Background:Despite therapeutic advances, survival following relapse for neuroblastoma patients remains poor. We investigated clinical and biological factors associated with length of progression-free and overall survival following relapse in UK neuroblastoma patients.Methods:All cases of relapsed neuroblastoma, diagnosed during 1990–2010, were identified from four Paediatric Oncology principal treatment centres. Kaplan–Meier and Cox regression analyses were used to calculate post-relapse overall survival (PROS), post-relapse progression-free survival (PRPFS) between relapse and further progression, and to investigate influencing factors.Results:One hundred eighty-nine cases were identified from case notes, 159 (84.0%) high risk and 17 (9.0%), unresectable, MYCN non-amplified (non-MNA) intermediate risk (IR). For high-risk patients diagnosed >2000, median PROS was 8.4 months (interquartile range (IQR)=3.0–17.4) and median PRPFS was 4.7 months (IQR=2.1–7.1). For IR, unresectable non-MNA patients, median PROS was 11.8 months (IQR 9.0–51.6) and 5-year PROS was 24% (95% CI 7–45%). MYCN amplified (MNA) disease and bone marrow metastases at diagnosis were independently associated with worse PROS for high-risk cases. Eighty percent of high-risk relapses occurred within 2 years of diagnosis compared with 50% of unresectable non-MNA IR disease.Conclusions:Patients with relapsed HR neuroblastomas should be treatment stratified according to MYCN status and PRPFS should be the primary endpoint in early phase clinical trials. The failure to salvage the majority of IR neuroblastoma is concerning, supporting investigation of intensification of upfront treatment regimens in this group to determine whether their use would diminish likelihood of relapse.

Background:A frequent mechanism of acquired multidrug resistance in human cancers is overexpression of ATP-binding cassette transporters such as the Multi-Drug Resistance Protein 1 (MDR-1). Nutlin-3, an MDM2–p53 antagonist, has previously been reported to be a competitive MDR-1 inhibitor.Methods:This study assessed whether the structurally diverse MDM2–p53 antagonists, MI-63, NDD0005, and RG7388 are also able to modulate MDR-1 function, particularly in p53 mutant neuroblastoma cells, using XTT-based cell viability assays, western blotting, and liquid chromatography–mass spectrometry analysis.Results:Verapamil and the MDM2–p53 antagonists potentiated vincristine-mediated growth inhibition in a concentration-dependent manner when used in combination with high MDR-1-expressing p53 mutant neuroblastoma cell lines at concentrations that did not affect the viability of cells when given alone. Liquid chromatography–mass spectrometry analyses showed that verapamil, Nutlin-3, MI-63 and NDD0005, but not RG7388, led to increased intracellular levels of vincristine in high MDR-1-expressing cell lines.Conclusions:These results show that in addition to Nutlin-3, other structurally unrelated MDM2–p53 antagonists can also act as MDR-1 inhibitors and reverse MDR-1-mediated multidrug resistance in neuroblastoma cell lines in a p53-independent manner. These findings are important for future clinical trial design with MDM2–p53 antagonists when used in combination with agents that are MDR-1 substrates.

Mental health benefits of a pedometer-based exercise intervention for parents of children with cancer were identified. Such programs should be included in a holistic approach to improve the psychological outcomes of parents whose children are receiving treatment for cancer.

Central nervous system primitive neuro-ectodermal tumors (CNS-PNETs), have recently been re-classified in the most recent 2016 WHO Classification into a standby catch all category, "CNS Embryonal Tumor, not otherwise specified" (CNS embryonal tumor, NOS) based on epigenetic, biologic and histopathologic criteria. CNS embryonal tumors (NOS) are a rare, histologically and molecularly heterogeneous group of tumors that predominantly affect children, and occasionally adults. Diagnosis of this entity continues to be challenging and the ramifications of misdiagnosis of this aggressive class of brain tumors are significant. We report the case of a 45-year-old woman who was diagnosed with a central nervous system embryonal tumor (NOS) based on immunohistochemical analysis of the patient's tumor at diagnosis. However, later genome-wide methylation profiling of the diagnostic tumor undertaken to guide treatment, revealed characteristics most consistent with IDH-mutant astrocytoma. DNA sequencing and immunohistochemistry confirmed the presence of IDH1 and ATRX mutations resulting in a revised diagnosis of high-grade small cell astrocytoma, and the implementation of a less aggressive treatment regime tailored more appropriately to the patient's tumor type. This case highlights the inadequacy of histology alone for the diagnosis of brain tumours and the utility of methylation profiling and integrated genomic analysis for the diagnostic verification of adults with suspected CNS embryonal tumor (NOS), and is consistent with the increasing realization in the field that a combined diagnostic approach based on clinical, histopathological and molecular data is required to more accurately distinguish brain tumor subtypes and inform more effective therapy.

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To the Editor: Congenital leukemia is rare, accounting for less than 1% of childhood leukemia.[1] Acute myeloid leukemia (AML) occurs more frequently than acute lymphoblastic leukemia during the first four weeks of life, with acute monoblastic leukemia accounting for approximately 50% of cases, followed by acute myelomonocytic leukemia in 20%.[1] Acute erythroleukemia is extremely rare, with six reported cases. [2][3][4][5][6][7] We report a term male with congenital acute erythroleukemia who achieved sustained remission with low-dose cytosine arabinoside (Ara-C) alone. He presented with respiratory distress following a normal delivery. Examination revealed pallor, costal recession, and hepatomegaly, with no dysmorphic features. A full blood count showed leukocytosis (72.95 Â 10 9

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Children with a Central Nervous System (CNS) tumour have frequent magnetic resonance imaging (MRI) scans during their disease trajectory. Younger children routinely have these performed under general anaesthetic (GA) with an associated risk and inconvenience. Our project over a two-year period was to introduce a structured programme to any child over the age of five years old to achieve an MRI scan without the need for a GA. Thirty-six patients took part. The motivation behind this project was to enhance the hospital experience for patients and their families, lessen time spent in hospital and minimise risk. In addition, there was an added incentive of cost saving and increased availability of GA scans for other specialities within the hospital setting. During the COVID pandemic, it has also resulted in a reduction of our patients requiring COVID swabs, and isolation and in turn a reduction in aerosol generating procedures. As part of the structured programme, each child had an initial assessment with the nurse specialist followed by a minimum of one play preparation session with the play specialist. Children were required to demonstrate they could follow simple instructions, engage in social stories and role-play with hospital equipment and specialised resources. During these sessions, the children visited the MRI department where they practiced lying flat on the MRI bed as it moved into the scanner. Over the two-year period, of the total number of MRI scans performed, the amount of MRI scans requiring a GA reduced from 41% to 31%. The quality of the MRI scans was scrutinised and shown not to be significantly affected. In summary, by introducing a structured programme, it is possible to significantly reduce the need for GA in children requiring CNS imaging as part of their tumour journey.