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Diffuse intrinsic brainstem gliomas constitute 15-20% of all CNS tumours in children, and are the main cause of death in children with brain tumours. Many clinical trials have been done over the past three decades, but survival has remained static. More than 90% of children die within 2 years of diagnosis, and conventional fractionated radiation remains the standard treatment. However, median survival differs substantially between clinical trials, suggesting a survival benefit with some strategies. We appraised the consistency between protocols in terms of eligibility criteria, definition and assessment of response and progression, statistical design, and endpoints. Study designs varied substantially, which could explain the differences in outcome, and no treatment has shown a benefit over conventional radiotherapy. However, consistency between protocols (eg, eligibility criteria and outcome measures) is important to measure the progress in management of diffuse pontine gliomas. [ABSTRACT FROM AUTHOR]

Adolescents with brain tumours have been, and in most cases still are, haphazardly assigned, on referral, to either ‘paediatric’ or ‘adult’-based treatment centres. In this age group, there is therefore a history of inconsistent treatment, delivery of inappropriate ‘maturity-related’ care and a reduced chance of gathering vital biological, clinical and treatment-related information germane to this group of patients and their tumours. These days, adolescents with brain tumours should be actively targeted for recruitment into clinical trials and admission into dedicated neuro-oncology centres or programmes that can deliver the necessary and age appropriate multidisciplinary management. [Copyright &y& Elsevier]

In the last 20 years, the survival rate for children with acute lymphoblastic leukaemia (ALL) has markedly improved, largely owing to a decrease in relapses. However, children still die from complications of treatment and these are potentially preventable. We have analysed data from three large consecutive national protocols for ALL from 1980 to 1997 [Medical Research Council United Kingdom ALL (MRC UKALL) trials VIII, X and XI] to compare the incidence and causes of treatment-related deaths (TRD). The percentage of TRD has fallen from 9% to 2% (UKALL VIII to XI), largely as a result of a decrease in fatal infections. Deaths during induction have fallen from 3% to 1%, the main causes of death being bacterial, followed by fungal infection, while other causes, chiefly haemorrhage, have not declined. Remission deaths also decreased from 6% to 1%, particularly those deaths due to measles and pneumocystis carinii. More guidelines for surveillance and treatment of infections have been included within progressively more intensive protocols. Risk factor analysis showed increased TRD in patients with Down's syndrome, high leucocyte count and older age in UKALL XI. In contrast, the introduction of blocks of intensification was not associated with an increased death rate. While improved supportive care has reduced the incidence of TRD, there is still scope for further reduction by prompt treatment of suspected infection. Maintenance of herd immunity remains of vital importance in avoiding deaths from measles. [ABSTRACT FROM AUTHOR]

SummaryAims To examine active and passive tobacco smoke exposure in children and adolescents attending a diabetic clinic. Methods Salivary cotinine concentrations were measured by gas chromatography and questionnaire data on the smoking habits of patients, families and friends were analysed as well as recording of glycosylated haemoglobin (HbA1c), body mass index (BMI) and social deprivation score. Results Salivary cotinine concentrations identified 7% of the patients as active smokers and 72% as passive smokers. The mean cotinine concentration in those with no identifiable source of exposure was 0.10 (95% confidence interval 0.05–0.14) ng/ml, 2.81 (2.24–3.38) ng/ml in the passive smoking group and 103.69 (55.96–151.41) ng/ml in the active smokers. Cotinine concentrations in passive smokers increased with the number of sources of exposure. The mean cotinine concentration was also higher when the mother was the sole source compared to other sources. There was no statistically significant correlation to smoking exposure and HbA1c, BMI and deprivation scores. Conclusion Tobacco smoke exposure may pose serious health risks to children and adolescents with diabetes and additional public health measures are required to reduce overall exposure. Diabet. Med. 16, 31–34 (1999). [ABSTRACT FROM AUTHOR]

The method for the assay in mice of the α2 glycoprotein fraction of serum with immunosuppressive activity is described. The crude fraction has been shown to be effective in mice only with intravenous injection. When an antigen which is rapidly cleared from the blood is given, a single injection of the protein fraction given 10–20 hours before the exposure to antigen will inhibit the immune response in most animals. Time intervals outside this range are associated with a diminished or absent immunosuppressive effect. The protein fraction does not show activity immediately after preparation, or after reconstitution of freeze-dried material. Within 40 days, however, the activity is restored by storage alone, either frozen or at 4°. The presence of ribonuclease in the fraction is demonstrated, and its possible significance in relation to the immuno- suppressive effect is discussed. [ABSTRACT FROM AUTHOR]

Purpose: Atypical teratoid/rhabdoid tumours (ATRTs) are malignant embryonal tumours of childhood that affect the central nervous system (CNS). We aim to determine which factors, including patient age, extent of resection (EOR), presence of distal metastasis and use of adjuvant therapies, affect overall survival in children with atypical teratoid/rhabdoid tumours (ATRTs) treated at this single centre. Methods: Retrospective cohort review of patients with histological diagnosis of ATRT treated over 21 years (1999–2020) was conducted. Data on demographics, tumour location, presence of metastasis, use of adjuvant therapy, extent of resection (EOR), complications, neurological outcome post-surgery, and overall survival were collected. Kaplan-Meier survival analysis was performed. Results: A total of 45 children (mean age 2 years) underwent 64 operations. 25 patients were <1 year of age. Gross-total resection (GTR) pre-adjuvant therapy was achieved in 15, near-total resection (NTR) in 15, subtotal resection (STR) in 9, and biopsy in 6 children. Most children had good neurological outcomes post-operatively (28/45 with GOS 5). Fourteen patients survived longer than 4 years. Survival analysis showed a significant difference in median survival in favour of GTR and localised disease. There was no significant difference in median survival between patients <1 year vs >1 year of age (p=0.84). Conclusion: We find that presence of metastasis was an important factor in poor survival in patients with ATRT. GTR, where possible, may confer significant survival benefit in ATRT. Children aged <1 year appear to have performed as well as those >1 year and therefore should still be considered for radical surgery. [ABSTRACT FROM AUTHOR]

The Test of Memory Malingering is one of the most popular and heavily researched validity tests available for use in neuropsychological evaluations. Recent research has suggested, however, that the original indices and cutoffs may require modifications to increase sensitivity rates. Some of these modifications lack cross-validation and no study has examined all indices in a single sample. This study compares Trial 1, Trial 2, the Retention Trial, and the newly created Albany Consistency Index in a criterion group forensic neuropsychological sample. Findings lend support for the newly created indices and cutoff scores. Implications and cautionary statements are provided and discussed. [ABSTRACT FROM PUBLISHER]

Abstract: The aims of this study were to determine the maximum tolerated dose (MTD), toxicity and pharmacokinetics of oral temozolomide administered over 42 d in children with recurrent/refractory brain tumours. Cohorts of 3–6 patients were treated for 42 d, followed by a 7-d rest period for a maximum of 6 cycles. Patients were stratified as heavily pre-treated (HPT) and non-heavily pre-treated (NHPT). Starting doses were 50 mg/m2 (HPT) or 75 mg/m2 (NHPT). Out of 28 patients enrolled, 20 were evaluable for toxicity and 19 for pharmacokinetics. Three patients in the NHPT group developed grade 3/4 haematological toxicity, 2 experienced dose-limiting toxicity (thrombocytopenia) at 100 mg/m2, and 9/20 developed grade 3 lymphopenia. MTD in both strata was 85 mg/m2. Responses were observed in 4 patients: 2 complete responses (CR) in medulloblastoma and supratentorial primitive neuroectodermal tumours (PNET), and 2 partial responses (PR) in high-grade glioma, respectively. Overall cumulative exposure was at least 1.5 times higher than in the 5-d administration schedule. In conclusion, the recommended dose of temozolomide is 85 mg/m2 ×42 d. Dose-limiting toxicities are thrombocytopenia and lymphopenia. The observed response rate warrants phase II studies. [Copyright &y& Elsevier]

Congenital melanocytic naevi (CMN) are a known risk factor for melanoma, with the greatest risk currently thought to be in childhood. There has been controversy over the years about the incidence of melanoma, and therefore over the clinical management of CMN, due partly to the difficulties of histological diagnosis and partly to publishing bias towards cases of malignancy. Large cohort studies have demonstrated that melanoma risk in childhood is related to the severity of the congenital phenotype. New understanding of the genetics of CMN offers the possibility of improvement in diagnosis of melanoma, identification of those at highest risk, and new treatment options. We review the world literature and our centre's experience over the last 25 years, including the molecular characteristics of melanoma in these patients and new melanoma incidence and outcome data from our prospective cohort. Management strategies are proposed for presentation of suspected melanoma of the skin and the central nervous system in patients with CMN, including use of oral mitogen-activated protein kinase kinase inhibitors in NRAS-mutated tumours. [ABSTRACT FROM AUTHOR]

Abstract: Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis with no chemotherapy regimen so far resulting in any significant improvement over standard radiotherapy. In this trial, a prolonged regimen (21/28d) of temozolomide was studied with the aim of overcoming O6-methylguanine methyltransferase (MGMT) mediated resistance. Forty-three patients with a defined clinico-radiological diagnosis of DIPG received radiotherapy and concomitant temozolomide (75mg/m2) after which up to 12 courses of 21d of adjuvant temozolomide (75–100mg/m2) were given 4 weekly. The trial used a 2-stage design and passed interim analysis. At diagnosis median age was 8years (2–20years), 81% had cranial nerve abnormalities, 76% ataxia and 57% long tract signs. Median Karnofsky/Lansky score was 80 (10–100). Patients received a median of three courses of adjuvant temozolomide, five received all 12 courses and seven did not start adjuvant treatment. Three patients were withdrawn from study treatment due to haematological toxicity and 10 had a dose reduction. No other significant toxicity related to temozolomide was noted. Overall survival (OS) (95% confidence interval (CI)) was 56% (40%, 69%) at 9months, 35% (21%, 49%) at 1year and 17% (7%, 30%) at 2years. Median survival was 9.5months (range 7.5–11.4months). There were five 2-year survivors with a median age of 13.6years at diagnosis. This trial demonstrated no survival benefit of the addition of dose dense temozolomide, to standard radiotherapy in children with classical DIPG. However, a subgroup of adolescent DIPG patients did have a prolonged survival, which needs further exploration. [ABSTRACT FROM AUTHOR]

Abstract: Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis with no chemotherapy regimen so far resulting in any significant improvement over standard radiotherapy. In this trial, a prolonged regimen (21/28d) of temozolomide was studied with the aim of overcoming O6-methylguanine methyltransferase (MGMT) mediated resistance. Forty-three patients with a defined clinico-radiological diagnosis of DIPG received radiotherapy and concomitant temozolomide (75mg/m2) after which up to 12 courses of 21d of adjuvant temozolomide (75–100mg/m2) were given 4 weekly. The trial used a 2-stage design and passed interim analysis. At diagnosis median age was 8years (2–20years), 81% had cranial nerve abnormalities, 76% ataxia and 57% long tract signs. Median Karnofsky/Lansky score was 80 (10–100). Patients received a median of three courses of adjuvant temozolomide, five received all 12 courses and seven did not start adjuvant treatment. Three patients were withdrawn from study treatment due to haematological toxicity and 10 had a dose reduction. No other significant toxicity related to temozolomide was noted. Overall survival (OS) (95% confidence interval (CI)) was 56% (40%, 69%) at 9months, 35% (21%, 49%) at 1year and 17% (7%, 30%) at 2years. Median survival was 9.5months (range 7.5–11.4months). There were five 2-year survivors with a median age of 13.6years at diagnosis. This trial demonstrated no survival benefit of the addition of dose dense temozolomide, to standard radiotherapy in children with classical DIPG. However, a subgroup of adolescent DIPG patients did have a prolonged survival, which needs further exploration. [Copyright &y& Elsevier]

Objectifs: le but de cette étude était d’évaluer l’activité de la vinblastine (VB) chez les enfants porteurs de gliome de bas grade (GBG) en rechute. Méthodes: La VB était administrée une fois/semaine par voie IV à la dose de 6/m2 pendant 1 an. Les critères d’éligibilité étaient : 1) patient porteur ou non de neurofibromatose de type 1 (NF1) et <18 ans au moment de l’inclusion dans l’étude – 2) déjà traité par chimiothérapie et/ou irradiation pour un GBG inopérable ou incomplètement réséqué. Résultats: l’étude a été initiée en 2003 et a atteint ses objectifs d’inclusion en 2006. 51 patients (âge médian 7,4 ans, sexe ratio F/M : 27/24) ont été inclus (9 avec NF1). Le diagnostic histologique était astrocyotme pilocytique (29), GBG sans autre précision (9), gangliogliome (2), astrocy-tome pilomyxoide (1). Chez 10 patients, le diagnostic avait été porté sur les données d’IRM uniquement. 37 patients avaient reçu auparavant 1 ligne de chimiothérapie, 11 deux lignes, 2 trois lignes et 9 avaient reçu une irradiation. 29 patients ont reçu la totalité du traitement (1 an). 3 patients ont arrêté le traitement en raison d’effets indésirables (2 neuropathies périphériques et une éruption cutanée récidivante). 27 patients ont nécessité une adaptation de dose. 20 patients ont progressé en cours de traitement. L’un de ces patients a poursuivi le traitement et a ultérieurement présenté une réponse partielle (RP). La revue centralisée de l’imagerie a été conduite par 2 radiologues indépendants : sur 31 dossiers revus, il a été observé 1 rémission complète, 3 RP, 9 réponses mineures, 10 maladies stables et 10 progressions. Avec un recul médian de 31 mois, 19/29 patients qui ont reçu la totalité du traitement sont en vie sans progression. Conclusion: cette étude représente le plus large essai de phase II mené chez les patients porteurs de GBG en rechute. Elle a permis de montrer qu’il est possible d’obtenir des rémissions prolongées en utilisant un traitement simple et bien toléré. La toxicité faible de ce traitement et la possibilité de prolonger l’administration au delà d’un an sans risque sérieux de toxicité cumulative fait de la VB un agent au potentiel prometteur dans la traitement des GBG de l’enfant. Financé par une bourse de l’Ontario Cancer Research Network. [Copyright &y& Elsevier]