Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004.

BACKGROUND: Retinoblastoma is an eye tumour of childhood that occurs in heritable and non-heritable forms. In the heritable form, there is a predisposition to the development of non-ocular subsequent primary tumours (SPTs). METHODS: This study included 1927 retinoblastoma patients diagnosed in Britain from 1951 to 2004. Ascertainment was through the (UK) National Registry of Childhood Tumours; cases were followed-up for the occurrence of SPTs. Standardised incidence ratios (SIRs) were calculated. RESULTS: We identified 169 SPTs in 152 patients. The SIR analysis included 145 SPTs with cancer registrations from the years 1971 to 2009. These tumours occurred in 132 patients: 112 of the 781 heritable and 20 of the 1075 (presumed) non-heritable cases under surveillance at the start of this period developed at least one registered SPT. The SIRs for all tumours combined were 13.7 (95% confidence interval 11.3-16.5) in heritable cases and 1.5 (0.9-2.3) in non-heritable cases. The main types of SPT in the heritable cases were leiomyosarcoma, (31 cases; SIR 1018.7 (692.2-1446.0)), osteosarcoma (26 cases; SIR 444.6 (290.4-651.4)), and skin melanoma (12 cases; SIR 18.6 (9.6-32.4)). CONCLUSION: The risk of SPTs in heritable retinoblastoma is extremely high. This has important implications for the clinical follow-up and counselling of survivors and their families.

Non-ocular tumours following retinoblastoma in Great Britain 1951 to 2004.

BACKGROUND: Retinoblastoma occurs in both a heritable and a non-heritable form. In the heritable form, there is a predisposition to the development of non-ocular tumours. OBJECTIVES: To identify the types of non-ocular tumour occurring in retinoblastoma survivors and to produce estimates of risk for these tumours. METHODS: We carried out a cohort study that included 1927 cases of retinoblastoma diagnosed in Great Britain between 1951 and 2004. Cases were ascertained through the National Registry of Childhood Tumours and followed up for the occurrence of non-ocular tumours using the routine notification system based on the National Health Service Central Registers in Britain. RESULTS: Of the 1927 cases, 809 were known to have the heritable form of the disease and 1118 assumed to have the non-heritable form. 102 of the heritable and 13 of those classified as non-heritable developed a non-ocular tumour. The cumulative risk of developing such a tumour 50 years after retinoblastoma diagnosis was 48.3% (95% confidence interval: 38.1 to 59.7%) in the heritable and 4.9% (1.9 to 12.4%) in the non-heritable cases. The main categories of non-ocular tumours observed in the heritable cases were soft-tissue sarcomas (36 of which 21 were leiomyosarcoma), osteosarcoma (32), carcinoma (13), brain and central nervous system tumours (10), melanoma (9), leukaemia (4) and others (4). There were a total of 108 non-ocular tumours in 102 cases. CONCLUSIONS: There is a high risk of non-ocular tumours occurring in survivors of heritable retinoblastoma. These results have important implications for the clinical follow-up and counselling of survivors.

Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981-2002.

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0-14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981-2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27-2.99) for osteosarcoma, 1.90 (1.58-2.21) for Ewing sarcoma and 0.21 (0.11-0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6-5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981-2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91-0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98-1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered.

Is postal follow-up of childhood cancer survivors worthwhile?

BACKGROUND: Childhood cancer survival has increased over the last 30 years, but long-term effects necessitate continued monitoring of survivors. Since not all of them attend follow-up clinics, this study assesses the efficacy of obtaining information from general practitioners (GPs) through a 5-year rolling postal program. PROCEDURE: Survivors were included who had been diagnosed with a malignancy in the West Midlands since 1957 and were not attending central long-term follow-up clinics. RESULTS: One thousand twenty-seven patients were followed up between 1993 and 2004. Replies were received on 903 (88% response). There were 44 subsequent malignancies and 42 deaths. No medical problems were reported in 341/935 patients (36.5%); in the other 594 endocrine effects were the most common, with visual effects the biggest single problem. Brain tumor survivors had the largest proportion of problems. CONCLUSIONS: The response rate and information quality achieved show that this method of follow-up is feasible, in cases of discharged or defaulting patients. These data will complement those derived from hospital-based follow-up studies, to give a broader understanding of the spectrum of late effects experienced by survivors and may inform the development of specific long-term follow-up protocols.

A study of soft tissue sarcomas after childhood cancer in Britain.

Among 16 541 3-year survivors of childhood cancer in Britain, 39 soft tissue sarcomas (STSs) occurred and 1.1 sarcomas were expected, yielding a standardised incidence ratio (SIR) of 16.1. When retinoblastomas were excluded from the cohort, the SIR for STSs was 15.9, and the cumulative risk of developing a soft tissue tumour after childhood cancer within 20 years of 3-year survival was 0.23%. In the case-control study, there was a significant excess of STSs in those patients exposed to both radiotherapy (RT) and chemotherapy, which was five times that observed among those not exposed (P=0.02). On the basis of individual radiation dosimetry, there was evidence of a strong dose-response effect with a significant increase in the risk of STS with increasing dose of RT (P<0.001). This effect remained significant in a multivariate model. The adjusted risk in patients exposed to RT doses of over 3000 cGy was over 50 times the risk in the unexposed. There was evidence of a dose-response effect with exposure to alkylating agents, the risk increasing substantially with increasing cumulative dose (P=0.05). This effect remained after adjusting for the effect of radiation exposure.

Long-term population-based risks of second malignant neoplasms after childhood cancer in Britain.

In a population-based, retrospective cohort study of 16 541 3-year survivors of childhood cancer treated in Britain up to the end of 1987, 278 second malignant neoplasms (SMNs) were identified against 39.4 expected giving a standardised incidence ratio (SIR) of 6.2. The overall cumulative risk of an SMN by 25 years from 3-year survival from childhood cancer was 4.2%. Analysis of the cohort of nonretinoblastoma childhood cancers combined revealed a significant decline in SIR of SMN with increasing duration of follow-up. There was a greater risk of developing a SMN, particularly secondary acute myeloid leukaemia, in those diagnosed with childhood cancer from 1980 onwards. However, on multivariate modeling, this was not an independent risk factor. There was significant heterogeneity (P<0.001) in SIR of SMN across different treatment groups, the greatest risk observed in the group exposed to both radiotherapy and chemotherapy. The risks of SMN observed were comparable with those in other population-based studies. While the decline in SIR with duration of follow-up and the small excess numbers of cancers observed over later decades after diagnosis are reassuring, the high excess risk, particularly of leukaemia, associated with recent more intense therapy is of concern.

Orthotopic liver transplantation for unresectable hepatoblastoma: a single center's experience.

BACKGROUND/PURPOSE: Complete surgical resection after chemotherapy is the definitive treatment for hepatoblastoma. However, orthotopic liver transplantation (OLT) is now accepted as a treatment modality for patients with unresectable tumours. The aim of this study was to review a single center's experience of OLT for unresectable hepatoblastoma. METHODS: A retrospective review of 8 patients with unresectable hepatoblastoma who were referred for liver transplantation was conducted. RESULTS: The patients assessed had an age range of 5 to 105 months at presentation; median, 24 months, (5 boys; 3 girls). Two patients have familial adenomatous polyposis, and one has right hemihypertrophy. All 8 patients had received standard chemotherapy according to SIOP (International Society of Pediatric Oncology) protocols. Extrahepatic metastases were found in 3 patients at diagnosis, but none had detectable metastases at the time of OLT. Four patients continued chemotherapy while awaiting OLT. Three patients received whole grafts, and 5 received reduced grafts. The median follow-up period was 22 months (range, 2 to 78 months). Five patients are alive and well, although 1 patient had a second OLT for biliary cirrhosis secondary to biliary stricture at 6 years. Three patients died: one 26 days post OLT of sepsis and two of disease recurrence at 22 months and 70 months posttransplant. The actuarial survival rate is 88% and 65% at 1 and 5 years, respectively, whereas the overall survival rate is 62.5%. CONCLUSION: OLT for unresectable hepatoblastoma without extra hepatic metastases is highly successful with a low recurrence rate.