Hypofractionated re-irradiation for diffuse intrinsic pontine glioma.

BACKGROUND: Re-irradiation (reRT) increases survival in locally recurrent diffuse intrinsic pontine glioma (DIPG). There is no standard dose and fractionation for reRT, but conventional fractionation (CF) is typically used. We report our institutional experience of reRT for DIPG, which includes hypofractionation (HF). METHODS: We reviewed pediatric patients treated with brainstem reRT for DIPG at our institution from 2012 to 2022. Patients were grouped by HF or CF. Outcomes included steroid use, and overall survival (OS) was measured from both diagnosis and start of reRT. RESULTS: Of 22 patients who received reRT for DIPG, two did not complete their course due to clinical decline. Of the 20 who completed reRT, the dose was 20-30 Gy in 2-Gy fractions (n = 6) and 30-36 Gy in 3-Gy fractions (n = 14). Median age was 5 years (range: 3-14), median interval since initial RT was 8 months (range: 3-20), and 12 received concurrent bevacizumab. Median OS from diagnosis was 18 months [95% confidence interval: 17-24]. Median OS from start of reRT for HF versus CF was 8.2 and 7.5 months, respectively (p = .20). Thirteen (93%) in the HF group and three (75%) in the CF group tapered pre-treatment steroid dose down or off within 2 months after reRT due to clinical improvement. There was no significant difference in steroid taper between HF and CF (p = .4). No patients developed radionecrosis. CONCLUSION: reRT with HF achieved survival duration comparable to published outcomes and effectively palliated symptoms. Future investigation of this regimen in the context of new systemic therapies and upfront HF is warranted.

Laser interstitial thermal therapy as a radiation-sparing approach for central nervous system tumors in children with cancer predisposition syndromes: report of a child with Li-Fraumeni syndrome. Illustrative case.

BACKGROUND: Ionizing radiation and alkylating chemotherapies increase secondary malignancy risk in patients with cancer predisposition syndromes (CPSs), such as Li-Fraumeni syndrome. Laser interstitial thermal therapy (LITT) is a minimally invasive ablation technique that has not been associated with mutagenic risks. We describe the case of a child with LFS and a history of treated choroid plexus carcinoma (CPC) who developed a second primary glial tumor that was safely treated with magnetic resonance imaging (MRI)-guided LITT. OBSERVATIONS: A 4-year-old male with left parietal World Health Organization grade III CPC associated with a TP53 germline mutation was evaluated. The patient underwent neoadjuvant platinum-based chemotherapy before near-total resection, followed by 131I-8H9 immunotherapy and 30 fractions of 54-Gy proton radiotherapy. He remained without evidence of disease for 2 years before developing a slow-growing mass adjacent to the left frontal ventricular horn. Stereotactic biopsy revealed a glial neoplasm. Given the nonsuperficial location and focality of the lesion, MRI-guided LITT was performed for ablative therapy. There were no complications, and 2 years of surveillance revealed continued retraction of the ablated tumor focus and no subsequent disease. LESSONS: Alternatives to mutagenic therapies for brain tumors should be explored for patients with CPS. LITT paired with imaging surveillance is a logical strategy to ensure durable outcomes and mitigate treatment-related secondary neoplasms.

The Role of Virtual Surgical Planning in Surgery for Complex Craniosynostosis.

Background: Virtual surgical planning (VSP) decreases reliance on intraoperative subjective assessment of aesthetic and functional outcomes in craniofacial surgery. Here, we describe our experience of using VSP for complex craniosynostosis surgery to inform preoperative decision making and optimize postoperative outcomes. Methods: Chart review was performed for children treated with craniosynostosis at our institution from 2015 to 2021. Eight VSP maneuvers were defined and assigned to each patient when applicable: (1) complex cranioplasty: combined autologous and synthetic; (2) autologous cranioplasty; (3) synthetic cranioplasty; (4) vector analysis and distractor placement; (5) complex osteotomies; (6) multilayered intraoperative plans; (7) volume analysis; and (8) communication with parents. Outcomes between VSP and non-VSP cohorts were compared. Results: Of 166 total cases, 32 were considered complex, defined by multisutural craniosynostosis, syndromic craniosynostosis, or revision status. Of these complex cases, 20 underwent VSP and 12 did not. There was no difference in mean operative time between the VSP and non-VSP groups (541 versus 532 min, P = 0.82) or in unexpected return to operating room (10.5% versus 8.3%, P = 0.84). VSP was most often used to communicate the surgical plan with parents (90%) and plan complex osteotomies (85%). Conclusions: In this cohort, VSP was most often used to communicate the surgical plan with families and plan complex osteotomies. Our results indicate that VSP may improve intraoperative efficiency and safety for complex craniosynostosis surgery. This tool can be considered a useful adjunct to plan and guide intraoperative decisions in complex cases, reducing variability and guiding parental expectations.

Diffuse Midline Gliomas: Challenges and New Strategies in a Changing Clinical Landscape.

Diffuse intrinsic pontine glioma (DIPG) was first described by Harvey Cushing, the father of modern neurosurgery, a century ago. Since then, the classification of this tumor changed significantly, as it is now part of the broader family of diffuse midline gliomas (DMGs), a heterogeneous group of tumors of midline structures encompassing the entire rostro-caudal space, from the thalamus to the spinal cord. DMGs are characterized by various epigenetic events that lead to chromatin remodeling similarities, as two decades of studies made possible by increased tissue availability showed. This new understanding of tumor (epi)biology is now driving novel clinical trials that rely on targeted agents, with finally real hopes for a change in an otherwise unforgiving prognosis. This biological discovery is being paralleled with equally exciting work in therapeutic drug delivery. Invasive and noninvasive platforms have been central to early phase clinical trials with a promising safety track record and anecdotal benefits in outcome.

Management of Total Frontal Bone Loss After Surgery for Craniosynostosis: The Modified Visor Bone Flap With Brain Cage.

Complications after craniosynostosis surgery occur in 11% to 36% of cases and may be precipitated by poor soft tissue coverage and concomitant exposure of non-sterile regions; sequelae may result in infection, osteomyelitis, and bone loss requiring complex reconstruction. In the pediatric population, autologous cranioplasty remains the gold standard due to growth potential and a more favorable complication profile than synthetic cranioplasty. Virtual surgery planning (VSP) and computer-assisted design (CAD)/computer-assisted manufacturing (CAM) technology can be utilized to create innovative, patient-specific autologous solutions, similar to the approach with synthetic cranioplasty. A novel surgical approach using VSP was used for an 18-month-old female with near total bifrontal bone loss. Surface area measurements were used to determine the amount of bone available to replace the infected frontal bone. VSP was utilized to determine the most efficient construct configuration possible to achieve maximal coverage via calculation of cranial bone surface area measurements. Surgical reconstruction of the defect was planned as a Modified Visor Bone Flap with Posterior Brain Cage. A construct was fashioned from available cranial bone struts to obtain widespread coverage. 3D Recon images from before and after surgery demonstrate almost complete re-ossification of the cranial vault with significant resulting clinical improvement. Reconstruction of total frontal bone loss is possible by utilizing this technique. VSP can improve the safety and efficiency of complex autologous cranial bone reconstructions. We propose a treatment algorithm to address the problem of near total frontal bone loss in young children for whom alloplastic implants are not suitable.

Neuroendoscopy: How We Got Here.

From its inception in ancient Egyptian rituals, neuroendoscopy always promised a minimally invasive route to the cerebrum. Early visionaries, however, hit the proverbial wall of technical development until the 20th century, when new technologies allowed for light to be transmitted across a tube for visualization of intracranial structures. Despite a hiccupping start, with surgical microscopy hampering initial excitement, the development and transformation of neuroendoscopy continued, and today it is a widespread and reliable surgical option for the treatment of numerous varied and complex pathologies.

Neuroendoscopy: The State of the Art.

Over the past century, neuroendoscopy developed into a mainstay of neurosurgical practice, allowing for minimally invasive approaches to the ventricles, skull base, and spine. Its development, however, is far from over. Current challenges are inherent in the very feature that renders neuroendoscopy appealing-the small channels of the modern endoscope allow surgery to be performed with minimal tissue retraction, but they also make hemostasis and resection of large masses difficult. New optics allow for significantly improved image quality; yet open craniotomy often allows for 3-dimensional visualization and bimanual dissection and is part of everyday neurosurgical training. Finally, the utilization of neuroendoscopy remains limited, presenting ongoing challenges for neurosurgical teaching and achievement of technical mastery.

The Future of Neuroendoscopy: Looking Ahead Through a Lens.

Neuroendoscopy has progressed remarkably in the past few decades. Ventriculoscopy, skull base endoscopy, and spinal endoscopy are now part of routine practice in the neurosurgical treatment of numerous pathologies. Like other developing fields, however, it faces numerous challenges and obstacles that must be overcome for the field to continue to evolve and expand. This brief review of new and exciting developments in neuroendoscopy describes some of the most interesting directions the field is starting to steer towards.

Influence of focused ultrasound on locoregional drug delivery to the brain: Potential implications for brain tumor therapy.

INTRODUCTION: Efficient delivery of therapeutics across the blood-brain barrier (BBB) for the treatment of central nervous system (CNS) tumors is a major challenge to the development of safe and efficacious therapies. Locoregional drug delivery platforms offer an improved therapeutic index by achieving high drug concentrations in the target tissue with negligible systemic exposure. Intrathecal (intraventricular) [IT] and convection-enhanced delivery [CED] are two clinically relevant methods being employed for various CNS malignancies. Both of these standalone platforms suffer from passive post-administration distribution forces, sometimes limiting the desired distribution for tumor therapy. Focused ultrasound and microbubble-mediated blood-brain barrier opening (FUS-BBBO) is a recent modality used for enhanced drug delivery. It is postulated that coupling of FUS with these alternative delivery routes may provide benefits. Multimodality FUS may provide the desired ability to increase the depth of parenchymal delivery following IT administration and provide a means for contour directionality with CED. Further, the transient enhanced permeability achieved with FUS-BBBO is well established, but drug residence and transit times, important to clinical dose scheduling, have not yet been defined. The present investigation comprises two discrete studies: 1. Conduct a comprehensive quantitative evaluation to elucidate the effect of FUS-BBBO as it relates to varying routes of administration (IT and IV) in its capacity to facilitate drug penetration within the striatal-thalamic region. 2. Investigate the impact of combining FUS-BBBO with CED on drug distribution, with a specific focus on the temporal dynamics of drug retention within the target region. METHODS: Firstly, we quantitatively assessed how FUS-BBBO coupled with IT and IV altered fluorescent dye (Dextran 2000 kDa and 70 kDa) distribution and concentration in a predetermined striatal-thalamic region in naïve mice. Secondly, we analyzed the pharmacokinetic effects of using FUS mediated BBB disruption coupled with CED by measuring the volume of distribution and time-dependent concentration of the dye. RESULTS: Our results indicate that IV administration coupled with FUS-BBBO successfully enhances delivery of dye into the pre-defined sonication targets. Conversely, measurable dye in the sonication target was consistently less after IT administration. FUS enhances the distribution volume of dye after CED. Furthermore, a shorter time of residence was observed when CED was coupled with FUS-BBBO application when compared to CED alone. CONCLUSION: 1. Based on our findings, IV delivery coupled with FUS-BBBO is a more efficient means for delivery to deep targets (i.e. striatal-thalamic region) within a predefined spatial conformation compared to IT administration. 2. FUS-BBBO increases the volume of distribution (Vd) of dye after CED administration, but results in a shorter time of residence. Whether this finding is reproducible with other classes of agents (e.g., cytotoxic agents, antibodies, viral particles, cellular therapies) needs to be studied.

The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer.

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.

Comparative Analysis of 2D and 3D Metrics for Evaluation of Postoperative Outcomes Following Endoscopic Suturectomy for Sagittal Craniosynostosis.

To assess whether 3-dimensional (3D) volumetrics can be used to track and evaluate postoperative course of patients treated with endoscopic suturectomy for nonsyndromic sagittal synostosis, we compared changes in 2-dimensional (2D) measurements along with 3D volumetric correlates throughout the period of helmet therapy. Forty-six patients treated at our institution with endoscopic suturectomy for sagittal synostosis were retrospectively reviewed. Head circumference (HC), cephalic index (CI), and total cranial volumes (TCVs) were measured at 3 timepoints following surgery using optical surface scans obtained for helmet orthotics. All measurements showed significant differences between timepoints on the analysis of variance ( P <0.001). There was a significant correlation between CI and TCV (r=0.35, P =0.004) and between HC and TCV (r=0.81, P <0.001). The normalized rate of change over the course of treatment was significantly higher for TCV (36.7%) than for CI (8.8%) and HC (8.4%, P <0.001), with no difference between HC and CI. The authors conclude that 3D metrics were able to reliably follow the course of postoperative 2D metrics. There was a direct and linear correlation between HC and CI with TCV. Total cranial volumes showed the highest rate of sustained change at every timepoint. Although CI and HC plateau after the first measurement, TCV continues to adapt over the course of treatment. These results demonstrate the feasibility and value of volumetrics from 3D imaging to provide a more comprehensive evaluation of postoperative surgical outcomes than traditional 2D metrics without the ionizing radiation traditionally utilized for CT to obtain 3D metrics.

Fifty years of DIPG: looking at the future with hope.

Diffuse intrinsic pontine glioma (DIPG) is a primary brainstem tumor of childhood that carries a dismal prognosis, with median survival of less than 1 year. Because of the brain stem location and pattern of growth within the pons, Dr. Harvey Cushing, the father of modern neurosurgery, urged surgical abandonment. Such a dismal prognosis remained unchanged for decades, coupled with a lack of understanding of tumor biology and an unchanging therapeutic panorama. Beyond palliative external beam radiation therapy, no therapeutic approach has been widely accepted. In the last one to two decades, however, increased tissue availability, an improving understanding of biology, genetics, and epigenetics have led to the development of novel therapeutic targets. In parallel with this biological revolution, new methods intended to enhance drug delivery into the brain stem are contributing to a surge of exciting experimental therapeutic strategies.

Leptomeningeal dissemination in pediatric brain tumors.

Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) is a poorly understood and categorized phenomenon. LMD incidence rates, as well as diagnosis, treatment, and screening practices, vary greatly depending on the primary tumor pathology. While LMD is encountered most frequently in medulloblastoma, reports of LMD have been described across a wide variety of PBT pathologies. LMD may be diagnosed simultaneously with the primary tumor, at time of recurrence, or as primary LMD without a primary intraparenchymal lesion. Dissemination and seeding of the cerebrospinal fluid (CSF) involves a modified invasion-metastasis cascade and is often the result of direct deposition of tumor cells into the CSF. Cells develop select environmental advantages to survive the harsh, nutrient poor and turbulent environment of the CSF and leptomeninges. Improved understanding of the molecular mechanisms that underlie LMD, along with improved diagnostic and treatment approaches, will help the prognosis of children affected by primary brain tumors.

Predictors of extent of resection and recurrence following endoscopic endonasal resection of craniopharyngioma.

OBJECTIVE: Craniopharyngioma is a benign but surgically challenging brain tumor. Controversies exist regarding its ideal treatment strategy, goals of surgery, efficacy of radiation, and the long-term outcomes of these decisions. The authors of this study performed a detailed analysis of factors predictive of the extent of resection and recurrence in large series of craniopharyngiomas removed via an endoscopic endonasal approach (EEA) with long-term follow-up. METHODS: From a prospective database of all EEAs done at Weill Cornell Medical College by the senior author from 2004 to 2022, a consecutive series of histologically proven craniopharyngiomas were identified. Gross-total resection (GTR) was generally the goal of surgery. Radiation was often given if GTR had not been achieved. The stalk was preserved if not infiltrated with tumor but was sacrificed to achieve GTR. Intentional subtotal resection (STR) was performed in select cases to avoid hypothalamic injury. RESULTS: Among the 111 identified cases were 88 adults and 23 children. Newly diagnosed cases comprised 58.6% of the series. GTR was attempted in 77.5% of the patients and among those cases was achieved in 89.5% of treatment-naive tumors and 72.4% of recurrent tumors. An inability to achieve GTR was predicted by prior surgical treatment (OR 0.13, 95% CI 0.03-0.6, p = 0.009), tumor diameter ≥ 3.5 cm (OR 0.11, 95% CI 0.02-0.53, p = 0.006), and encasement of the optic nerve or a major artery (OR 0.11, 95% CI 0.01-0.8, p = 0.03). GTR with stalk preservation maintained some anterior pituitary function in 64.5% of cases and prevented diabetes insipidus in 25.8%. After a median follow-up of 51 months (IQR 17-80 months), the recurrence rate after GTR was 12.5% compared with 38.5% after non-GTR. The median recurrence-free survival was 5.5 years after STR, 8.3 years after near-total resection (≥ 98%), and not reached after GTR (p = 0.004, log-rank test). GTR was the strongest predictor of recurrence-free survival (OR 0.09, 95% CI 0.02-0.42, p = 0.002), whereas radiation did not show a statistically significant impact (OR 1.17, 95% CI 0.45-3.08). In GTR cases, the recurrence rate was higher if the stalk had been preserved (22.6%) as opposed to a sacrificed stalk (4.9%; OR 5.69, 95% CI 1.09-29.67). CONCLUSIONS: The study data show that GTR should be the goal of surgery in craniopharyngiomas if it can be achieved safely. Although stalk preservation can maintain some endocrine function, the risk of recurrence is higher in such cases. Radiation may not be as effective as previously reported.

Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma.

Choroid plexus carcinoma (CPC) is a rare infantile brain tumor with an aggressive clinical course that often leaves children with debilitating side effects due to aggressive and toxic chemotherapies. Development of novel therapeutical strategies for this disease have been extremely limited owing to the rarity of the disease and the paucity of biologically relevant substrates. We conducted the first high-throughput screen (HTS) on a human patient-derived CPC cell line (Children Cancer Hospital Egypt, CCHE-45) and identified 427 top hits highlighting key molecular targets in CPC. Furthermore, a combination screen with a wide variety of targets revealed multiple synergistic combinations that may pave the way for novel therapeutical strategies against CPC. Based on in vitro efficiency, central nervous system (CNS) penetrance ability and feasible translational potential, two combinations using a DNA alkylating or topoisomerase inhibitors in combination with an ataxia telangiectasia mutated and rad3 (ATR) inhibitor (topotecan/elimusertib and melphalan/elimusertib respectively) were validated in vitro and in vivo. Pharmacokinetic assays established increased brain penetrance with intra-arterial (IA) delivery over intra-venous (IV) delivery and demonstrated a higher CNS penetrance for the combination melphalan/elimusertib. The mechanisms of synergistic activity for melphalan/elimusertib were assessed through transcriptome analyses and showed dysregulation of key oncogenic pathways (e.g. MYC, mammalian target of rapamycin mTOR, p53) and activation of critical biological processes (e.g. DNA repair, apoptosis, hypoxia, interferon gamma). Importantly, IA administration of melphalan combined with elimusertib led to a significant increase in survival in a CPC genetic mouse model. In conclusion, this study is, to the best of our knowledge, the first that identifies multiple promising combinatorial therapeutics for CPC and emphasizes the potential of IA delivery for the treatment of CPC.

Durability of an endoscopic management strategy for recurrent choroid plexus carcinoma with a comprehensive molecular characterization: illustrative case.

OBJECTIVE: Choroid plexus carcinoma (CPC) is a rare, primarily intraventricular neoplasm. Extent of resection correlates with improved outcomes but is limited due to tumor vascularity and size. Evidence on optimal surgical management and molecular drivers of recurrence remains limited. Here the authors characterize a case of multiply recurrent CPC treated with sequential endoscopic removals over 10 years and highlight its genomic properties. OBSERVATIONS: Five years after standard treatment, a 16-year-old female presented with a distant intraventricular recurrence of CPC. Whole exome sequencing revealed NF1, PER1, and SLC12A2 mutations, FGFR3 gain, and no TP53 alterations. Repeat sequencing on recurrences 4 and 5 years later showed persistent NF1 and FGFR3 alterations. Methylation profiling was consistent with plexus tumor, subclass pediatric B. Short-term magnetic resonance imaging detected four total isolated recurrences, all treated with complete endoscopic resections at 5, 6.5, 9, and 10 years after initial diagnosis. Mean hospital stay for all recurrences was 1 day with no complications. LESSONS: The authors describe a patient with four isolated recurrences of CPC over a decade, each treated with complete endoscopic removal, and identify unique molecular alterations that persisted without TP53 alterations. These outcomes support frequent neuroimaging to facilitate endoscopic surgical removal following early detection of CPC recurrence.

Treatment of Pediatric Low-Grade Gliomas.

PURPOSE OF REVIEW: Pediatric low-grade gliomas and glioneuronal tumors (pLGG) account for approximately 30% of pediatric CNS neoplasms, encompassing a heterogeneous group of tumors of primarily glial or mixed neuronal-glial histology. This article reviews the treatment of pLGG with emphasis on an individualized approach incorporating multidisciplinary input from surgery, radiation oncology, neuroradiology, neuropathology, and pediatric oncology to carefully weigh the risks and benefits of specific interventions against tumor-related morbidity. Complete surgical resection can be curative for cerebellar and hemispheric lesions, while use of radiotherapy is restricted to older patients or those refractory to medical therapy. Chemotherapy remains the preferred first-line therapy for adjuvant treatment of the majority of recurrent or progressive pLGG. RECENT FINDINGS: Technologic advances offer the potential to limit volume of normal brain exposed to low doses of radiation when treating pLGG with either conformal photon or proton RT. Recent neurosurgical techniques such as laser interstitial thermal therapy offer a "dual" diagnostic and therapeutic treatment modality for pLGG in specific surgically inaccessible anatomical locations. The emergence of novel molecular diagnostic tools has enabled scientific discoveries elucidating driver alterations in mitogen-activated protein kinase (MAPK) pathway components and enhanced our understanding of the natural history (oncogenic senescence). Molecular characterization strongly supplements the clinical risk stratification (age, extent of resection, histological grade) to improve diagnostic precision and accuracy, prognostication, and can lead to the identification of patients who stand to benefit from precision medicine treatment approaches. The success of molecular targeted therapy (BRAF inhibitors and/or MEK inhibitors) in the recurrent setting has led to a gradual and yet significant paradigm shift in the treatment of pLGG. Ongoing randomized trials comparing targeted therapy to standard of care chemotherapy are anticipated to further inform the approach to upfront management of pLGG patients.

Outcomes of intraventricular 131-I-omburtamab and external beam radiotherapy in patients with recurrent medulloblastoma and ependymoma.

PURPOSE: Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Little is known regarding outcomes after re-irradiation as part of multimodality therapy including cRIT. This study evaluates predictors of response, patterns of failure, and radiologic events after cRIT. METHODS: Patients with recurrent medulloblastoma or ependymoma who received 131-I-omburtamab on a prospective clinical trial were included. Extent of disease at cRIT initiation (no evidence of disease [NED] vs measurable disease [MD]) was assessed as associated with progression-free (PFS) and overall survival (OS) by Kaplan-Meier analysis. RESULTS: All 27 patients (20 medulloblastoma, 7 ependymoma) had EBRT preceding cRIT: most (22, 81%) included CSI (median dose 2340 cGy, boost to 5400 cGy). Twelve (44%) also received EBRT at relapse as bridging to cRIT. There were no cases of radionecrosis. At cRIT initiation, 11 (55%) medulloblastoma and 3 (43%) ependymoma patients were NED, associated with improved PFS (p = 0.002) and OS (p = 0.048) in medulloblastoma. Most relapses were multifocal. With medium follow-up of 3.0 years (95% confidence interval, 1.8-7.4), 6 patients remain alive with NED. CONCLUSION: For patients with medulloblastoma, remission at time of cRIT was associated with significantly improved survival outcomes. Relapses are often multifocal, particularly in the setting of measurable disease at cRIT initiation. EBRT is a promising tool to achieve NED status at cRIT initiation, with no cases of radiation necrosis.

Defining Occult High-Risk Cysts of the Pineal Region: A Case Series.

BACKGROUND: Absence of hydrocephalus on neuroimaging may impart a false sense of security for patients with pineal cysts. In this case series, we characterize a subset of patients with pineal cysts having an occult presentation. Unifying features of worsening paroxysmal headaches suggesting intermittent obstructive hydrocephalus and radiographic evidence of third ventricular invagination characterize these patients as high risk. OBJECTIVE: To define features of occult, high-risk pineal cysts and outcomes of endoscopic cyst fenestration. METHODS: Charts were retrospectively reviewed for patients with pineal cysts evaluated at our institution between 2018 and 2021 who underwent endoscopic cyst fenestration. To capture cysts presenting as occult, patients were excluded if hydrocephalus was noted at presentation. Relevant clinical history, imaging, operative data, and clinical outcomes were reviewed. RESULTS: Of 50 pineal cyst patients, 4 satisfied inclusion criteria. All patients presented with worsening paroxysmal headaches. In addition, 75% (3/4) also experienced intermittent syncope. Patients exhibited no hydrocephalus (n = 3) or fluctuating ventricular size on longitudinal imaging (n = 1). In all cases, high-resolution sagittal 3-dimensional T2 magnetic resonance imaging demonstrated invagination of the cyst anteriorly into the posterior third ventricle. All patients underwent endoscopic cyst fenestration with complete symptom resolution (mean follow-up of 20.6 months; range 3.5-37.4 months). CONCLUSION: The clinical history for occult, high-risk pineal cysts is notable for worsening paroxysmal headaches and episodic alterations of consciousness suggesting intermittent obstructive hydrocephalus. Because ventricular size can appear normal on standard imaging protocols, clinical suspicion should trigger workup with high-resolution magnetic resonance imaging designed to detect these cysts. Endoscopic cyst fenestration is a safe and efficacious management strategy.