Treatment-related mortality in children with cancer:Prevalence and risk factors

Aim: Intensive treatment regimens have contributed to a marked increase in childhood cancer survival rates. Death due to treatment-related adverse effects becomes an increasingly important area to further improve overall survival. In this study, we examined 5-year survival in children with cancer to identify risk factors for treatment-related mortality (TRM). Methods: All children (aged <18 years at diagnosis) diagnosed with cancer in 2 Dutch university hospitals between 2003 and 2013 were included, survival status was determined and causes of death were analysed. Various demographic and treatment factors were evaluated, for which a multivariable competing risks analysis was performed. Results: A total of 1764 patients were included; overall 5-year survival was 78.6%. Of all 378 deaths, 81 (21.4%) were treatment-related, with infection being responsible for more than half of these deaths. Forty percent of TRM occurred in the first three months after initial diagnosis. Factors associated with TRM in the multivariable competing risks analysis were diagnosis of a haematological malignancy, age at diagnosis <1 year and receipt of allogeneic haematopoietic stem cell transplantation. In children suffering from haematological malignancies, TRM accounted for 56.3% of 103 deaths. Conclusion: Over one in five deaths in children with cancer death was related to treatment, mostly due to infection. In children suffering from a haematological malignancy, more children died due to their treatment than due to progression of their disease. To further increase overall survival, clinical and research focus should be placed on lowering TRM rates without compromising anti-tumour efficacy. The findings presented in this study might help identifying areas for improvement

A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecin

Polymeric drug conjugates are a new and experimental class of drug delivery systems with pharmacokinetic promises. The antineoplastic drug camptothecin was linked to a water-soluble polymeric backbone (MAG-CPT) and administrated as a 30 min infusion over 3 consecutive days every 4 weeks to patients with malignant solid tumours. The objectives of our study were to determine the maximal tolerated dose, the dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document anti-tumour activity. The starting dose was 17 mg m−2 day−1. Sixteen patients received 39 courses at seven dose levels. Maximal tolerated dose was at 68 mg m−2 day−1 and dose-limiting toxicities consisted of cumulative bladder toxicity. MAG-CPT and free camptothecin were accumulated during days 1–3 and considerable amounts of MAG-CPT could still be retrieved in plasma and urine after 4–5 weeks. The half-lives of bound and free camptothecin were equal indicating that the kinetics of free camptothecin were release rate dependent. In summary, the pharmacokinetics of camptothecin were dramatically changed, showing controlled prolonged exposure of camptothecin. Haematological toxicity was relatively mild, but serious bladder toxicity was encountered which is typical for camptothecin and was found dose limiting

Development of the SIOPE DIPG network, registry and imaging repository : a collaborative effort to optimize research into a rare and lethal disease

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.Peer reviewe

REDUCTION OF CATHETER ASSOCIATED BLOODSTREAM INFECTIONS IN PAEDIATRIC ONCOLOGY PATIENTS USING ETHANOL LOCKS; A RANDOMIZED CONTROLLED TRIAL

Development and application of statistical models for medical scientific researc

PREVALENCE OF SYMPTOMATIC AND ASYMPTOMATIC THROMBOSIS IN PEDIATRIC ONCOLOGY PATIENTS WITH TUNNELED CENTRAL VENOUS CATHETERS

Development and application of statistical models for medical scientific researc

Site of childhood cancer care in the Netherlands

Background: Due to the complexity of diagnosis and treatment, care for children and young adolescents with cancer preferably occurs in specialised paediatric oncology centres with potentially better cure rates and minimal late effects. This study assessed where children with cancer in the Netherlands were treated since 2004. Methods: All patients aged under 18 diagnosed with cancer between 2004 and 2013 were selected from the Netherlands Cancer Registry (NCR) and linked with the Dutch Childhood Oncology Group (DCOG) database. Associations between patient and tumour characteristics and site of care were tested statistically with logistic regression analyses. Results: This population-based study of 6021 children diagnosed with cancer showed that 82% of them were treated in a paediatric oncology centre. Ninety-four percent of the patients under 10 years of age, 85% of the patients aged 10-14 and 48% of the patients aged 15-17 were treated in a paediatric oncology centre. All International Classification of Childhood Cancers (ICCC), 3rd edition, ICCC-3 categories, except embryonal tumours, were associated with a higher risk of treatment outside a paediatric oncology centre compared to leukaemia. Multivariable analyses by ICCC-3 category revealed that specific tumour types such as chronic myelogenous leukaemia (CML), embryonal carcinomas, bone tumours other type than osteosarcoma, non-rhabdomyosarcomas, thyroid carcinomas, melanomas and skin carcinomas as well as lower-staged tumours were associated with treatment outside a paediatric oncology centre. Conclusion: The site of childhood cancer care in the Netherlands depends on the age of the cancer patient, type of tumour and stage at diagnosis. Collaboration between paediatric oncology centre(s), other academic units is needed to ensure most up-to-date paediatric cancer care for childhood cancer patients at the short and long term. (C) 2017 Elsevier Ltd. All rights reserve