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Background: The prognosis for patients with central nervous system (CNS) retinoblastoma (RB) (trilateral or stage 4b metastatic RB) treated with high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) remains poor. The impact of irradiation when administered as part of upfront therapy post HDC-ASCT on treatment outcomes and survival is unknown., Methods: We performed a retrospective review of all patients with CNS RB (seven stage 4b, eight trilateral, one pineal lesion belonging to methylation group RB) who underwent induction chemotherapy with an intent to proceed to HDC-ASCT at two institutions., Results: Twelve of 16 patients (n = 75%) achieved an objective response to induction chemotherapy, while four patients had progressive/refractory disease; two patients responded to subsequent therapy and proceeded to ASCT, and two patients did not. Seven of 14 patients who underwent HDC-ASCT, received radiotherapy as part of upfront therapy post HDC-ASCT in the form of craniospinal irradiation (CSI) (n = 3), intraventricular radioimmunotherapy (n = 3), or both CSI and intraventricular radioimmunotherapy (n = 1). The Kaplan-Meier estimate of overall survival for these patients was 62.5% at 5 years; no patients developed second malignant neoplasms within the radiation fields. For the seven patients who did not receive radiotherapy, the overall survival was 28.6% at 5 years., Conclusions: CSI (23.4 Gy) alone or in conjunction with intraventricular RIT may have clinical utility in eliminating persistent MRD post HDC-ASCT, contributing to improved disease-free survival in patients with CNS RB. This treatment strategy merits evaluation in a prospective, multicenter clinical trial for patients with CNS metastatic RB., (© 2024 Wiley Periodicals LLC.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Safe sampling of central nervous system tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need exists to develop less invasive diagnostic tests., Methods: We report our clinical experience with minimally invasive molecular diagnostics using a clinically validated assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA). All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families., Results: We analyzed 64 CSF samples from 45 pediatric, adolescent and young adult (AYA) patients (pediatric = 25; AYA = 20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n = 10), medulloblastoma (n = 10), pineoblastoma (n = 5), low-grade glioma (n = 4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n = 4), retinoblastoma (n = 4), ependymoma (n = 3), and other (n = 5). Somatic alterations were detected in 30/64 samples (46.9%) and in at least one sample per unique patient in 21/45 patients (46.6%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (81.5% of samples from patients with disseminated disease were positive). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient's disease course., Conclusions: We identified three general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: (1) diagnosis and/or identification of actionable alterations; (2) monitor response to therapy; and (3) tracking tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population to improve care., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

NF1-associated malignant peripheral nerve sheath tumors (MPNSTs) are the major cause of mortality in neurofibromatosis. MPNSTs arise from benign peripheral nerve plexiform neurofibromas that originate in the embryonic neural crest cell lineage. Using reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models, we discover and characterize a rare MPNST cell population with stem-cell-like properties, including quiescence, that is essential for tumor initiation and relapse. Following isolation of these cells, we derive a cancer-stem-cell-specific gene expression signature that includes consensus embryonic neural crest genes and identify Nestin as a marker for the MPNST cell of origin. Combined targeting of cancer stem cells along with antimitotic chemotherapy yields effective tumor inhibition and prolongs survival. Enrichment of the cancer stem cell signature in cognate human tumors supports the generality and relevance of cancer stem cells to MPNST therapy development., Competing Interests: Declaration of interests The authors declare no competing interests, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Infantile fibrosarcoma usually presents as a rapidly growing mass on the extremities or trunk. We describe spontaneous regression in a 5-month-old female infant with biopsy proven, molecularly confirmed, right leg infantile fibrosarcoma currently at 26 months of age with no signs of local recurrence. Previously reported cases of spontaneous regression are reviewed, suggesting a benign clinical course in some cases. Although evidence for spontaneous regression is anecdotal in this rare tumor type, physicians should weigh the risks and benefits of surgery and chemotherapy against watchful waiting.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of assisted reproduction technology. The syndrome is characterized by cystic enlargement of the ovaries and a fluid shift from the intravascular to the third space due to increased capillary permeability and ovarian neoangiogenesis. Its occurrence is dependent on the administration of human chorionic gonadotrophin (hCG). β-hCG and its analogs, estrogen, estradiol, prolactin, histamine and prostaglandins have all been implicated in OHSS but now it is increasingly better understood that the vasoactivesubstances such as interleukins, tumor necrosis factor-α, endothelin-1, and vascular endothelial growth factor (VEGF) secreted by the ovaries have been implicated in increasing vascular permeability. Enlargement of the ovaries causes abdominal pain, nausea and vomiting. Leakage of fluid from follicles, increased capillary permeability leading to third spacing (due to the release of vasoactive substances), or frank rupture of follicles can all cause ascites. Due to leakage of fluid through the impaired blood vessels both within and outside the ovary there is massive fluid-shift from the intra-vescular bed to the third compartment results in intravascular hypovolemia with concomitant development of edema, ascites, hydrothorax and/or hydropericardium. Low-dose gonadotrophin protocols have been implemented to reduce the risks of fertility treatment in polycystic ovary syndrome patients. Prophylactic albumin administration may interrupt the development of OHSS by increasing the plasma oncotic pressure and binding mediators of ovarian origin. OHSS is significantly lower in an antagonist protocol than in an agonist protocol. Cabergoline inhibits partially the VEGF receptor 2 phosphorylation levels and associated vascular permeability without affecting luteal angiogenesis reduces the 'early' (within the first 9 days after hCG) onset of OHSS. To prevent thrombosis, subcutaneous heparin 5000-7500 U/d is begun on the first day of admission. These patients need a hospital ward where the clinical picture is well understood and the personnel have expertise in its treatment and follow-up. Admission to an intensive care unit is necessary when critical OHSS develops.

Concept of a 'therapeutic window' of luteinizing hormone (LH) for successful conception in assisted reproductive technology and ovulation induction has been reviewed in this literature. The separate but complementary roles of follicle stimulating hormone and LH in stimulating folliculogenesis and ovulation are well established. Levels under which low LH concentrations may be equally or suboptimally needed for oocyte quality and subsequent embryonic development competence has been reviewed along with the data related to the high levels of LH promoting follicular atresia.