Medulloblastoma (MB) is one of the most common malignant childhood brain tumors (WHO grade IV). Its high degree of malignancy leads to an unsatisfactory prognosis, requiring more precise and personalized treatment in the near future. Multi-omics and artificial intelligence have been playing a significant role in precise medical research, but their implementation needs a large amount of clinical information and biomaterials. For these reasons, it is urgent for current MB researchers to establish a large sample-size database of MB that contains complete clinical data and sufficient biomaterials such as blood, cerebrospinal fluid (CSF), cancer tissue, and urine. Unfortunately, there are few biobanks of pediatric central nervous system (CNS) tumors throughout the world for limited specimens, scarce funds, different standards collecting methods and et cl. Even though, China falls behind western countries in this area. The present research set up a standard workflow to construct the Beijing Children\'s Hospital Medulloblastoma (BCH-MB) biobank. Clinical data from children with MB and for collecting and storing biomaterials, along with regular follow-up has been collected and recorded in this database. In the future, the BCH-MB biobank could make it possible to validate the promising biomarkers already identified, discover unrevealed MB biomarkers, develop novel therapies, and establish personalized prognostic models for children with MB upon the support of its sufficient data and biomaterials, laying the foundation for individualized therapies of children with MB.

There is a lack of clinical protocols for re-irradiation in paediatric central nervous system (CNS) tumours. To fill this void, the Swedish Workgroup of Paediatric Radiotherapy (SBRTG) compiled national guidelines on re-irradiation in paediatric CNS tumours (diffuse intrinsic pontine glioma, ependymoma, germinoma and medulloblastoma). These have been in clinical practice since 2019 in all paediatric radiotherapy centres in Sweden. Since the implementation, the guidelines have been complemented with a yearly review on clinical outcome and toxicities in all paediatric patients treated according to the guidelines. This article presents the Swedish national guidelines on re-irradiation in paediatric CNS tumours.

Medulloblastoma is a highly aggressive \"small round blue cell tumor\" of the posterior fossa predominantly seen in children. Historically aggressive multimodality regimens have achieved encouraging outcomes with the caveat of severe long-term toxicities. The last decade has unleashed a revolution in terms of evolved understanding of this heterogeneous disease entity in terms of molecular biology. Medulloblastoma as of today is grouped into one of four canonical molecular subgroups (WNT, SHH, Group 3, and Group 4) each characterized by different putative cells of origin, characteristic aberrations at the molecular level, radiogenomics, and outcomes. Our understanding continues to grow in this regard. The future promises much in terms of personalized medicine in tailoring therapy to the needs of individual patients based on their clinical and molecular profile in order to maximize individual and population based outcomes at the cost of minimizing toxicity.

Recent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

Medulloblastoma is a rare brain tumor that occurs in both children and adults, with patients aged 15 to 39 years accounting for 30% of all cases. In adults, guidelines for diagnosis and treatment are often based on retrospective data and extrapolated from the pediatric experience due to limited availability of prospective trials or registries involving adults. Importantly, adult patients differ from pediatric patients in many aspects, including the molecular features of the tumor and tolerance to treatment. In 2017, the NCI was granted support from the Cancer Moonshot initiative to address the challenges and unmet needs of adults with rare central nervous system (CNS) tumors through the NCI Comprehensive Oncology Network for Evaluating Rare CNS Tumors (NCI-CONNECT). On November 25, 2019, NCI-CONNECT convened a multidisciplinary workshop on adult medulloblastoma. Working groups identified unmet needs in clinical care and research and developed specific action items, including a proposal for inclusion of new items in the NCCN Guidelines for Adult Medulloblastoma, delineated in this review along with the evidence supporting their incorporation. Recommendations included facilitating referral of patients to centers of excellence; promoting patient participation in clinical trials or registries; encouraging use of DNA methylation for confirmation of diagnosis and subgrouping; offering counseling on contraception and fertility preservation; evaluating patients for symptoms and medical management of endocrine, vision, hearing, and neurocognitive deficits; providing psychosocial support and referral to neurorehabilitation; minimizing delays in therapy; and incorporating imaging standards and criteria for progression.

The ubiquitin proteasome system regulates key cellular processes in normal and in cancer cells. Herein, we review published data on the role of ubiquitin ligases in the four major subgroups of medulloblastoma (MB). While conventional literature serves as an initial source of information on cellular pathways in MB, large publicly available datasets of gene expression can be used to add information not previously identified in the literature. By analysing the publicly available Cavalli dataset, we show that increased expression of ZNRF3 characterizes the WNT subgroup of MB. The ZNRF3 gene codes for an E3 ligase associated with WNT receptors. Loss of a copy of chromosome 6 in a subtype of the WNT group was associated with decreased expression of the gene encoding the E3 ligase RNF146. While the E3 ligase SMURF regulates SHH receptors, increased expression of the gene encoding the Cullin Ring E3 adaptor PPP2R2C was statistically a better genetic marker of the SHH group. Genes whose expression was statistically strongly related to Group 3 included the E3 ligase gene TRIM58, and the gene for the E3 ligase adaptor, PPP2R2B. Group 4 MB was associated with expression of genes encoding several E3 ligases and E3 ligase adaptors involved in ribosome biogenesis. Increased expression of the genes encoding the E3 ligase adaptors and transcription repressors ZBTB18 and ZBTB38 were also noted in subgroup 4. These data suggest that several E3 ligases and their adaptors should be investigated as therapeutic targets for subgroup specific MB brain tumors.

The European Association of Neuro-Oncology (EANO) and EUropean RAre CANcer (EURACAN) guideline provides recommendations for the diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma. The guideline is based on the 2016 WHO classification of tumours of the CNS and on scientific developments published since 1980. It aims to provide direction for diagnostic and management decisions, and for limiting unnecessary treatments and cost. In view of the scarcity of data in adults with medulloblastoma, we base our recommendations on adult data when possible, but also include recommendations derived from paediatric data if justified. Our recommendations are a resource for professionals involved in the management of post-pubertal and adult patients with medulloblastoma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment.

Thiotepa, a highly lipophilic, alkylating agent, and/or its active metabolites may be excreted in part via skin in patients receiving high-dose therapy. We present a case of cutaneous toxicity observed in a 4.5-year-old girl patient with medulloblastoma treated with a high-dose thiotepa conditioning regimen before autologous stem cell transplantation. Skin lesions, as well as their pattern and locations, were evocative of thiotepa toxidermia. After the case herein described, preventive care guidelines were implemented in our unit as from 2014. A retrospective follow-up of 26 pediatric patients receiving thiotepa prior to stem cell transplantation was performed until March 2018. In this series of patients, only one patient experienced cutaneous toxicity as reported herein. Thereafter, only mild cutaneous toxicity was observed, even with double or triple transplantation protocols with high-dose thiotepa. Clear preventive care instructions should be detailed in the Summary of Product Characteristics in order to minimize the cutaneous toxicity of thiotepa.

BACKGROUND: The high success rate in the management medulloblastoma achieved in the western world is not exactly mirrored in developing countries including India. Socio-demographic differences, health-care disparity, and lack in uniformity of care with resultant widespread variations in the clinical practice are some of the reasons that may partly explain this difference in outcomes. Patients with medulloblastoma require a multi-disciplinary team approach involving but not limited to neuro-radiology, neurosurgery; neuropathology, molecular biology, radiation oncology, pediatric medical oncology and rehabilitative services for optimizing outcomes.
METHODS: The Indian Society of Neuro-Oncology (ISNO) constituted an expert multi-disciplinary panel with adequate representation from all stakeholders to prepare national consensus guidelines for the contemporary management of medulloblastoma.
RESULTS: Minimum desirable, as well as preferable though optional recommendations (as appropriate), were developed and adopted for the pre-surgical work-up including neuroimaging; neurosurgical management including surgical principles, techniques, and complications; neuropathology reporting and molecular testing; contemporary risk-stratification in the molecular era; appropriate adjuvant therapy (radiotherapy and chemotherapy); and follow-up schedule in medulloblastoma.
CONCLUSIONS: The current document represents a broad consensus reached amongst various stakeholders within the neuro-oncology community involved in the contemporary curative-intent management of children with medulloblastoma. It provides both general as well as specific guidelines and recommendations to be adopted by physicians and health care providers across India to achieve uniformity of care, improve disease-related outcomes, and compare results between institutions within the country.

The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma. The genetically defined component comprises the four entities WNT-activated, SHH-activated and TP53 wildtype, SHH-activated and TP53 mutant, or non-WNT/non-SHH medulloblastoma. Robust and validated methods are available to allow a precise diagnosis of these medulloblastoma entities according to the updated WHO classification, and for differential diagnostic purposes. A combination of immunohistochemical markers including β-catenin, Yap1, p75-NGFR, Otx2, and p53, in combination with targeted sequencing and copy number assessment such as FISH analysis for MYC genes allows a precise assignment of patients for risk-adapted stratification. It also allows comparison to results of study cohorts in the past and provides a robust basis for further treatment refinement.
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