Socio-economic and ethnic disparities in childhood cancer survival, Yorkshire, UK.

BACKGROUND: Establishing the existence of health inequalities remains a high research and policy agenda item in the United Kingdom. We describe ethnic and socio-economic differences in paediatric cancer survival, focusing specifically on the extent to which disparities have changed over a 20-year period. METHODS: Cancer registration data for 2674 children (0-14 years) in Yorkshire were analysed. Five-year survival estimates by ethnic group (south Asian/non-south Asian) and Townsend deprivation fifths (I-V) were compared over time (1997-2016) for leukaemia, lymphoma, central nervous system (CNS) and other solid tumours. Hazard ratios (HR: 95% CI) from adjusted Cox models quantified the joint effect of ethnicity and deprivation on mortality risk over time, framed through causal interpretation of the deprivation coefficient. RESULTS: Increasing deprivation was associated with significantly higher risk of death for children with leukaemia (1.11 (1.03-1.20)) and all cancers between 1997 and 2001. While we observed a trend towards reducing differences in survival over time in this group, a contrasting trend was observed for CNS tumours whereby sizeable variation in outcome remained for cases diagnosed until 2012. South Asian children with lymphoma had a 15% reduced chance of surviving at least 5 years compared to non-south Asian, across the study period. DISCUSSION: Even in the United Kingdom, with a universally accessible healthcare system, socio-economic and ethnic disparities in childhood cancer survival exist. Findings should inform where resources should be directed to provide all children with an equitable survival outcome following a cancer diagnosis.

Ceftriaxone pharmacokinetic properties during continuous veno-veno haemofiltration using an in vitro adult, paediatric and neonatal model.

During continuous venoveno haemofiltration (CVVH), extracorporeal drug clearance is dependant on blood flow, ultrafiltration rate, albumin binding, and the drug's molecular weight and volume of distribution. Drug doses are adjusted assuming reduced drug clearance by the renal system and CVVH. High volume haemofiltration, pre-dilution and different filter membranes can greatly alter drug clearance. Consequently, assessing the adequacy of cephalosporin dosing during CVVH is complex; under- or overdosing may occur. We studied the pharmacokinetic properties of ceftriaxone during CVVH in vitro. Renaflow filters were used to model 6, 20 and 50 kg patients. Each circuit and reservoir was prepared with a known volume of Hartmann's solution, human albumin solution 4.5% or blood. Pump speed and exchange rate were standardised for weight. Haemosol BO was used as the replacement fluid with 70% pre-dilution. Following paired sampling from the circuit and ultrafiltrate fluid, ceftriaxone was injected into the circuit. Paired samples were taken up to 720 minutes. Ceftraxione concentrations were determined using high performance liquid chromatography (HPLC). Maximum circuit concentrations (Cmax) at 2 minutes for albumin were 3.5, 2.65 and 4.85 mg/l, for blood were 4.5, 6.5 and 5.55 mg/l and for Hartmann's were 1.65, 2.95 and 3.65 mg/l for 6 kg, 20 kg and 50 kg models. The sieving coefficients (Sc) from blood (ratio of mean concentrations in the ultrafiltrate/circuits samples) were 0.31 and 0.51 with T1/2 (the half life) 62 and 20 minutes in the 6 kg and the 20 kg circuits, respectively. The data suggest in an in vitro model of ceftriaxone is rapidly cleared during CVVH. Albumin circuits had the lowest Sc and longest terminal T1/2, reflecting protein binding of the drug and suggest ceftriaxone clearance may be more rapid in hypoalbuminaemic patients. The Cmax was lower in the Hartmann circuits, possibly reflecting precipitation of the drug with calcium in this solution.

Discussing fertility preservation at the time of cancer diagnosis: dissatisfaction of young females.

BACKGROUND: Sperm banking is widely available for post-pubertal male cancer patients but options for females remain limited. Anecdotal evidence suggests that fertility issues may be inadequately discussed with females. To understand the experience of both sexes in the UK, surveys of young cancer survivors were performed 7 years apart. PROCEDURE: Data were collected from young cancer survivors aged over 13 years at diagnosis, attending support group conferences held in 2004 and 2011. Data were collected anonymously using remote handsets in response to questions projected on the screen during plenary sessions. RESULTS: A total of 81 female and 69 males responded in 2004, and 69 females and 71 males in 2011. In both years, most males reported fertility discussions taking place before treatment started and they were generally satisfied with it. However in both years, fewer females recall a discussion about fertility and they were generally less satisfied. Although in 2011 more females reported a fertility discussion prior to the beginning of treatment, they were no more satisfied than the females in 2004 whose fertility discussion were more likely to take place after treatment had started. CONCLUSIONS: Whilst male cancer survivors in the UK are generally satisfied about the frequency and timing of discussions about fertility, females are not. Although in 2011 fertility discussions with females more often took place before treatment began, they were no more satisfied than females in 2004. This may reflect the approach by professionals or the absence of effective fertility preservation strategies for them.

High dose chemotherapy and autologous hematopoietic cell transplantation for Wilms tumor: a study of the European Society for Blood and Marrow Transplantation.

Survival for subgroups of patients with Wilms tumor (WT), such as those who suffer from relapse, is disappointing. Some patients' treatment plans include high-dose chemotherapy (HDT) with autologous hematopoietic cell transplantation (aHCT), although proof for its benefit is lacking. To increase the level of evidence regarding children with WT receiving aHCT as consolidation of first or second remission (after first relapse), we extracted relevant data from the European Blood and Marrow Transplantation Registry concerning 69 patients. Different HDT regimens were administered, mostly either melphalan-containing (n = 34) or thiotepa-containing (n = 14). For the whole population, 5-year overall survival (OS) and event-free survival (EFS) probabilities were 0.67 (±0.06) and 0.63 (±0.06), respectively (median observation time 7.8 years); for children transplanted in first remission, OS and EFS were 0.69 (±0.09) and 0.72 (±0.08). In univariate analysis, male gender and relapse in multiple sites were associated with lower OS probabilities. The use of a given pretransplant regimen (i.e. melphalan alone versus regimens with multiple drugs) did not seem to influence EFS/OS probability after aHCT, but significantly influenced platelet engraftment (more delayed with thiotepa). We here provide further data to improve the basis for future evidence-based clinical decision-making when using HDT and aHCT in relapsed/refractory WT.

Care of children with brain and spine tumours - a review of practice.

Aims and method were to assess the current practice in paediatric tumour management by the departments of neurosurgery and oncology, compare these with nationally agreed recommendations and examine for areas of improvement. Patient records were identified from departmental databases - 30 patients treated from October 2004 to May 2006. Factors assessed included treatment timelines (e.g., referral to admission and imaging, admission to surgery, surgery to further treatment), imaging, MDT discussion, and paediatric neurosurgery & neuro-oncology treatments. Of acute referrals, all patients were admitted within 2 days. All surgery was undertaken by a dedicated paediatric neurosurgeon with paediatric anaesthesia. All cases were discussed in a neuro-oncology MDT prior to surgery and 97% after surgery. In the first 6-months 57% received adjuvant treatment within 40 days; in the remaining period this improved to 91%. When measured against recognised benchmark standards, the SCH paediatric neuro-oncology service appears satisfactory. This study has identified the need to improve certain aspects of care to offer further improvements to the specialist service delivered.

Observational study of the development and evaluation of a fertility preservation patient decision aid for teenage and adult women diagnosed with cancer: the Cancer, Fertility and Me research protocol.

INTRODUCTION: Women diagnosed with cancer and facing potentially sterilising cancer treatment have to make time-pressured decisions regarding fertility preservation with specialist fertility services while undergoing treatment of their cancer with oncology services. Oncologists identify a need for resources enabling them to support women's fertility preservation decisions more effectively; women report wanting more specialist information to make these decisions. The overall aim of the 'Cancer, Fertility and Me' study is to develop and evaluate a new evidence-based patient decision aid (PtDA) for women with any cancer considering fertility preservation to address this unmet need. METHODS AND ANALYSIS: This is a prospective mixed-method observational study including women of reproductive age (16 years +) with a new diagnosis of any cancer across two regional cancer and fertility centres in Yorkshire, UK. The research involves three stages. In stage 1, the aim is to develop the PtDA using a systematic method of evidence synthesis and multidisciplinary expert review of current clinical practice and patient information. In stage 2, the aim is to assess the face validity of the PtDA. Feedback on its content and format will be ascertained using questionnaires and interviews with patients, user groups and key stakeholders. Finally, in stage 3 the acceptability of using this resource when integrated into usual cancer care pathways at the point of cancer diagnosis and treatment planning will be evaluated. This will involve a quantitative and qualitative evaluation of the PtDA in clinical practice. Measures chosen include using count data of the PtDAs administered in clinics and accessed online, decisional and patient-reported outcome measures and qualitative feedback. Quantitative data will be analysed using descriptive statistics, paired sample t-tests and CIs; interviews will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Research Ethics Committee approval (Ref: 16/EM/0122) and Health Research Authority approval (Ref: 194751) has been granted. Findings will be published in open access peer-reviewed journals, presented at conferences for academic and health professional audiences, with feedback to health professionals and program managers. The Cancer, Fertility and Me patient decision aid (PtDA) will be disseminated via a diverse range of open-access media, study and charity websites, professional organisations and academic sources. External endorsement will be sought from the International Patient Decision Aid Standards (IPDAS) Collaboration inventory of PtDAs and other relevant professional organisations, for example, the British Fertility Society. TRIAL REGISTRATION NUMBER: NCT02753296; pre-results.