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.

A ten-year study of Retinoblastoma in Uganda: An approach to improving outcome with limited resources.

BACKGROUND: Survival of children with cancer in resource-limited regions is very poor compared to better-resourced regions. Retinoblastoma (RB) is a childhood cancer that is commonly reported in many regions of Africa. RB may be safely and effectively treated by non-specialists, which could facilitate more widespread availability of treatment in under-resourced areas. METHODS: A ten-year consecutive series of children with RB treated at Ruharo Eye Centre between December 2009 and November 2019 was prospectively followed up. Chemoreduction followed by surgery is the standard approach to therapy. Costs of therapy and also of travel and food are borne by the program which is unaffordable to most families and necessitates donors. Survival by stage of RB and number of eyes affected was described using Kaplan-Meier plots. Visual acuity was assessed for all children with bilateral disease and the retention of sight during follow-up assessed. RESULTS: Among 665 children with RB, 18.2 % (121 children) presented with metastatic (Stage 4) RB with only two of these children surviving >24 months. Five-year survival was 60.2 % among all children with RB rising to 93.3 % and 87.2 % for children with unilateral and bilateral Stage 1 disease, respectively. Among 184 children with bilateral disease, 130 (70.7 %) retained some level of sight following primary treatment with 91 of those (49.5 % of all bilateral children) retaining vision up to their death or to the end of follow-up. CONCLUSION: Many children in Uganda present with advanced RB and curative treatment is not possible in this setting. Children diagnosed and treated early have good prospects of survival. Retention of sight among many bilaterally affected children is achievable, facilitating access to normal education. Therefore, the strategic priorities for improving survival are changing community perceptions so that children with eye problems are brought without delay, and widening access to modern treatment by using genereal health workers with standard drugs, backed by financial, social and peer support.

Incidence and survival of children and young people with central nervous system embryonal tumours in the North of England, 1990-2013.

BACKGROUND: Medulloblastoma and primitive neuroectodermal tumours (PNET) are the most common central nervous system (CNS) embryonal tumours diagnosed in childhood. Survival outcomes are worse for children diagnosed with CNS PNET compared to medulloblastoma. Less is known about survival outcomes in teenagers and young adults (TYA). METHODS: Data were extracted from two population-based cancer registries of children and young people (0-24 years) in the north of England for all diagnoses of medulloblastoma and CNS PNET between 1990 and 2013. Incidence and survival trends were analysed using Poisson and Cox regression. RESULTS: Between 1990 and 2013, 197 medulloblastomas and 58 CNS PNET were diagnosed, age-standardised incidence rates of 3.8 and 1.5 per million, respectively. Medulloblastoma incidence decreased over time while there was no significant change in trend for CNS PNET. The overall 5-year survival rate was 54%. The risk of death was 2.4 times higher (95% confidence interval [CI] 1.6, 3.7) for patients with CNS PNET compared to medulloblastoma, after adjustment for patient characteristics. There was a 39% reduction (95% CI 0.43, 0.87) in the risk of death for patients diagnosed between 2000 and 2013 compared to 1990-1999. Risk of death did not differ for TYA (15-24 years) compared to children aged 5-9 years. CONCLUSIONS: Medulloblastoma incidence decreased over time and differences in survival between medulloblastoma and PNET emerged within the first-year post diagnosis leading to poorer outcomes for children and young adults diagnosed with PNET; however, a significant improvement in survival over time was observed.

Changes in the patterns of care of central nervous system tumours among 16-24 year olds and the effect on survival in Yorkshire between 1990 and 2009.

AIM: There is a paucity of work documenting the influence of patterns of care on survival for teenagers and young adults with primary central nervous system tumours. Therefore, the aim of this study was to undertake a detailed assessment examining any changes in the patterns of care over time and how these related to survival outcomes for 16-24 year olds diagnosed with a primary central nervous system tumour between 1990 and 2009. MATERIALS AND METHODS: We used high-quality data from one population-based cancer registry in Yorkshire, UK to describe primary central nervous system tumours in teenagers and young adults (16-24 years) diagnosed between 1990 and 2009. The Birch classification scheme was used to identify differences by tumour subgroup. Incidence, patterns of care and survival trends were described using Poisson and Cox regression. RESULTS: There were 163 cases comprising 98 astrocytomas, 17 'other gliomas', 14 ependymomas, 11 medulloblastomas and 23 'other intracranial and intraspinal neoplasms' yielding an overall incidence of 18.1 million person-years. Care varied significantly over time and by principal treatment centre (Leeds 77%, Hull 23%), co-ordinating specialty (neurosurgery 53%, clinical oncology 22%, paediatrics 17%, other adult services 8%) and treatment received. Cox regression showed no significant difference in survival by age, gender, treatment centre, level of deprivation, year of diagnosis or co-ordinating specialty, but a significant difference by tumour grade and diagnostic group. Survival improved for all diagnostic groups except astrocytoma, although only the medulloblastoma group showed a significant change over time. CONCLUSION: The lack of any significant improvement in survival over time in most diagnostic groups warrants further investigation and provides justification for a more collaborative regional approach to the care of central nervous system tumours, perhaps through the development of regional guidelines for this unique population. More detailed analysis of relapse patterns and prediagnostic symptoms would also be informative for this cohort.

Survival trends of cancer amongst the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK.

INTRODUCTION: Several studies have shown differences in survival trends between ethnic groups across adults with cancer in the UK. It is unclear whether these differences exist exclusively in the older adult population or whether they begin to emerge in children and young adults. METHODS: Subjects (n=3534) diagnosed with cancer under 30 years of age in Yorkshire between 1990 and 2005 were analysed. Differences in survival rates for diagnostic subgroups were estimated by ethnic group (south Asian or not) using Kaplan-Meier estimation and Cox regression. RESULTS: When compared to non-south Asians (all other ethnic groups excluding south Asians) a significant increased risk of death was seen for south Asians with leukaemia (hazard ratio (HR)=1.75; 95% confidence interval (CI)=1.11-2.76) and lymphoma (HR=2.05; 95% CI=1.09-3.87), whereas south Asians with solid tumours other than central nervous system tumours had a significantly reduced risk of death(HR=0.50; 95% CI=0.28-0.89). This was independent of socioeconomic deprivation. CONCLUSION: We found evidence of poorer survival outcomes for south Asians compared to non-south Asian children and young adults with leukaemia and lymphoma, but better outcomes for south Asian children and young adults with other solid tumours. This needs to be explained, and carefully addressed in the on-going development of cancer services.

Cancer incidence among the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK.

BACKGROUND: Few studies have examined epidemiological differences between ethnic groups for children and young adults with cancer. METHODS: Subjects aged 0-29 years, diagnosed between 1990 and 2005 in the former Yorkshire Regional Health Authority, were included in the analysis. Ethnicity (south Asian or not) was assigned using name analysis program and Hospital Episode Statistics data. Differences in incidence (per 1,000,000 person-years) rates and trends were analysed using joinpoint and Poisson regression analysis. RESULTS: Overall cancer incidence was similar for south Asians (12.1, 95% CI: 10.7-13.5; n=275) and non-south Asians (12.6, 95% CI: 12.2-13.1; n=3259). Annual incidence rates increased significantly by 1.9% per year on average (95% CI: 1.2-2.6%), especially for south Asians (7.0%; 95% CI: 4.2-9.9%). CONCLUSION: If present trends continue, the higher rate of increase seen among south Asians aged 0-29 years in Yorkshire will result in three times higher cancer incidence than non-south Asians by 2020.

The effect of high-dose enteral glutamine on the incidence and severity of mucositis in paediatric oncology patients.

BACKGROUND/OBJECTIVE: The study was conducted to determine if enteral glutamine, 0.65 g kg(-1) daily for 7 days, is effective in reducing the incidence and severity of mucositis in paediatric oncology patients when given alongside chemotherapy. The study was carried out at St James's University Hospital, Leeds, UK. SUBJECTS/METHODS: This was a randomized study using the patients as their own controls. Seventy-six patients undergoing treatment for paediatric malignancy having at least two identical courses of chemotherapy and at risk of developing mucositis participated in the study. Patients received one course of chemotherapy with glutamine and an identical course without. Alternate patients were allocated to have glutamine with course 1 or with course 2. The severity of symptoms of mucositis and the duration of enteral and parenteral nutrition were recorded. Daily ammonia levels were measured. RESULTS: Fifty patients completed the study. No statistical significance with regard to symptoms of mucositis was found. Fewer children receiving glutamine required parenteral nutrition (P=0.049), and the duration of parenteral nutrition was less (P=0.023). No adverse effects attributed to taking the glutamine were observed. CONCLUSIONS: The study showed that high-dose enteral glutamine did not reduce the incidence and severity of oral mucositis as determined by subjective toxicity measurements, but did show a significant reduction in parenteral nutrition usage. No adverse cumulative effect of this oral glutamine dose was observed.

Therapeutic monitoring of carboplatin dosing in a premature infant with retinoblastoma.

INTRODUCTION: Carboplatin dosing based on renal function and therapeutic monitoring have been previously shown to be beneficial in the treatment of children with cancer. However, the applicability of such approaches to the treatment of premature or newborn infants, where kidney function may change markedly with advancing gestational and postnatal age, is unknown. Diagnosis of retinoblastoma in a preterm infant provided a rare opportunity to carry out adaptive carboplatin dosing in a patient with immature renal function. CASE REPORT: A preterm female infant born at a gestational age of 32 weeks was diagnosed with bilateral retinoblastoma at 35 weeks. Carboplatin treatment with real-time pharmacokinetic monitoring was initiated on day 26 of life at an initial dose of 6.6 mg/kg. Plasma samples were obtained at specified time points and carboplatin levels quantified by atomic absorption spectrometry. Additional doses of carboplatin were determined by pharmacokinetic monitoring based on the achievement of carboplatin AUC values of 5.2-7.8 mg/ml min on three courses of treatment. Increased carboplatin doses administered on successive courses of treatment reflected a greater than twofold increase in drug clearance, from 3.4-7.1 ml/min over a 7-week period. Pharmacokinetically-guided carboplatin dosing led to the attainment of AUCs within 10% of target values on each course of treatment. The patient completed five courses of carboplatin with both tumours defined as inactive after this treatment period. CONCLUSIONS: Data obtained from studying this patient suggests that adaptive carboplatin monitoring represents a feasible and beneficial clinical approach in preterm infants or neonates.

Fatal pneumonitis in children with metastatic rhabdomyosarcoma following whole lung radiotherapy and sequential epirubicin.

Interstitial pneumonitis is a recognized complication following whole lung radiotherapy. We report two cases in which fatal pneumonitis appeared to be precipitated by the administration of epirubicin-containing combination chemotherapy within 7 weeks of completion of whole lung radiotherapy. These cases highlight a potentially fatal interaction between radiotherapy and modern chemotherapy regimens.

Renal medullary carcinoma: prolonged remission with chemotherapy, immunohistochemical characterisation and evidence of bcr/abl rearrangement.

BACKGROUND: Renal medullary carcinoma (RMC), an extremely rare tumour of the kidney, carries a dismal prognosis, with no reports to date of significant response to chemotherapy or radiotherapy. A case of this tumour in a male child, who showed a dramatic response to chemotherapy, is described. PROCEDURE: A detailed histological evaluation of the tumour and cytogenetic analysis using fluorescent in situ hybridisation (FISH) was carried out. The child was treated with multiagent chemotherapy, followed by abdominal radiotherapy. RESULTS: A detailed histopathological and immunohistochemical portrait of this tumour is described, and FISH studies confirmed the presence of a bcr/abl rearrangement. The child obtained complete radiological remission following chemotherapy, although he later relapsed and died of progressive disease despite further attempts at treatment with chemotherapy. CONCLUSIONS: Although there are no previous reports of response of this tumour to chemotherapy, this case illustrates that treatment of this disease is justified. The responses of other cases to similar drug regimens would be of interest to confirm whether the encouraging response described for this case could be reproduced. Cytogenetic analysis of other cases of RMC may clarify whether the abnormalities seen in this case are typical.

Extraosseous osteogenic sarcoma--a rare pediatric malignancy: case report and review of the literature.

BACKGROUND: Osteogenic sarcoma rarely occurs in soft tissues and generally affects individuals beyond the second decade of life. METHODS: The authors report a rare case of an extra osseous osteogenic sarcoma arising in the retroperitoneum of an adolescent, review the literature, and outline the diagnostic and therapeutic dilemmas. The role of adjuvant chemotherapy, using drugs used in managing bony osteosarcomas, is discussed. CONCLUSIONS: Retroperitoneal sarcomas may simulate ovarian teratomas. Careful consideration of the differential diagnosis of large cystic abdominal masses in adolescent females when size precludes adequate assessment of tumor mobility and imaging fails to demonstrate the ovaries is essential if these rare tumors are to be managed effectively.

Aspects of altered metabolism in children with cancer.

Severe weight loss associated with cancer continues to be a major cause of morbidity in cases of childhood malignancy. The etiology is not completely understood but is probably multifactorial, including reduced ingestion and altered metabolism of nutrients. Changes in the host metabolism of protein, fat and carbohydrate in the cancer-bearing host have been demonstrated both in animal models and in patients. Changes include increased protein turnover and loss of the normal compensatory mechanisms seen in starvation. Additionally, increased lipid breakdown results in depletion of lipid stores and changes in carbohydrate metabolism result in an energy-losing cycle. The increase in protein turnover seen in children with leukemia may be related to the tumor, the chemotherapy administered or to related conditions such as febrile neutropenia. The role of endogenous mediators of cancer cachexia has not yet been clearly elucidated, although tumor necrosis factor, interleukin I and interleukin 6 appear to be involved. Studies of energy expenditure in children with cancer have indicated that certain patients with a raised metabolic rate are at particular risk of severe weight loss. The challenge is to identify these vulnerable patients and to provide adequate nutritional support early in treatment and therefore avoid the deleterious effects of cachexia.

Simultaneous choriocarcinoma in mother and newborn infant.

A male infant, born following an uncomplicated pregnancy, was severely anaemic at birth following significant foeto-maternal haemorrhage. At three weeks of age a tumour was found in the liver with evidence of metastatic disease in the lungs. The infant died before treatment could be started. Postmortem revealed choriocarcinoma which led to subsequent diagnosis in the mother who also had pulmonary metastases. The mother has been successfully treated. The case is described in detail and followed by a discussion and a literature review of reported cases of simultaneous choriocarcinoma in infant and mother.