Medulloblastomas in Pediatric and Adults.

Medulloblastoma is the primary malignant embryonic tumor of the cerebellum and the most common malignant tumor of childhood, accounting up to 25% of all CNS tumors in children, but is extremely rare in adults. Despite the fact that medulloblastomas are one of the most malignant human tumors, it is worthy to note that a great breakthrough has been achieved in our understanding of oncogenesis and the development of real methods of treatment. The main objective of surgical treatment is a maximum resection of tumor with minimal impairment of neurological functions, in order to reduce the volume, remove tumor tissue, get the biopsy, and restore the cerebrospinal fluid flow.

Stereotactic Gamma Knife® Radiosurgery of Intraocular Retinoblastoma: Six-Year Experience.

Background External beam radiotherapy for resistant retinoblastoma is now seen as a last resort to saving the eye because of the risk of severe side effects: secondary cancers and cosmetic problems of orbital bone growth retardation. To reduce such complications, treatment modalities have shifted towards new radiation therapy techniques. No information on single fraction Gamma Knife® radiosurgery (GKRS) for intraocular retinoblastoma exists.

Reparative properties of human glioblastoma cells after single exposure to a wide range of X-ray doses.

Radiation therapy induces double-stranded DNA breaks in tumor cells, which leads to their death. A fraction of glioblastoma cells repair such breaks and reinitiate tumor growth. It was necessary to identify the relationship between high radiation doses and the proliferative activity of glioblastoma cells, and to evaluate the contribution of DNA repair pathways, homologous recombination (HR), and nonhomologous end joining (NHEJ) to tumor-cell recovery.

Gamma Knife capsulotomy for correction of obsessive-compulsive symptoms in a patient with schizophrenia: Case report.

The treatment of mental illnesses that are resistant to conservative therapy poses a serious problem. Surgical methods with proven efficacy have been proposed for only a small group of psychiatric diseases, while in practice non-classical clinical situations are seen rather often. A 36-year-old man with a 18-year history of "schizophrenia with a predominant obsessive-compulsive syndrome" was referred to the Burdenko National Medical Research Center of Neurosurgery for consideration of neurosurgical treatment.

Discrepancies between frame- and CBCT-based stereotactic space definition on the Gamma Knife Icon.

Purpose: To assess differences between frame-based and cone beam computed tomography (CBCT)-defined stereotactic space and to identify predictors of the observed findings.

Methods And Materials: Differences between frame-based and CBCT-defined stereotactic space after image co-registration were reviewed for 529 patients. Treatment planning system reported the information about the shifts in X, Y, and Z coordinates of the center of the stereotactic space (i.

LINAC-based radiosurgery for functional and psychiatric disorders: Problems and their solutions.

Stereotactic radiosurgery (SRS) is practically non-invasive treatment option, and its application for ablative procedures in functional and psychiatric brain disorders seems rather promising. In such cases, gamma knife surgery (GKS) is considered a standard option due to its proved accuracy in targeting and dosimetry. However, modern linear accelerators (LINAC), which are the most commonly used radiosurgical device, provide comparable treatment preciseness.

Systematic Clinical Evaluation of a Deep Learning Method for Medical Image Segmentation: Radiosurgery Application.

We systematically evaluate a Deep Learning model in a 3D medical image segmentation task. With our model, we address the flaws of manual segmentation: high inter-rater contouring variability and time consumption of the contouring process. The main extension over the existing evaluations is the careful and detailed analysis that could be further generalized on other medical image segmentation tasks.

Clinically Tractable Outcome Prediction of Non-WNT/Non-SHH Medulloblastoma Based on TPD52 IHC in a Multicohort Study.

Purpose: International consensus and the 2021 WHO classification recognize eight molecular subgroups among non-WNT/non-SHH (Group 3/4) medulloblastoma, representing approximately 60% of tumors. However, very few clinical centers worldwide possess the technical capabilities to determine DNA methylation profiles or other molecular parameters of high risk for group 3/4 tumors. As a result, biomarker-driven risk stratification and therapy assignment constitutes a major challenge in medulloblastoma research.

Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B.

Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9).

Accelerating 3D Medical Image Segmentation by Adaptive Small-Scale Target Localization.

The prevailing approach for three-dimensional (3D) medical image segmentation is to use convolutional networks. Recently, deep learning methods have achieved human-level performance in several important applied problems, such as volumetry for lung-cancer diagnosis or delineation for radiation therapy planning. However, state-of-the-art architectures, such as U-Net and DeepMedic, are computationally heavy and require workstations accelerated with graphics processing units for fast inference.

Subgroup and subtype-specific outcomes in adult medulloblastoma.

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium.

The last decade's experience of management of central neurocytomas: Treatment strategies and new options.

Background: The purpose of the presented work is to evaluate the last decade's experience in surgical management of central neurocytoma (CN) and elucidate on the treatment strategies and new options.

Methods: The current series consists of the remaining 125 patients (70 females and 55 males) operated on during the past decade from 2008 to 2018. Most tumors were resected through transcortical ( = 76, 61%), or transcallosal ( = 40, 32%) approaches.

Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study.

Background: Only few data are available on treatment-associated behavior of distinct rare CNS embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumors with multilayered rosettes (ETMR) are needed for development of differentiated treatment strategies.

Methods: Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n = 307).

Challenges in Building of Deep Learning Models for Glioblastoma Segmentation: Evidence from Clinical Data.

In this article, we compare the performance of a state-of-the-art segmentation network (UNet) on two different glioblastoma (GB) segmentation datasets. Our experiments show that the same training procedure yields almost twice as bad results on the retrospective clinical data compared to the BraTS challenge data (in terms of Dice score). We discuss possible reasons for such an outcome, including inter-rater variability and high variability in magnetic resonance imaging (MRI) scanners and scanner settings.

CyberKnife for the management of Cushing's disease: our institutional experience and review of literature.

Introduction: Surgery is the primary treatment for Cushing's disease(CD). In cases with no biochemical remission after surgical resection or when recurrence occurs after a period of remission stereotactic radiosurgery (SRS) is used as alternative/adjuvant treatment. The aim of this study is to demonstrate the effectiveness of SRS and FSRS(Fractionated stereotactic radiosurgery) for the treatment of CD in a long term follow up.

Integrated molecular analysis of adult sonic hedgehog (SHH)-activated medulloblastomas reveals two clinically relevant tumor subsets with VEGFA as potent prognostic indicator.

Background: Up to now, adult medulloblastoma (MB) patients are treated according to the protocols elaborated for pediatric MB although these tumors are different in terms of clinical outcomes and biology. Approximately 70% of adult MB disclose a sonic hedgehog (SHH) molecular signature in contrast to about 30% in pediatric cohorts. In addition, adult SHH-MB (aSHH-MB) are clinically heterogeneous but there is consensus neither on their optimal treatment nor on risk stratification.

Molecular analysis of pediatric CNS-PNET revealed nosologic heterogeneity and potent diagnostic markers for CNS neuroblastoma with FOXR2-activation.

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly malignant neoplasms posing diagnostic challenge due to a lack of defining molecular markers. CNS neuroblastoma with forkhead box R2 (FOXR2) activation (CNS_NBL) emerged as a distinct pediatric brain tumor entity from a pool previously diagnosed as primitive neuroectodermal tumors of the central nervous system (CNS-PNETs). Current standard of identifying CNS_NBL relies on molecular analysis.

Modern Methods of Stereotactic Radiosurgery and Radiotherapy for the Treatment of Cushing Disease.

Cushing's disease is caused by a pituitary tumor causing increased production of adrenocorticotropic hormone, which leads to chronic hypersecretion of cortisol through adrenal cortices. Endoscopic trans-sphenoidal adenomectomy is the first choice of treatment with greatest efficiency for the treatment of the disease. However, in the absence of remission or recurrence of hypercortisolism after neurosurgical resection (adenomectomy), as well as in cases when surgical intervention cannot be carried due to medical contraindications to surgical intervention, radiation treatment is used as an alternative or adjoining therapy.

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort.

Purpose: The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.

Patients And Methods: From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression.

Transcriptional profiling of medulloblastoma with extensive nodularity (MBEN) reveals two clinically relevant tumor subsets with VSNL1 as potent prognostic marker.

Medulloblastoma with extensive nodularity (MBEN) is one of the few central nervous system (CNS) tumor entities occurring in infants which is traditionally associated with good to excellent prognosis. Some MBEN, however, have been reported with an unfavorable clinical course. We performed an integrated DNA/RNA-based molecular analysis of a multi-institutional MBEN cohort (n = 41) to identify molecular events which might be responsible for variability in patients' clinical outcomes.

Desmoplastic/nodular medulloblastomas (DNMB) and medulloblastomas with extensive nodularity (MBEN) disclose similar epigenetic signatures but different transcriptional profiles.

Desmoplastic/nodular medulloblastomas (DNMB) and medulloblastomas with extensive nodularity (MBEN) were outlined in the current WHO classification of tumors of the nervous system as two distinct histological MB variants. However, they are often considered as cognate SHH MB entities, and it is a reason why some clinical MB trials do not separate the patients with DNMB or MBEN histology. In the current study, we performed an integrated DNA/RNA-based molecular analysis of 83 DNMB and 36 MBEN to assess the etiopathogenetic relationship between these SHH MB variants.

Spontaneous Transformation of Vestibular Schwannoma into Malignant Peripheral Nerve Sheath Tumor.

Although radiosurgery-induced transformation of vestibular schwannoma (VS) into malignant peripheral nerve sheath tumor (MPNST) is being widely discussed, little attention is paid to the spontaneous transition of these tumors. Although the pathogenesis of this phenomenon remains uncertain, growing number of reported cases might call to notice them. We present a case of a 29-year-old woman who suffered right-sided hearing loss which remained untreated for 4.

DNA methylation profiling is a method of choice for molecular verification of pediatric WNT-activated medulloblastomas.

Background: Wingless-activated medulloblastoma (WNT MB) represents a well-characterized molecular variant accounting for 10-15% of all MB and is associated with a favorable clinical outcome. Patients with localized WNT MBs could benefit from de-intensification of combined treatment, which would require an accurate diagnosis of these tumors. However, despite the presence of molecular features related with a WNT MB signature (nuclear ß-catenin immunoexpression, CTNNB1 mutation, and monosomy 6), a prompt and reliable diagnostic verification of these tumors is not yet feasible.