UNASSIGNED: Metastasis from cancers of the cervix to the central nervous system is relatively uncommon. Small-cell neuroendocrine cancer of the cervix is a very rare tumor with a high tendency to spread early.
UNASSIGNED: A 33-year-old-woman was diagnosed with a small-cell neuroendocrine cancer of the cervix after complaining about a long time of post-coital bleeding. The patient was treated with eight cycles of chemotherapy and whole pelvis consolidation radiotherapy. One year later, the patient experienced local recurrence with metastases to the liver, left adrenal, and brain. Brain metastases were treated with radiosurgery. The patient started immunotherapy. Two months later, the patient was presented to the emergency department with urinary incontinence, neck pain, and difficulty walking. She was then diagnosed with craniospinal leptomeningeal disease (LMD). The patient received craniospinal palliative radiation therapy. The disease activity was severely progressive, and the patient passed out within 10 days after being diagnosed with cranial LMD.
UNASSIGNED: A high index of suspicion for LMD is essential in patients diagnosed with cervix cancer who present with unexplained neurologic symptoms, especially with the high-grade neuroendocrine cancer type. Implementing robust research to uncover the biology of these aggressive tumors is important due to the rarity of this pathology.

BACKGROUND: The specific patterns of subependymal enhancement (SE) that frequently occur as radiation-induced changes in high-grade gliomas following radiotherapy are often overlooked. Perfusion MRI may offer a diagnostic clue.
OBJECTIVE: To distinguish between radiation-induced SE and progression in adult high-grade diffuse gliomas after standard treatment.
METHODS: Retrospective.
METHODS: Ninety-four consecutive high-grade diffuse glioma patients (mean age, 55 ± 14 years; 54 [57.4%] males) with new SE identified in follow-up MRI after completion of surgery plus chemoradiation: progression (N = 74) vs. regression (N = 20).
UNASSIGNED: 3 T, gradient-echo dynamic susceptibility contrast-enhanced MRI, 3D gradient-echo contrast-enhanced T1-weighted imaging.
RESULTS: To differentiate between radiation changes and progression in SE evaluation, multivariable logistic regression was performed using significant variables among SE appearance interval, IDH mutation, morphological features, and rCBV. Cox regression was performed to predict the tumor progression. For the added value of the rCBV, a log-rank test was conducted between the multivariable logistic regression models with and without the rCBV.
METHODS: Logistic regression, Cox regression, receiver operating characteristic analysis, log-rank test.
RESULTS: 38.3% (36/94) patients had first specific SE (9.2 ± 9.5 months after surgery), which disappeared in 21.3% (20/94) after 5.8 ± 5.8 months after initial appearance on post-radiation MRI. IDH mutation, elongated, small lesions with lower rCBV tended to regress: IDH mutation, elongation, diameter, and rCBV_p95; odds ratio, 0.32, 1.92, 1.70, and 2.47, respectively. Qualitative evaluation of shape revealed that thin and curvilinear-shaped SE tended to regress, indicating a significant correlation with quantitative shape features (r = 0.31). In Cox regression, rCBV and lesion shape were significant (hazard ratio = 1.09 and 0.54, respectively). For sub-centimeter lesions, the rCBV showed added value in predicting outcomes (area under the curve, 0.873 vs. 0.836; log-rank test).
CONCLUSIONS: Smaller, elongated lesions with lower rCBV and IDH mutation are associated with regression when differentiating radiation changes from progression in high-grade glioma with post-radiotherapy SE.
METHODS: 3 TECHNICAL EFFICACY: Stage 2.

Leptomeningeal disease (LMD) is a devastating sequelae of metastatic spread that affects approximately 5% of cancer patients. The incidence of LMD is increasing due to advancements in systemic therapy and enhanced detection methods. The purpose of this review is to provide a detailed overview of the evidence in the detection, prognostication, and treatment of LMD. A comprehensive literature search of PUBMED was conducted to identify articles reporting on LMD including existing data and ongoing clinical trials. We found a wide array of treatment options available for LMD including chemotherapy, targeted agents, and immunotherapy as well as several choices for radiotherapy including whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and craniospinal irradiation (CSI). Despite treatment, the prognosis for patients with LMD is dismal, typically 2-4 months on average. Novel therapies and combination approaches are actively under investigation with the aim of improving outcomes and quality of life for patients with LMD. Recent prospective data on the use of proton CSI for patients with LMD have demonstrated its potential survival benefit with follow-up investigations underway. There is a need for validated metrics to predict prognosis and improve patient selection for patients with LMD in order to optimize treatment approaches.

Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs\' presence in the patient\'s cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.

UNASSIGNED: Melanoma leptomeningeal disease (LMD) has a poor prognosis. However, the management of patients with advanced melanoma has evolved with time, including those with LMD. We reviewed a large cohort of melanoma LMD patients to assess factors associated with survival.
UNASSIGNED: Retrospective clinical data was collected on patients diagnosed with LMD at MD Anderson Cancer Center from 2015 to 2020. Overall survival (OS) was determined from LMD diagnosis to date of death or last follow-up. The Kaplan-Meier method and log-rank test were used to estimate OS and to assess univariate group differences, respectively. Multivariable associations of survival with variables of interest were determined using Cox proportional hazards regression models.
UNASSIGNED: A total of 172 patients were identified. The median age at LMD diagnosis was 53 (range 20-79) years, and all patients had radiographic evidence of LMD on magnetic resonance imaging of either brain or spine. In total 143 patients previously received systemic therapy (83%), with a median of 2 prior treatments (range 0-5). 81 patients (47%) had concurrent uncontrolled systemic disease and 80 patients (53%) had elevated serum LDH at the time of diagnosis. With a median follow-up of 4.0 months (range 0.1-65.3 months), median OS for all patients from LMD diagnosis was 4.9 months. Patients (n = 45) who received intrathecal therapy or systemic immunotherapy for LMD had a median OS of 8.0 months and 10.2 months, respectively. On multivariable analysis, decreased performance status, positive CSF cytology, elevated LDH, and whole brain radiation were associated with worse OS.
UNASSIGNED: Despite many advances in therapeutic options, the outcomes of melanoma patients with LMD remains poor. However, a subset of patients appears to derive benefit from LMD-directed treatment.

Leptomeningeal disease (LMD) refers to the infiltration of cancer cells into the leptomeningeal compartment. Leptomeninges are the two membranous layers, called the arachnoid membrane and pia mater. The diffuse nature of LMD poses a challenge to its effective diagnosis and successful management. Furthermore, the predominant phenotype; solid masses or freely floating cells, has altering implications on the effectiveness of drug delivery systems. The standard of care is the intrathecal delivery of chemotherapy drugs but it is associated with increased instances of treatment-related complications, low patient compliance, and suboptimal drug distribution. An alternative involves administering the drugs systemically, after which they must traverse fluid barriers to arrive at their destination within the leptomeningeal space. However, this route is known to cause off-target effects as well as produce subtherapeutic drug concentrations at the target site within the central nervous system. The development of new drug delivery systems such as liposomal cytarabine has improved drug delivery in leptomeningeal metastatic disease, but much still needs to be done to effectively target this challenging condition. In this review, we discuss about the anatomy of leptomeninges relevant for drug penetration, the conventional and advanced drug delivery methods for LMD. We also discuss the future directions being set by different clinical trials.

Leptomeningeal disease (LMD) is a devastating complication of melanoma with a dismal prognosis. We present the case of a young man with stage IV BRAF V600E mutant melanoma with lung, lymph node, and brain metastases initially treated with ipilimumab and nivolumab, who subsequently developed LMD. Upon change to BRAF/MEK targeted therapy with nivolumab, a durable complete response was achieved and remains ongoing, off treatment, 7 years from diagnosis. Management of symptomatic LMD remains a critical unmet clinical challenge, with limited clinical trial data. This exceptional case is instructive, as the first published case of the use of the triplet, and the first durable response with therapy discontinuation, in melanoma LMD. The triple-drug regimen may be considered a viable option in fit patients. This case highlights the potential for long-term disease control and the critical and urgent need to develop clinical trials inclusive of patients with LMD to define the best treatment strategies.

UNASSIGNED: This retrospective study compares the real-world performance of cerebrospinal fluid (CSF) CNSide™ versus cytology in leptomeningeal disease (LMD).
UNASSIGNED: Consecutive patients with suspected LMD who underwent lumbar punctures for CSF cytology and CNSide™ from January 2020 to December 2022 were reviewed. LMD was classified by EANO criteria. Descriptive statistics, confusion matrix, Kaplan-Meier curves, and Cox proportional regression were used.
UNASSIGNED: Median age for 87 evaluable patients was 63 years (range: 23-93); 82 (94%) met EANO criteria for possible/probable/confirmed LMD (EANO/LMD). The commonest primary cancers were breast (36,44.0%) and lung (34,41.5%). Primary lung harbored actionable mutations in 18 (53.0%); primary breast expressed hormone receptors in 27 (75%), and HER2 amplification in 8 (22%). Uncontrolled systemic disease was detected in 35 (40%), while 25 (46%) received systemic therapy with medium/high CNS penetrance at LMD diagnosis. The median time from initial cancer to LMD diagnosis was 31 months (range: 13-73). LMD was confirmed by CSF cytology in 23/82 (28%), all identified by CNSide™. CNSide™ identified 13 additional cases (36/82, 43.9%), increasing diagnostic yield by 56.5%. Median overall survival (mOS) was 31 weeks (95%CI: 21-43), significantly worse for CNSide™ positive versus negative: 4.0 versus 16.0 weeks, respectively (HR = 0.50, P = .010). While survival since LMD diagnosis did not differ by histology, time to LMD diagnosis from initial cancer diagnosis was longer for breast (48.5 months, IQR: 30.0-87.5) versus lung (8 months, IQR:0.5-16.0) cohorts. mOS was longer for patients eligible for intrathecal chemotherapy (HR: 0.189, 95%CI: 0.053-0.672, P = .010).
UNASSIGNED: This retrospective, real-world analysis of CNSide™ showed increased sensitivity versus cytology and provided clinically relevant molecular CSF analyses.

Leptomeningeal metastases are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options and clinical research protocols for patients with leptomeningeal metastases from solid tumors have similarly evolved to improve survival within specific populations. Recent expansion in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions. These include leptomeningeal metastasis biology and preferred animal modeling, epidemiology in the modern cancer population, ensuring validation and accessibility of newer leptomeningeal metastasis diagnostics, best clinical practices with multi-modality treatment options, clinical trial design and standardization of response assessments, and avenues worthy of further research. An international group of multi-disciplinary experts in the research and management of leptomeningeal metastases, supported by the Society for Neuro-Oncology and American Society of Clinical Oncology, were assembled to reach a consensus opinion on these pressing topics and provide a roadmap for future directions. Our hope is that these recommendations will accelerate collaboration and progress in the field of leptomeningeal metastases and serve as a platform for further discussion and patient advocacy.

OBJECTIVE: Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and treatment outcomes, including patients in a modern cohort.
METHODS: In this single center retrospective cohort study, we identified patients with MBC and LMD who received care from 2000 to 2024 and abstracted key clinical, treatment, and survival data.
RESULTS: We identified 111 patients with MBC and LMD, including patients with the following subtypes: HR+/HER2- (n = 53, 47.7%), HER2+ (n = 30, 27.0%), and triple negative breast cancer (TNBC; n = 28, 25.2%). Median time from the diagnosis of MBC to LMD was 16.4 months (range 0-101.3 months). After the diagnosis of LMD, most patients received systemic therapy (n = 66, 59.5%) and/or central nervous system (CNS)-directed therapy (n = 94, 84.7%) including intrathecal therapy (n = 42, 37.8%) and/or CNS-directed radiation therapy (n = 70, 63.1%). In all patients, median overall survival (OS) from the diagnosis of LMD to death was 4.1 months (range 0.1-78.1 months) and varied by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC (4.2 and 6.8 months respectively vs. 2.0 months, p < 0.01, HR 2.15, 95% CI 1.36-3.39). Patients who received CNS-directed therapy lived longer than those who did not (4.2 vs. 1.3, p = 0.02 HR 0.54, 0.32-0.91). Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014 (6.4 vs. 2.9 months, p = 0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p = 0.004, HR 2.03, 95% CI 1.25-3.30).
CONCLUSIONS: This is one of the largest case series of patients with MBC and LMD. Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014, although median OS was short overall. Patients with TNBC and LMD had particularly short OS. Novel therapeutic strategies for LMD remain an area of unmet clinical need.