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.

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.

Prevalence of Symptomatic and Asymptomatic Thrombosis in Pediatric Oncology Patients With Tunneled Central Venous Catheters.

BACKGROUND: Pediatric oncology patients with tunneled central venous catheters (CVCs) are at increased risk to develop venous thromboembolic events (VTEs), but the true prevalence of (a)symptomatic VTE is unknown. Aim of this study was to evaluate the prevalence of (a)symptomatic VTE in pediatric oncology patients with tunneled CVCs. PROCEDURE: All patients were included in the Aristocaths study: a randomized controlled multicenter trial investigating the prophylactic effect of 70% ethanol locks on CVC-associated bloodstream infections (CABSIs) were eligible for this study. We assessed the following outcomes: (i) symptomatic VTE and (ii) asymptomatic CVC-related VTE (using ultrasound [US]). Follow-up was 6 months, unless patients developed one of the following events: VTE, CABSI, CVC removal, or death. RESULTS: We included 305 patients (hematologic malignancy, n = 148; solid tumor, n = 157), median age 9 years (range, 1-18 years). Symptomatic VTE was detected in 8 of 305 patients (2.6%; 95% confidence interval [CI]: 1.1-5.1%), which was related to the CVC in three patients. Patients (185/305) were evaluated with US: 11 of 185 (5.9%; 95% CI: 3.0-10.4%) patients had asymptomatic CVC-related VTE. CONCLUSIONS: Prevalence of both symptomatic VTE and asymptomatic CVC-related VTE was low compared to other studies, which may be explained by the inclusion of patients with solid tumors, reduction of CABSI by ethanol, use of tunneled CVCs, and use of US.

Prevention of central venous catheter-associated bloodstream infections in paediatric oncology patients using 70% ethanol locks: A randomised controlled multi-centre trial.

BACKGROUND: The prevention of central venous catheter (CVC) associated bloodstream infections (CABSIs) in paediatric oncology patients is essential. Ethanol locks can eliminate pathogens colonising CVCs and microbial resistance is rare. Aim of this study was to determine whether two hour 70% ethanol locks can reduce CABSI in paediatric oncology patients. METHODS: We conducted a randomised, double blind, multi-centre trial in paediatric oncology patients (1-18 years) with newly inserted CVCs. Patients were randomly assigned to receive two hour ethanol locks (1.5 or 3 ml 70%) or heparin locks (1.5 or 3 ml 100 IU/ml), whenever it was needed to use the CVC, maximum frequency once weekly. Primary outcomes were time to CABSI or death due to CABSI. RESULTS: We recruited 307 patients (ethanol, n=153; heparin, n=154). In the ethanol group, 16/153 (10%) patients developed a CABSI versus 29/154 (19%) in the heparin group. The incidence of CABSI was 0.77/1000 and 1.46/1000 catheter days respectively (p=0.039). The number-needed-to-treat was 13. No patients died of CABSI. In particular, Gram-positive CABSIs were reduced (ethanol, n=8; heparin, n=21; p=0.012). Fewer CVCs were removed because of CABSI in the ethanol group (p=0.077). The ethanol lock patients experienced significantly more transient symptoms compared to the heparin lock patients (maximum grade 2) (nausea, p=0.030; taste alteration, p<0.001; dizziness, p=0.001; blushing, p<0.001), no suspected unexpected serious adverse reactions (SUSAR) occurred. CONCLUSIONS: This is the first randomised controlled trial to show that ethanol locks can prevent CABSI in paediatric oncology patients, in particular CABSI caused by Gram-positive bacteria. Implementation of ethanol locks in clinical practice should be considered.

Renal dysfunction and elevated blood pressure in long-term childhood cancer survivors.

BACKGROUND AND OBJECTIVES: Little is known about renal function and blood pressure (BP) in long-term childhood cancer survivors. This cross-sectional study evaluated prevalence of these outcomes and associated risk factors in long-term childhood cancer survivors at their first visit to a specialized outpatient clinic. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Estimated GFR; percentages of patients with albuminuria, hypomagnesemia, and hypophosphatemia; and BP were assessed in 1442 survivors ≥5 years after diagnosis. Multivariable logistic regression analyses were used to estimate effect of chemotherapy, nephrectomy, and radiation therapy on the different outcomes. RESULTS: At a median age of 19.3 years (interquartile range, 15.6-24.5 years), 28.1% of all survivors had at least one renal adverse effect or elevated BP. The median time since cancer diagnosis was 12.1 years (interquartile range, 7.8-17.5 years). High BP and albuminuria were most prevalent, at 14.8% and 14.5%, respectively. Sixty-two survivors (4.5%) had an estimated GFR <90 ml/min per 1.73 m(2). Survivors who had undergone nephrectomy had the highest risk for diminished renal function (odds ratio, 8.6; 95% confidence interval [CI], 3.4-21.4). Combined radiation therapy and nephrectomy increased the odds of having elevated BP (odds ratio, 4.92; 95% CI, 2.63-9.19), as did male sex, higher body mass index, and longer time since cancer treatment. CONCLUSION: Almost 30% of survivors had renal adverse effects or high BP. Therefore, monitoring of renal function in high-risk groups and BP in all survivors may help clinicians detect health problems at an early stage and initiate timely therapy to prevent additional damage.