Treatment patterns of Central Nervous System Tumors in the Veneto Region, Italy: A Population-Based Registry Study (2016-2020)

Treatment patterns of Central Nervous System Tumors in the Veneto Region, Italy: A Population-Based Registry Study (2016-2020) | 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 Treatment patterns of Central Nervous System Tumors in the Veneto Region, Italy: A Population-Based Registry Study (2016-2020) Eliana Ferroni, Alessandra Andreotti, Stefano Guzzinati, Susanna Baracco, and 19 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8171188/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose This study provides the first population-based overview of therapeutic approaches for adult CNS tumors in Italy using integrated cancer registry and administrative healthcare data. Methods All adult CNS tumors diagnosed between 2016 and 2020 were identified in the Veneto Cancer Registry. Tumor grade was extracted using a validated text-mining algorithm, and surgical and oncologic treatments were retrieved from administrative datasets and analyzed by histology, grade, and diagnostic approach. Results A total of 1,634 histologically confirmed CNS tumors were included. Glioblastoma was the most frequent subtype (64.6%), followed by grade 2–3 meningiomas (18.2%). Most glioblastomas (80%) and all meningiomas underwent resection, whereas biopsies were more common in grade 2–3 astrocytomas (23–30%) and oligodendrogliomas (10–11%). Adjuvant chemoradiotherapy was the predominant treatment in glioblastoma (60.2%), grade 3 astrocytoma (65.2%) and oligodendroglioma (58%). In recurrent grade 4 astrocytomas, nitrosoureas and regorafenib were the most frequently used therapies. Among low-grade tumors, 68.9% of astrocytomas and 63.9% of oligodendrogliomas received radiotherapy, chemotherapy, or both as adjuvant therapy. Non-biopsied patients rarely received active treatment and had poor survival, with better 1-year survival observed in those who received chemotherapy or radiotherapy alone. Conclusions This population-based study outlines real-world CNS tumor management in the Veneto Region, showing that most patients undergo surgery and that oncologic strategies vary by tumor type and grade. Integrating registry and administrative data allows effective monitoring of treatment patterns and supports improvements in multidisciplinary care and access. Central Nervous System Tumors Follow-up Histology Tumor Grade Cancer Registry Introduction Primary brain and central nervous system (CNS) tumors - hereafter referred to as CNS tumors - affect both children and adults and can arise in all anatomical regions of the central nervous system. The vast majority (over 90%) occur in the brain, with the remaining cases affecting the meninges, spinal cord, and cranial nerves [ 1 ]. The most common histological type of primary CNS cancer is glioma, which includes a broad spectrum of malignant brain tumors. These range from high-grade gliomas, such as glioblastomas, to low-grade gliomas like astrocytomas and oligodendrogliomas. Other less common histological types include glial-origin tumors such as ependymomas and schwannomas, as well as medulloblastomas, CNS lymphomas, and meningiomas. According the latest GLOBOCAN estimates produced by the International Agency for Research on Cancer (IARC), approximately 340,000 new cases of CNS cancer are diagnosed globally in 2025 [ 1 ]. Although CNS cancers account for only about 2% of all cancers, they represent a major source of morbidity and mortality worldwide. The 5-year overall survival rate for malignant CNS tumors is less than 35% [ 2 ]. In the 27-member European Union (EU27), approximately 28,000 brain tumors are diagnosed annually. Unlike some industrialized countries, such as the United States and the United Kingdom, where incidence rates have shown a steady increase, the incidence of CNS tumors in Italy has remained relatively stable in recent years [ 3 ]. Several studies based on cancer registries have been published, with reported incidence rates ranging from 9.53 per 100,000 in Liguria to 25.3 per 100,000 in Sicily [ 4 – 7 ]. However, while incidence and survival have been recently characterized in the Veneto Region, data on treatment patterns and care pathways are still lacking. Several key principles guide treatment options (surgery, chemotherapy, radiotherapy) for adults with brain tumors. Regardless of tumor histology, the best outcomes are generally achieved when neurosurgeons perform a maximal safe resection - removing as much of the tumor as possible while minimizing surgical morbidity and preserving neurological function. Equally important is obtaining an accurate diagnosis by collecting a sufficient amount of representative tumor tissue [ 8 ]. To our knowledge, data on treatment of CNS tumors by histologic grade or differentiation remain limited. The aim of our study was to describe the treatment approaches of malignant brain tumors and meningiomas grade 2–3 among residents of the Veneto Region (Northeastern Italy) during the period 2016–2020, based on data from the Veneto Cancer Registry, with a specific focus on the most common histological subtypes. Materials and methods This study is based on the cohort of adult patients with CNS tumors from the Veneto Region, previously described in our analysis of incidence and survival for the period 2016–2020 [ 9 ]. Inclusion criteria, data sources, and data collection methods remain consistent, allowing for an integrated analysis of surgical interventions and therapeutic treatments within the established population-based framework. The CNS tumor groups analised are: Glioblastoma, IDH-wildtype and IDH-mutant (IDH - Isocitrate Dehydrogenase); Astrocytoma grade 2–3; Meningioma grade 2–3; Oligodendroglioma grade 2–3; Ependymoma grade 2–3; CNS embryonal tumor (medulloblastoma) [ 9 ]. In order to analyse the clinical pathways of the study population, patients were individually linked to the main regional administrative healthcare databases. These include Hospital Admissions (HA), Outpatient Services (OPS), Drug Prescriptions (DP), and Hospital Drugs (HD). Surgical procedures for CNS tumors were identified within the HA database looking for specific ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification ) codes [ 10 ], both in the primary procedure and in the secondary ones (01.11, 01.13&01.18, 01.14, 01.19, 01.23, 01.24, 01.25, 01.31, 01.39, 01.51, 01.52, 01.53, 01.59, 02.99, 03.09, 03.4). Within the HA database, also chemotherapy (diagnosis codes V58.11-V58.12 or surgical procedure code 99.25) and radiotherapy (diagnosis code V58.0 or procedure codes 92.20-92.29) were detected. Within the OPS database, chemotherapy was traced using ICD-9-CM code 99.25.1, 99.25.2 while radiotherapy was identified using ICD-9-CM codes 92.2*. The pharmaceutical data flows, which comprise both HD and DP databases, were also used to identify chemotherapy treatments (ATC - Anatomical Therapeutic Chemical - codes L01AX03, L01EX05, L01AD02, L01AD05). An exploratory analysis was undertaken to characterize the subgroup of 918 patients with CNS tumors diagnosed through radiological imaging, without histopathological confirmation. Descriptive statistical analyses were conducted considering clinical and demographic variables. Data were stratified by sex, age group (18–49, 50–69, and ≥ 70 years), morphology and grade. For continuous variables, measures of central tendency and variability were reported as appropriate; while categorical variables were summarized using absolute and relative frequencies. Statistical analyses were performed using the R software, release 4.3.2 [ 11 ], and SAS Enterprise Guide 7.1 software [ 12 ]. Results We described the follow-up of 1,634 incident adult cases, diagnosed with CNS tumors from 2016 to 2020, and recorded in the Veneto Cancer Registry (VCR). This cohort included different histological subtypes of CNS tumors with intermediate to high-grade confirmed pathology. Compared to the results reported in a previous paper [ 9 ], two patients were excluded from these analyses because they had histopathological confirmation based on brain tissue obtained during autopsy procedures. Main characteristics of CNS tumors Glioblastoma was the most common type of CNS tumor, accounting for 64.6% of cases, followed by meningiomas grade 2–3 (18.2%) and astrocytomas grade 2–3 (9.4%) (Table 1 ). Glioblastomas and astrocytomas were more frequently observed in males (61.4% and 57.5%, respectively), whereas meningiomas were more prevalent in females (58%). Table 1 Characteristics of CNS tumors, by cancer type, sex, age group and tumor grade Cancer type Male N (%) Female N (%) 18–49 y N (%) 50–69 y N (%) 70 + y N (%) Grade 2 N (%) Grade 3 N (%) Grade 4 N (%) Total N (%) Glioblastoma IDH-wildtype and IDH-mutant 648 (61.4) 407 (38.6) 121 (11.5) 596 (56.5) 338 (32.0) - - 1,055 (100.0) 1,055 (64.6) Astrocytoma grade 2–3 88 (57.5) 65 (42.5) 70 (45.8) 58 (37.9) 25 (16.3) 61 (39.9) 92 (60.1) - 153 (9.4) Meningioma grade 2–3 125 (42.0) 173 (58.0) 47 (15.8) 120 (40.2) 131 (44.0) 272 (91.3) 26 (8.7) - 298 (18.2) Oligodendroglioma grade 2–3 46 (62.2) 28 (37.8) 38 (51.4) 28 (37.8) 8 (10.8) 36 (48.7) 38 (51.3) - 74 (4.5) Ependymoma grade 2–3 23 (59.0) 16 (41.0) 20 (51.3) 17 (43.6) 2 (5.1) 34 (87.2) 5 (12.8) - 39 (2.4) CNS embryonal tumor (medulloblastoma) 8 (53.3) 7 (46.7) 11 (73.3) 1 (6.7) 3 (20.0) - - 15 (100.0) 15 (0.9) Total 938 (57.4) 696 (42.6) 307 (18.8) 820 (50.2) 507 (31.0) 403 (24.7) 161 (9.8) 1,070 (65.5) 1,634 (100.0) Most CNS tumors were diagnosed in patients aged 50–69 years (50.2%), followed by those aged 70 and older (31.0%) and 18–49 years (18.8%). Glioblastomas were most common in the 50–69 age group (56.5%), while astrocytomas grade 2–3 and oligodendrogliomas grade 2–3 showed a younger age distribution, with 45.8% and 51.4% of cases occurring in patients aged 18–49, respectively (Table 1 ). High-grade meningiomas were more frequent in older patients (84.2% aged ≥ 50); while medulloblastomas predominantly affected the youngest group (73.3% aged 18–49). High-grade tumors (grade 4) accounted for the majority of cases (65.5%), with glioblastomas accounted for almost all of the grade 4 tumors in the cohort (98.6%) (Table 1 ). Astrocytomas grade 2–3 and oligodendrogliomas grade 2–3 were more evenly distributed across grades 2 and 3, with 60.1% of astrocytomas and 51.3% of oligodendrogliomas classified as grade 3. Meningiomas and ependymomas were predominantly grade 2 (91.3% and 87.2%, respectively). [Insert Table 1 here] Patterns of neurosurgical management of CNS tumors Most patients underwent one surgical intervention (80.6%), while 9.3% had two or more surgeries and 10.1% only had a biopsy (Table 2 ). Table 2 Characteristics of patients by cancer type and surgical procedure (biopsy or surgery) Cancer type Only biopsy N (%) Only 1 surgery N (%) More than 1 surgery* N (%) Total N (%) Glioblastoma IDH-wildtype and IDH-mutant 121 (11.5) 849 (80.4) 85 (8.1) 1,055 (64.6) Astrocytoma grade 2 14 (23.0) 36 (59.0) 11 (18.0) 61 (3.7) Astrocytoma grade 3 28 (30.4) 54 (58.7) 10 (10.9) 92 (5.6) Meningioma grade 2 0 (0.0) 242 (89.0) 30 (11.0) 272 (16.7) Meningioma grade 3 0 (0.0) 20 (76.9) 6 (23.1) 26 (1.6) Oligodendroglioma grade 2 2 (5.6) 30 (83.3) 4 (11.1) 36 (2.2) Oligodendroglioma grade 3 0 (0.0) 34 (89.5) 4 (10.5) 38 (2.3) Ependymoma grade 2 0 (0.0) 33 (97.1) 1 (2.9) 34 (2.1) Ependymoma grade 3 0 (0.0) 4 (80.0) 1 (20.0) 5 (0.3) CNS embryonal tumor (medulloblastoma) 0 (0.0) 15 (100.0) 0 (0.0) 15 (0.9) Total 165 (10.1) 1,317 (80.6) 152 (9.3) 1,634 (100.0) * The category “ More than 1 surgery ” includes patients who underwent two or more re-operations at different time points. In general, patients who had surgery within three months of the initial biopsy were classified under the “ Only 1 surgery ” group; otherwise, they were included in the “ More than 1 surgery ” category. Patients with glioblastoma were most likely to have one surgery (80.4%), whereas 11.5% just had a biopsy. Nearly one-third (23% and 30.4% for grade 2 and 3, respectively) of patients with astrocytomas only had a biopsy, whereas about 59% had a single surgical procedure. On the other hand, nearly all meningioma patients (89% grade 2 and 76.9% grade 3) had only one surgery. Similar trends have been observed for oligodendroglioma, ependymoma, and medulloblastoma, where the most frequent treatment was surgical resection (Table 2 ). [Insert Table 2 here] The overall proportion of patients undergoing any neurosurgical procedure (biopsy or resection) remained stable between 2016 and 2020, indicating consistent access to surgical treatment across the study period. However, the proportion of patients undergoing more than one surgical procedure during the disease course increased, particularly among those with glioblastoma. In this group, repeated surgeries rose from approximately 8% in 2016 to more than 30% in 2020, suggesting a gradual shift toward a more proactive surgical approach in selected recurrent cases (Supplementary Material 1: Table 1 and Table 2 ). Patterns of oncologic treatments of CNS tumors Significant differences in the use of chemotherapy and radiotherapy among CNS tumor types and grades were found (Table 3 ). Overall, 46.6% of patients underwent both chemo and radiotherapy, 12.9% only chemotherapy, 8.6% only radiotherapy. One third of the study cohort (n = 521) received no therapy, of which 231 patients had meningioma grade 2 and 196 had glioblastoma. Astrocytoma grade 3 and glioblastoma patients received both treatment in 65.2% and 60.1% of cases, respectively. Grade 3 oligodendroglioma frequently were treated with both chemo and radiotherapy (57.9%). Among patients with recurrent histologically diagnosed grade 4 astrocytoma who received active therapy after progression, the most frequently used treatments were fotemustine or lomustine in approximately 70% of cases, whereas the remaining patients were treated with regorafenib or temozolomide rechallenge (data not shown). These data reflect current real-world practice in Italy although, regorafenib became available in Italy only in 2020, which may have limited its use during the study period. Table 3 Characteristics of patients by cancer type and oncological treatments (chemotherapy and radiotherapy) Cancer type Only chemo Only radio Both None N (%) N (%) N (%) N (%) Glioblastoma IDH-wildtype and IDH-mutant 149 (14.1) 75 (7.1) 635 (60.2) 196 (18.6) Astrocytoma grade 2 13 (21.3) 7 (11.5) 22 (36.1) 19 (31.1) Astrocytoma grade 3 16 (17.4) 5 (5.4) 60 (65.2) 11 (12.0) Meningioma grade 2 5 (1.8) 33 (12.1) 3 (1.1) 231 (84.9) Meningioma grade 3 0 (0.0) 11 (42.3) 0 (0.0) 15 (57.7) Oligodendroglioma grade 2 12 (33.3) 2 (5.6) 9 (25.0) 13 (36.1) Oligodendroglioma grade 3 12 (31.6) 1 (2.6) 22 (57.9) 3 (7.9) Ependymoma grade 2 1 (2.9) 2 (5.9) 2 (5.9) 29 (85.3) Ependymoma grade 3 1 (20.0) 0 (0.0) 2 (40.0) 2 (40.0) CNS embryonal tumor (medulloblastoma) 2 (13.3) 4 (26.7) 7 (46.7) 2 (13.3) Total 211 (12.9) 140 (8.6) 762 (46.6) 521 (31.9) Among low-grade gliomas (grade 2), postoperative oncologic treatment was frequently adopted. Specifically, 68.9% of astrocytoma grade 2 cases and 63.9% of oligodendroglioma grade 2 cases received adjuvant therapy with radiotherapy, chemotherapy, or both, whereas the remaining patients were managed with surgery alone (Table 2 ). Among low-grade ependymomas, 85.3% of patients did not receive any oncological treatment. Treatment patterns varied significantly by grade for meningiomas. Although most grade 2 meningiomas (84.9%) did not receive treatment, grade 3 patients were more likely to receive only radiotherapy (42.3%). [Insert Table 3 here] Summary description of surgical and treatment pathway of CNS patients In general, 68.1% of patients had combined treatment (surgery with oncological therapy), whereas 31.9% only received surgery (Table 4 ). The majority of glioblastoma patients (81.4%) underwent surgery before receiving treatment. Likewise, the majority of patients with medulloblastoma (86.7%), oligodendroglioma grade 3 (92.1%) and astrocytoma grade 3 (88%) also underwent both (surgery and treatment). On the other hand, surgery was the only treatment for the majority of meningioma grade 2 (84.9%) and ependymoma grade 2 (85.3%) cases. Table 4 Characteristics of patients by cancer type, surgical procedure and oncological treatment (chemotherapy and radiotherapy) Cancer type Only surgery Surgery + treatment N (%) N (%) Glioblastoma IDH-wildtype and IDH-mutant 196 (18.6) 859 (81.4) Astrocytoma grade 2 19 (31.1) 42 (68.9) Astrocytoma grade 3 11 (12.0) 81 (88.0) Meningioma grade 2 231 (84.9) 41 (15.1) Meningioma grade 3 15 (57.7) 11 (42.3) Oligodendroglioma grade 2 13 (36.1) 23 (63.9) Oligodendroglioma grade 3 3 (7.9) 35 (92.1) Ependymoma grade 2 29 (85.3) 5 (14.7) Ependymoma grade 3 2 (0.4) 3 (0.6) CNS embryonal tumor (medulloblastoma) 2 (13.3) 13 (86.7) Total 521 (31.9) 1,113 (68.1) [Insert Table 4 here] Focus on patients without microscopic confirmation We recorded 918 patients with CNS tumors diagnosed only through radiological imaging, without any histological type and grade. Most of these CNS tumors occurred in older adults, with 702 cases (76.5%) involving people 70 years of age or older (Table 5 ), mainly men (54.9%). In the first year after diagnosis, the majority (67.5%) of the CNS tumor cases without microscopic confirmation did not undergo oncologic treatment. Most of these patients were older (84.7%). Among those with oncological treatment (n = 298), radiotherapy was administered more frequently than chemotherapy, regardless of age. Table 5 Characteristics of patients without microscopic confirmation by gender, age group and oncological treatments (chemotherapy and radiotherapy) Only chemo N (%) Only radio N (%) Both N (%) None N (%) Total N (%) Male 66 (13.1) 105 (20.8) 14 (2.8) 319 (63.3) 504 (54.9) Female 41 (9.9) 65 (15.7) 7 (1.7) 301 (72.7) 414 (45.1) Total 107 (11.7) 170 (18.5) 21 (2.3) 620 (67.5) 918 (100.0) 18–49 y 8 (25.0) 11 (34.4) 3 (9.4) 10 (31.2) 32 (3.5) 50–69 y 21 (11.4) 70 (38.0) 8 (4.4) 85 (46.2) 184 (20.0) 70 + y 78 (11.1) 89 (12.7) 10 (1.4) 525 (74.8) 702 (76.5) Total 107 (11.7) 170 (18.5) 21 (2.3) 620 (67.5) 918 (100.0) [Insert Table 5 here] Men were slightly more likely than women to undergo therapy of any kind (36.7% vs. 27.3%, respectively), while the remaining 72.7% of women and 63.3% of men did not receive any treatment (Table 5 ). Oncologic treatment was not received by 74.8% of patients aged 70 years and older, compared to 46.2% of patients aged 50–69 and 31.2% of patients aged 18–49. Patients aged 50–69 years had a higher probability of receiving active treatment, especially radiotherapy (38.0%). Among patients without histopathological confirmation, who did not undergo surgery, we observed a significant difference on 1-year relative survival according to treatment: in those receiving no treatment it was 3.3%, while in those treated with either modality alone it raised to 62.7%. Among those receiving both radiotherapy and chemotherapy as adjuvant therapy 1-year relative survival was 20.2% (data not shown). Discussion This population-based study provides, for the first time in Italy, a comprehensive description of treatment patterns for adults diagnosed with Central Nervous System (CNS) tumors, based on the integration of the Veneto Cancer Registry (VCR) with regional administrative healthcare databases. By combining data from multiple sources, we were able to reconstruct the therapeutic trajectories of patients with histologically confirmed CNS tumors, offering a multidimensional overview of surgical and oncologic care delivered in real-world clinical practice. This study complements our previous population-based analysis on incidence and survival of CNS tumors in the Veneto Region [ 9 ], extending the epidemiologic characterization of these neoplasms to their treatment patterns and clinical management. Our results confirm that treatment pathways differ substantially according to histologic type and grade. As expected, most glioblastoma patients underwent a single surgical procedure followed by combined chemoradiation as adjuvant treatment, in accordance with current international standards [ 13 – 15 ]. Over the five-year period analyzed, the proportion of patients undergoing either biopsy or surgery remained relatively stable, reflecting homogeneous surgical access within the regional network. Nevertheless, a progressive increase in repeated surgical interventions, mainly observed in glioblastoma, was documented. This trend may be attributed to improved perioperative care and advances in neuro-navigation and functional mapping, as well as to an evolving clinical attitude favoring reoperation in fit patients with localized recurrences. These findings are consistent with contemporary real-world evidence supporting the role of surgery at recurrence when technically feasible and clinically appropriate. The proportion of patients receiving both radiotherapy and chemotherapy treatments (about 60%) is slightly lower than in clinical trials, where eligibility criteria and performance status selection usually favor younger and fitter populations. These findings mirror real-world data from population-based analyses in Europe and North America, showing that up to one third of glioblastoma patients do not complete standard concurrent and adjuvant therapy, mainly due to age, comorbidities, or early clinical decline [ 16 – 18 ]. For diffuse astrocytomas and oligodendrogliomas grade 2–3, combined treatment (surgery followed by radiotherapy and/or chemotherapy) was observed in the majority of cases, consistent with guideline-based management [ 19 , 20 ]. In our cohort, a substantial proportion of low-grade gliomas (grade 2) received postoperative oncologic treatment, with 68.9% of astrocytomas and 63.9% of oligodendrogliomas undergoing radiotherapy, chemotherapy, or both. These figures reflect current real-world practice, where adjuvant therapy is often considered in patients with residual disease, symptomatic tumors, or clinical features suggesting higher risk. However, treatment patterns for low-grade gliomas are expected to evolve following the recent positive results of the INDIGO trial, in which vorasidenib demonstrated a significant progression-free survival benefit in patients with IDH-mutant, low-risk grade 2 gliomas [ 21 ]. The availability of a well-tolerated targeted agent may reduce reliance on upfront radiotherapy and chemotherapy in selected patients, potentially shifting management toward delayed use of cytotoxic treatments and a more personalized, molecularly driven therapeutic approach. As vorasidenib becomes integrated into clinical practice, future registry-based analyses will be essential to monitor how its adoption influences real-world treatment pathways and long-term outcomes for low-grade glioma patients. Meningiomas, by contrast, were predominantly treated with surgery alone - particularly grade 2 tumors (85%) - whereas radiotherapy as adjuvant therapy was mainly used for grade 3 or recurrent lesions. Only recently have international and national guidelines, including both European (EANO) and American recommendations, clarified that adjuvant radiotherapy should be reserved for patients with residual disease or incomplete resection in grade 2 tumors, while observation is appropriate after gross total resection. This reflects a therapeutic trend observed in other European registry studies, where postoperative radiotherapy for atypical meningiomas remains heterogeneous and often influenced by surgical extent and institutional policy [ 22 – 24 ]. In addition, our data confirm that most patients with medulloblastoma in our cohort underwent postoperative combined therapy (radiotherapy with chemotherapy), reflecting adherence to international standards of care for these rare adult cases [ 25 , 26 ]. Patients diagnosed radiologically without histological confirmation accounted for more than one third of all CNS tumor cases during the study period. The majority were elderly (≥ 70 years) and did not receive active oncologic therapy. These data are consistent with other population-based reports indicating that diagnostic and therapeutic aggressiveness decreases with age and comorbidity burden [ 27 – 29 ]. However, treatment decisions for elderly patients should be guided primarily by biological rather than chronological age, as older patients in good clinical condition and with limited comorbidities can safely undergo surgery and receive oncologic adjuvant therapies. The absence of histologic verification may also restrict access to targeted or experimental therapies, such as targeted approaches with IDH inhibitors (e.g., vorasidenib) in low-grade gliomas, and hinders inclusion of these patients in clinical trials. Additional evidence from EANO 2021 and NCCN 2025 guidelines underscores this approach, highlighting the role of biological age and comprehensive geriatric assessment in defining optimal treatment for older adults [ 30 , 31 ]. While the absence of histologic verification may lead to underestimation of specific tumor types, its inclusion provides a realistic representation of the total clinical burden and healthcare needs associated with CNS tumors in the general population. The survival analysis among patients without histopathological confirmation showed striking differences according to the administered treatment: one-year survival was only 3.3% in those receiving no treatment, compared with 62.7% among those treated with a single modality (either radiotherapy or chemotherapy), and 20.2% among those treated with both radiotherapy and chemotherapy. These findings highlight the extremely poor prognosis of patients managed without histological diagnosis - particularly those untreated - and underline the potential one-year survival benefit associated with active oncologic therapy even in the absence of microscopic confirmation, although survival in these patients also depends on other factors and unaccounted biases. The integration of cancer registry data with administrative databases allowed us to map the entire patient journey, from diagnosis to treatment, providing an evidence-based framework for health policy and resource allocation. The observed variability in treatment intensity across tumor types and age groups underscores the importance of multidisciplinary networks and specialized neuro-oncology centers to ensure uniform access to evidence-based care. Furthermore, this approach may serve as a model for other regional and national registries aiming to monitor quality indicators and adherence to clinical guidelines. Some limitations should be acknowledged. Molecular data (e.g., IDH mutation, 1p/19q codeletion, MGMT methylation) were not available in the current dataset, preventing the analysis of treatment patterns according to molecular subgroups. Additionally, administrative data do not capture information on performance status, extent of resection, or clinical outcomes. Nevertheless, the linkage between registry and healthcare databases provides a robust, population-level picture of treatment delivery, reducing selection bias and ensuring near-complete coverage of the regional population. Future linkage of molecular data and clinical outcomes will further enhance the value of the Veneto Cancer Registry as a tool for monitoring precision oncology implementation and to evaluate real-world effectiveness of novel therapies such as IDH inhibitors (e.g., vorasidenib) in low-grade gliomas [ 21 ]. In conclusion, this study complements our previous registry-based report on incidence and survival of CNS tumors in the Veneto Region, providing a comprehensive population-level description of real-world treatment patterns across histologic subtypes and grades. The integration of cancer registry and administrative data offers valuable insights into current clinical practice, identifies gaps in care, and supports evidence-based planning of neuro-oncology services. Future registry developments incorporating molecular and outcome data will be crucial to monitor the evolving landscape of CNS tumor management in the era of personalized medicine. Statements and Declarations Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions A.A., G.L., E.F., S.G. and M.Z. contributed to the study conception and design. Data collection were performed by S.B., M.B., E.B., E.C., A.D.C., A.G., A.R.F., L.M., D.M., S.R., J.E.S., C.S., S.Z.. Data analysis was performed by A.A. and S.G.. Interpretation of data was performed by A.A., G.L., E.F., S.G. and M.Z.. The first draft of the manuscript was written by E.F., A.A., G.L., S.G. and M.Z.. All authors commented on previous versions of the manuscript, read and approved the final manuscript. G.L. and M.Z. jointly supervised this work and should be considered co-last authors. Data Availability The datasets generated and/or analysed during the current study are not publicly available because of privacy reasons. Ethics approval and Consent to participate This study is a descriptive analysis based on anonymous aggregate data collected for routine public health surveillance in accordance with Italian legislation. Under the national legal framework, regional and national health authorities are authorized to collect and process surveillance data without requiring individual informed consent (Decreto del Presidente del Consiglio dei Ministri, 3/3/2017, Identificazione dei sistemi di sorveglianza e dei registri di mortalità, di tumori e di altre patologie, 17A03142, GU Serie Generale n.109 del 12-05-2017). As the data were fully anonymized and aggregated, and no direct or indirect interaction with human subjects occurred, approval from an institutional ethics committee was not required, and informed consent was not applicable. All methods were carried out in accordance with relevant guidelines and regulations. Clinical trial number Not applicable. Consent to publish Not applicable References Ferlay J, Laversanne M, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024). Global Cancer Observatory: Cancer Tomorrow (version 1.1). 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J Clin Oncol. 2021;39:2530–2540. Goldbrunner R, et al. EANO guideline on the diagnosis and management of meningiomas. Lancet Oncol. 2021;22:e281–e292. National Comprehensive Cancer Network (NCCN). Central Nervous System Cancers, Version 1.2025. NCCN Clinical Practice Guidelines in Oncology. Ramaswamy V, et al. Adult medulloblastoma: molecular characteristics, treatment, and outcomes. Neuro Oncol. 2016;18:104–114. Brandes AA, et al. Adult medulloblastoma: a multicenter retrospective study of the Italian Neuro-Oncology Group. Neuro Oncol. 2012;14:842–850. Caccese M, et al. Elderly patients with glioblastoma: current management and future perspectives. Cancers (Basel). 2022;14:1983. Girardi F, et al. Global survival trends for brain tumors, by histology: CONCORD-3 analysis. Neuro Oncol. 2023;25:580–592. Lapointe S, Perry A, Butowski NA. Primary brain tumours in adults. Lancet. 2018;392:432–446. Weller M, et al. EANO guidelines on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas, including recommendations for elderly patients. Lancet Oncol. 2021;22:e391–e403. National Comprehensive Cancer Network (NCCN). Central Nervous System Cancers, Version 1.2025. NCCN Clinical Practice Guidelines in Oncology – Section on Elderly and Comorbidity Assessment. Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial1.pdf Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-8171188","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":551713431,"identity":"42693393-bdae-477b-b823-3df2c7e46707","order_by":0,"name":"Eliana Ferroni","email":"","orcid":"","institution":"Veneto Cancer Registry, Epidemiological Department, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Eliana","middleName":"","lastName":"Ferroni","suffix":""},{"id":551713432,"identity":"f7080a73-b59d-4eb5-b34e-deec474ee079","order_by":1,"name":"Alessandra 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brain and central nervous system (CNS) tumors - hereafter referred to as CNS tumors - affect both children and adults and can arise in all anatomical regions of the central nervous system. The vast majority (over 90%) occur in the brain, with the remaining cases affecting the meninges, spinal cord, and cranial nerves [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe most common histological type of primary CNS cancer is glioma, which includes a broad spectrum of malignant brain tumors. These range from high-grade gliomas, such as glioblastomas, to low-grade gliomas like astrocytomas and oligodendrogliomas. Other less common histological types include glial-origin tumors such as ependymomas and schwannomas, as well as medulloblastomas, CNS lymphomas, and meningiomas. According the latest GLOBOCAN estimates produced by the International Agency for Research on Cancer (IARC), approximately 340,000 new cases of CNS cancer are diagnosed globally in 2025 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough CNS cancers account for only about 2% of all cancers, they represent a major source of morbidity and mortality worldwide. The 5-year overall survival rate for malignant CNS tumors is less than 35% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the 27-member European Union (EU27), approximately 28,000 brain tumors are diagnosed annually. Unlike some industrialized countries, such as the United States and the United Kingdom, where incidence rates have shown a steady increase, the incidence of CNS tumors in Italy has remained relatively stable in recent years [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Several studies based on cancer registries have been published, with reported incidence rates ranging from 9.53 per 100,000 in Liguria to 25.3 per 100,000 in Sicily [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, while incidence and survival have been recently characterized in the Veneto Region, data on treatment patterns and care pathways are still lacking.\u003c/p\u003e\u003cp\u003eSeveral key principles guide treatment options (surgery, chemotherapy, radiotherapy) for adults with brain tumors. Regardless of tumor histology, the best outcomes are generally achieved when neurosurgeons perform a maximal safe resection - removing as much of the tumor as possible while minimizing surgical morbidity and preserving neurological function. Equally important is obtaining an accurate diagnosis by collecting a sufficient amount of representative tumor tissue [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTo our knowledge, data on treatment of CNS tumors by histologic grade or differentiation remain limited. The aim of our study was to describe the treatment approaches of malignant brain tumors and meningiomas grade 2\u0026ndash;3 among residents of the Veneto Region (Northeastern Italy) during the period 2016\u0026ndash;2020, based on data from the Veneto Cancer Registry, with a specific focus on the most common histological subtypes.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eThis study is based on the cohort of adult patients with CNS tumors from the Veneto Region, previously described in our analysis of incidence and survival for the period 2016\u0026ndash;2020 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Inclusion criteria, data sources, and data collection methods remain consistent, allowing for an integrated analysis of surgical interventions and therapeutic treatments within the established population-based framework.\u003c/p\u003e\u003cp\u003eThe CNS tumor groups analised are: Glioblastoma, IDH-wildtype and IDH-mutant (IDH - Isocitrate Dehydrogenase); Astrocytoma grade 2\u0026ndash;3; Meningioma grade 2\u0026ndash;3; Oligodendroglioma grade 2\u0026ndash;3; Ependymoma grade 2\u0026ndash;3; CNS embryonal tumor (medulloblastoma) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn order to analyse the clinical pathways of the study population, patients were individually linked to the main regional administrative healthcare databases. These include Hospital Admissions (HA), Outpatient Services (OPS), Drug Prescriptions (DP), and Hospital Drugs (HD). Surgical procedures for CNS tumors were identified within the HA database looking for specific ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification ) codes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], both in the primary procedure and in the secondary ones (01.11, 01.13\u0026amp;01.18, 01.14, 01.19, 01.23, 01.24, 01.25, 01.31, 01.39, 01.51, 01.52, 01.53, 01.59, 02.99, 03.09, 03.4). Within the HA database, also chemotherapy (diagnosis codes V58.11-V58.12 or surgical procedure code 99.25) and radiotherapy (diagnosis code V58.0 or procedure codes 92.20-92.29) were detected.\u003c/p\u003e\u003cp\u003eWithin the OPS database, chemotherapy was traced using ICD-9-CM code 99.25.1, 99.25.2 while radiotherapy was identified using ICD-9-CM codes 92.2*.\u003c/p\u003e\u003cp\u003eThe pharmaceutical data flows, which comprise both HD and DP databases, were also used to identify chemotherapy treatments (ATC - Anatomical Therapeutic Chemical - codes L01AX03, L01EX05, L01AD02, L01AD05). An exploratory analysis was undertaken to characterize the subgroup of 918 patients with CNS tumors diagnosed through radiological imaging, without histopathological confirmation.\u003c/p\u003e\u003cp\u003eDescriptive statistical analyses were conducted considering clinical and demographic variables. Data were stratified by sex, age group (18\u0026ndash;49, 50\u0026ndash;69, and \u0026ge;\u0026thinsp;70 years), morphology and grade. For continuous variables, measures of central tendency and variability were reported as appropriate; while categorical variables were summarized using absolute and relative frequencies.\u003c/p\u003e\u003cp\u003eStatistical analyses were performed using the R software, release 4.3.2 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and SAS Enterprise Guide 7.1 software [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe described the follow-up of 1,634 incident adult cases, diagnosed with CNS tumors from 2016 to 2020, and recorded in the Veneto Cancer Registry (VCR). This cohort included different histological subtypes of CNS tumors with intermediate to high-grade confirmed pathology. Compared to the results reported in a previous paper [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], two patients were excluded from these analyses because they had histopathological confirmation based on brain tissue obtained during autopsy procedures.\u003c/p\u003e\n\u003ch3\u003eMain characteristics of CNS tumors\u003c/h3\u003e\n\u003cp\u003eGlioblastoma was the most common type of CNS tumor, accounting for 64.6% of cases, followed by meningiomas grade 2\u0026ndash;3 (18.2%) and astrocytomas grade 2\u0026ndash;3 (9.4%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Glioblastomas and astrocytomas were more frequently observed in males (61.4% and 57.5%, respectively), whereas meningiomas were more prevalent in females (58%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of CNS tumors, by cancer type, sex, age group and tumor grade\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer type\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18\u0026ndash;49 y\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50\u0026ndash;69 y\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e70\u0026thinsp;+\u0026thinsp;y\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eGrade 4\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlioblastoma IDH-wildtype and IDH-mutant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e648\u003c/p\u003e\u003cp\u003e(61.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e407\u003c/p\u003e\u003cp\u003e(38.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e121\u003c/p\u003e\u003cp\u003e(11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e596\u003c/p\u003e\u003cp\u003e(56.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e338\u003c/p\u003e\u003cp\u003e(32.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1,055\u003c/p\u003e\u003cp\u003e(100.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e1,055\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(64.6)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAstrocytoma grade 2\u0026ndash;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e88\u003c/p\u003e\u003cp\u003e(57.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e65\u003c/p\u003e\u003cp\u003e(42.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e70\u003c/p\u003e\u003cp\u003e(45.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e58\u003c/p\u003e\u003cp\u003e(37.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e25\u003c/p\u003e\u003cp\u003e(16.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e61\u003c/p\u003e\u003cp\u003e(39.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e92\u003c/p\u003e\u003cp\u003e(60.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e153\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(9.4)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeningioma grade 2\u0026ndash;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e125\u003c/p\u003e\u003cp\u003e(42.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e173\u003c/p\u003e\u003cp\u003e(58.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e47\u003c/p\u003e\u003cp\u003e(15.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e120\u003c/p\u003e\u003cp\u003e(40.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e131\u003c/p\u003e\u003cp\u003e(44.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e272\u003c/p\u003e\u003cp\u003e(91.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e26\u003c/p\u003e\u003cp\u003e(8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e298\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(18.2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOligodendroglioma grade 2\u0026ndash;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e46\u003c/p\u003e\u003cp\u003e(62.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28\u003c/p\u003e\u003cp\u003e(37.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e38\u003c/p\u003e\u003cp\u003e(51.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28\u003c/p\u003e\u003cp\u003e(37.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e8\u003c/p\u003e\u003cp\u003e(10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e36\u003c/p\u003e\u003cp\u003e(48.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e38\u003c/p\u003e\u003cp\u003e(51.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e74\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(4.5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEpendymoma grade 2\u0026ndash;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23\u003c/p\u003e\u003cp\u003e(59.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003cp\u003e(41.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20\u003c/p\u003e\u003cp\u003e(51.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e17\u003c/p\u003e\u003cp\u003e(43.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e(5.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e34\u003c/p\u003e\u003cp\u003e(87.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003cp\u003e(12.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e39\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(2.4)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCNS embryonal tumor (medulloblastoma)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003cp\u003e(53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003cp\u003e(46.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003cp\u003e(73.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e(20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e15\u003c/p\u003e\u003cp\u003e(100.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e15\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(0.9)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e938\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(57.4)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e696\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(42.6)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e307\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(18.8)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e820\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(50.2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e507\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(31.0)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e403\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(24.7)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e161\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(9.8)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e1,070\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(65.5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e1,634\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(100.0)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMost CNS tumors were diagnosed in patients aged 50\u0026ndash;69 years (50.2%), followed by those aged 70 and older (31.0%) and 18\u0026ndash;49 years (18.8%). Glioblastomas were most common in the 50\u0026ndash;69 age group (56.5%), while astrocytomas grade 2\u0026ndash;3 and oligodendrogliomas grade 2\u0026ndash;3 showed a younger age distribution, with 45.8% and 51.4% of cases occurring in patients aged 18\u0026ndash;49, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). High-grade meningiomas were more frequent in older patients (84.2% aged\u0026thinsp;\u0026ge;\u0026thinsp;50); while medulloblastomas predominantly affected the youngest group (73.3% aged 18\u0026ndash;49).\u003c/p\u003e\u003cp\u003eHigh-grade tumors (grade 4) accounted for the majority of cases (65.5%), with glioblastomas accounted for almost all of the grade 4 tumors in the cohort (98.6%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Astrocytomas grade 2\u0026ndash;3 and oligodendrogliomas grade 2\u0026ndash;3 were more evenly distributed across grades 2 and 3, with 60.1% of astrocytomas and 51.3% of oligodendrogliomas classified as grade 3. Meningiomas and ependymomas were predominantly grade 2 (91.3% and 87.2%, respectively).\u003c/p\u003e\u003cp\u003e\u003cem\u003e[Insert\u003c/em\u003e Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e\n\u003ch3\u003ePatterns of neurosurgical management of CNS tumors\u003c/h3\u003e\n\u003cp\u003eMost patients underwent one surgical intervention (80.6%), while 9.3% had two or more surgeries and 10.1% only had a biopsy (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of patients by cancer type and surgical procedure (biopsy or surgery)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer type\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOnly biopsy\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOnly 1 surgery\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMore than 1 surgery*\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlioblastoma IDH-wildtype and IDH-mutant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e121 (11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e849 (80.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e85 (8.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1,055 (64.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAstrocytoma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (23.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e36 (59.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11 (18.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e61 (3.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAstrocytoma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e28 (30.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e54 (58.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10 (10.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e92 (5.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeningioma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e242 (89.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e30 (11.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e272 (16.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeningioma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20 (76.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6 (23.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e26 (1.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOligodendroglioma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30 (83.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e36 (2.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOligodendroglioma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e34 (89.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4 (10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e38 (2.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEpendymoma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e33 (97.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e34 (2.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEpendymoma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (80.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5 (0.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCNS embryonal tumor (medulloblastoma)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15 (100.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15 (0.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e165 (10.1)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e1,317 (80.6)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e152 (9.3)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e1,634 (100.0)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e* The category \u0026ldquo;\u003cb\u003eMore than 1 surgery\u003c/b\u003e\u0026rdquo; includes patients who underwent two or more re-operations at different time points. In general, patients who had surgery within three months of the initial biopsy were classified under the \u0026ldquo;\u003cb\u003eOnly 1 surgery\u003c/b\u003e\u0026rdquo; group; otherwise, they were included in the \u0026ldquo;\u003cb\u003eMore than 1 surgery\u003c/b\u003e\u0026rdquo; category.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePatients with glioblastoma were most likely to have one surgery (80.4%), whereas 11.5% just had a biopsy. Nearly one-third (23% and 30.4% for grade 2 and 3, respectively) of patients with astrocytomas only had a biopsy, whereas about 59% had a single surgical procedure. On the other hand, nearly all meningioma patients (89% grade 2 and 76.9% grade 3) had only one surgery. Similar trends have been observed for oligodendroglioma, ependymoma, and medulloblastoma, where the most frequent treatment was surgical resection (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cem\u003e[Insert\u003c/em\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThe overall proportion of patients undergoing any neurosurgical procedure (biopsy or resection) remained stable between 2016 and 2020, indicating consistent access to surgical treatment across the study period. However, the proportion of patients undergoing more than one surgical procedure during the disease course increased, particularly among those with glioblastoma. In this group, repeated surgeries rose from approximately 8% in 2016 to more than 30% in 2020, suggesting a gradual shift toward a more proactive surgical approach in selected recurrent cases (Supplementary Material 1: Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003ePatterns of oncologic treatments of CNS tumors\u003c/h3\u003e\n\u003cp\u003eSignificant differences in the use of chemotherapy and radiotherapy among CNS tumor types and grades were found (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Overall, 46.6% of patients underwent both chemo and radiotherapy, 12.9% only chemotherapy, 8.6% only radiotherapy. One third of the study cohort (n\u0026thinsp;=\u0026thinsp;521) received no therapy, of which 231 patients had meningioma grade 2 and 196 had glioblastoma. Astrocytoma grade 3 and glioblastoma patients received both treatment in 65.2% and 60.1% of cases, respectively. Grade 3 oligodendroglioma frequently were treated with both chemo and radiotherapy (57.9%). Among patients with recurrent histologically diagnosed grade 4 astrocytoma who received active therapy after progression, the most frequently used treatments were fotemustine or lomustine in approximately 70% of cases, whereas the remaining patients were treated with regorafenib or temozolomide rechallenge (data not shown). These data reflect current real-world practice in Italy although, regorafenib became available in Italy only in 2020, which may have limited its use during the study period.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of patients by cancer type and oncological treatments (chemotherapy and radiotherapy)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCancer type\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOnly chemo\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOnly radio\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBoth\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlioblastoma IDH-wildtype and IDH-mutant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e149 (14.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e75 (7.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e635 (60.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e196 (18.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAstrocytoma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13 (21.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e22 (36.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e19 (31.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAstrocytoma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16 (17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (5.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e60 (65.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e11 (12.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeningioma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e33 (12.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3 (1.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e231 (84.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeningioma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11 (42.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15 (57.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOligodendroglioma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e13 (36.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOligodendroglioma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12 (31.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (2.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e22 (57.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3 (7.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEpendymoma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e29 (85.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEpendymoma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2 (40.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCNS embryonal tumor (medulloblastoma)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (26.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7 (46.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e211 (12.9)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e140 (8.6)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e762 (46.6)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e521 (31.9)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAmong low-grade gliomas (grade 2), postoperative oncologic treatment was frequently adopted. Specifically, 68.9% of astrocytoma grade 2 cases and 63.9% of oligodendroglioma grade 2 cases received adjuvant therapy with radiotherapy, chemotherapy, or both, whereas the remaining patients were managed with surgery alone (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Among low-grade ependymomas, 85.3% of patients did not receive any oncological treatment.\u003c/p\u003e\u003cp\u003eTreatment patterns varied significantly by grade for meningiomas. Although most grade 2 meningiomas (84.9%) did not receive treatment, grade 3 patients were more likely to receive only radiotherapy (42.3%).\u003c/p\u003e\u003cp\u003e\u003cem\u003e[Insert\u003c/em\u003e Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e\n\u003ch3\u003eSummary description of surgical and treatment pathway of CNS patients\u003c/h3\u003e\n\u003cp\u003eIn general, 68.1% of patients had combined treatment (surgery with oncological therapy), whereas 31.9% only received surgery (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The majority of glioblastoma patients (81.4%) underwent surgery before receiving treatment. Likewise, the majority of patients with medulloblastoma (86.7%), oligodendroglioma grade 3 (92.1%) and astrocytoma grade 3 (88%) also underwent both (surgery and treatment). On the other hand, surgery was the only treatment for the majority of meningioma grade 2 (84.9%) and ependymoma grade 2 (85.3%) cases.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of patients by cancer type, surgical procedure and oncological treatment (chemotherapy and radiotherapy)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCancer type\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOnly surgery\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;treatment\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlioblastoma IDH-wildtype and IDH-mutant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e196 (18.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e859 (81.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAstrocytoma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19 (31.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e42 (68.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAstrocytoma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e81 (88.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeningioma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e231 (84.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e41 (15.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeningioma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15 (57.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11 (42.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOligodendroglioma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13 (36.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23 (63.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOligodendroglioma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (7.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e35 (92.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEpendymoma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e29 (85.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (14.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEpendymoma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (0.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCNS embryonal tumor (medulloblastoma)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13 (86.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e521 (31.9)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e1,113 (68.1)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e[Insert\u003c/em\u003e Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eFocus on patients without microscopic confirmation\u003c/h2\u003e\u003cp\u003eWe recorded 918 patients with CNS tumors diagnosed only through radiological imaging, without any histological type and grade.\u003c/p\u003e\u003cp\u003eMost of these CNS tumors occurred in older adults, with 702 cases (76.5%) involving people 70 years of age or older (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), mainly men (54.9%). In the first year after diagnosis, the majority (67.5%) of the CNS tumor cases without microscopic confirmation did not undergo oncologic treatment. Most of these patients were older (84.7%). Among those with oncological treatment (n\u0026thinsp;=\u0026thinsp;298), radiotherapy was administered more frequently than chemotherapy, regardless of age.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of patients without microscopic confirmation by gender, age group and oncological treatments (chemotherapy and radiotherapy)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOnly chemo\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOnly radio\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBoth\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e66 (13.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e105 (20.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e319 (63.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e504 (54.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41 (9.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e65 (15.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e301 (72.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e414 (45.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e107 (11.7)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e170 (18.5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e21 (2.3)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e620 (67.5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e918 (100.0)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18\u0026ndash;49 y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11 (34.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3 (9.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e10 (31.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e32 (3.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e50\u0026ndash;69 y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21 (11.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e70 (38.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8 (4.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e85 (46.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e184 (20.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e70\u0026thinsp;+\u0026thinsp;y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e78 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e89 (12.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10 (1.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e525 (74.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e702 (76.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e107 (11.7)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e170 (18.5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e21 (2.3)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e620 (67.5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e918 (100.0)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e[Insert\u003c/em\u003e Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e\u003cp\u003eMen were slightly more likely than women to undergo therapy of any kind (36.7% vs. 27.3%, respectively), while the remaining 72.7% of women and 63.3% of men did not receive any treatment (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Oncologic treatment was not received by 74.8% of patients aged 70 years and older, compared to 46.2% of patients aged 50\u0026ndash;69 and 31.2% of patients aged 18\u0026ndash;49. Patients aged 50\u0026ndash;69 years had a higher probability of receiving active treatment, especially radiotherapy (38.0%).\u003c/p\u003e\u003cp\u003eAmong patients without histopathological confirmation, who did not undergo surgery, we observed a significant difference on 1-year relative survival according to treatment: in those receiving no treatment it was 3.3%, while in those treated with either modality alone it raised to 62.7%. Among those receiving both radiotherapy and chemotherapy as adjuvant therapy 1-year relative survival was 20.2% (data not shown).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e This population-based study provides, for the first time in Italy, a comprehensive description of treatment patterns for adults diagnosed with Central Nervous System (CNS) tumors, based on the integration of the Veneto Cancer Registry (VCR) with regional administrative healthcare databases. By combining data from multiple sources, we were able to reconstruct the therapeutic trajectories of patients with histologically confirmed CNS tumors, offering a multidimensional overview of surgical and oncologic care delivered in real-world clinical practice. This study complements our previous population-based analysis on incidence and survival of CNS tumors in the Veneto Region [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], extending the epidemiologic characterization of these neoplasms to their treatment patterns and clinical management.\u003c/p\u003e\u003cp\u003eOur results confirm that treatment pathways differ substantially according to histologic type and grade. As expected, most glioblastoma patients underwent a single surgical procedure followed by combined chemoradiation as adjuvant treatment, in accordance with current international standards [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Over the five-year period analyzed, the proportion of patients undergoing either biopsy or surgery remained relatively stable, reflecting homogeneous surgical access within the regional network. Nevertheless, a progressive increase in repeated surgical interventions, mainly observed in glioblastoma, was documented. This trend may be attributed to improved perioperative care and advances in neuro-navigation and functional mapping, as well as to an evolving clinical attitude favoring reoperation in fit patients with localized recurrences. These findings are consistent with contemporary real-world evidence supporting the role of surgery at recurrence when technically feasible and clinically appropriate.\u003c/p\u003e\u003cp\u003eThe proportion of patients receiving both radiotherapy and chemotherapy treatments (about 60%) is slightly lower than in clinical trials, where eligibility criteria and performance status selection usually favor younger and fitter populations. These findings mirror real-world data from population-based analyses in Europe and North America, showing that up to one third of glioblastoma patients do not complete standard concurrent and adjuvant therapy, mainly due to age, comorbidities, or early clinical decline [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFor diffuse astrocytomas and oligodendrogliomas grade 2\u0026ndash;3, combined treatment (surgery followed by radiotherapy and/or chemotherapy) was observed in the majority of cases, consistent with guideline-based management [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In our cohort, a substantial proportion of low-grade gliomas (grade 2) received postoperative oncologic treatment, with 68.9% of astrocytomas and 63.9% of oligodendrogliomas undergoing radiotherapy, chemotherapy, or both. These figures reflect current real-world practice, where adjuvant therapy is often considered in patients with residual disease, symptomatic tumors, or clinical features suggesting higher risk. However, treatment patterns for low-grade gliomas are expected to evolve following the recent positive results of the INDIGO trial, in which vorasidenib demonstrated a significant progression-free survival benefit in patients with IDH-mutant, low-risk grade 2 gliomas [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The availability of a well-tolerated targeted agent may reduce reliance on upfront radiotherapy and chemotherapy in selected patients, potentially shifting management toward delayed use of cytotoxic treatments and a more personalized, molecularly driven therapeutic approach. As vorasidenib becomes integrated into clinical practice, future registry-based analyses will be essential to monitor how its adoption influences real-world treatment pathways and long-term outcomes for low-grade glioma patients.\u003c/p\u003e\u003cp\u003eMeningiomas, by contrast, were predominantly treated with surgery alone - particularly grade 2 tumors (85%) - whereas radiotherapy as adjuvant therapy was mainly used for grade 3 or recurrent lesions. Only recently have international and national guidelines, including both European (EANO) and American recommendations, clarified that adjuvant radiotherapy should be reserved for patients with residual disease or incomplete resection in grade 2 tumors, while observation is appropriate after gross total resection. This reflects a therapeutic trend observed in other European registry studies, where postoperative radiotherapy for atypical meningiomas remains heterogeneous and often influenced by surgical extent and institutional policy [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In addition, our data confirm that most patients with medulloblastoma in our cohort underwent postoperative combined therapy (radiotherapy with chemotherapy), reflecting adherence to international standards of care for these rare adult cases [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePatients diagnosed radiologically without histological confirmation accounted for more than one third of all CNS tumor cases during the study period. The majority were elderly (\u0026ge;\u0026thinsp;70 years) and did not receive active oncologic therapy. These data are consistent with other population-based reports indicating that diagnostic and therapeutic aggressiveness decreases with age and comorbidity burden [\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. However, treatment decisions for elderly patients should be guided primarily by biological rather than chronological age, as older patients in good clinical condition and with limited comorbidities can safely undergo surgery and receive oncologic adjuvant therapies.\u003c/p\u003e\u003cp\u003eThe absence of histologic verification may also restrict access to targeted or experimental therapies, such as targeted approaches with IDH inhibitors (e.g., vorasidenib) in low-grade gliomas, and hinders inclusion of these patients in clinical trials. Additional evidence from EANO 2021 and NCCN 2025 guidelines underscores this approach, highlighting the role of biological age and comprehensive geriatric assessment in defining optimal treatment for older adults [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. While the absence of histologic verification may lead to underestimation of specific tumor types, its inclusion provides a realistic representation of the total clinical burden and healthcare needs associated with CNS tumors in the general population. The survival analysis among patients without histopathological confirmation showed striking differences according to the administered treatment: one-year survival was only 3.3% in those receiving no treatment, compared with 62.7% among those treated with a single modality (either radiotherapy or chemotherapy), and 20.2% among those treated with both radiotherapy and chemotherapy. These findings highlight the extremely poor prognosis of patients managed without histological diagnosis - particularly those untreated - and underline the potential one-year survival benefit associated with active oncologic therapy even in the absence of microscopic confirmation, although survival in these patients also depends on other factors and unaccounted biases.\u003c/p\u003e\u003cp\u003eThe integration of cancer registry data with administrative databases allowed us to map the entire patient journey, from diagnosis to treatment, providing an evidence-based framework for health policy and resource allocation. The observed variability in treatment intensity across tumor types and age groups underscores the importance of multidisciplinary networks and specialized neuro-oncology centers to ensure uniform access to evidence-based care. Furthermore, this approach may serve as a model for other regional and national registries aiming to monitor quality indicators and adherence to clinical guidelines.\u003c/p\u003e\u003cp\u003eSome limitations should be acknowledged. Molecular data (e.g., IDH mutation, 1p/19q codeletion, MGMT methylation) were not available in the current dataset, preventing the analysis of treatment patterns according to molecular subgroups. Additionally, administrative data do not capture information on performance status, extent of resection, or clinical outcomes. Nevertheless, the linkage between registry and healthcare databases provides a robust, population-level picture of treatment delivery, reducing selection bias and ensuring near-complete coverage of the regional population.\u003c/p\u003e\u003cp\u003eFuture linkage of molecular data and clinical outcomes will further enhance the value of the Veneto Cancer Registry as a tool for monitoring precision oncology implementation and to evaluate real-world effectiveness of novel therapies such as IDH inhibitors (e.g., vorasidenib) in low-grade gliomas [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn conclusion, this study complements our previous registry-based report on incidence and survival of CNS tumors in the Veneto Region, providing a comprehensive population-level description of real-world treatment patterns across histologic subtypes and grades. The integration of cancer registry and administrative data offers valuable insights into current clinical practice, identifies gaps in care, and supports evidence-based planning of neuro-oncology services. Future registry developments incorporating molecular and outcome data will be crucial to monitor the evolving landscape of CNS tumor management in the era of personalized medicine.\u003c/p\u003e"},{"header":"Statements and Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA.A., G.L., E.F., S.G. and M.Z. contributed to the study conception and design. Data collection were performed by S.B., M.B., E.B., E.C., A.D.C., A.G., A.R.F., L.M., D.M., S.R., J.E.S., C.S., S.Z.. Data analysis was performed by A.A. and S.G.. Interpretation of data was performed by A.A., G.L., E.F., S.G. and M.Z.. The first draft of the manuscript was written by E.F., A.A., G.L., S.G. and M.Z.. All authors commented on previous versions of the manuscript, read and approved the final manuscript. G.L. and M.Z. jointly supervised this work and should be considered co-last authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available because of privacy reasons.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and Consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a descriptive analysis based on anonymous aggregate data collected for routine public health surveillance in accordance with Italian legislation. Under the national legal framework, regional and national health authorities are authorized to collect and process surveillance data without requiring individual informed consent (Decreto del Presidente del Consiglio dei Ministri, 3/3/2017, Identificazione dei sistemi di sorveglianza e dei registri di mortalità, di tumori e di altre patologie, 17A03142, GU Serie Generale n.109 del 12-05-2017).\u003c/p\u003e\n\u003cp\u003eAs the data were fully anonymized and aggregated, and no direct or indirect interaction with human subjects occurred, approval from an institutional ethics committee was not required, and informed consent was not applicable. All methods were carried out in accordance with relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eFerlay J, Laversanne M, Ervik M, Lam F, Colombet M, Mery L, Pi\u0026ntilde;eros M, Znaor A, Soerjomataram I, Bray F (2024). Global Cancer Observatory: Cancer Tomorrow (version 1.1). Lyon, France: International Agency for Research on Cancer. Available from https://gco.iarc.who.int/tomorrow, accessed 09 October 2025\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLapointe S, Perry A, Butowski NA. Primary brain tumours in adults. Lancet. 2018 Aug 4;392(10145): 432\u0026ndash;46.\u003c/li\u003e\n \u003cli\u003eAIOM, AIRTUM, Fondazione AIOM, ONS, PASSI, PASSI d\u0026rsquo;Argento e SIAPeC-IAP. I numeri del cancro in Italia 2023.\u003c/li\u003e\n \u003cli\u003eChebil C, Boumediene F, Cicero CE, Rascun\u0026agrave; C, Di Prima A, Torrisi AAM, Ippolito A, Sciacca S, Zappia M, Preux PM, Ferrante M, Nicoletti A; CT-ME-EN Cancer Registry Workers.\u0026nbsp;Epidemiology of Primary Brain Tumors in the Province of Catania during the 2003-2016 Period. Neuroepidemiology. 2021;55(6):473-483. doi: 10.1159/000519512. Epub 2021 Nov 18. PMID: 34794152.\u003c/li\u003e\n \u003cli\u003eFrosina G, Casella C, Puppo A, Marani E, Campanella D, Boni L, Fontana V. Epidemiology of malignant brain tumors in Genova, Italy. 1993-2017. Sci Rep. 2024 Nov 8;14(1):27300. doi: 10.1038/s41598-024-79170-z. PMID: 39516674; PMCID: PMC11549322.\u003c/li\u003e\n \u003cli\u003eCaldarella A, Crocetti E, Paci E. Is the incidence of brain tumors really increasing? A population-based analysis from a cancer registry. J Neurooncol. 2011 Sep; 104(2): 589\u0026ndash;94.\u003c/li\u003e\n \u003cli\u003eD\u0026rsquo;Alessandro G, Di Giovanni M, Iannizzi L, Guidetti E, Bottacchi E. Epidemiology of primary intracranial tumors in the Valle d\u0026rsquo;Aosta (Italy) during the 6-year period 1986\u0026ndash;1991.\u0026nbsp;Neuroepidemiology. 1995; 14(3): 139\u0026ndash;46.\u003c/li\u003e\n \u003cli\u003eSawaya R, Hammoud M, Schoppa D, et al. Neurosurgical outcomes in a modern series of 400 craniotomies for treatment of parenchymal tumors. Neurosurgery. 1998;42:1044\u0026ndash;1055. doi: 10.1097/00006123-199805000-00054.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAndreotti A, Ferroni E, Guzzinati S, Baracco S, Baracco M, Bovo E, Carpin E, Dal Cin A, Greco A, Fiore AR, Memo L, Monetti D, Rizzato S, Stocco JE, Stocco C, Zamberlan S, Bosio A, Lonardi S, Lombardi G, Zorzi M. Incidence and survival of adult central nervous system tumors in the Veneto region: a population-based registry study (2016-2020). J Neurooncol. 2025 Oct 15;176(1):9. doi: 10.1007/s11060-025-05257-w.\u003c/li\u003e\n \u003cli\u003eU.S. Department of Health and Human Services. (1997). International classification of diseases, 9th revision, clinical modifications (ICD-9-CM) (6th ed.). Washington, DC: Health Care Financing Administration. DHHS Publication No. (PHS) 96-1260.\u003c/li\u003e\n \u003cli\u003eR Core Team (2023) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. [Software] https://www.R-project.org/\u003c/li\u003e\n \u003cli\u003eSAS Institute Inc (2016) SAS Enterprise Guide 7.1 [Software]. SAS Institute Inc\u003c/li\u003e\n \u003cli\u003eStupp R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987\u0026ndash;996.\u003c/li\u003e\n \u003cli\u003eWeller M, et al. EANO guidelines on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 2017;18:e315\u0026ndash;e329.\u003c/li\u003e\n \u003cli\u003eOstrom QT, et al. CBTRUS Statistical Report: Primary brain and other CNS tumors diagnosed in the United States in 2016\u0026ndash;2020. Neuro Oncol. 2023;25(Suppl 4):iv1\u0026ndash;iv99.\u003c/li\u003e\n \u003cli\u003ePerry JR, et al. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med. 2017;376:1027\u0026ndash;1037.\u003c/li\u003e\n \u003cli\u003eJohnson DR, et al. Patterns of care and survival in glioblastoma in the elderly: a population-based analysis. Cancer. 2012;118:4549\u0026ndash;4559.\u003c/li\u003e\n \u003cli\u003eLombardi G, et al. Validation of the comprehensive geriatric assessment as a predictor of mortality in elderly glioblastoma patients. Cancers (Basel). 2019;11:1509.\u003c/li\u003e\n \u003cli\u003eBaumert BG, et al. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033\u0026ndash;26033): a randomized phase 3 study. Lancet Oncol. 2016;17:1521\u0026ndash;1532.\u003c/li\u003e\n \u003cli\u003eVan den Bent MJ, et al. Adjuvant PCV improves progression-free and overall survival in anaplastic oligodendroglial tumors. J Clin Oncol. 2013;31:344\u0026ndash;350.\u003c/li\u003e\n \u003cli\u003eMellinghoff IK, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 2023;389:1959\u0026ndash;1972.\u003c/li\u003e\n \u003cli\u003eRogers L, et al. Postoperative radiotherapy for atypical meningioma: patterns of care and outcomes in the NRG Oncology/RTOG 0539 study. J Clin Oncol. 2021;39:2530\u0026ndash;2540.\u003c/li\u003e\n \u003cli\u003eGoldbrunner R, et al. EANO guideline on the diagnosis and management of meningiomas. Lancet Oncol. 2021;22:e281\u0026ndash;e292.\u003c/li\u003e\n \u003cli\u003eNational Comprehensive Cancer Network (NCCN). Central Nervous System Cancers, Version 1.2025. NCCN Clinical Practice Guidelines in Oncology.\u003c/li\u003e\n \u003cli\u003eRamaswamy V, et al. Adult medulloblastoma: molecular characteristics, treatment, and outcomes. Neuro Oncol. 2016;18:104\u0026ndash;114.\u003c/li\u003e\n \u003cli\u003eBrandes AA, et al. Adult medulloblastoma: a multicenter retrospective study of the Italian Neuro-Oncology Group. Neuro Oncol. 2012;14:842\u0026ndash;850.\u003c/li\u003e\n \u003cli\u003eCaccese M, et al. Elderly patients with glioblastoma: current management and future perspectives. Cancers (Basel). 2022;14:1983.\u003c/li\u003e\n \u003cli\u003eGirardi F, et al. Global survival trends for brain tumors, by histology: CONCORD-3 analysis. Neuro Oncol. 2023;25:580\u0026ndash;592.\u003c/li\u003e\n \u003cli\u003eLapointe S, Perry A, Butowski NA. Primary brain tumours in adults. Lancet. 2018;392:432\u0026ndash;446.\u003c/li\u003e\n \u003cli\u003eWeller M, et al. EANO guidelines on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas, including recommendations for elderly patients. Lancet Oncol. 2021;22:e391\u0026ndash;e403.\u003c/li\u003e\n \u003cli\u003eNational Comprehensive Cancer Network (NCCN). Central Nervous System Cancers, Version 1.2025. NCCN Clinical Practice Guidelines in Oncology \u0026ndash; Section on Elderly and Comorbidity Assessment.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Central Nervous System Tumors, Follow-up, Histology, Tumor Grade, Cancer Registry","lastPublishedDoi":"10.21203/rs.3.rs-8171188/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8171188/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eThis study provides the first population-based overview of therapeutic approaches for adult CNS tumors in Italy using integrated cancer registry and administrative healthcare data.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eAll adult CNS tumors diagnosed between 2016 and 2020 were identified in the Veneto Cancer Registry. Tumor grade was extracted using a validated text-mining algorithm, and surgical and oncologic treatments were retrieved from administrative datasets and analyzed by histology, grade, and diagnostic approach.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 1,634 histologically confirmed CNS tumors were included. Glioblastoma was the most frequent subtype (64.6%), followed by grade 2\u0026ndash;3 meningiomas (18.2%). Most glioblastomas (80%) and all meningiomas underwent resection, whereas biopsies were more common in grade 2\u0026ndash;3 astrocytomas (23\u0026ndash;30%) and oligodendrogliomas (10\u0026ndash;11%). Adjuvant chemoradiotherapy was the predominant treatment in glioblastoma (60.2%), grade 3 astrocytoma (65.2%) and oligodendroglioma (58%). In recurrent grade 4 astrocytomas, nitrosoureas and regorafenib were the most frequently used therapies. Among low-grade tumors, 68.9% of astrocytomas and 63.9% of oligodendrogliomas received radiotherapy, chemotherapy, or both as adjuvant therapy. Non-biopsied patients rarely received active treatment and had poor survival, with better 1-year survival observed in those who received chemotherapy or radiotherapy alone.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis population-based study outlines real-world CNS tumor management in the Veneto Region, showing that most patients undergo surgery and that oncologic strategies vary by tumor type and grade. Integrating registry and administrative data allows effective monitoring of treatment patterns and supports improvements in multidisciplinary care and access.\u003c/p\u003e","manuscriptTitle":"Treatment patterns of Central Nervous System Tumors in the Veneto Region, Italy: A Population-Based Registry Study (2016-2020)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-28 08:28:56","doi":"10.21203/rs.3.rs-8171188/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"25358014-45a6-4eac-a515-8ecfe450bda5","owner":[],"postedDate":"November 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-14T14:08:56+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-28 08:28:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8171188","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8171188","identity":"rs-8171188","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}