up to 14 patients with cerebellar glioblastoma between 1975 and 2011, several previous retrospective studies have reported worse OS for cerebellar glioblastoma compared to supratentorial located glioblastoma (Babu et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2013\u003c/span\u003e, Gopalakrishnan et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). In contrast, analyzing a more contemporary single-center experience with 5 patients between 2002 and 2012, Milinkovic et al. in turn described a significant survival advantage of cerebellar glioblastoma patients compared to a pooled cohort of patients with supratentorial glioblastoma with an OS of 18 months (Milinkovic et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2014\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSuch inconsistent outcome data might partly be ascribed to molecular, histopathological as well as clinical and surgical intrinsic individual features that might lead to a selection bias in a vanishingly low number of patients with cerebellar glioblastoma.\u003c/p\u003e \u003cp\u003eKey factors influencing glioblastoma prognosis include patient age at surgery, KPS at admission, the extent of tumor resection in terms of STR and GTR, and MGMT promoter methylation status (Li et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2016\u003c/span\u003e, McGirt et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2009\u003c/span\u003e, Radke et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2019\u003c/span\u003e, Smrdel et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Furthermore, advancements in microsurgical techniques and more tailored chemotherapeutic strategies based on MGMT-promoter methylation status over the past 10 to 20 years have influenced survival outcomes. This progress, coupled with the implementation of the Stupp protocol since 2005 (Stupp et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2005\u003c/span\u003e) as the standard care, has markedly improved survival rates. Therefore, comparing current survival data with those from earlier periods (up to 30\u0026ndash;50 years ago) may not accurately reflect the outcomes of patients treated under contemporary standards (Jeswani et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2013\u003c/span\u003e, Takahashi et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2014\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, the present study is the first to apply propensity score matching using established prognostic factors to facilitate a more robust comparative survival analysis between cerebellar and supratentorial glioblastoma patients that had undergone surgical resection starting in 2005. Our findings suggest, that survival rates for patients with cerebellar glioblastoma do not significantly differ from those with supratentorial glioblastoma.\u003c/p\u003e \u003cp\u003eIn particular, the OS rate of our patient cohort with cerebellar glioblastoma was comparable to the latest available data from other institutions (Milinkovic et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2014\u003c/span\u003e, Cho et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e, Utsuki et al. \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Further, PFS rates did not significantly differ between these entities of different glioblastoma localizations. Although there are only few publications reporting data on PFS of patient with cerebellar glioblastoma, the acknowledged data appears to be similar to our population (Hong et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2018\u003c/span\u003e, Picart et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2018\u003c/span\u003e, Milinkovic et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2014\u003c/span\u003e, Gopalakrishnan et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2012\u003c/span\u003e, Utsuki et al. \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, there is a lack of sufficient data from multi-center studies that allows a valid assessment of survival of cerebellar glioblastoma patients especially taking into account possible histological or histochemical heterogeneity.\u003c/p\u003e \u003cp\u003eFurther multicenter-based studies are instantly needed in order to become able to sufficiently cope with the challenges during interdisciplinary modern treatment and aftercare of patients suffering from cerebellar glioblastoma.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe present study has several limitations. Statistical analysis and data collection of the institutional data was retrospective and comprised only a small cohort. Additionally, the diagnoses followed the 2016 WHO classification. A subsequent reclassification according to the 2021 WHO classification was not possible, as some tumor samples were no longer available. Furthermore, all extracted individual data within the systematic review of the literature was also previously collected in a retrospective manner. Given the rarity of cerebellar glioblastoma, provisioning of Level I evidence with a Grade A recommendation is highly uncertain. Nevertheless, the use of a matched pair approach might outweigh some confounding factors regarding the comparison to supratentorial glioblastoma. This could provide sufficient support in order to justify the conception and establishment of a large-scale, cross-regional database for further analysis of the rare entity of cerebellar glioblastoma.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe present findings indicate no significant difference in the prognosis between patients with supratentorial and infratentorial glioblastomas. Current data on cerebellar glioblastomas is notably scarce and predominantly derives from single center series encompassing only a small cohort of patients. The establishment of large-scale, multicenter databases will be instantly needed in order to be capable to sufficiently cope with this inadequately represented subpopulation of glioblastoma patients.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interests:\u003c/strong\u003e The authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e Conceptualization: P.S. and M.S.; methodology: Y.L. and A.-L.P.; software: A.-L.P.; validation: Y.L., P.S. and M.S.; writing \u0026ndash; original draft preparation: P.S. and M.S.; writing \u0026ndash; review and editing: Y.L., A.-L.P., N.S., A.W., V.B., U.H., H.V., P.S. and M.S.; visualization: Y.L. and A.-L.P.; supervision: P.S. and M.S..\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e The present study was approved by the local ethics committee of the University of Bonn\u0026nbsp;(228/19).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e Informed consent was not sought in regard of the retrospective design.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u003c/strong\u003e The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAdams H, Chaichana KL, Avenda\u0026ntilde;o J et al (2013) Adult Cerebellar Glioblastoma: Understanding Survival and Prognostic Factors Using a Population-Based Database from 1973 to 2009. 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Clinics 78:100120. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.clinsp.2022.100120\u003c/span\u003e\u003cspan address=\"10.1016/j.clinsp.2022.100120\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003ePatient characteristics in the present series (value represents number of patients unless indicated otherwise).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"619\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCerebellar localization\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSupratentorial localization\u0026nbsp;\u003cbr\u003e\u0026nbsp;n= 32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMatching parameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian age (years, IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e70 (64-76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e66 (55-74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian KPS at admission (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e65 (60-70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e70 (60-80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEOR (STR/GTR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1/7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8/24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIDH-Status (wt/-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7/-\u003csup\u003eΩ\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32/0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMGMT-promoter methylation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOutcome parameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian PFS\u0026nbsp;(mo, 95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (4-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;7 (0-16)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian OS (mo, 95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18 (11-25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;23 (0-62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003eΩ\u003c/sup\u003e 7 patients due to 1 patient with missing IDH status\u003c/p\u003e\n\u003cp\u003eEOR, extent of resection; IDH,\u0026nbsp;isocitrate dehydrogenase; GTR, gross total resection; KPS, Karnofsky performance scale; mo, months; MGMT, O-6-methylguanine-DNA methyltransferase; OS, overall survival; PFS, progression-free survival; STR, subtotal resection; wt, Wild-type; yrs, years.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u0026nbsp;\u003c/strong\u003eContemporary systematic review of the literature for cerebellar glioblastoma\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFirst author (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNumber of Patients included in further analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMean age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMean KPS pre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eEOR (STR/GTR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMGMT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMedian PFS (m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMedian OS (m)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eHong B. et al. (2018)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 / 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCho HJ. et al. (2019)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ePicart T. et al. (2018)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena/8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eTakahashi Y. et al. (2014)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMilinkovic VP. et al. (2014)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eGopalakrishnan C. et al. (2012)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0/4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eUtsuki S. et al. (2012)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 / 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ePresent series (2023)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e68.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1/7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e53.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eEOR, extent of resection; IDH, isocitrate dehydrogenase; GTR, gross total resection; KPS, Karnofsky performance scale; mo, months; MGMT, O-6-methylguanine-DNA methyltransferase; OS, overall survival; PFS, progression-free survival; STR, subtotal resection.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"cerebellar glioblastoma, supratentorial glioblastoma, matched pair analysis, overall survival, propensity score matching","lastPublishedDoi":"10.21203/rs.3.rs-4590644/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4590644/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe rarity of cerebellar glioblastoma presents a significant challenge in clinical practice due to the lack of extensive prognostic data on long-term survival rates, rendering it an underrepresented entity compared to its supratentorial counterpart. This study aims to analyze potential differences in survival outcome between patients with cerebellar and supratentorial glioblastomas.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFrom 2009 to 2020, 8 patients underwent surgical treatment for cerebellar glioblastoma at the authors\u0026rsquo; institution. These patients were individually matched with a cohort of 205 consecutive patients from our institutional database with supratentorial glioblastoma, taking into account key prognostic parameters. We compared progression-free survival (PFS) and overall survival (OS) rates and performed a systematic literature review to compile additional survival data on cerebellar glioblastoma.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe median OS for cerebellar glioblastoma patients was 18 months (95% CI 11\u0026ndash;25). The balanced matched-pair analysis showed no significant difference in survival when compared to patients with supratentorial glioblastoma, exhibiting a median OS of 23 months (95% CI 0\u0026ndash;62) (p\u0026thinsp;=\u0026thinsp;0.63). Respective values for PFS were 8 months (95% CI 4\u0026ndash;12) for cerebellar and 7 months (95% CI 0\u0026ndash;16) for supratentorial glioblastoma (p\u0026thinsp;=\u0026thinsp;0.2). The systematic review revealed that median OS for cerebellar glioblastoma in current literature ranges from 7 to 21 months.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe present findings indicate that patients with supra- and infratentorial glioblastoma do not significantly differ in regard to survival outcome parameters. This similarity in prognosis might encourage clinicians to consider surgical interventions for both supra- and infratentorial BMs in a similar manner.\u003c/p\u003e","manuscriptTitle":"Cerebellar glioblastoma in adults: a comparative single-center matched pair analysis and systematic review of the literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-16 21:55:35","doi":"10.21203/rs.3.rs-4590644/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-16T13:56:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-03T17:39:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-02T21:15:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-02T03:40:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-01T00:03:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"204196385591450960386492348479532758056","date":"2024-06-28T17:24:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"255983621652056195994090329403513587659","date":"2024-06-25T22:51:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"25098377377835351453287964598753051988","date":"2024-06-23T18:18:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-21T15:47:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97319875769946160463421083525268416076","date":"2024-06-21T06:51:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"104267030787965916891015089048999521893","date":"2024-06-21T03:42:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"212353407899783972533251078803028508208","date":"2024-06-21T00:49:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-20T16:42:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"23311605845768420663756353814658284060","date":"2024-06-20T09:52:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-18T18:04:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-18T12:00:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-18T11:58:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cancer Research and Clinical Oncology","date":"2024-06-16T17:56:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"cfcfdd0e-a789-4119-9457-e847df864d12","owner":[],"postedDate":"July 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-30T16:00:34+00:00","versionOfRecord":{"articleIdentity":"rs-4590644","link":"https://doi.org/10.1007/s00432-024-05959-0","journal":{"identity":"journal-of-cancer-research-and-clinical-oncology","isVorOnly":false,"title":"Journal of Cancer Research and Clinical Oncology"},"publishedOn":"2024-09-28 15:57:06","publishedOnDateReadable":"September 28th, 2024"},"versionCreatedAt":"2024-07-16 21:55:35","video":"","vorDoi":"10.1007/s00432-024-05959-0","vorDoiUrl":"https://doi.org/10.1007/s00432-024-05959-0","workflowStages":[]},"version":"v1","identity":"rs-4590644","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4590644","identity":"rs-4590644","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}