Abstract Background Leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC) has entered a new therapeutic era, yet no validated composite prognostic score jointly captures functional, molecular, anatomical, and cerebrospinal fluid (CSF) dynamic dimensions. We developed and internally validated the Cerebrospinal System Failure Score (CSF-Score), a pre-specified five-dimensional prognostic score for NSCLC-LM. Methods We retrospectively analyzed 123 consecutive patients with cytology-confirmed NSCLC-LM between January 2022 and June 2025. The CSF-Score (0-10 points) was constructed a priori and integrates host resilience, molecular engine, anatomical burden, fluid dynamics, and biological toxicity, with a Karnofsky Performance Status <60 gatekeeper directing patients to the high-risk stratum. Patients were classified as low- (0-2), intermediate- (3-6), or high-risk (≥7 or gatekeeper). Discrimination was assessed using Harrell’s C-index with 1,000-resample bootstrap internal validation and temporal split validation. Results Median OS was 20.5 months (95% CI, 16.6-23.9), 12.6 months (95% CI, 8.9-15.8), and 4.5 months (95% CI, 3.2-5.7) in the low- (n = 32), intermediate- (n = 49), and high-risk (n = 42) groups, respectively (log-rank P < .001). The C-index was 0.741 (95% CI, 0.705-0.779), with negligible optimism after bootstrap correction and stable temporal split validation (training 0.742 vs testing 0.733). Four of five dimensions retained independent significance on multivariable analysis; fluid dynamics showed a mediation-consistent attenuation pattern. The total score remained independently associated with OS after adjustment for treatment covariates (HR 1.28 per point, P < .001). Conclusions The pre-specified CSF-Score achieved clear three-tier prognostic stratification in NSCLC-LM while incorporating dimensions relevant to CSF system status. External multicenter validation is required before clinical adoption.
Abstract Background Survivors of primary brain tumors (SPBT) frequently struggle to return to work. This study investigated work status and outcomes after tele-based vocational cognitive rehabilitation (t-VCR) in SPBT. Methods We retrospectively reviewed adults (≤65 years) with SPBT at an academic medical center who completed objective cognitive and patient-reported outcome measures between 5/2018 and 5/2022. Participants were grouped by employment status and compared on demographic and clinical characteristics. Work outcomes were analyzed in a subgroup who underwent t-VCR during standard clinical care. t-VCR treatment response was defined as return to work, increase to full-time work, or graduation from a workplace improvement plan versus baseline. Analyses used t-tests, chi-square, and McNemar tests, with content analysis identifying key interventions in responders. Results Of 77 participants, 35 were working and 42 were unemployed upon referral. Unemployment was associated with worsened verbal learning and memory (P < .003). Among the 28 people who received t-VCR (mean-10 sessions), 82% returned to work after t-VCR. In those who had improved work status, content analysis identified t-VCR interventions, including executive and organizational skills training, mental health counseling, job simulations/accommodations, and fatigue/stimulation education were most common. Conclusion Worsened verbal learning and memory were associated with unemployment, highlighting the impact these cognitive symptoms can have on occupational functioning. Work status improved in the context of t-VCR and warrants further study. Among participants who demonstrated improvement, t-VCR was delivered as a multimodal, individualized intervention that addressed cognitive, emotional, fatigue, and practical workplace-related challenges.
Abstract Background Patients with isocitrate dehydrogenase (IDH)-mutant gliomas often experience prolonged survival but frequently have persistent psychological distress and impaired quality of life (QOL). While prior research has characterized symptomatology and functional outcomes, less is known about how factors such as age and developmental stage shape distress and coping in this population. Our study sought to better understand these psychosocial dimensions of living with an IDH-mutant glioma, to inform the design of tailored supportive care. Methods We conducted semistructured interviews with adults aged 18-65 years diagnosed with IDH-mutant gliomas (n = 20) receiving care at a large academic medical center. We used stratified purposeful sampling to ensure variation in age. Our multidisciplinary team coded and analyzed interview transcripts using reflexive thematic analysis. Results Participants’ experiences coalesced around a central concept of destabilized identity, reflected in 5 interrelated themes: (1) yearning for an idealized past self; (2) shifting social roles; (3) existential uncertainty; (4) informational uncertainty; and (5) diverse emotional responses to identity conflict. Participants reported a loss of continuity with their premorbid selves, uncertainty about the future, and worries about sustaining cognitive and social functioning. This identity disruption was particularly distressing for younger adults navigating careers, relationships, and long-term life planning. Many expressed unmet support needs despite ongoing oncologic care. Conclusions Disruption of personal identity emerged as a central feature of the experience of living with an IDH-mutant glioma. Supportive care that acknowledges and helps patients adapt to changes in their sense of self may improve overall psychosocial well-being and QOL.
Abstract Background Meningiomas are increasingly detected incidentally due to widespread neuroimaging and are sometimes managed surgically despite the absence of preoperative symptoms. Although surgery in these patients is often considered to be of low risk, long-term patient-reported outcomes such as fatigue remain insufficiently characterized. Objective To assess the prevalence and severity of long-term fatigue in patients surgically treated for asymptomatic meningiomas. Methods In this population-based retrospective cohort study, adult (≥18 years) patients with asymptomatic meningioma treated surgically at Karolinska University Hospital between 2007 and 2013 (n = 69) were included. Patients were assessed using the Multidimensional Fatigue Inventory (MFI-20) and compared with age- and sex-matched normative values. The proportion of patients with clinically significant fatigue was estimated using validated cut-off scores based on previous studies. Results The median total fatigue score was 55 (IQR 45-63), corresponding to approximately 0.7 SDs above age- and sex-matched normative values. Patients reported significantly higher fatigue levels than normative values across all MFI-20 dimensions (all P < .001). Fatigue was present in 33% of patients based on total fatigue scores, while 48%-64% exceeded cut-off values in individual fatigue dimensions present in MFI-20. Descriptive differences in fatigue scores were observed across age groups and between sexes Conclusion Patients surgically treated for asymptomatic meningiomas experience elevated multidimensional fatigue at long-term follow-up. These findings challenge assumptions of benign postoperative recovery in this patient population and highlight the importance of systematic fatigue assessment and targeted management strategies even in previously asymptomatic patients.
Abstract Background The CeTeG/NOA-09 trial showed improved survival with lomustine (CCNU) plus temozolomide (TMZ) over TMZ alone in O6-methylguanine-DNA-methyltransferase (MGMT) promoter-methylated glioblastoma patients aged 18-70 years. Data on feasibility, tolerability, and outcomes in patients over 70 receiving this regimen are lacking and were evaluated in this study. Methods We conducted a retrospective multicenter cohort study including patients aged >70 years with newly diagnosed, histologically confirmed, MGMT promoter-methylated glioblastoma treated with first-line radiotherapy and CCNU/TMZ. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events v5.0. Results Eighteen patients (median age of 72 years, range 71-78) were included. Most patients had a good clinical status (median Karnofsky Performance Status of 90%, interquartile range [IQR] 80-90). Patients received a median of 5.5 (IQR 3.5-6) TMZ and 5 (IQR 3-6) CCNU cycles. Hematotoxicity occurred in 50% of patients, with grade ≥3 hematotoxicity in 33%. Hepatotoxicity was observed in two cases (11%), both grade 3. Toxicity-related treatment discontinuation occurred in 11%, with no treatment-related deaths. Median follow-up was 15.8 months (range: 4-82.5), median PFS was 11.5 months (95% CI, 8.9-21.1), and median OS was 19.1 months (95% CI, 13.3-46.4). Conclusions In this highly selected multicenter cohort of patients with MGMT promoter-methylated glioblastoma, first-line CCNU/TMZ combined with radiotherapy was feasible and tolerable. Survival outcomes were encouraging but descriptive, warranting prospective studies that include geriatric assessment before broader implementation in elderly patients.
Abstract Gliomas are among the most common primary CNS tumors in adolescents and young adults (AYAs; ages 15–39 years), and several subtypes are associated with prolonged survival. As a result, fertility preservation and pregnancy management have become increasingly important components of survivorship care; however, current evidence remains scarce. Despite family planning needs, many patients receive limited counselling, and both referral to and access to reproductive specialists remains inconsistent. Glioma‑directed therapies may impair fertility through gonadotoxic chemotherapy, hypothalamic–pituitary dysfunction, or prolonged exposure to targeted agents with poorly defined reproductive effects. Pregnancy after glioma diagnosis introduces additional complexities, including concerns regarding tumor progression, optimal timing of conception, antiseizure medication selection, and obstetric and neonatal risks. Evidence describing the interaction between pregnancy and glioma biology is limited to small retrospective series with heterogeneous imaging practices and minimal molecular characterization. Available data suggest that tumor behavior during pregnancy largely reflects underlying histology, grade, and prior treatment, with progression more frequently reported in higher‑grade disease and transient increases in growth kinetics described in some IDH‑mutant diffuse gliomas. Overall survival does not appear adversely affected by pregnancy. This review synthesizes current guidelines and evidence across fertility preservation, preconception planning, and cancer management during pregnancy, emphasizing multidisciplinary care and highlighting key evidence gaps—particularly regarding targeted therapies, optimal surveillance, and molecularly informed risk stratification—to guide future research and clinical practice.
Abstract Brain tumors are the second most common malignancy in children and adolescents and the leading cause of cancer-related death in this population. While survival rates have improved, survivors are at risk of neurocognitive, motor, and psychosocial sequelae due to both tumor location and treatments used. Participation in sport is increasingly recognized as beneficial for functional recovery, cardiorespiratory fitness, and overall well-being in children and adolescents treated for brain tumors. However, return to play (RTP) may pose some challenges, particularly in the presence of neurosurgical devices, cranial radiotherapy, or residual neurological deficits. This narrative clinical review summarizes current evidence on the risks of sport-related injuries in pediatric brain tumor patients and survivors, highlighting factors influencing vulnerability, including treatment history and specific sport characteristics. We propose a risk-based framework for RTP evaluation emphasizing individualized coordinated assessment by pediatric oncologists, neurosurgeons, and sports medicine specialists. Protective strategies are discussed, although evidence for concussion prevention remains limited. A safe RTP should be enhanced by the here-proposed structured evaluation, balancing safety with the physical, cognitive, and psychosocial benefits of active participation. This framework aims to support clinicians and families in facilitating safe and effective reintegration of pediatric brain tumor survivors into both recreational and competitive sports.
Background There is limited knowledge about how diagnosis and treatment for brain tumors affect intimacy and sex life in young adults. This study examined sexual function and activity and identified factors associated with sexual function in a national cohort of young adults up to 5 years after being diagnosed with a primary brain tumor. Methods Patients diagnosed with a malignant or benign brain tumor at ages 18-39 years were identified through the Swedish Quality Registry for CNS tumors and approached with a comprehensive survey at 1.5-, 3-, and 5-year postdiagnosis. In total, 123 responded (58%) and 72 (31 men and 41 women) of them completed the full set of surveys. Sexual function was assessed with the PROMIS SexFS v2.0. Changes over time were examined using repeated measures ANOVA, and multivariable linear regression models were conducted to identify factors associated with sexual dysfunction. Results Most participants were sexually active (>80%) and satisfied with their sex life, although a substantial proportion reported low interest in sexual activities. No changes over time were observed in the domains Satisfaction with sex life (F(2, 104) = 0.49, P = .66) or Interest in sexual activity (F(2, 136) = 0.58, P = .56). Sexual dysfunction was associated with depressive symptoms and body image disturbance. Clinical characteristics were not associated with sexual dysfunction. Conclusions Most young adults diagnosed with a brain tumor were sexually active and reported satisfaction with their sex life. A subgroup reported low interest in sexual activities, underscoring the need to include discussions about possible cancer-related impact on sex life into follow-up care.
Background Neurofibromatosis type 1 (NF1) is a genetic condition that affects an estimated 1 in 3000 people worldwide. Between 30% and 50% of patients with NF1 develop symptomatic, inoperable plexiform neurofibromas. To identify the unmet needs and understand the potential value of new treatments, the treatment patterns, healthcare resource utilization (HCRU), and clinical outcomes were evaluated in a real-world cohort of 102 pediatric patients with NF1 and PN.Methods Retrospective data were collected from patients diagnosed with NF1 and symptomatic, inoperable PNs from 2000 to 2018 across 3 US sites. Data on clinical characteristics, site visits, treatments, and outcomes were collected through 2019.Results Patients with NF1, on average, developed 3.5 symptomatic, inoperable PNs during the study. PN complications included pain (76.5%), disfigurement (45.1%), and motor dysfunction (13.7%). During the study period, which was prior to Food and Drug Administration (FDA) approval of mitogen-activated protein kinase inhibitors for NF1, available treatments attempted to address the symptoms caused by PNs but did not typically slow or prevent their growth. Surgery was performed for 38.1% of study patients. At follow-up of >= 12 months, 62.5% of PNs regrew after surgery. Each year, patients made, on average, 6 visits to an outpatient care center and 1 visit to an oncologist. Nearly all patients (99.0%) received at least 1 diagnostic imaging scan, with 3.4 scans per year on average.Conclusions This study describes the high burden of HCRU among pediatric patients with NF1-PN prior to FDA approval of pharmacologic therapies for PN and demonstrates the need for effective treatment options. Neurofibromatosis type 1 (NF1) is a hereditary condition that can cause painful tumors. These tumors affect appearance and physical function. We studied children with NF1 in the United States before medication specific to NF1 was available. We reviewed medical records to better understand NF1 symptoms, treatments, and outcomes. Patients developed more than 3 tumors over the course of the study and had around 6 doctor visits every year. Many treatments helped relieve symptoms but did not prevent tumor growth. This study illustrates the hardships NF1 patients face and the need for better treatments.
Abstract Background Cognitive impairment is common among patients with primary brain tumors and significantly impacts quality of life. Surgical resection can affect cognition, but postoperative outcomes vary widely across individuals. Identifying presurgical factors that predict cognitive outcomes could help clinicians stratify risk, guide preoperative counseling, and inform interventions to reduce the risk of postoperative cognitive decline. This systematic review aimed to identify, synthesize, and critically evaluate research on presurgical predictors of cognitive outcomes following brain tumor resection. Methods Five databases were searched from inception to April 2025. Studies were included if they examined presurgical predictors of postoperative cognitive outcomes in adults undergoing surgery to remove a primary brain tumor, using multivariate analysis. Risk of bias was assessed using the Quality In Prognosis Studies tool. Results Fifteen studies met the inclusion criteria. Higher baseline preoperative cognitive performance consistently predicted better postoperative outcomes, including stability or improvement in processing speed, executive function, memory, and visuospatial skills. In comparison, sociodemographic factors and tumor-related characteristics were less reliable predictors. Modifiable presurgical predictors were largely unexplored. Methodological heterogeneity limited direct comparisons across studies, underscoring the need for standardized approaches to assessing cognition in neuro-oncology research. Conclusion The review emphasizes the importance of incorporating baseline cognitive assessments into routine clinical care to help identify patients most vulnerable to cognitive decline. Future research should focus on identifying modifiable factors to prevent cognitive decline, and until then, developing interventions to reduce the impact of cognitive decline on recovery and quality of life is crucial.
Background Intracranial meningiomas are associated with substantial psychological morbidity. We aimed to characterize patients' subjective experience of their disease trajectories.Methods We conducted an exploratory interview study. Ten adults with meningioma participated in semistructured interviews 6-36 months post-diagnosis. Data were analyzed using Braun and Clarke's Reflexive Thematic Analysis.Results Patients consistently framed meningioma as a recurrent threat, with 3 temporal anchors: diagnosis, surgery, and long-term postoperative surveillance. Threat encompassed identity, daily functioning, and bodily trust, with persistent uncertainty. Coping strategies included humor, social connectedness, and structured rehabilitation, whereas avoidance and internet searching often amplified distress. Clinical conversations could reframe the threat and restore a sense of safety.Conclusions Intracranial meningioma is commonly experienced as a persistent, multifaceted threat. Care pathways should incorporate crisis-informed communication, expectation-setting regarding prognosis and surveillance, and distress triage using validated tools to align clinical care with lived experience and help prevent a smoldering crisis in patients and families. We explored how people with meningioma experience their illness from diagnosis through surgery and follow-up scans. We asked this because most meningiomas are low grade, yet many people still report emotional strain, and this is not yet well understood. Through interviews, we found that diagnosis, surgery, and follow-up scans could each contribute to persistent fear and uncertainty. Participants also described changes in trust in their body and in everyday life. These findings suggest that clearer communication, better emotional support, and attention to distress during follow-up may improve care for people living with meningioma.
Background Brain tumors cause more than 248 000 deaths annually, and their incidence continues to rise. Despite medical advances, outcomes have improved marginally, and the associated economic burden is substantial. European spending was estimated at & euro;37.8 billion in 2019. Although several cost drivers have been identified, robust and methodologically sound cost evaluations remain limited. This study aimed to quantify 30-day in-hospital healthcare consumption and identify cost drivers in brain tumor surgery.Methods Adult patients undergoing brain tumor surgery in 2023 at a single regional referral center were retrospectively analyzed. The primary outcome was total 30-day in-hospital costs, calculated using a bottom-up microcosting approach. Univariable and multivariable analyses were performed to identify key cost drivers.Results A total of 322 patients (mean age 61 years; 51.2% female) were included in this study. Median length of stay (LOS) was 3 days (interquartile range; 2-6), and mean in-hospital costs were & euro; 6988 per patient (SD +/- & euro; 4273). Tumor pathology was associated with significantly increased surgical costs (P = .035) but did not significantly influence overall costs (P = .376). Multivariable analysis identified surgery type, preoperative Karnofsky Performance Status, total LOS, intensive care unit LOS, and Clavien-Dindo complication grade as independent cost drivers. Repeat surgery, readmission, and 30-day mortality further increased costs.Conclusions Thirty-day in-hospital costs following brain tumor surgery are substantial, mainly driven by operative and hospitalization factors. Identifying modifiable cost determinants is essential for developing targeted interventions to improve efficiency and optimize resource utilization. This study explores the real costs of hospital care after brain tumor surgery. Using detailed hospital records, the researchers examined how healthcare resources were used during the first 30 days after surgery, when increased amount of care is needed. They found that costs were mainly influenced by how long patients stayed in hospital, whether they were admitted to the intensive care, the type of surgery, patients' physical condition before surgery, complications, and short-term outcomes. These results highlight opportunities to improve care efficiency, such as better recovery pathways and preventing complications while maintaining high-quality patient care.
Abstract Grade 2 and most grade 3 isocitrate dehydrogenase (IDH) mutant diffuse gliomas are slow growing tumors, for which however no curative treatment is available. Although surgery as extensive as possible improves outcome, for virtually all patients at some point in time further treatment is necessary. Treatment with radiotherapy and chemotherapy is very effective in controlling tumor growth in most patients, but has side effects. Therefore, in many patients these are postponed and a postoperative “watch-and-wait” observational strategy is followed. With the approval of IDH inhibitors, another effective strategy has emerged allowing further delay of treatment with radiotherapy and chemotherapy. This underscores the need for guidance how to best follow these patients during their subsequent phases of treatment, but most guidelines give only minimal recommendations for follow-up. Follow-up should not be limited to imaging only, but should also routinely assess seizures and cognition of patients. Follow-up intervals should be based on the risk of progression, allowing longer intervals for patients with oligodendroglioma, for more definitively treated patients and for patients with longer lasting disease stabilization. Evidence justifying a more intensive follow-up of patients on IDH inhibitors than for patients on a “watch-and-wait” strategy is lacking. Assessing a growth trajectory over time and routine two-dimensional or three-dimensional tumor assessment will allow identification of early changes in growth rate. This manuscript provides guidance for optimal follow-up of these patients with perspectives from all involved disciplines, as indeed the follow-up of these patients needs to be truly multidisciplinary, at every step along the pathway of these patients.
Background Pediatric brain tumors are the leading cause of cancer-related mortality in children. Despite therapeutic advances, outcomes remain poor, and trial conduct is challenged by disease rarity, limited accrual pools, and complex multimodal regimens. Premature trial termination compounds these challenges, wasting resources and delaying progress. A comprehensive evaluation of the US pediatric neuro-oncology trial landscape and determinants of early discontinuation has not been performed. Methods We queried ClinicalTrials.gov for US-based interventional pediatric neuro-oncology trials initiated between January 1, 2010, and December 31, 2024. Trials were categorized by design features, tumor type, sponsor, and consortium involvement. Temporal trends, trial duration, and reasons for discontinuation were analyzed. Multivariable Cox proportional hazards models assessed factors associated with trial completion among trials initiated between 2010 and 2019. Results Of 819 identified trials, 243 met inclusion criteria. Most trials were early phase (phase 1/1-2, 69.5%) and focused on recurrent/progressive disease (68.3%), with targeted therapy (53.9%) and immunotherapy (26.3%) most common. Trial opening declined significantly over time (Poisson regression, P < .001), although the proportion of closed trials remained stable (chi & sup2; P = .97). Mean time to accrual was 4.8 +/- 1.2 years, with modest improvement after 2018. Among 52 (21.4%) prematurely closed trials, poor accrual was the leading reason (50%), followed by funding issues (19.2%). Multivariable analysis identified greater site numbers decreasing the risk of premature discontinuation (hazard ratio = 0.55; 95% CI, 0.35-0.83). Conclusions Multisite reach is a key determinant of trial persistence. Strategies to optimize accrual and reduce early termination should prioritize interinstitutional networks and trial platform site networks.
Abstract Background Pediatric, adolescent, and young adult brain tumor survivors face a myriad of physical and emotional health challenges due to the effects of their tumors and the treatments they receive. Survivors experience worse neurocognitive, psychosocial, and general health outcomes, and often receive fragmented care from seeing multiple subspecialists. With the goal of informing best practices on survivorship care, we reviewed and critically appraised the available evidence and guidelines for survivorship care in child, adolescent, and young adult (CAYA) brain tumor patients. Methods We systematically identified clinical practice guidelines, consensus statements, position papers, and formal recommendations addressing surveillance or long-term follow-up care in CAYA survivors of CNS tumors published up to April 18, 2026. Extracted data were synthesized descriptively and organized by surveillance domain. Areas of concordance and discordance across guidelines were identified, with particular attention to variability in recommended surveillance strategies, frequency, and evidence grading systems. Results We identified 24 relevant clinical practice guidelines, consensus statements, position papers, and formal recommendations addressing surveillance or long-term follow-up care in CAYA brain tumor survivors. We summarized the data descriptively and organized by surveillance domain, including recommendations for surveillance for secondary malignancy, medical complications, neurologic complications, education, employment, psychosocial and behavioral outcomes as well as supportive care. Conclusions Our study discusses current practices in regard to surveillance and long-term follow-up care in CAYA survivors of CNS tumors. We also highlight areas of uncertainty and provide recommendations for future studies to address knowledge gaps in terms of surveillance and clinical management for this patient population.
Abstract Background Diffuse gliomas in adults are rare aggressive CNS (central nervous system) tumors whose outcomes are strongly influenced by molecular features. In Brazil, data on epidemiology, molecular diagnostics, and survival are scarce, particularly following the WHO CNS 2021 classification. The LACOG 0619 RWD (Real-World Data) addresses this gap by characterizing Brazilian diffuse glioma patients and evaluating diagnostic disparities. Methods This retrospective, multicenter cohort included adults (≥18 years) with histologically confirmed diffuse gliomas from nine centers in Brazil (2010–2019). Reclassification followed WHO CNS 2021 criteria. Completeness of molecular workup was compared between public and private institutions. Results 828 patients were included (median age 52 years, 56.0% male, 57.6% from private centers). Glioblastoma was the most frequent histology (57%). The central finding was a marked disparity in access to molecular diagnostics: IDH (Isocitrate Dehydrogenase), 1p/19q, MGMT (O6-Methylguanine-DNA Methyltransferase), and NGS (Next-Generation Sequencing) testing were far more frequent in private institutions. Although testing rates improved after 2016, <20% of eligible cases underwent IDH sequencing. Survival differed by histology and WHO 2021 criteria, with five-year OS ranging from 20.2% in IDH-wildtype glioblastoma to 90.9% in IDH-mutant grade 2 gliomas (p < 0.001), confirming the prognostic impact of molecular testing. Conclusions LACOG 0619 is the first and largest RWD to assess molecular diagnostic gaps in diffuse gliomas in Brazil. The study reveals profound inequities between public and private healthcare institutions, underscoring the urgent need to expand equitable access to molecular testing as an essential step toward enhancing patient care and ensuring inclusion in precision oncology.
