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Nigeria, the most populous country in Africa, has the highest incidence of central nervous system (CNS) tumors on the continent, yet faces limited access to neuro-oncology care, particularly for pediatric patients. Given the sparse literature on pediatric neuro-oncology in the country, this study provides an epidemiologic overview of the presentation, diagnosis, treatment, and outcomes of pediatric CNS tumor cases in Nigeria. We conducted a systematic review across six databases, covering January 1962 to December 2023, including articles specifically addressing pediatric CNS tumor care in Nigeria. Extracted variables included demographics, presentation, diagnostics, treatment, complications, and outcomes. Twenty-nine studies met the inclusion criteria, encompassing 507 pediatric patients (56.6% male) with a mean age of 8.68 years (SD: 4.32). Headache (27.2%) was the most common presenting symptom. Diagnostic imaging included MRI (34.7%), CT (26.4%), and X-ray (8.9%), with all diagnoses histologically confirmed. Surgical resection was the most common treatment (40.2%), while a few patients received systemic therapy. Hydrocephalus was the most frequently reported complication. The post-intervention mortality rate was 13%, and the five-year mortality rate was 11%. Pediatric CNS tumors in Nigeria present with diverse symptoms and are primarily managed surgically. Despite access to modern diagnostics, outcomes remain suboptimal, underscoring the need for improved infrastructure, timely diagnosis, and standardized care pathways to enhance pediatric neuro-oncology outcomes in Nigeria.

Consolidation therapy for primary CNS lymphoma (PCNSL) includes high-dose chemotherapy with autologous stem-cell transplantation (HCT-ASCT), yet its efficacy compared with non-myeloablative chemoimmunotherapy remains uncertain. This study aimed to provide randomised comparative evidence on the efficacy and safety of thiotepa-based HCT-ASCT versus non-myeloablative R-DeVIC consolidation after uniform MATRix induction in newly diagnosed PCNSL. This open-label, randomised, phase 3 trial was conducted across 56 university and academic non-university hospitals with established transplantation facilities in five European countries. Eligible for inclusion were untreated, immunocompetent patients with B-cell PCNSL, aged 18-65 years regardless of Eastern Cooperative Oncology Group (ECOG) performance status, or 66-70 years with ECOG performance status 0-2. Pretreatment corticosteroids were permitted. Exclusion criteria included lymphoma manifestation outside the CNS, and congenital or acquired immunodeficiency. Patients received four cycles of MATRix induction (comprising rituximab, high-dose cytarabine, and thiotepa, in addition to high-dose methotrexate). Patients reaching at least partial response were randomly assigned (1:1) to two cycles of R-DeVIC (rituximab plus dexamethasone, etoposide, ifosfamide, and carboplatin) or HCT-ASCT with carmustine and thiotepa. The primary endpoint was progression-free survival, assessed in the full analysis set (excluding patients with major violations of entry criteria). The safety analysis set contained all randomised patients who initiated therapy. This study is registered with ClinicalTrials.gov (NCT02531841) and the EU Clinical Trials Register (EudraCT number 2012-000620-17). The study is completed. Between July 16, 2014, and Aug 31, 2019, 368 patients were enrolled. 346 (94%) patients started induction treatment, and 230 were randomly assigned; 229 patients were analysed (R-DeVIC group, n=115; HCT-ASCT group, n=114). After a median follow-up of 45·3 months, 3-year progression-free survival was significantly superior in the HCT-ASCT group (hazard ratio 0·43 [95% CI 0·27-0·68]; p=0·0003). The 3-year progression-free survival was 78% (95% CI 69-85) in the HCT-ASCT group compared with 51% (41-60) in the R-DeVIC group. The mean number of adverse events per patient was 9·3 (SD 4·4) in the R-DeVIC group and 14·6 (5·8) in the HCT-ASCT group. Fatal serious adverse events following consolidation treatment occurred in two patients in the R-DeVIC group (both acute myeloid leukaemia) and in five patients in the HCT-ASCT group (infections and infestations [n=4], pulmonary embolism [n=1]); all of these events apart from the pulmonary embolism were judged to be possibly related to treatment. In the largest randomised trial in untreated PCNSL to date, HCT-ASCT significantly improved progression-free and overall survival compared with non-myeloablative consolidation in patients who had completed induction treatment, establishing it as the preferred consolidation strategy in fit patients. German Federal Ministry of Research, Technology and Space; Swiss Cancer Research Foundation; and Riemser Pharma.

Early palliative care referral for new oncologic diagnoses has been widely recognized as integral to comprehensive care, but there exists a paucity of research assessing referral patterns in pediatric oncology. The objective of this study is to review the change in referral patterns at the Children's Hospital of Eastern Ontario (CHEO) before and after a set of referral criteria were implemented for routine consultation of pediatric palliative care (PPC) for all newly diagnosed oncology patients. This was a retrospective single-centre chart review of all patients with a new oncologic diagnosis from 21 October 2017 to 1 January 2024 using information available in the patient's electronic medical record. Data was evaluated for referral patterns and the time from diagnosis to referral to PPC comparing the period before and after referral criteria were initiated (1 July 2019). A total of 504 chart reviews were completed and 226 patients were referred to PPC. The proportion of patients referred to PPC showed a statistically significant increase from 36.8% to 75.4% after introduction of PPC referral criteria (&#x3c7;2(1) = 44.98, p < 0.001). The time from diagnosis to referral showed a statistically significant decrease from a median of 267 days (IQR 116-551.5) prior to criteria to 11 days (IQR 4-27) post-criteria (Mann-Whitney U test, p < 0.001). Time to referral decreased significantly across all diagnostic subgroups except for CNS tumours. Having referral criteria for consultation to PPC increased the proportion of oncology patients referred to PPC and resulted in a significant decrease in time to referral. These findings suggest that structured referral criteria support earlier integration of pediatric palliative care within oncology programmes.

De novo neuroendocrine prostate cancer is an aggressive, androgen receptor-independent subtype of prostate cancer with poor prognosis. Central nervous system (CNS) metastases from de novo neuroendocrine prostate tumors are rare, and evidence guiding treatment is limited. Lurbinectedin, approved for small cell lung cancer (SCLC), has shown activity in neuroendocrine tumors, though CNS-specific data remain sparse. A 57-year-old man presenting with tenesmus, dyschezia, and urinary retention was diagnosed with high-grade neuroendocrine prostate carcinoma with low prostate-specific antigen (PSA) and high proliferative index. Genomic profiling revealed alterations in ATM and BRCA2 and was negative for Rb1 and TP53. He achieved complete systemic response following platinum-based chemoradiotherapy and immunotherapy but later developed multifocal brain metastases with suspected leptomeningeal involvement. After progression on whole-brain radiotherapy and topotecan, lurbinectedin was initiated. Imaging demonstrated marked intracranial response, including resolution and reduction of multiple lesions. Disease progression occurred after six cycles. This case underscores similarities between neuroendocrine prostate carcinoma and SCLC, supporting the use of SCLC-based therapies. The observed response suggests that lurbinectedin may have clinically meaningful CNS activity, even after failure of standard CNS-directed treatments. Lurbinectedin may be a therapeutic option in CNS-dominant neuroendocrine prostate carcinomas. Further studies are needed to better define its intracranial efficacy and durability of response.

Osteopontin (OPN), encoded by the SPP1/Spp1 gene, is increasingly recognized as an extracellular matrix-associated immunoregulatory molecule in the central nervous system (CNS). In CNS-related contexts, OPN does not act as a uniformly protective or detrimental factor. Instead, its effects depend on the producing cell type, molecular form, receptor axis, disease stage, and lesion compartment. Accumulating evidence indicates that OPN may participate in reparative processes, including tissue preservation, debris clearance, vascular remodeling, and support of myelin-related repair, while sustained or ectopic OPN activity may contribute to synaptic injury, persistent glial reactivity, remyelination failure, and immunosuppressive tumor progression. In this review, we summarize the molecular basis of SPP1/Spp1 expression and OPN protein signaling, with emphasis on isoforms, proteolytic processing, receptor usage, and secreted versus intracellular OPN. We then discuss its roles in CNS development, chronic neurological diseases, acute CNS injury, and neuro-oncology, and highlight the need to distinguish biomarker associations, omics-based candidate pathways, and functionally validated mechanisms when considering OPN-related diagnostic or therapeutic strategies.

ALK-negative anaplastic large cell lymphoma (ALCL) is a rare primary central nervous system lymphoma (PCNSL). Although DUSP22 rearrangement is considered favorable in systemic ALK-negative ALCL, survival remains poor in PCNSL. We report a case of PCNSL ALK-negative ALCL with DUSP22-IRF4 rearrangement and an unusual gain of the ALK gene (2p23), complicated by transaminitis, treated with high-dose methotrexate followed by whole-brain radiation therapy, achieving durable remission exceeding 3 years. To our knowledge, this is the first reported case in the CNS setting, suggesting that DUSP22 rearrangement and ALK gain may confer a favorable prognosis. The authors have confirmed clinical trial registration is not needed for this submission.

Secondary Central Nervous Lymphoma (SCNSL) is an aggressive lymphoma with poor outcomes. Consensus regarding consolidation with thiotepa-based autologous transplant (ASCT) for SCNSL is lacking. Our retrospective Singapore study examined survival outcomes post ASCT in 27 patients (median age 57 years) with SCNSL in two tertiary cancer centres from 2013 to 2024. Five (18.5%) patients had de novo SCNSL, 14 (51.9%) patients had isolated CNS relapsed SCNSL and 8 (29.6%) patients had synchronous relapsed SCNSL. At the time of ASCT, 16 (59.3%), 7 (25.9%) and 4 (14.8%) patients were in CR, PR and SD/PD respectively. Median follow up for the 22 relapsed SCNSL patients was 63 (5-109) months with a median PFS and OS of 11.5 and 30 months, respectively, and 4-year PFS and OS rates of 35.0% and 48.0%, respectively. In our analysis, females demonstrated superior median and 4-year PFS and OS compared to males, likely related to difference in age and performance status. On multivariate analysis, CR/PR at time of ASCT trended toward an improved OS (HR 7.86, p&#x2009;=&#x2009;0.06) although this was not statistically significant. Our data suggests that in secondary CNSL, chemo-sensitivity would likely confer good outcomes with thiotepa-based consolidation ASCT. Conversely, patients responding poorly to salvage chemotherapy may consider alternatives including CAR-T cell therapy.

Ocular manifestations of acute lymphoblastic leukaemia (ALL) are often under-recognised, with leukaemic retinopathy and optic nerve infiltration being rare signs of relapse. We report a boy in middle childhood with relapsed B cell ALL presenting with bilateral proptosis and visual disturbances. Ophthalmic examination revealed leukaemic retinopathy and optic nerve infiltration, while neuroimaging and cerebrospinal fluid analysis documented central nervous system (CNS) involvement. Also, testicular examination and imaging found leukaemic infiltration, confirming simultaneous extramedullary relapse. Despite aggressive systemic and intrathecal chemotherapy, the prognosis was poor due to advanced disease progression. Although optic nerve infiltration alone is a recognised entity, the simultaneous occurrence of bilateral optic nerve infiltration, serous retinal detachment, and concurrent CNS and testicular relapse represents an exceptionally rare and aggressive manifestation of B cell ALL relapse. This report highlights the need for vigilant multidisciplinary surveillance of extramedullary sanctuary sites and emphasises prompt ophthalmological evaluation in ALL patients who develop visual symptoms during remission.

Brain metastases (BM) causes significant morbidity and mortality in epidermal growth factor (EGFR) mutated non-small cell lung cancer (NSCLC). The effect of EGFR alteration subtypes on CNS-specific outcomes is poorly defined. Patients with EGFR-mutated NSCLC and BM treated with firstline osimertinib with or without SRS were retrospectively identified from 11 institutions. The primary endpoint was time to CNS progression. Time-to-event outcomes were analyzed using Kaplan-Meier methods. Hazard ratios were estimated with Cox proportional hazards models. Fine Gray models were used for competing risk endpoints. Between 2016 and 2024, 470 patients were identified with the following alterations: exon 19 deletion (57%), L858R (33%), and atypical mutations (9.6%). At 24 months, cumulative incidence of CNS progression was 30% (95% CI: 25%-36%) for exon 19 deletions, 47% (95% CI: 39%-55%) for L858R, and 76% (95% CI: 59%-87%) for atypical mutations (p<0.001). In multivariable models, CNS progression was higher among patients with atypical alterations (HR 4.33, 95% CI: 2.72-6.91) and L858R mutations (HR 1.68, 95% CI: 1.27-2.23) compared with exon 19 deletions. Stratified outcomes for exon 19, L858R, and atypical mutations were similar across local and distant CNS progression, and neurological mortality. Upfront SRS was associated with improved CNS outcomes, with greatest benefit in patients with atypical alterations. Patients with atypical and L858R EGFR mutations had significantly worse CNS outcomes compared to those with exon 19 deletions. Upfront SRS reduced the risk of CNS progression, with the greatest benefit in patients with atypical alterations. EGFR subtype may help identify patients who benefit from SRS.

Intrathecal delivery for central nervous system (CNS) therapy lacks spatiotemporal control due to spinal canal anatomical constraints, especially at human scale. We developed an adaptive magnetic nanorobotic platform enabling multimode swarm mobility for in vivo spinal canal navigation in mice and nonhuman primates. Programmable chain-like, vortex-like, and ribbon-like swarm were accomplished, and vortex swarm was indicated as optimal strategy for adaptive intrathecal navigation. Driven by a robotic arm-generated magnetic field, the vortex swarms indicate navigation within spinal canal over centimeter distances, which magnetically enhanced accumulation at CNS target sites and prolonged their in vivo retention, thereby substantially enhancing their therapeutic efficacy compared with conventional passive intravascular delivery, with minimal side effects. Tests in nonhuman primates indicate that the nanorobotic swarm migration is from the gap between the bundles of cauda equina and then the spin cord, revealing their morphological adaption at the cauda equina interface to circumvent anatomical constraints.

Pediatric cancer remains a leading cause of morbidity and mortality worldwide, particularly in low-and middle-income countries. Cancer treatment may impair nutritional status, alter body composition, and exacerbate cancer-related fatigue (CRF). Phase angle (PhA), a bioelectrical impedance-derived marker of cellular integrity, has emerged as a potential noninvasive indicator associated with functional status, yet its role in pediatric oncology remains underexplored. To investigate longitudinal changes in nutritional status and CRF and to examine the association between PhA and CRF in children/adolescents with cancer during the first 3 months of treatment. Prospective longitudinal study included children/adolescents (0-18 years) newly diagnosed with cancer or central nervous system (CNS) tumors. Participants were assessed at diagnosis-[T0], 1 month-[T1], and 3 months-[T2] after treatment initiation. Data collected included clinical/sociodemographic characteristics, nutritional status (anthropometry/STRONGkids), body composition, and CRF (PedsQLMFS). Repeated measures analyses and linear mixed models were performed, with &#x3b1;&#xa0;=&#xa0;5%. A total of 23 patients (mean age 5.7 years old; 65.2% female) were included. Over time, significant reductions were observed in body mass index (p&#xa0;=&#xa0;0.044), PhA (p&#xa0;=&#xa0;0.013), and lean mass (p&#xa0;=&#xa0;0.037). Self-reported fatigue worsened, particularly in the general fatigue domain (p&#xa0;=&#xa0;0.043). Correlation analyses demonstrated significant associations between fatigue and body composition indicators, particularly calf circumference (r&#xa0;=&#xa0;0.809-0.861), body fat mass (r&#xa0;=&#xa0;0.756-0.844), and PhA (r&#xa0;=&#xa0;0.521-0.752) in self-reports. In linear mixed-effects models, PhA was independently associated with total fatigue over time (&#x3b2;&#xa0;=&#xa0;19.97; p&#xa0;=&#xa0;0.011). Children and adolescents undergoing cancer treatment experience early deterioration in nutritional status and body composition, accompanied by worsening CRF. Fatigue was consistently associated with PhA and lean mass-related indicators, suggesting that body composition and cellular integrity may be associated with fatigue severity during treatment. PhA emerged as a particularly promising noninvasive marker, independently associated with fatigue over time. These findings support the incorporation of PhA and comprehensive nutritional assessment beyond conventional weight- and height-based measures to improve the early identification of patients at risk.

Involvement of the central nervous system (CNS) is an adverse complication of acute lymphoblastic leukemia (ALL) associated with poor patient outcomes. Clinical challenges in the diagnosis and treatment of ALL in the CNS arise from an incomplete understanding of CNS disease pathogenesis, a significant barrier to developing novel therapeutics and biomarkers to address these challenges. A concerted research effort over recent years has significantly improved our understanding of CNS disease pathogenesis in ALL. Numerous CNS-infiltrating mechanisms by ALL cells have been uncovered, so recent research focuses on how ALL persists in this site. The role of the CNS microenvironment in the survival and therapy resistance of ALL is emerging, driven by ALL cell adhesion and metabolic reprogramming, revealing pathways with therapeutic potential. Here, we integrate recent advances in CNS infiltration and persistence in ALL, focusing on the signaling and metabolic frameworks that enable leukemic survival and therapy resistance once established in this site. We also evaluate novel therapeutic avenues and emerging targeted therapies that could enhance the efficacy of CNS-directed therapy in ALL.

The molecular subtype characterized by co-occurring MYD88 and CD79B alterations (MCD) represents a biologically distinct subset of diffuse large B-cell lymphoma (DLBCL) with chronic active B-cell receptor signaling and a high risk of central nervous system (CNS) involvement. The clinical impact of Bruton tyrosine kinase inhibitors (BTKi) in this subtype remains unclear. We retrospectively analyzed 155 patients with newly diagnosed DLBCL harboring genetic features consistent with the MCD subtype. At a median follow-up of 34.1&#xa0;months, the estimated 3-year progression-free survival (PFS) rate was 76.1%. BTKi exposure (n&#xa0;=&#xa0;56) was associated with significantly improved PFS compared with no BTKi exposure (3-year PFS: 93.8% vs. 66.6%, p&#xa0;<&#xa0;0.001) and remained independently associated with improved PFS after adjustment for IPI risk (HR 0.16, p&#xa0;<&#xa0;0.001). Overall survival did not differ significantly between groups. Notably, all 15 CNS relapse events occurred in patients who did not receive BTKi, whereas no CNS relapse was observed in the BTKi-treated group. BTKi exposure was independently associated with a markedly reduced risk of CNS relapse (HR 0.06, p&#xa0;=&#xa0;0.002) after adjustment for CNS-IPI risk and CNS prophylaxis. These findings suggest that BTK inhibition may improve outcomes and mitigate CNS relapse in MCD DLBCL.

Glioblastoma remains one of the most aggressive primary brain tumors in adults, with a survival rarely exceeding 15 months despite multimodal therapy. Novel immunotherapeutic strategies, particularly chimeric antigen receptor T-cell therapy, have emerged as promising approaches to overcome the limitations of conventional treatments. This review summarizes recent early-phase clinical trials investigating locoregional chimeric antigen receptor T-cell delivery in recurrent glioblastoma and highlights key considerations for multidisciplinary neuro-oncology teams involved in this evolving therapeutic paradigm. Phase I studies of intratumoral, intracavitary, intraventricular, or combined delivery routes have demonstrated technical feasibility and safety, with most adverse events being manageable. Dual-route delivery may enhance chimeric antigen receptor T-cell distribution and produce early radiographic and clinical responses in selected patients. However, therapeutic durability remains limited by tumor heterogeneity, antigen loss, and the immunosuppressive tumor microenvironment. Multidisciplinary care teams play a critical role in catheter and reservoir placement, infusion planning, and management of neuroinflammatory toxicities. Although current findings are preliminary, ongoing optimization of target selection, dosing strategies, and combination therapies may expand treatment options for recurrent glioblastoma and further integrate immunotherapy into contemporary neuro-oncology care.

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Psychosocial, neuropsychological, social, and academic difficulties may persist after pediatric cancer treatment. We described parent/caregiver-reported functioning and support needs and explored their associations with clinical, family-related, socio-economic, premorbid, and place-based characteristics in an Italian survivorship setting. This single-center cross-sectional exploratory study included 93 of 130 families approached between November 2022 and January 2023 (response rate, 71.5%). One parent or caregiver completed a purpose-built questionnaire for each survivor. The cohort included 38 survivors with central nervous system (CNS) tumors and 55 with non-CNS tumors. Outcomes were evaluated relative to retrospectively reported pre-diagnosis functioning. Exact confidence intervals, effect estimates, multivariable Firth logistic regression, and Benjamini-Hochberg false discovery rate correction were used. Worsening internalizing difficulties were reported for 48/90 survivors (53.3%), neuropsychological difficulties for 42/90 (46.7%), academic worsening for 30/85 (35.3%), and social integration difficulties for 27/90 (30.0%). CNS survivors more frequently had social integration difficulties than non-CNS survivors (47.4% versus 17.3%; odds ratio, 4.22; 95% confidence interval, 1.50-12.73; q = 0.015) and underwent cognitive assessment after cancer (50.0% versus 17.0%; odds ratio, 4.80; 95% confidence interval, 1.71-14.44; q = 0.013). Municipality size and geographic area showed no nominal associations with parent-reported outcomes. No candidate-variable association in the exploratory screen remained significant after false discovery rate correction. Parent-reported difficulties and support needs were common, with differences by CNS versus non-CNS tumor site. Family-related, premorbid, and place-based patterns are hypothesis-generating and require prospective evaluation using validated multi-informant measures.

Patients with CNS tumors have high rates of chronic cancer pain and headache but are more sensitive to cognitive and sedation side effects from full-opioid agonists. Buprenorphine, a partial opioid agonist, offers potential advantages over full agonist opioids but real-world insights on prescribing patterns is lacking. This study examines prescribing patterns, clinical use, and pain score changes associated with buprenorphine use in patients with CNS tumors. We retrospectively analyzed the clinical notes of 28 primary or secondary patients with CNS tumors, seen in the neuro-oncology outpatient clinic of a comprehensive cancer center, who had a record of being prescribed buprenorphine for pain. We collected information on patients' buprenorphine use, formulation, dosage, duration, adverse effects, discontinuation reason, and information on what opioids they took before and after buprenorphine. The average age was 57 years old and 71% were female. Most (82%) patients were taking short-acting full-agonists prior to being prescribed buprenorphine, with oxycodone being the most prescribed opioid. Among the 19 patients who had pain scores available, the median change in pain score -3 points (5 to 2 out of 10). Patients were prescribed buprenorphine for an average of 137 days. The transdermal patch was the most prescribed formulation. The most common uses were for headache (10; 39%), back pain (9; 35%), and chronic/diffuse pain (8; 31%). This is the first study exploring buprenorphine use among patients with CNS tumors. Buprenorphine may be a viable analgesic option for patients with CNS tumors and warrants further prospective study.

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The integration of novel systemic therapies including antibody-drug conjugates (ADCs), immune checkpoint inhibitors (ICIs), and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors with radiotherapy (RT) presents new opportunities in breast cancer (BC) management. However, clinical guidance on concurrent administration remains limited, particularly for advanced techniques. A multidisciplinary panel of radiation and medical oncologists from AROME and the Moroccan Medical Oncology Association conducted a literature review and established expert consensus recommendations during the fourth Moroccan Congress of Medical Oncology Private Practice. An evidence-informed, structured consensus process was used to achieve agreement on safety profiles across six RT modalities. Trastuzumab deruxtecan has shown a favorable safety profile with whole-breast irradiation and palliative RT, while trastuzumab emtansine combined with stereotactic radiosurgery shows elevated radionecrosis risk. ICIs are generally feasible with most RT modalities and toxicity monitoring applied; however, risk is context dependent, and evidence supporting stereotactic body radiotherapy-ICI benefit in oligometastatic BC remains limited. The use of CDK4/6 inhibitors concurrently with conventional and stereotactic RT seems feasible, although caution is advised for visceral metastases. These experts' agreements are supported by retrospective data and preclinical evidence, highlighting the need for prospective validation. This expert consensus statement provides pragmatic, modality-specific guidance on combining contemporary RT techniques with selected novel systemic agents in BC, complementing existing European Society for Medical Oncology /European Society for Radiotherapy and Oncology&#x2011;oriented frameworks and highlighting areas where prospective data are still needed. The findings underscore the importance of toxicity monitoring, particularly for ADCs in CNS-directed therapies, and call for biomarker-driven studies to optimize combination strategies. These recommendations aim to guide safe integration of novel agents with RT across resource-variable settings, including low- and middle-income countries.