Relapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment

Relapsed medulloblastoma (rMB) accounts for a considerable, and disproportionate amount of childhood cancer deaths. Recent advances have gone someway to characterising disease biology at relapse including second malignancies that often cannot be distinguished from relapse on imaging alone. Furthermore, there are now multiple international early-phase trials exploring drug–target matches across a range of high-risk/relapsed paediatric tumours. Despite these advances, treatment at relapse in pre-irradiated patients is typically non-curative and focuses on providing life-prolonging and symptom-modifying care that is tailored to the needs and wishes of the individual and their family. Here, we describe the current understanding of prognostic factors at disease relapse such as principal molecular group, adverse molecular biology, and timing of relapse. We provide an overview of the clinical diagnostic process including signs and symptoms, staging investigations, and molecular pathology, followed by a summary of treatment modalities and considerations. Finally, we summarise future directions to progress understanding of treatment resistance and the biological mechanisms underpinning early therapy-refractory and relapsed disease. These initiatives include development of comprehensive and collaborative molecular profiling approaches at relapse, liquid biopsies such as cerebrospinal fluid (CSF) as a biomarker of minimal residual disease (MRD), modelling strategies, and the use of primary tumour material for real-time drug screening approaches.

Operative Procedure in a Suprasellar Paediatric Lesion of the Optic Chiasm with Hydrocephalus Caused by a Papillary Glioneuronal Tumour

<b><i>Introduction:</i></b> Paediatric tumours in the sellar and parasellar regions present clinical and surgical challenges due to anatomical position and behaviour. We illustrate a rare case which caused obstructive hydrocephalus. <b><i>Case Presentation:</i></b> The study included a 14-year-old girl with a glioneuronal tumour (40 mm) originating from the optic chiasm, obliterating the aqueduct, with consequent triventricular hydrocephalus. The patient underwent extended endoscopic endonasal surgery and repair of the skull-base deficiency using a multi-layer technique with fascia lata. The 12-month follow-up showed no complications or recurrences, with recovery in visual acuity. <b><i>Conclusion:</i></b> The immediate placement of external ventricular drainage, in combination with an extended trans-sphenoidal approach, is a safe and feasible option to treat suprasellar paediatric lesions with hydrocephalus.

Multimodal management of locally advanced rhabdoid tumour of the kidney in an adult

Malignant rhabdoid tumours of the kidney (MRTK) are rare paediatric tumours known for their aggressive nature and early metastasis. However, MRTK in adults are even more rare with only a few cases reported in the literature. Herein, we report a case of 65-year-old woman with rapidly progressive left renal mass requiring en-bloc radical nephrectomy, splenectomy and distal pancreatectomy. Histopathology revealed a malignant rhabdoid tumour with characteristic histological and immunohistochemical findings with negative margins. To the best of our knowledge, this is the first reported case of aggressive surgical management of locally advanced MRTK. Despite surgery with curative intent, the patient developed early recurrence and started on tyrosine kinase inhibitor. Unfortunately, the patient expired after 8 months of surgery due to disease progression.

Recent Advances in Understanding the Role of Autophagy in Paediatric Brain Tumours

Autophagy is a degradative process occurring in eukaryotic cells to maintain homeostasis and cell survival. After stressful conditions including nutrient deprivation, hypoxia or drugs administration, autophagy is induced to counteract pathways that could lead to cell death. In cancer, autophagy plays a paradoxical role, acting both as tumour suppressor—by cleaning cells from damaged organelles and inhibiting inflammation or, alternatively, by promoting genomic stability and tumour adaptive response—or as a pro-survival mechanism to protect cells from stresses such as chemotherapy. Neural-derived paediatric solid tumours represent a variety of childhood cancers with unique anatomical location, cellular origins, and clinical presentation. These tumours are a leading cause of morbidity and mortality among children and new molecular diagnostics and therapies are necessary for longer survival and reduced morbidity. Here, we review advances in our understanding of how autophagy modulation exhibits antitumor properties in experimental models of paediatric brain tumours, i.e., medulloblastoma (MB), ependymoma (EPN), paediatric low-grade and high-grade gliomas (LGGs, HGGs), atypical teratoid/rhabdoid tumours (ATRTs), and retinoblastoma (RB). We also discuss clinical perspectives to consider how targeting autophagy may be relevant in these specific paediatric tumours.

Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours

Malignant rhabdoid tumour (MRT) is an often lethal childhood cancer that, like many paediatric tumours, is thought to arise from aberrant fetal development. The embryonic root and differentiation pathways underpinning MRT are not firmly established. Here, we study the origin of MRT by combining phylogenetic analyses and single-cell mRNA studies in patient-derived organoids. Comparison of somatic mutations shared between cancer and surrounding normal tissues places MRT in a lineage with neural crest-derived Schwann cells. Single-cell mRNA readouts of MRT differentiation, which we examine by reverting the genetic driver mutation underpinning MRT, SMARCB1 loss, suggest that cells are blocked en route to differentiating into mesenchyme. Quantitative transcriptional predictions indicate that combined HDAC and mTOR inhibition mimic MRT differentiation, which we confirm experimentally. Our study defines the developmental block of MRT and reveals potential differentiation therapies.

RARE-34. UK CHILDREN’S CANCER AND LEUKAEMIA GROUP (CCLG): GUIDELINES FOR THE MANAGEMENT OF MENINGIOMA IN CHILDREN, TEENAGERS AND YOUNG ADULTS

Primary tumours of the meninges are rare accounting for only 0.4–4.6% of all paediatric tumours of the central nervous system. Due to the rarity of these tumours in children, and the consequent absence of collaborative prospective trials, there is no clear consensus on how the unique characteristics of paediatric meningiomas impact clinical status, management approach, and survival. Much of the evidence and treatment recommendations for paediatric meningiomas are extrapolated from adult data. Translating and adapting adult treatment recommendations into paediatric practice can be challenging and might inadvertently lead to inappropriate management. In 2009 Traunecker et al. published guidelines for the management of intracranial meningioma in children and young people on behalf of UK Children’s Cancer and Leukaemia Group (CCLG). Ten years later we have developed the updated guidelines following a comprehensive appraisal of the literature. Complete surgical resection is the treatment of choice for symptomatic meningiomas, while radiotherapy remains the only available adjuvant therapy and may be necessary for those tumours that cannot be completely removed. However, significant advances have been made in the identification of the genetic and molecular alterations of meningioma, which has not only a potential value in development of therapeutic agents but in surveillance of childhood meningioma survivors. This guideline builds upon the CCLG 2009 guideline. We summarise recommendations for the diagnosis, treatment, surveillance and long-term follow up of children and adolescents with meningioma.

LINC-12. COMBINED ADULT AND PAEDIATRIC NEURO-ONCOLOGY LONG-TERM SURVIVOR CLINIC EXPERIENCE FROM A TERTIARY CANCER CENTRE IN A LOW-MIDDLE-INCOME COUNTRY

NeuroOncology survivor clinics (NOS) is uncommon in low-middle-income countries. We started combined (paediatric and adult) NOS clinic in our tertiary a cancer centre (Jan-2017) and review here the demographic, clinical-pathological and treatment spectrum for our paediatric (0-18years) and adult (&gt;18years) survivors (&gt;5years since their initial diagnosis) till date. Of total 312 patients registered, 198 (63.5%) were adults while 114 (36.5%) were paediatric at-diagnosis with median age (IQR) at presentation: 34 (23–41) and 9(6 – 13) years respectively. In both groups, only 33% were females. The median (IQR) time since diagnosis was 9 (9–14) and 8 (6–12) years respectively with 60% of paediatric turning into adult survivors. The commonest paediatric tumours were glioma (52, 45.6%), embryonal (34, 29.8%), and ependymoma (12, 10.5%) versus gliomas (114, 57.6%) and benign tumours (42, 21.2%) in adults. The low-grade-glioma comprised 90.4% of all pediatric gliomas and intermediate-grade (90%) in adults. The primary treatment consisted of radiotherapy and chemotherapy in 95% and 43% versus 99% and 36% in adults versus paediatric patients respectively. Temozolomide and multi-drug combinations were the commonest chemotherapy used in adults and paediatrics respectively. Relapse and retreatments were seen in 16.6 and 14% of adults and paediatric patients. There were two deaths each in each group since registration (median 12 months). Although the baseline diagnosis/treatment characteristics are different, survivors of both group had a similar number of retreatments and deaths. Combined survivor clinics may present an interesting and unique opportunity to learn and provide challenging service in this part of the world.