Incidence and Survival of adult Central Nervous System Tumors in the Veneto Region: A Population-Based Registry Study (2016-2020)

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Despite the relatively low incidence, they account for considerable morbidity and mortality. In Italy, population-based data on incidence and survival by histological subtype and tumor grade remain limited, particularly for rarer CNS tumor entities. Methods We conducted a retrospective population-based study using data from the Veneto Cancer Registry, including adults diagnosed with CNS tumors between 2016 and 2020. A dedicated text-mining algorithm was applied to pathology reports to extract tumor grade. Tumors were categorized into six main histological groups. We estimated incidence rates, relative survival, and 5-year conditional relative survival, stratified by sex, age, tumor type, and grade. Results A total of 1,636 incident CNS tumors with confirmed histopathology and intermediate to high-grade behavior were identified. Glioblastoma was the most frequent subtype (64.6%), followed by grade 2–3 meningiomas (18.2%) and astrocytomas (9.4%). The overall crude incidence was 8.0 per 100,000, higher in males (9.5) than females (6.6). Five-year relative survival varied substantially by tumor type and grade: glioblastoma had the poorest outcome (5.7%), while grade 2–3 ependymomas and oligodendrogliomas showed favorable prognosis (87.7% and 82.0%, respectively). Conditional 5-year survival after surviving one year remained low for glioblastoma (11.0%) but exceeded 85% for most lower-grade tumors. Conclusion Our findings underscore the prognostic relevance of tumor grade and histology, supporting the need for tailored clinical strategies, molecular diagnostics, and the development of innovative therapies for informed healthcare planning and resource allocation. Central Nervous System Tumors Incidence Survival Histology Tumor Grade Cancer Registry Figures Figure 1 Figure 2 Introduction Primary brain and central nervous system (CNS) tumors, hereafter referred to as CNS tumors, are a heterogenous tumors and rare disease in adults and are diagnosed in all anatomical regions of the central nervous system. The vast majority (over 90%) occur in the brain, with the remainder affecting the meninges, spinal cord, and cranial nerves [ 1 ]. The most prevalent histological type of primary CNS cancer is glioma, which encompasses a range of malignant brain tumors, such as high-grade gliomas or glioblastomas, as well as low-grade gliomas (astrocytomas, oligodendrogliomas). The rest consists of various other histologies, including glial-origin tumors like ependymomas and schwannomas, medulloblastomas, CNS lymphomas, and meningiomas. The latest report of the Global Cancer Observatory (IARC), reports about 322,000 new cases of CNS cancers globally in 2022 [ 1 ]. Although CNS cancers represent approximately 2% of all cancers in adult population, they are a significant source of morbidity and mortality worldwide, with a 5-year overall survival rate (SR) no greater than 35% for malignant tumors [ 2 ]. In the 27-country Europe (EU27), around 28,000 brain tumors are diagnosed every year. Unlike some industrialized countries, such as the USA and England, where there has been a constant increase, the incidence of CNS tumors in Italy in recent years appears to be fairly stable [ 3 ]. Some studies based on cancer registries have been published so far, with incidence rates ranging from 9.53 per 100,000 in Liguria to 25.3 per 100,000 in Sicily [ 4 – 7 ]. To our knowledge, data on incidence and survival of CNS tumors by histologic grade or differentiation are limited, and in most cases they regard glioblastoma, which has traditionally dominated the focus of epidemiological studies on CNS tumors [ 8 – 10 ]. Population-based data on other clinically relevant entities such as atypical and anaplastic meningiomas, oligodendrogliomas, ependymomas, or medulloblastomas in adults remain limited. Given their distinct biological behavior, prognostic implications, and therapeutic pathways, the inclusion of these tumor types in our analysis provides a more comprehensive understanding of the CNS tumor landscape and helps filling important gaps in the current literature. Overall, the aim of our study was to describe the incidence and survival of malignant brain tumors in adult residents of the Veneto Region (North-eastern Italy) during the period 2016–2020, using incidence cases registered by the Veneto Cancer Registry, and focusing on the most frequent and malignant histologic types. Materials and methods We included all adult patients, diagnosed with CNS tumors from 2016 to 2020, and recorded in the Veneto Cancer Registry (VCR). VCR collects information on new tumor diagnoses occurred in the resident population of the Veneto region, Northeastern of Italy (almost 4,900,000 inhabitants). The registration procedure uses a variety of complementing data sources, of which the pathologic report is the most reliable. We extracted the information of the tumor grade from the pathology reports, using a specific text mining algorithm. The detailed procedure is reported in the supplementary materials (Supplementary material 1). Then, we systematically mapped all CNS tumor subtypes based on their morphology, as coded according to the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) [ 11 ] and WHO 2016 classification [ 12 ], which was in use in the study period (2016–2020). In order to focus the analysis on the most significant entities from an epidemiological point of view, we selected the most common CNS tumor types in the study population (see Supplementary material 2). Six CNS tumor groups were, then, defined as follows: Glioblastoma, IDH-wildtype and IDH-mutant Astrocytoma grade 2–3 Meningioma grade 2–3 Oligodendroglioma grade 2–3 Ependymoma grade 2–3 CNS embryonal tumor (medulloblastoma) This categorization system made it possible to stratify the cohort based on tumor biology and prognosis, which constituted the framework for subsequent evaluations of treatment trajectories. Statistical analysis In order to understand the epidemiological profile of the study cohort, crude incidence rates, relative survival and conditional relative survival have been estimated. The latter describes the probability of surviving up to five years among patients who were alive at one year after diagnosis. Moreover, descriptive statistical analysis based on important clinical and demographic factors were carried out. Stratifications were performed by sex, age group (18–49 years, 50–69 years, and ≥ 70 years), and CNS tumor type. Where appropriate, measures of central tendency and dispersion were used for continuous data, whereas frequencies and proportions were computed for categorical variables. Statistical analyses were performed using the R software, release 4.3.2 [ 13 ], SAS Enterprise Guide 7.1 software [ 14 ] and SEER*Stat software, release 8.4.3 [ 15 ]. Results Definition of the population-based cohort The flow chart describing the definition of the study cohort is shown in supplementary material 3. In the period 2016–2020, we identified 2,526 incident cases of malignant CNS tumors and 1,243 cases of meningioma with benign or uncertain behavior (codes /0 or /1) occurred in adult resident of the Veneto Region (Supplementary material 3). A number of exclusion criteria were used to ensure analytical rigor. In particular, 10 cases identified through Death Certificate Only (DCO) and 918 patients without microscopic confirmation - diagnosed only through radiological imaging - were excluded, yielding a cohort of 2,841 cases with microscopically confirmed diagnoses. For a subset analysis, emphasis was placed on the assessment of tumor grade. It was possible to extract tumor grading information only for 2,662 incident cases; as a consequence, 179 cases were excluded due to the unavailability of digitized pathology reports required for text mining and grade retrieval. Lastly, since our study was focused on tumors with more aggressive biological behaviour, we included only grade 2 and 3 meningiomas (n = 298). The resulting population (1,698 incident cases) included different histological subtypes of CNS tumors with intermediate to high-grade confirmed pathology. The most prevalent diagnosis was glioblastoma, including both IDH-wildtype (1,049 cases) and IDH-mutant (7 patients) variants, with a total of 1,056 cases. Additionally, there were 154 cases of grade 2–3 astrocytomas, 74 patients with grade 2–3 oligodendrogliomas, and 39 patients with grade 2 or 3 ependymomas. Medulloblastomas, categorized as embryonal tumors of the CNS, were present in 15 cases. Lastly, 298 cases were attributed to meningiomas classified as WHO grade 2 or 3. The final cohort analyzed in this study included 1,636 CNS incident cases. Incidence rates From 2016 to 2020, the incidence rate was 8.0 per 100,000 inhabitants, with glioblastomas showing the highest incidence (5.2 per 100,000), followed by meningiomas grade 2–3 (1.5 per 100,000) and astrocytomas grade 2–3 (0.8 per 100,000) (Table 1 ). According to sex, incidence rates were consistently higher in males than in females (9.5 and 6.6 per 100,000, respectively). In contrast, meningioma grade 2–3 were slightly more common in females than in males (1.6 and 1.3 per 100,000, respectively). Table 1 Crude incidence rate (per 100,000 inhabitants) by cancer type and sex Cancer type Male Female Total Glioblastoma IDH-wildtype and IDH-mutant 6.6 3.9 5.2 Astrocytoma grade 2–3 0.9 0.6 0.8 Meningioma grade 2–3 1.3 1.6 1.5 Oligodendroglioma grade 2–3 0.5 0.3 0.4 Ependymoma grade 2–3 0.2 0.2 0.2 CNS embryonal tumor (medulloblastoma) 0.1 0.1 0.1 Total 9.5 6.6 8.0 [Insert Table 1 here] The crude incidence rates of CNS tumors per 100,000 inhabitants, stratified by age group, are shown in Fig. 1. In general, we observed an increase in the incidence of CNS tumors among the elderly population (70 years and over), from 9.1 in 2016 to 15.6 in 2020, whereas incidence in younger age groups appeared stable. [Insert Fig. 1 here] Specifically, crude incidence rates for glioblastoma (the most frequent SNC tumor) consistently increased with age, with the highest rates observed in patients aged 70 and over (Fig. 2). In this age group, the incidence nearly doubled, rising from 5.6 in 2016 to 10.6 in 2020. In contrast, the incidence among individuals aged 18–49 remains low and relatively stable throughout the five years. Notably, a slight increase was observed from 2016 (0.7) to 2017 (1.8), followed by a gradual decline and stabilization around 1.1–1.3 in the subsequent years. [Insert Fig. 2 here] Main characteristics of CNS tumors Glioblastoma was the most prevalent CNS tumor type (64.6%), followed by meningioma grade 2–3 (18.2%), and astrocytoma grade 2–3 (9.4%) (Table 2 ). Glioblastomas and astrocytomas were more common in males (61.5% and 57.8%, respectively), while meningiomas were more common in females (58%). Table 2 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 649 (61.5) 407 (38.5) 121 (11.5) 596 (56.4) 339 (32.1) - - 1,056 (100.0) 1,056 (64.6) Astrocytoma grade 2–3 89 (57.8) 65 (42.2) 71 (46.1) 58 (37.7) 25 (16.2) 62 (40.3) 92 (59.7) - 154 (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 940 (57.5) 696 (42.5) 308 (18.8) 820 (50.1) 508 (31.1) 404 (24.7) 161 (9.8) 1,071 (65.5) 1,636 (100.0) [Insert Table 2 here] Across age groups, the study cohort's distribution of CNS tumor types differed significantly. Patients aged 50 to 69 years old accounted for 56.4% of glioblastoma diagnoses, whereas those aged 70 and older accounted for 32.1%. On the other hand, grade 2–3 astrocytomas showed a distinct age pattern, with a significant concentration in younger patients (46.1% in the 18–49 age group). Finally, high-grade meningiomas seem to be relatively rare in younger adults, registering the majority of cases in the 70+ (44%) and in the 50–69 age group (40.2%). To further describe the biological aggressiveness of CNS tumors, the distribution of tumor types by histological grade was examined. As expected, glioblastoma cases accounted for almost all of the grade 4 tumors in the cohort (98.6%), highlighting their key role in the high-grade burden of CNS tumors. The distribution of astrocytomas grade 2–3 was bimodal, with 40.3% of cases classified as grade 2 and 59.7% as grade 3. The majority of meningiomas (91.3%) were grade 2 tumors, with a smaller percentage (8.7%) being categorized as grade 3. Similar to astrocytomas, the distribution of oligodendrogliomas was roughly symmetrical, with 51.3% of cases being classified as grade 3 and 48.7% as grade 2. Ependymomas were grade 2 in most of the cases (87.2%) and all CNS embryonal tumors (medulloblastomas) diagnosed were categorized as grade 4. In summary, the study cohort was characterized by a predominance of high-grade tumors, with nearly two-thirds (65.5%) of cases classified as grade 4. Relative survival rates In general, the overall relative survival for patients with CNS tumors decreased steadily over time, indicating the severity of these cancers (Table 3 ). The relative survival at one year after diagnosis was 65.6%, decreasing to 43.0% at 2 years and to 29.6% after 5 years, indicating a significant short-term mortality burden. Table 3 1, 2 and 5 year relative survival and 5 year relative survival conditioned on the 1-year survival, by cancer type and tumor grade Cancer type 1-year 2-year 5-year 5-year conditional Glioblastoma IDH-wildtype and IDH-mutant 52.0% 21.4% 5.7% 11.0% Astrocytoma grade 2–3 79.7% 62.3% 45.8% 57.4% Astrocytoma grade 2 90.6% 84.5% 67.7% 74.7% Astrocytoma grade 3 72.3% 47.4% 30.5% 42.1% Meningioma grade 2–3 93.5% 90.0% 82.5% 88.3% Meningioma grade 2 94.2% 92.1% 87.0% 92.3% Meningioma grade 3 85.2% 67.3% 34.3% 39.9% Oligodendroglioma grade 2–3 95.0% 89.9% 82.0% 86.4% Oligodendroglioma grade 2 97.5% 94.7% 92.2% 94.5% Oligodendroglioma grade 3 92.6% 85.1% 71.4% 77.1% Ependymoma grade 2–3 97.6% 90.3% 87.7% 89.7% CNS embryonal tumor (medulloblastoma) 86.9% 73.8% 73.8% 84.8% Total 65.6% 43.0% 29.6% 45.1% [Insert Table 3 here] Looking at the cancer type and grade, prognosis differed significantly. As expected, glioblastomas had the worst prognosis, with a 5-year relative of 5.7%, highlighting its extremely aggressive nature and poor long-term survival. On the other hand, grade 2 meningiomas, oligodendrogliomas, and ependymomas were linked to higher 5- year relative survival rates (87%, 82% and 87.7% respectively). Survival rates stratified by tumor grade showed how higher histological grade was linked to worse relative survival, as expected (Table 3 ). Patients with grade 2 tumors performed much better in the short and long term than those with grade 3 tumors for each type of tumor. While oligodendrogliomas maintained a relatively high survival even in grade 3 cases (71.4%), but still lower than grade 2 (92.2%), this gradient was most noticeable in astrocytomas and meningiomas. Specifically, in patients with astrocytoma, survival rates dropped from 67.7–30.5%; a similar pattern was observed for meningiomas, with a 5-year survival passing from 87–34.3%. Furthermore, the 5-year relative survival, conditioned on the first-year survival, was computed (Table 3 ), in order to better understand the long term prognosis of CNS tumors. Patients who survived the first year of treatment for glioblastoma, continued to have high mortality in later years, as seen by the 5-year conditional relative survival equal to 11.0%, illustrating the biologically aggressiveness of this tumor. On the other hand, patients with grade 2–3 astrocytomas had a significantly higher conditional survival rate of 57.4%, with significant variation by tumor grade (74.7% grade 2 and 42.1% grade 3). Additionally, meningiomas had generally positive long-term results, with an overall conditional 5-year survival rate of 88.3%. This estimate was especially high for grade 2 meningiomas (92.3%), but grade 3 tumors had a much lower conditional survival of 39.9%, which was indicative of a higher risk of progression. Looking at the less frequent CNS tumors, oligodendrogliomas had a high 5-year conditional survival rate of up to 94.5% for grade 2, and ependymomas had the highest conditional survival rate (89.7%), indicating an optimistic perspective for individuals surviving the first year. Supplementary material 4 describes the distribution by sex and age and relative survival of 918 patients diagnosed with a CNS tumor with no histopathological confirmation. Discussion To our knowledge, this is the first Italian study, based on a regional cancer registry, reporting incidence and survival of CNS tumors according to histological grade. We observed an annual incidence rate of malignant neoplasms of 8.0 per 100,000 inhabitants between 2016 and 2020, with glioblastoma representing the most frequent tumor, followed by grade 2–3 meningiomas and astrocytomas. Tumor distribution varied by sex and age, glioblastomas being more frequent in males and meningiomas in females. Incidence rates increased significantly in older age groups [ 16 ]. Relative survival varied widely by tumor type and grade. Five-year relative survival was lowest for glioblastoma) and highest for grade 2 meningioma, grade 2–3 ependymoma (and grade 2–3 oligodendroglioma Conditional survival analysis confirmed the prognostic significance of tumor grade: patients surviving beyond one year had significantly better 5-year outcomes, except for glioblastoma, where the conditional 5-year survival remained low. A regional study conducted in Genoa (Liguria Region, Italy) reported stable incidence rates of malignant brain tumors between 1993 and 2017, with a slight increase in glioblastoma incidence attributed mainly to improved diagnostic precision rather than to a real increase in disease burden [ 5 ]. Similarly, the population-based registry of Catania (Sicily, Italy) reported a high incidence of meningioma (9.8 per 100,000) and a glioblastoma incidence of 2.9 per 100,000 between 2003 and 2016, without any significant temporal trend [ 4 ]. Our findings are consistent with international cancer registries, including the Central Brain Tumor Registry of the United States (CBTRUS) [ 17 ] and the CONCORD program [ 18 ]. However, while overall incidence estimates for CNS tumors in the Veneto Region align with those from other Italian registries, some differences emerge when comparing specific tumor types. For instance, glioblastoma incidence in our cohort (5.2 per 100,000) was higher than that reported in Catania (2.9 per 100,000), possibly reflecting improved histologic confirmation or diagnostic access in more recent years. In contrast, the incidence of meningioma was lower in our data since we included only grade 2–3 tumors, which are considered malignant, whereas other registries include all histological grades. These discrepancies underline the importance of methodological consistency when comparing regional registry data. Glioblastoma incidence and survival rates matched closely with those reported in other Italian regions (e.g., Liguria, Sicily). These findings are consistent with broader global trends, with approximately 322,000 new CNS cancer cases reported worldwide in 2022 [ 1 ], and with national data estimating over 6,000 new diagnoses annually in Italy [ 3 ]. The strong sex difference in meningioma incidence and age-related increase across all tumor types align with prior studies [ 17 ]. The poor prognosis of glioblastoma, despite modest advances, remains a critical challenge. Conversely, the favorable long-term survival of grade 2 oligodendrogliomas and ependymomas supports their distinction in epidemiologic and clinical stratification. Importantly, this study also included rarer CNS tumors such as low-grade gliomas, medulloblastomas, and ependymomas. These entities are often underrepresented in population-based research due to their lower frequency in the adult population. In our cohort, grade 2–3 astrocytomas accounted for 9.4% of cases, oligodendrogliomas for 4.5%, ependymomas for 2.4%, and medulloblastomas for 0.9%. Despite their relative rarity, these tumors carry distinct clinical trajectories and management needs, particularly in younger adults. By analyzing these tumor types separately, our study contributes novel insights into their incidence patterns and long-term survival outcomes, helping to inform tailored treatment strategies and long-term care planning. The availability of a dedicated cancer registry that includes less frequent CNS tumors such as IDH-mutant low-grade gliomas is becoming increasingly important in light of emerging therapeutic options. The recent approval of Vorasidenib, a dual inhibitor of mutant IDH1 and IDH2, offers a new treatment avenue for patients with IDH-mutant grade 2 gliomas. Data from the phase III INDIGO trial have shown a significant progression-free survival benefit compared to placebo in this population [ 19 ]. This advance highlights the relevance of accurately capturing and monitoring these tumor types in population-based registries, not only for clinical epidemiology but also to inform future pharmacoeconomic evaluations and treatment planning. Our data reinforce the prognostic value of WHO grading and highlight the importance of including intermediate-grade tumors (e.g., grade 2–3 meningiomas, oligodendrogliomas) in registry-based analyses. These tumors, although often excluded from classic cancer statistics, have relevant recurrence rates and healthcare needs. Their inclusion provides a more accurate estimation of clinical burden and resource allocation. Conditional survival analysis provides clinically relevant information for follow-up and counseling. This metric estimates the probability of surviving additional years, conditional on having already survived a specific period (generally, one year) after diagnosis. For many CNS tumors, prognosis improves markedly after the initial year, providing reassurance to patients, guiding clinicians in adapting follow-up intensity and expectations over time and underlining the importance of long-term survivorship care. A substantial portion of CNS tumor diagnoses (especially in older adults) lacked histologic confirmation. These patients, often inoperable or unfit for biopsy, had poor outcomes. While their inclusion may lower survival estimates, it reflects real-world epidemiology and highlights the need for supportive and palliative pathways. Notably, most of these patients were elderly, and the decision to forego biopsy may be influenced by age-related factors such as frailty or significant comorbidities. However, in the absence of clear contraindications, efforts should be made to pursue histologic confirmation whenever feasible, as it remains essential for diagnosis, prognosis, and treatment planning. This subgroup of patients would particularly benefit from multidisciplinary assessment, including integration with geriatric oncology services and the use of comprehensive geriatric assessment (CGA) tools, to better evaluate operability and guide therapeutic decisions. Limitations and Future Directions According to the study period, the 2016 WHO classification was used and the absence of molecular markers prevented a possible comparison with the 2021 WHO categories. Molecular profiling should be integrated into future registry efforts. A further limitation of this study is represented by the exclusion of pediatric tumors, which represent approximatively 3% of the total cases, that warrant separate investigation. Despite these limitations, this is one of the first population-based studies in Italy and among the few internationally to provide detailed incidence and survival estimates for a wide spectrum of CNS tumors, including rarer subtypes such as low-grade gliomas, ependymomas, and medulloblastomas in the adult population. This level of granularity is essential to improve disease characterization, inform public health strategies, and support the implementation of precision medicine approaches at a population level. It provides a foundation for future research, health planning, and benchmarking of neuro-oncology care. 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 Alessandra Andreotti, Giuseppe Lombardi, Eliana Ferroni, Stefano Guzzinati and Manuel Zorzi contributed to the study conception and design. Data collection were performed by Susanna Baracco, Maddalena Baracco, Emanuela Bovo, Eva Carpin, Antonella Dal Cin, Alessandra Greco, Anna Rita Fiore, Laura Memo, Daniele Monetti, Silvia Rizzato, Jessica Elisabeth Stocco, Carmen Stocco, Sara Zamberlan. Data analysis was performed by Alessandra Andreotti and Stefano Guzzinati. Interpretation of data were performed by Alessandra Andreotti, Giuseppe Lombardi, Eliana Ferroni, Stefano Guzzinati and Manuel Zorzi. The first draft of the manuscript was written by Alessandra Andreotti, Giuseppe Lombardi, Eliana Ferroni, Stefano Guzzinati and Manuel Zorzi. All authors commented on previous versions of the manuscript, read and approved the final manuscript. Giuseppe Lombardi and Manuel Zorzi 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 The Italian legislation identifies regional and national health authorities as collectors of personal data for surveillance purposes without explicit individual consent. The approval of a research ethic committee is not required, because this study is a descriptive analysis of anonymous aggregate data without any direct or indirect intervention on patients (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). Available at: www.gazzettaufficiale.it/eli/id/2017/05/12/17A03142/sg (last accessed July 30, 2025). Consent to publish Not applicable References Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024) Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today , accessed [19 June 2025] Lapointe S, Perry A, Butowski NA (2018) Primary brain tumours in adults. 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Lancet. 17;391(10125):1023–1075. 10.1016/S0140-6736(17)33326-3 Mellinghoff IK, van den Bent MJ, Blumenthal DT, Touat M, Peters KB, Clarke J, Mendez J, Yust-Katz S, Welsh L, Mason WP, Ducray F, Umemura Y, Nabors B, Holdhoff M, Hottinger AF, Arakawa Y, Sepulveda JM, Wick W, Soffietti R, Perry JR, Giglio P, de la Fuente M, Maher EA, Schoenfeld S, Zhao D, Pandya SS, Steelman L, Hassan I, Wen PY, Cloughesy TF, INDIGO Trial Investigators (2023) Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med. 17;389(7):589–601. 10.1056/NEJMoa2304194 Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial1.pdf Supplementarymaterial2.pdf Supplementarymaterial3.pdf Supplementarymaterial4.pdf Cite Share Download PDF Status: Published Journal Publication published 15 Oct, 2025 Read the published version in Journal of Neuro-Oncology → Version 1 posted Editorial decision: Revision requested 11 Sep, 2025 Reviews received at journal 04 Sep, 2025 Reviews received at journal 29 Aug, 2025 Reviewers agreed at journal 25 Aug, 2025 Reviewers agreed at journal 20 Aug, 2025 Reviewers invited by journal 08 Aug, 2025 Editor assigned by journal 08 Aug, 2025 Submission checks completed at journal 08 Aug, 2025 First submitted to journal 08 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7325745","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":499540015,"identity":"ba8d4b0e-99af-47bb-9b0a-c98d4993a1e1","order_by":0,"name":"Alessandra Andreotti","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Alessandra","middleName":"","lastName":"Andreotti","suffix":""},{"id":499540016,"identity":"72b3d137-5527-4684-8979-8898f79ca6a2","order_by":1,"name":"Eliana Ferroni","email":"data:image/png;base64,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","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":true,"prefix":"","firstName":"Eliana","middleName":"","lastName":"Ferroni","suffix":""},{"id":499540020,"identity":"a6b1be4c-19e8-4c09-96bf-6d2f9974d3cb","order_by":2,"name":"Stefano Guzzinati","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Guzzinati","suffix":""},{"id":499540021,"identity":"e4489103-a921-4a8d-b53f-e7272ca07daf","order_by":3,"name":"Susanna Baracco","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Susanna","middleName":"","lastName":"Baracco","suffix":""},{"id":499540022,"identity":"8a366a85-17a7-4022-8f42-f1e318f5a2a8","order_by":4,"name":"Maddalena Baracco","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Maddalena","middleName":"","lastName":"Baracco","suffix":""},{"id":499540023,"identity":"c794972a-834e-4cf3-a624-d837a32314fd","order_by":5,"name":"Emanuela Bovo","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda 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Zero","correspondingAuthor":false,"prefix":"","firstName":"Daniele","middleName":"","lastName":"Monetti","suffix":""},{"id":499540041,"identity":"711c6401-03b0-4d91-ab5d-720a1d097330","order_by":12,"name":"Silvia Rizzato","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Silvia","middleName":"","lastName":"Rizzato","suffix":""},{"id":499540043,"identity":"7c4c55f0-3542-4a46-9822-b1b18296de65","order_by":13,"name":"Jessica Elisabeth Stocco","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"Elisabeth","lastName":"Stocco","suffix":""},{"id":499540044,"identity":"e7684b8b-cf9d-42ee-98b6-a491623b2c32","order_by":14,"name":"Carmen Stocco","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Carmen","middleName":"","lastName":"Stocco","suffix":""},{"id":499540046,"identity":"f985ad00-5ed2-481b-84f8-1fc2537192ab","order_by":15,"name":"Sara Zamberlan","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Zamberlan","suffix":""},{"id":499540051,"identity":"1806f944-c45b-45a5-bcc2-5a521928d306","order_by":16,"name":"Alberto Bosio","email":"","orcid":"","institution":"Veneto Institute of Oncology IOV-IRCCS","correspondingAuthor":false,"prefix":"","firstName":"Alberto","middleName":"","lastName":"Bosio","suffix":""},{"id":499540052,"identity":"7a776197-ab3b-44af-bbc4-fc8aef4ac7cf","order_by":17,"name":"Sara Lonardi","email":"","orcid":"","institution":"Veneto Institute of Oncology IOV-IRCCS","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Lonardi","suffix":""},{"id":499540053,"identity":"372caa9e-cecb-4696-92a4-6f5e5eaf911c","order_by":18,"name":"Giuseppe Lombardi","email":"","orcid":"","institution":"Veneto Institute of Oncology IOV-IRCCS","correspondingAuthor":false,"prefix":"","firstName":"Giuseppe","middleName":"","lastName":"Lombardi","suffix":""},{"id":499540055,"identity":"4237343e-d197-4355-b5a2-c24ff4d57074","order_by":19,"name":"Manuel Zorzi","email":"","orcid":"","institution":"Veneto Cancer Registry, Azienda Zero","correspondingAuthor":false,"prefix":"","firstName":"Manuel","middleName":"","lastName":"Zorzi","suffix":""}],"badges":[],"createdAt":"2025-08-08 09:23:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7325745/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7325745/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11060-025-05257-w","type":"published","date":"2025-10-15T15:57:23+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89091152,"identity":"ed161d30-8e59-488a-9289-660a61c64daf","added_by":"auto","created_at":"2025-08-14 14:49:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1113447,"visible":true,"origin":"","legend":"\u003cp\u003eCrude incidence rate trend (per 100,000 inhabitants) by age group\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7325745/v1/cb22805616405e198e0a205d.png"},{"id":89091153,"identity":"cdbfd90c-c5e9-4b5a-8e6f-5331c7f35f64","added_by":"auto","created_at":"2025-08-14 14:49:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":594325,"visible":true,"origin":"","legend":"\u003cp\u003eGlioblastoma’s crude incidence rate trend (per 100,000 inhabitants), by age group\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-7325745/v1/ca2215d45e3f38f0e35e33e0.png"},{"id":93956118,"identity":"bc1b4cc2-c398-42ca-9f11-a0341a26f2d6","added_by":"auto","created_at":"2025-10-20 16:10:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3500882,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7325745/v1/b0914a2c-69a8-44b8-877a-531795b3e4d3.pdf"},{"id":89092481,"identity":"72531ce6-a216-4640-80b5-382092c12b96","added_by":"auto","created_at":"2025-08-14 14:57:24","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":163743,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7325745/v1/b0641dd63da513f12e4b5743.pdf"},{"id":89091160,"identity":"d5782e98-4709-4d5d-ae10-ef5ac41dd4ba","added_by":"auto","created_at":"2025-08-14 14:49:24","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":131158,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7325745/v1/aa38b5891bf1b8972a1ac881.pdf"},{"id":89091156,"identity":"449289b5-bcd3-470a-92e9-2e3c21a10154","added_by":"auto","created_at":"2025-08-14 14:49:24","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":112847,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7325745/v1/fdf310e94a46261c94bc54e5.pdf"},{"id":89091163,"identity":"e1bf6824-bac1-4cde-af5b-c92a6e6877d2","added_by":"auto","created_at":"2025-08-14 14:49:24","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":436479,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7325745/v1/adb7289192660093861eae55.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Incidence and Survival of adult Central Nervous System Tumors in the Veneto Region: A Population-Based Registry Study (2016-2020)","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary brain and central nervous system (CNS) tumors, hereafter referred to as CNS tumors, are a heterogenous tumors and rare disease in adults and are diagnosed in all anatomical regions of the central nervous system. The vast majority (over 90%) occur in the brain, with the remainder affecting the meninges, spinal cord, and cranial nerves [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe most prevalent histological type of primary CNS cancer is glioma, which encompasses a range of malignant brain tumors, such as high-grade gliomas or glioblastomas, as well as low-grade gliomas (astrocytomas, oligodendrogliomas). The rest consists of various other histologies, including glial-origin tumors like ependymomas and schwannomas, medulloblastomas, CNS lymphomas, and meningiomas. The latest report of the Global Cancer Observatory (IARC), reports about 322,000 new cases of CNS cancers globally in 2022 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough CNS cancers represent approximately 2% of all cancers in adult population, they are a significant source of morbidity and mortality worldwide, with a 5-year overall survival rate (SR) no greater than 35% for malignant tumors [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the 27-country Europe (EU27), around 28,000 brain tumors are diagnosed every year. Unlike some industrialized countries, such as the USA and England, where there has been a constant increase, the incidence of CNS tumors in Italy in recent years appears to be fairly stable [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Some studies based on cancer registries have been published so far, with 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].\u003c/p\u003e\u003cp\u003eTo our knowledge, data on incidence and survival of CNS tumors by histologic grade or differentiation are limited, and in most cases they regard glioblastoma, which has traditionally dominated the focus of epidemiological studies on CNS tumors [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Population-based data on other clinically relevant entities such as atypical and anaplastic meningiomas, oligodendrogliomas, ependymomas, or medulloblastomas in adults remain limited. Given their distinct biological behavior, prognostic implications, and therapeutic pathways, the inclusion of these tumor types in our analysis provides a more comprehensive understanding of the CNS tumor landscape and helps filling important gaps in the current literature.\u003c/p\u003e\u003cp\u003eOverall, the aim of our study was to describe the incidence and survival of malignant brain tumors in adult residents of the Veneto Region (North-eastern Italy) during the period 2016\u0026ndash;2020, using incidence cases registered by the Veneto Cancer Registry, and focusing on the most frequent and malignant histologic types.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eWe included all adult patients, diagnosed with CNS tumors from 2016 to 2020, and recorded in the Veneto Cancer Registry (VCR). VCR collects information on new tumor diagnoses occurred in the resident population of the Veneto region, Northeastern of Italy (almost 4,900,000 inhabitants). The registration procedure uses a variety of complementing data sources, of which the pathologic report is the most reliable.\u003c/p\u003e\u003cp\u003eWe extracted the information of the tumor grade from the pathology reports, using a specific text mining algorithm. The detailed procedure is reported in the supplementary materials (Supplementary material 1). Then, we systematically mapped all CNS tumor subtypes based on their morphology, as coded according to the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and WHO 2016 classification [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], which was in use in the study period (2016\u0026ndash;2020). In order to focus the analysis on the most significant entities from an epidemiological point of view, we selected the most common CNS tumor types in the study population (see Supplementary material 2). Six CNS tumor groups were, then, defined as follows:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eGlioblastoma, IDH-wildtype and IDH-mutant\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eAstrocytoma grade 2\u0026ndash;3\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMeningioma grade 2\u0026ndash;3\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eOligodendroglioma grade 2\u0026ndash;3\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eEpendymoma grade 2\u0026ndash;3\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCNS embryonal tumor (medulloblastoma)\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eThis categorization system made it possible to stratify the cohort based on tumor biology and prognosis, which constituted the framework for subsequent evaluations of treatment trajectories.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eIn order to understand the epidemiological profile of the study cohort, crude incidence rates, relative survival and conditional relative survival have been estimated. The latter describes the probability of surviving up to five years among patients who were alive at one year after diagnosis.\u003c/p\u003e\u003cp\u003eMoreover, descriptive statistical analysis based on important clinical and demographic factors were carried out. Stratifications were performed by sex, age group (18\u0026ndash;49 years, 50\u0026ndash;69 years, and \u0026ge;\u0026thinsp;70 years), and CNS tumor type. Where appropriate, measures of central tendency and dispersion were used for continuous data, whereas frequencies and proportions were computed for categorical variables.\u003c/p\u003e\u003cp\u003eStatistical analyses were performed using the R software, release 4.3.2 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], SAS Enterprise Guide 7.1 software [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and SEER*Stat software, release 8.4.3 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eDefinition of the population-based cohort\u003c/h2\u003e\u003cp\u003eThe flow chart describing the definition of the study cohort is shown in supplementary material 3.\u003c/p\u003e\u003cp\u003eIn the period 2016\u0026ndash;2020, we identified 2,526 incident cases of malignant CNS tumors and 1,243 cases of meningioma with benign or uncertain behavior (codes /0 or /1) occurred in adult resident of the Veneto Region (Supplementary material 3).\u003c/p\u003e\u003cp\u003eA number of exclusion criteria were used to ensure analytical rigor. In particular, 10 cases identified through Death Certificate Only (DCO) and 918 patients without microscopic confirmation - diagnosed only through radiological imaging - were excluded, yielding a cohort of 2,841 cases with microscopically confirmed diagnoses.\u003c/p\u003e\u003cp\u003eFor a subset analysis, emphasis was placed on the assessment of tumor grade. It was possible to extract tumor grading information only for 2,662 incident cases; as a consequence, 179 cases were excluded due to the unavailability of digitized pathology reports required for text mining and grade retrieval. Lastly, since our study was focused on tumors with more aggressive biological behaviour, we included only grade 2 and 3 meningiomas (n\u0026thinsp;=\u0026thinsp;298).\u003c/p\u003e\u003cp\u003eThe resulting population (1,698 incident cases) included different histological subtypes of CNS tumors with intermediate to high-grade confirmed pathology. The most prevalent diagnosis was glioblastoma, including both IDH-wildtype (1,049 cases) and IDH-mutant (7 patients) variants, with a total of 1,056 cases. Additionally, there were 154 cases of grade 2\u0026ndash;3 astrocytomas, 74 patients with grade 2\u0026ndash;3 oligodendrogliomas, and 39 patients with grade 2 or 3 ependymomas. Medulloblastomas, categorized as embryonal tumors of the CNS, were present in 15 cases. Lastly, 298 cases were attributed to meningiomas classified as WHO grade 2 or 3. The final cohort analyzed in this study included 1,636 CNS incident cases.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eIncidence rates\u003c/h3\u003e\n\u003cp\u003eFrom 2016 to 2020, the incidence rate was 8.0 per 100,000 inhabitants, with glioblastomas showing the highest incidence (5.2 per 100,000), followed by meningiomas grade 2\u0026ndash;3 (1.5 per 100,000) and astrocytomas grade 2\u0026ndash;3 (0.8 per 100,000) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). According to sex, incidence rates were consistently higher in males than in females (9.5 and 6.6 per 100,000, respectively). In contrast, meningioma grade 2\u0026ndash;3 were slightly more common in females than in males (1.6 and 1.3 per 100,000, respectively).\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\" class=\"fr-table-selection-hover\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCrude incidence rate (per 100,000 inhabitants) by cancer type and sex\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCancer type\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGlioblastoma IDH-wildtype and IDH-mutant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAstrocytoma grade 2\u0026ndash;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMeningioma grade 2\u0026ndash;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOligodendroglioma grade 2\u0026ndash;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEpendymoma grade 2\u0026ndash;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCNS embryonal tumor (medulloblastoma)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e9.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e8.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003e[Insert\u003c/em\u003e Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe crude incidence rates of CNS tumors per 100,000 inhabitants, stratified by age group, are shown in Fig.\u0026nbsp;1. In general, we observed an increase in the incidence of CNS tumors among the elderly population (70 years and over), from 9.1 in 2016 to 15.6 in 2020, whereas incidence in younger age groups appeared stable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e[Insert Fig. 1 here]\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSpecifically, crude incidence rates for glioblastoma (the most frequent SNC tumor) consistently increased with age, with the highest rates observed in patients aged 70 and over (Fig.\u0026nbsp;2). In this age group, the incidence nearly doubled, rising from 5.6 in 2016 to 10.6 in 2020. In contrast, the incidence among individuals aged 18\u0026ndash;49 remains low and relatively stable throughout the five years. Notably, a slight increase was observed from 2016 (0.7) to 2017 (1.8), followed by a gradual decline and stabilization around 1.1\u0026ndash;1.3 in the subsequent years.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e[Insert Fig. 2 here]\u003c/em\u003e\u003c/p\u003e\n\u003ch3\u003eMain characteristics of CNS tumors\u003c/h3\u003e\n\u003cp\u003eGlioblastoma was the most prevalent CNS tumor type (64.6%), followed by meningioma grade 2\u0026ndash;3 (18.2%), and astrocytoma grade 2\u0026ndash;3 (9.4%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Glioblastomas and astrocytomas were more common in males (61.5% and 57.8%, respectively), while meningiomas were more common in females (58%).\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 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\u003e649 (61.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e407 (38.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e121 (11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e596 (56.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e339 (32.1)\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\u003e1,056 (100.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e1,056 (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\u003e89 (57.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e65 (42.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e71 (46.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e58 (37.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e25 (16.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e62 (40.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e92 (59.7)\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\u003e154 (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 (42.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e173 (58.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e47 (15.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e120 (40.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e131 (44.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e272 (91.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e26 (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 (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 (62.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28 (37.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e38 (51.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28 (37.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e8 (10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e36 (48.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e38 (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 (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 (59.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16 (41.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20 (51.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e17 (43.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2 (5.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e34 (87.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5 (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 (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 (53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (46.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11 (73.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e3 (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 (100.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e15 (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\u003e940 (57.5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e696 (42.5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e308 (18.8)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e820 (50.1)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e508 (31.1)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e404 (24.7)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e161 (9.8)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e1,071 (65.5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e1,636 (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=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAcross age groups, the study cohort's distribution of CNS tumor types differed significantly. Patients aged 50 to 69 years old accounted for 56.4% of glioblastoma diagnoses, whereas those aged 70 and older accounted for 32.1%. On the other hand, grade 2\u0026ndash;3 astrocytomas showed a distinct age pattern, with a significant concentration in younger patients (46.1% in the 18\u0026ndash;49 age group). Finally, high-grade meningiomas seem to be relatively rare in younger adults, registering the majority of cases in the 70+ (44%) and in the 50\u0026ndash;69 age group (40.2%).\u003c/p\u003e\u003cp\u003eTo further describe the biological aggressiveness of CNS tumors, the distribution of tumor types by histological grade was examined. As expected, glioblastoma cases accounted for almost all of the grade 4 tumors in the cohort (98.6%), highlighting their key role in the high-grade burden of CNS tumors. The distribution of astrocytomas grade 2\u0026ndash;3 was bimodal, with 40.3% of cases classified as grade 2 and 59.7% as grade 3. The majority of meningiomas (91.3%) were grade 2 tumors, with a smaller percentage (8.7%) being categorized as grade 3. Similar to astrocytomas, the distribution of oligodendrogliomas was roughly symmetrical, with 51.3% of cases being classified as grade 3 and 48.7% as grade 2. Ependymomas were grade 2 in most of the cases (87.2%) and all CNS embryonal tumors (medulloblastomas) diagnosed were categorized as grade 4. In summary, the study cohort was characterized by a predominance of high-grade tumors, with nearly two-thirds (65.5%) of cases classified as grade 4.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eRelative survival rates\u003c/h2\u003e\u003cp\u003eIn general, the overall relative survival for patients with CNS tumors decreased steadily over time, indicating the severity of these cancers (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The relative survival at one year after diagnosis was 65.6%, decreasing to 43.0% at 2 years and to 29.6% after 5 years, indicating a significant short-term mortality burden.\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\u003e1, 2 and 5 year relative survival and 5 year relative survival conditioned on the 1-year survival, by cancer type and tumor grade\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\u003e1-year\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2-year\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5-year\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5-year conditional\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\u003e52.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e11.0%\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\u003e79.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e62.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e45.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e57.4%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAstrocytoma grade 2\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003e90.6%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e84.5%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e67.7%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e74.7%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAstrocytoma grade 3\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003e72.3%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e47.4%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e30.5%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e42.1%\u003c/em\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\u003e93.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e90.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e82.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e88.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMeningioma grade 2\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003e94.2%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e92.1%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e87.0%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e92.3%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMeningioma grade 3\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003e85.2%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e67.3%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e34.3%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e39.9%\u003c/em\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\u003e95.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e89.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e82.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e86.4%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eOligodendroglioma grade 2\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003e97.5%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e94.7%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e92.2%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e94.5%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eOligodendroglioma grade 3\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003e92.6%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e85.1%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e71.4%\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e77.1%\u003c/em\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\u003e97.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e90.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e87.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e89.7%\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\u003e86.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e73.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e73.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e84.8%\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\u003e65.6%\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e43.0%\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e29.6%\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e45.1%\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=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e\u003cp\u003eLooking at the cancer type and grade, prognosis differed significantly. As expected, glioblastomas had the worst prognosis, with a 5-year relative of 5.7%, highlighting its extremely aggressive nature and poor long-term survival. On the other hand, grade 2 meningiomas, oligodendrogliomas, and ependymomas were linked to higher 5- year relative survival rates (87%, 82% and 87.7% respectively).\u003c/p\u003e\u003cp\u003eSurvival rates stratified by tumor grade showed how higher histological grade was linked to worse relative survival, as expected (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Patients with grade 2 tumors performed much better in the short and long term than those with grade 3 tumors for each type of tumor. While oligodendrogliomas maintained a relatively high survival even in grade 3 cases (71.4%), but still lower than grade 2 (92.2%), this gradient was most noticeable in astrocytomas and meningiomas. Specifically, in patients with astrocytoma, survival rates dropped from 67.7\u0026ndash;30.5%; a similar pattern was observed for meningiomas, with a 5-year survival passing from 87\u0026ndash;34.3%.\u003c/p\u003e\u003cp\u003eFurthermore, the 5-year relative survival, conditioned on the first-year survival, was computed (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), in order to better understand the long term prognosis of CNS tumors. Patients who survived the first year of treatment for glioblastoma, continued to have high mortality in later years, as seen by the 5-year conditional relative survival equal to 11.0%, illustrating the biologically aggressiveness of this tumor. On the other hand, patients with grade 2\u0026ndash;3 astrocytomas had a significantly higher conditional survival rate of 57.4%, with significant variation by tumor grade (74.7% grade 2 and 42.1% grade 3). Additionally, meningiomas had generally positive long-term results, with an overall conditional 5-year survival rate of 88.3%. This estimate was especially high for grade 2 meningiomas (92.3%), but grade 3 tumors had a much lower conditional survival of 39.9%, which was indicative of a higher risk of progression. Looking at the less frequent CNS tumors, oligodendrogliomas had a high 5-year conditional survival rate of up to 94.5% for grade 2, and ependymomas had the highest conditional survival rate (89.7%), indicating an optimistic perspective for individuals surviving the first year.\u003c/p\u003e\u003cp\u003eSupplementary material 4 describes the distribution by sex and age and relative survival of 918 patients diagnosed with a CNS tumor with no histopathological confirmation.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e To our knowledge, this is the first Italian study, based on a regional cancer registry, reporting incidence and survival of CNS tumors according to histological grade.\u003c/p\u003e\u003cp\u003eWe observed an annual incidence rate of malignant neoplasms of 8.0 per 100,000 inhabitants between 2016 and 2020, with glioblastoma representing the most frequent tumor, followed by grade 2\u0026ndash;3 meningiomas and astrocytomas. Tumor distribution varied by sex and age, glioblastomas being more frequent in males and meningiomas in females. Incidence rates increased significantly in older age groups [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRelative survival varied widely by tumor type and grade. Five-year relative survival was lowest for glioblastoma) and highest for grade 2 meningioma, grade 2\u0026ndash;3 ependymoma (and grade 2\u0026ndash;3 oligodendroglioma Conditional survival analysis confirmed the prognostic significance of tumor grade: patients surviving beyond one year had significantly better 5-year outcomes, except for glioblastoma, where the conditional 5-year survival remained low.\u003c/p\u003e\u003cp\u003eA regional study conducted in Genoa (Liguria Region, Italy) reported stable incidence rates of malignant brain tumors between 1993 and 2017, with a slight increase in glioblastoma incidence attributed mainly to improved diagnostic precision rather than to a real increase in disease burden [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Similarly, the population-based registry of Catania (Sicily, Italy) reported a high incidence of meningioma (9.8 per 100,000) and a glioblastoma incidence of 2.9 per 100,000 between 2003 and 2016, without any significant temporal trend [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Our findings are consistent with international cancer registries, including the Central Brain Tumor Registry of the United States (CBTRUS) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and the CONCORD program [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, while overall incidence estimates for CNS tumors in the Veneto Region align with those from other Italian registries, some differences emerge when comparing specific tumor types. For instance, glioblastoma incidence in our cohort (5.2 per 100,000) was higher than that reported in Catania (2.9 per 100,000), possibly reflecting improved histologic confirmation or diagnostic access in more recent years. In contrast, the incidence of meningioma was lower in our data since we included only grade 2\u0026ndash;3 tumors, which are considered malignant, whereas other registries include all histological grades. These discrepancies underline the importance of methodological consistency when comparing regional registry data. Glioblastoma incidence and survival rates matched closely with those reported in other Italian regions (e.g., Liguria, Sicily). These findings are consistent with broader global trends, with approximately 322,000 new CNS cancer cases reported worldwide in 2022 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and with national data estimating over 6,000 new diagnoses annually in Italy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The strong sex difference in meningioma incidence and age-related increase across all tumor types align with prior studies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe poor prognosis of glioblastoma, despite modest advances, remains a critical challenge. Conversely, the favorable long-term survival of grade 2 oligodendrogliomas and ependymomas supports their distinction in epidemiologic and clinical stratification.\u003c/p\u003e\u003cp\u003eImportantly, this study also included rarer CNS tumors such as low-grade gliomas, medulloblastomas, and ependymomas. These entities are often underrepresented in population-based research due to their lower frequency in the adult population. In our cohort, grade 2\u0026ndash;3 astrocytomas accounted for 9.4% of cases, oligodendrogliomas for 4.5%, ependymomas for 2.4%, and medulloblastomas for 0.9%. Despite their relative rarity, these tumors carry distinct clinical trajectories and management needs, particularly in younger adults. By analyzing these tumor types separately, our study contributes novel insights into their incidence patterns and long-term survival outcomes, helping to inform tailored treatment strategies and long-term care planning.\u003c/p\u003e\u003cp\u003eThe availability of a dedicated cancer registry that includes less frequent CNS tumors such as IDH-mutant low-grade gliomas is becoming increasingly important in light of emerging therapeutic options. The recent approval of Vorasidenib, a dual inhibitor of mutant IDH1 and IDH2, offers a new treatment avenue for patients with IDH-mutant grade 2 gliomas. Data from the phase III INDIGO trial have shown a significant progression-free survival benefit compared to placebo in this population [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This advance highlights the relevance of accurately capturing and monitoring these tumor types in population-based registries, not only for clinical epidemiology but also to inform future pharmacoeconomic evaluations and treatment planning.\u003c/p\u003e\u003cp\u003eOur data reinforce the prognostic value of WHO grading and highlight the importance of including intermediate-grade tumors (e.g., grade 2\u0026ndash;3 meningiomas, oligodendrogliomas) in registry-based analyses. These tumors, although often excluded from classic cancer statistics, have relevant recurrence rates and healthcare needs. Their inclusion provides a more accurate estimation of clinical burden and resource allocation.\u003c/p\u003e\u003cp\u003eConditional survival analysis provides clinically relevant information for follow-up and counseling. This metric estimates the probability of surviving additional years, conditional on having already survived a specific period (generally, one year) after diagnosis. For many CNS tumors, prognosis improves markedly after the initial year, providing reassurance to patients, guiding clinicians in adapting follow-up intensity and expectations over time and underlining the importance of long-term survivorship care.\u003c/p\u003e\u003cp\u003eA substantial portion of CNS tumor diagnoses (especially in older adults) lacked histologic confirmation. These patients, often inoperable or unfit for biopsy, had poor outcomes. While their inclusion may lower survival estimates, it reflects real-world epidemiology and highlights the need for supportive and palliative pathways. Notably, most of these patients were elderly, and the decision to forego biopsy may be influenced by age-related factors such as frailty or significant comorbidities. However, in the absence of clear contraindications, efforts should be made to pursue histologic confirmation whenever feasible, as it remains essential for diagnosis, prognosis, and treatment planning. This subgroup of patients would particularly benefit from multidisciplinary assessment, including integration with geriatric oncology services and the use of comprehensive geriatric assessment (CGA) tools, to better evaluate operability and guide therapeutic decisions.\u003c/p\u003e\n\u003ch3\u003eLimitations and Future Directions\u003c/h3\u003e\n\u003cp\u003eAccording to the study period, the 2016 WHO classification was used and the absence of molecular markers prevented a possible comparison with the 2021 WHO categories. Molecular profiling should be integrated into future registry efforts. A further limitation of this study is represented by the exclusion of pediatric tumors, which represent approximatively 3% of the total cases, that warrant separate investigation.\u003c/p\u003e\u003cp\u003eDespite these limitations, this is one of the first population-based studies in Italy and among the few internationally to provide detailed incidence and survival estimates for a wide spectrum of CNS tumors, including rarer subtypes such as low-grade gliomas, ependymomas, and medulloblastomas in the adult population. This level of granularity is essential to improve disease characterization, inform public health strategies, and support the implementation of precision medicine approaches at a population level. It provides a foundation for future research, health planning, and benchmarking of neuro-oncology care.\u003c/p\u003e"},{"header":"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\u003eAlessandra Andreotti, Giuseppe Lombardi, Eliana Ferroni, Stefano Guzzinati and Manuel Zorzi contributed to the study conception and design. Data collection were performed by Susanna Baracco, Maddalena Baracco, Emanuela Bovo, Eva Carpin, Antonella Dal Cin, Alessandra Greco, Anna Rita Fiore, Laura Memo, Daniele Monetti, Silvia Rizzato, Jessica Elisabeth Stocco, Carmen Stocco, Sara Zamberlan. Data analysis was performed by Alessandra Andreotti and Stefano Guzzinati. Interpretation of data were performed by Alessandra Andreotti, Giuseppe Lombardi, Eliana Ferroni, Stefano Guzzinati and Manuel Zorzi. The first draft of the manuscript was written by Alessandra Andreotti, Giuseppe Lombardi, Eliana Ferroni, Stefano Guzzinati and Manuel Zorzi. All authors commented on previous versions of the manuscript, read and approved the final manuscript. Giuseppe Lombardi and Manuel Zorzi 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\u003eThe Italian legislation identifies regional and national health authorities as collectors of personal data for surveillance purposes without explicit individual consent. The approval of a research ethic committee is not required, because this study is a descriptive analysis of anonymous aggregate data without any direct or indirect intervention on patients (Decreto del Presidente del Consiglio dei Ministri, 3/3/2017, Identificazione dei sistemi di sorveglianza e dei registri di mortalit\u0026agrave;, di tumori e di altre patologie, 17A03142, GU Serie Generale n.109 del 12-05-2017). Available at: www.gazzettaufficiale.it/eli/id/2017/05/12/17A03142/sg (last accessed July 30, 2025).\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\u003cli\u003e\u003cspan\u003eFerlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Pi\u0026ntilde;eros M, Znaor A, Soerjomataram I, Bray F (2024) Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. 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N Engl J Med. 17;389(7):589\u0026ndash;601. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa2304194\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa2304194\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Central Nervous System Tumors, Incidence, Survival, Histology, Tumor Grade, Cancer Registry","lastPublishedDoi":"10.21203/rs.3.rs-7325745/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7325745/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e\u003cp\u003eCentral nervous system (CNS) tumors represent a heterogeneous group of neoplasms with significant clinical impact and variable prognosis. Despite the relatively low incidence, they account for considerable morbidity and mortality. In Italy, population-based data on incidence and survival by histological subtype and tumor grade remain limited, particularly for rarer CNS tumor entities.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe conducted a retrospective population-based study using data from the Veneto Cancer Registry, including adults diagnosed with CNS tumors between 2016 and 2020. A dedicated text-mining algorithm was applied to pathology reports to extract tumor grade. Tumors were categorized into six main histological groups. We estimated incidence rates, relative survival, and 5-year conditional relative survival, stratified by sex, age, tumor type, and grade.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 1,636 incident CNS tumors with confirmed histopathology and intermediate to high-grade behavior were identified. Glioblastoma was the most frequent subtype (64.6%), followed by grade 2\u0026ndash;3 meningiomas (18.2%) and astrocytomas (9.4%). The overall crude incidence was 8.0 per 100,000, higher in males (9.5) than females (6.6). Five-year relative survival varied substantially by tumor type and grade: glioblastoma had the poorest outcome (5.7%), while grade 2\u0026ndash;3 ependymomas and oligodendrogliomas showed favorable prognosis (87.7% and 82.0%, respectively). Conditional 5-year survival after surviving one year remained low for glioblastoma (11.0%) but exceeded 85% for most lower-grade tumors.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOur findings underscore the prognostic relevance of tumor grade and histology, supporting the need for tailored clinical strategies, molecular diagnostics, and the development of innovative therapies for informed healthcare planning and resource allocation.\u003c/p\u003e","manuscriptTitle":"Incidence and Survival of adult Central Nervous System Tumors in the Veneto Region: A Population-Based Registry Study (2016-2020)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-14 14:49:19","doi":"10.21203/rs.3.rs-7325745/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-11T15:11:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-04T20:20:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-29T13:06:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"11641615500264452668658346493650107855","date":"2025-08-25T12:26:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"12149100972102638360610758482024185927","date":"2025-08-20T19:41:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-08T16:22:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-08T11:48:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-08T11:13:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Neuro-Oncology","date":"2025-08-08T09:13:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f0080a21-be9e-4b16-84fe-cfacb8f34f1e","owner":[],"postedDate":"August 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-20T16:05:15+00:00","versionOfRecord":{"articleIdentity":"rs-7325745","link":"https://doi.org/10.1007/s11060-025-05257-w","journal":{"identity":"journal-of-neuro-oncology","isVorOnly":false,"title":"Journal of Neuro-Oncology"},"publishedOn":"2025-10-15 15:57:23","publishedOnDateReadable":"October 15th, 2025"},"versionCreatedAt":"2025-08-14 14:49:19","video":"","vorDoi":"10.1007/s11060-025-05257-w","vorDoiUrl":"https://doi.org/10.1007/s11060-025-05257-w","workflowStages":[]},"version":"v1","identity":"rs-7325745","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7325745","identity":"rs-7325745","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}