No Association between Radiation Dose from Pediatric CT Scans and Risk of Subsequent Hodgkin Lymphoma.

Background: We examined the relationship between estimated radiation dose from CT scans and subsequent Hodgkin lymphoma in the UK pediatric CT scans cohort.Methods: A retrospective, record linkage cohort included patients ages 0 to 21 years who underwent CT scans between 1980 and 2002 and were followed up for cancer or death until 2008. Poisson regression analysis was used to evaluate the relationship between estimated radiation dose (lagged by 2 years) and incident Hodgkin lymphoma diagnosed at least 2 years after the first CT scan.Results: There were 65 incident cases of Hodgkin lymphoma in the cohort of 178,601 patients. Neither estimated red bone marrow dose nor mean lymphocyte dose from CT scans was clearly associated with an increased risk of Hodgkin lymphoma (RR for 20+ mGy vs. <5 mGy = 0.92 (0.38-2.22) Ptrend > 0.5 and 1.44 (0.60-3.48) Ptrend > 0.5), respectively.Conclusions: Radiation exposure from pediatric CT scans 2 or more years before diagnosis was not associated with Hodgkin lymphoma in this large UK cohort.Impact: These findings are consistent with the majority of previous studies, which do not support a link between ionizing radiation and Hodgkin lymphoma. The results contrast our previous positive findings in this cohort for brain tumors and leukemia, both of which are known to be strongly linked to radiation exposure during childhood. Cancer Epidemiol Biomarkers Prev; 26(5); 804-6. ©2017 AACR.

Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions.

BACKGROUND: We previously reported evidence of a dose-response relationship between ionising-radiation exposure from paediatric computed tomography (CT) scans and the risk of leukaemia and brain tumours in a large UK cohort. Underlying unreported conditions could have introduced bias into these findings. METHODS: We collected and reviewed additional clinical information from radiology information systems (RIS) databases, underlying cause of death and pathology reports. We conducted sensitivity analyses excluding participants with cancer-predisposing conditions or previous unreported cancers and compared the dose-response analyses with our original results. RESULTS: We obtained information from the RIS and death certificates for about 40% of the cohort (n∼180 000) and found cancer-predisposing conditions in 4 out of 74 leukaemia/myelodysplastic syndrome (MDS) cases and 13 out of 135 brain tumour cases. As these conditions were unrelated to CT exposure, exclusion of these participants did not alter the dose-response relationships. We found evidence of previous unreported cancers in 2 leukaemia/MDS cases, 7 brain tumour cases and 232 in non-cases. These previous cancers were related to increased number of CTs. Exclusion of these cancers reduced the excess relative risk per mGy by 15% from 0.036 to 0.033 for leukaemia/MDS (P-trend=0.02) and by 30% from 0.023 to 0.016 (P-trend<0.0001) for brain tumours. When we included pathology reports we had additional clinical information for 90% of the cases. Additional exclusions from these reports further reduced the risk estimates, but this sensitivity analysis may have underestimated risks as reports were only available for cases. CONCLUSIONS: Although there was evidence of some bias in our original risk estimates, re-analysis of the cohort with additional clinical data still showed an increased cancer risk after low-dose radiation exposure from CT scans in young patients.

Ewing Sarcoma: Current Management and Future Approaches Through Collaboration.

Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at any age with a peak incidence in adolescents and young adults. The treatment of ES relies on a multidisciplinary approach, coupling risk-adapted intensive neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between pediatric and medical oncologists. Successive first-line trials addressed the efficacy of various cyclic combinations of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin and identified prognostic factors now used to tailor therapies. The role of high-dose chemotherapy is still debated. Current 5-year overall survival for patients with localized disease is 65% to 75%. Patients with metastases have a 5-year overall survival < 30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrence have a dismal prognosis. The many insights into the biology of the EWS-FLI1 protein in the initiation and progression of ES remain to be translated into novel therapeutic strategies. Current options and future approaches will be discussed.

Socioeconomic patterning in the incidence and survival of children and young people diagnosed with malignant melanoma in northern England.

Previous studies have found marked increases in melanoma incidence. The increase among young people in northern England was especially apparent among females. However, overall 5-year survival has greatly improved. The present study aimed to determine whether socioeconomic factors may be involved in both etiology and survival. All 224 cases of malignant melanoma diagnosed in patients aged 10-24 years during 1968-2003 were extracted from a specialist population-based regional registry. Negative binomial regression was used to examine the relationship between incidence and area-based measures of socioeconomic deprivation and small-area population density. Cox regression was used to analyze the relationship between survival and deprivation and population density. There was significantly decreased risk associated with living in areas of higher unemployment (relative risk per 1% increase in unemployment=0.93; 95% confidence interval (CI) 0.90-0.96, P<0.001). Survival was better in less deprived areas (hazard ratio (HR) per tertile of household overcrowding=1.52; 95% CI 1.05-2.20; P=0.026), but this effect was reduced in the period 1986-2003 (HR=0.61; 95% CI 0.40-0.92; P=0.018). This study found that increased risk of melanoma was linked with some aspects of greater affluence. In contrast, worse survival was associated with living in a more deprived area.

Is fluoride a risk factor for bone cancer? Small area analysis of osteosarcoma and Ewing sarcoma diagnosed among 0-49-year-olds in Great Britain, 1980-2005.

BACKGROUND: Artificial fluoridation of drinking water to improve dental health has long been a topic of controversy. Opponents of this public health measure have cited the possibility of bone cancer induction. The study objective was to examine whether increased risk of primary bone cancer was associated with living in areas with higher concentrations of fluoride in drinking water. METHODS: Case data on osteosarcoma and Ewing sarcoma, diagnosed at ages 0-49 years in Great Britain (GB) (defined here as England, Scotland and Wales) during the period 1980-2005, were obtained from population-based cancer registries. Data on fluoride levels in drinking water in England and Wales were accessed through regional water companies and the Drinking Water Inspectorate. Scottish Water provided data for Scotland. Negative binomial regression was used to examine the relationship between incidence rates and level of fluoride in drinking water at small area level. RESULTS: The study analysed 2566 osteosarcoma and 1650 Ewing sarcoma cases. There was no evidence of an association between osteosarcoma risk and fluoride in drinking water [relative risk (RR) per one part per million increase in the level of fluoride = 1·001; 90% confidence interval (CI) 0·871, 1·151] and similarly there was no association for Ewing sarcoma (RR = 0·929; 90% CI 0·773, 1·115). CONCLUSIONS: The findings from this study provide no evidence that higher levels of fluoride (whether natural or artificial) in drinking water in GB lead to greater risk of either osteosarcoma or Ewing sarcoma.

CT Scans in Young People in Great Britain: Temporal and Descriptive Patterns, 1993-2002.

Background. Although using computed tomography (CT) can be greatly beneficial, the associated relatively high radiation doses have led to growing concerns in relation to potential associations with risk of future cancer. Very little has been published regarding the trends of CT use in young people. Therefore, our objective was to assess temporal and other patterns in CT usage among patients aged under 22 years in Great Britain from 1993 to 2002. Methods. Electronic data were obtained from the Radiology Information Systems of 81 hospital trusts within Great Britain. All included patients were aged under 22 years and examined using CT between 1993 and 2002, with accessible radiology records. Results. The number of CT examinations doubled over the study period. While increases in numbers of recorded examinations were seen across all age groups, the greatest increases were in the older patients, most notably those aged 15-19 years of age. Sixty percent of CT examinations were of the head, with the percentages varying with calendar year and patient age. Conclusions. In contrast to previous data from the North of England, the doubling of CT use was not accompanied by an increase in numbers of multiple examinations to the same individual.

Small-area analyses of bone cancer diagnosed in Great Britain provide clues to aetiology.

BACKGROUND: The aetiology of bone cancers is poorly understood. This study examined geographical patterning in incidence of primary bone cancers diagnosed in 0-49 year olds in Great Britain during 1980-2005 to provide information on factors linked with disease development. We investigated putative associations with deprivation and population density. METHODS: Data on osteosarcoma and Ewing sarcoma were obtained from national population-based registries. Negative binomial regression was used to examine the relationship between incidence rates and the Townsend deprivation score (and its component variables) and small-area population density. RESULTS: The study analyzed 2566 osteosarcoma and 1650 Ewing sarcoma cases. For females with osteosarcoma, statistically significant decreased risk was associated with higher levels of deprivation (relative risk [RR] per unit increase in deprivation score = 0.969; 95% confidence interval [CI] 0.946-0.993). For all Ewing sarcoma combined, statistically significant decreased risk was associated with greater area-level population density and higher levels of non-car ownership (RR per person per hectare increase = 0.984; 95% CI 0.976-0.993, RR per 1% increase in non-car ownership = 0.994; 95% CI 0.991-0.998). CONCLUSIONS: Higher incidence of osteosarcoma was observed for females in areas with lower deprivation levels indicating increased risk is linked to some aspect of affluent living. Higher incidence of Ewing sarcoma occurred in areas of low population density and where more people owned cars, both characteristic of rural environments. The study adds substantially to evidence associating Ewing sarcoma risk with rural environmental exposures. Putative risk factors include agricultural exposures, such as pesticides and zoonotic agents.

Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study.

BACKGROUND: Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults. METHODS: In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT. FINDINGS: During follow-up, 74 of 178,604 patients were diagnosed with leukaemia and 135 of 176,587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005-0·120; p=0·0097) and brain tumours (0·023, 0·010-0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46-6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50-74 mGy (mean dose 60·42 mGy) was 2·82 (1·33-6·03). INTERPRETATION: Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10,000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate. FUNDING: US National Cancer Institute and UK Department of Health.

How the Newcastle Thousand Families birth cohort study has contributed to the understanding of the impact of birth weight and early life socioeconomic position on disease in later life.

Much has been made of the potential influence of birth weight and early socioeconomic disadvantage in influencing adult health, but little has been published in terms of how important these associations may be with respect to exposures throughout the lifecourse. The objective of this review is to describe the contributions of the Newcastle Thousand Families Study in understanding the relative impacts of factors in early life, particularly birth weight and socio-economic position at birth, in influencing health in later life. The Newcastle Thousand Families Study is a prospective birth cohort established in 1947. It originally included all births to mothers resident in Newcastle upon Tyne, in northern England, in May and June of that year. Study members were followed extensively throughout childhood and intermittently in adulthood. At the age of 49-51 years, study members underwent a large-scale follow-up phase enabling an assessment of how early life may influence their later health, and also incorporating adult risk factors which enabled the relative contributions of factors at different stages of life to be assessed. While some findings from the study do support birth weight and early socio-economic position having influences on adult health status, the associations are generally small when compared to risk factors later in life. Using path analyses on longitudinal data of this nature enables mediating pathways between early life and later health to be assessed and if more studies were to take this approach, the relative importance of early life on adult disease risk could be better understood.

Socio-economic variation in CT scanning in Northern England, 1990-2002.

BACKGROUND: Socio-economic status is known to influence health throughout life. In childhood, studies have shown increased injury rates in more deprived settings. Socio-economic status may therefore be related to rates of certain medical procedures, such as computed tomography (CT) scans. This study aimed to assess socio-economic variation among young people having CT scans in Northern England between 1990 and 2002 inclusive. METHODS: Electronic data were obtained from Radiology Information Systems of all nine National Health Service hospital Trusts in the region. CT scan data, including sex, date of scan, age at scan, number and type of scans were assessed in relation to quintiles of Townsend deprivation scores, obtained from linkage of postcodes with census data, using χ2 tests and Spearman rank correlations. RESULTS: During the study period, 39,676 scans were recorded on 21,089 patients, with 38,007 scans and 19,485 patients (11344 male and 8132 female) linkable to Townsend scores. The overall distributions of both scans and patients by quintile of Townsend deprivation scores were significantly different to the distributions of Townsend scores from the census wards included in the study (p < 0.0001). There was a significant association between type of scan and deprivation quintile (p < 0.0001), primarily due to the higher proportions of head scans in the three most deprived quintiles, and slightly higher proportions of chest scans and abdomen and pelvis scans in the least deprived groups. There was also a significant association (p < 0.0001) between the patient's age at the time of the CT scan and Townsend deprivation quintiles, with slightly increasing proportions of younger children with increasing deprivation. A similar association with age (p < 0.0001) was seen when restricting the data to include only the first scan of each patient. The number of scans per patient was also associated with Townsend deprivation quintiles (p = 0.014). CONCLUSIONS: Social inequalities exist in the numbers of young people undergoing CT scans with those from deprived areas more likely to do so. This may reflect the rates of injuries in these individuals and implies that certain groups within the population may receive higher radiation doses than others due to medical procedures.

Seasonality in the incidence of cervical carcinoma in teenagers and young adults in Northern England, 1968-2005.

Infection with human papillomavirus is an established risk factor for cervical carcinoma. However, the role of other environmental factors is less well established. To further investigate whether other agents may be involved, the authors have analyzed seasonal variation in cervical cancer with respect to month of birth and separately month of diagnosis. All 85 cases diagnosed in 15-24-yr-olds during the period 1968-2005 were extracted from the specialist population-based Northern Region Young Persons' Malignant Disease Registry. The chi-square heterogeneity test was used to assess overall nonuniform variation in month of birth and separately month of diagnosis. Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data using month of birth and month of diagnosis in separate models. Based on month of birth, there was statistically significant heterogeneity (p=.03) and a significant sinusoidal pattern, with an incidence peak involving births in the autumn months (p=.03). Based on month of diagnosis, there was marginally significant heterogeneity (p=.06). The evidence of seasonal variation around time of birth for cervical carcinoma is highly novel and suggests possible early etiological involvement of environmental factors.

CT scans in young people in Northern England: trends and patterns 1993-2002.

BACKGROUND: Although CT can be greatly beneficial, its relatively high radiation doses have caused public health concerns. OBJECTIVE: To assess patterns in CT usage among patients aged less than 22 years in Northern England during the period 1993-2002. MATERIALS AND METHODS: Electronic data were obtained from radiology information systems of all nine National Health Service trusts in the region. RESULTS: A total of 38,681 scans had been performed in 20,483 patients aged less than 22 years. The number of CT examinations rose, with the steepest increase between 1997 and 2000. The number of patients scanned per year increased less dramatically, with 2.24/1,000 population aged less than 22 years having one scan or more in 1993 compared to 3.54/1,000 in 2002. This reflects an increase in the median number of scans per patient, which rose from 1 in 1993 to 2 by 1999. More than 70% of CT examinations were of the head, with the number of head examinations varying with time and patient age. CONCLUSION: The frequency of CT scans in this population more than doubled during the study period. This is partly, but not wholly, explained by an increase in the number of scans per patient.

Height at diagnosis and birth-weight as risk factors for osteosarcoma.

OBJECTIVES: Osteosarcoma typically occurs during puberty. Studies of the association between height and/or birth-weight and osteosarcoma are conflicting. Therefore, we conducted a large pooled analysis of height and birth-weight in osteosarcoma. METHODS: Patient data from seven studies of height and three of birth-weight were obtained, resulting in 1,067 cases with height and 434 cases with birth-weight data. We compared cases to the 2000 US National Center for Health Statistics Growth Charts by simulating 1,000 age- and gender-matched controls per case. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between height or birth-weight and risk of osteosarcoma for each study were estimated using logistic regression. All of the case data were combined for an aggregate analysis. RESULTS: Compared to average birth-weight subjects (2,665-4,045 g), individuals with high birth-weight (≥ 4,046 g) had an increased osteosarcoma risk (OR 1.35, 95% CI 1.01-1.79). Taller than average (51st - 89th percentile) and very tall individuals (≥ 90th percentile) had an increased risk of osteosarcoma (OR 1.35, 95% CI 1.18-1.54 and OR 2.60, 95% CI 2.19-3.07, respectively; P (trend) < 0.0001). CONCLUSIONS: This is the largest analysis of height at diagnosis and birth-weight in relation to osteosarcoma. It suggests that rapid bone growth during puberty and in utero contributes to OS etiology.

Glomerular toxicity persists 10 years after ifosfamide treatment in childhood and is not predictable by age or dose.

BACKGROUND: This prospective longitudinal single institution cohort study evaluated the natural history of and risk factors for chronic nephrotoxicity 10 years after ifosfamide treatment in childhood. PROCEDURE: Twenty-five patients (16 males) treated with ifosfamide were investigated at end of treatment (End), 1 and 10 years later. Glomerular filtration rate (GFR), serum phosphate (PO4) and bicarbonate (HCO3) and renal tubular threshold for phosphate (Tmp/GFR) were measured, and total nephrotoxicity score (Ns) graded. RESULTS: More patients had a low GFR at 1 (72%) and 10 (50%) years than at End (26%) (P = 0.006 for End vs. 1 year). Electrolyte supplementation requirements for tubular toxicity resolved by 10 years (0% vs. 32% at End and 24% at 1 year; both P < 0.05). At 10 years, 17% of patients had moderate overall nephrotoxicity and 13% clinically significant reduction of GFR (<60 ml/min/1.73 m2). Neither dose nor age at treatment predicted any measure of toxicity at 10 years or reduced GFR at any timepoint. Higher cumulative ifosfamide dose correlated with greater tubular and overall nephrotoxicity at End and/or 1 year (P < 0.05 for each of PO4, HCO3, Tmp/GFR, Ns), but age at treatment did not differ between patients with normal or abnormal results. CONCLUSIONS: Although clinically significant tubular toxicity had resolved by 10 years, GFR was <60 ml/min/1.73 m2 in 13% of patients, raising concerns about very long-term glomerular function. Higher cumulative dose was associated with greater tubular and overall toxicity at End and 1 year, but not at 10 years. Age at treatment did not predict nephrotoxicity at any timepoint.

Season of birth and diagnosis for childhood cancer in Northern England, 1968-2005.

The aim of this study was to investigate seasonal variation in the incidence of cancer in children aged 0-14 years. Details of 2959 primary malignant cases (1659 males, 1300 females), diagnosed during the period 1968-2005, were extracted from a specialist registry (the Northern Region Young Persons' Malignant Disease Registry). Seasonal variation was analysed with respect to month of birth and diagnosis. The chi-squared heterogeneity test was used to test for non-uniform variation. Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data, using month of birth and month of diagnosis, respectively, as covariates in separate models. There was significant sinusoidal variation based on month of birth for acute lymphoblastic leukaemia (ALL) aged 1-6 years (P = 0.04; peak in March). For 0- to 14-year-old boys, there was statistically significant sinusoidal variation in month of birth for acute non-lymphocytic leukaemia (P = 0.04; peak in September) and astrocytoma (P = 0.03; peak in October). Based on month of diagnosis, there was statistically significant sinusoidal variation in girls for all lymphomas (P = 0.048; peak in March) and Hodgkin lymphoma (HL) (P = 0.005; peak in January), and in boys for osteosarcoma (P = 0.049; peak in October). This study confirms previous findings of seasonal variation around the month of birth for childhood ALL (at the peak ages) and provides further evidence of seasonal variation around month of birth for astrocytoma and around month of diagnosis for HL. The results are consistent with a role for environmental factors in the aetiology of these diagnostic groups. Further studies are needed to examine putative candidate agents.

Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial.

PURPOSE EWS-ETS fusion genes are the driving force in Ewing's sarcoma pathogenesis. Because of the variable breakpoint locations in the involved genes, there is heterogeneity in fusion RNA and protein architecture. Since previous retrospective studies suggested prognostic differences among patients expressing different EWS-FLI1 fusion types, the impact of fusion RNA architecture on disease progression and relapse was studied prospectively within the Euro-E.W.I.N.G. 99 clinical trial. PATIENTS AND METHODS Among 1,957 patients who registered before January 1, 2007, 703 primary tumors were accessible for the molecular biology study. Fusion type was assessed by polymerase chain reaction on frozen (n = 578) or paraffin-embedded materials (n = 125). The primary end point was the time to disease progression or relapse. Results After exclusion of noninformative patients, 565 patients were entered into the prognostic factor analysis comparing type 1 (n = 296), type 2 (n = 133), nontype 1/nontype 2 EWS-FLI1 (n = 91) and EWS-ERG fusions (n = 45). Median follow-up time was 4.5 years. The distribution of sex, age, tumor volume, tumor site, disease extension, or histologic response did not differ between the four fusion type groups. We did not observe any significant prognostic value of the fusion type on the risk of progression or relapse. The only slight difference was that the risk of progression or relapse associated with nontype 1/nontype 2 EWS-FLI1 fusions was 1.38 (95% CI, 0.96 to 2.0) times higher than risk associated with other fusion types, but it was not significant (P = .10). CONCLUSION In contrast to retrospective studies, the prospective evaluation did not confirm a prognostic benefit for type 1 EWS-FLI1 fusions.

Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: relevance of age and dose as risk factors.

PURPOSE: The long-term outcome of platinum-induced nephrotoxicity is unknown. This prospective single-centre longitudinal cohort study evaluated long-term changes following treatment in childhood. METHODS: 63 children treated with platinum (27 cisplatin, 24 carboplatin and 12 both) were studied at the end of treatment (End), 1 year and 10 years later. No child received ifosfamide. Glomerular filtration rate (GFR), serum calcium and magnesium (Mg) were measured, and total nephrotoxicity score (N(s)) was graded. RESULTS: There was no significant overall change in renal function over time in any treatment group (cisplatin, carboplatin or combined). Apart from marginally reduced median GFR (84 ml/min/1.73 m(2)) and Mg (0.68 mmol/l) at End of cisplatin, median GFR, Ca and Mg were normal at all times in each group. At 10 years, GFR was <60 ml/min/1.7 3m(2) in 11%, N(s) grade was severe in 15% and oral Mg supplements were required in 7% cisplatin patients. After cisplatin, older age at treatment was correlated with lower GFR at 10 years (p=0.005), and higher N(s) at End and 10 years (both p=0.02). After carboplatin treatment, older age was associated with lower GFR at all times, and with higher N(s) at End and 1 year (all p<0.03). Higher cisplatin dose rate (>40 mg/m(2)/day) was associated with higher N(s) at 1 year (p=0.02) and higher carboplatin dose with lower Mg at 1 year and with higher N(s) at 1 and 10 years (all p<0.008). CONCLUSIONS: Platinum nephrotoxicity did not change significantly over 10 years. Its severity was correlated to older age at treatment, and at some time points to higher cisplatin dose rate and higher cumulative carboplatin dose.

Geographical analysis of thyroid cancer in young people from northern England: evidence for a sustained excess in females in Cumbria.

A previous study found a thyroid cancer excess in Cumbria following the Chernobyl explosion, but did not analyse sex-specific effects. This study examines sex differences in the incidence of thyroid cancer. Ninety-five primary thyroid carcinomas (69 females, 26 males) diagnosed in those aged 0-24 during 1968-2005 were identified from the Northern Region Young Persons' Malignant Disease Registry. Age-standardised incidence rates (ASRs), rate ratios (RRs) and 95% confidence intervals (CIs) were calculated. For males, the ASR was 0.6 per million person-years during the pre-Chernobyl period (1968-1986), and was 1.8 per million person-years during the post-Chernobyl period (1987-2005). For females, the ASR was 2.4 pre-Chernobyl and was 3.9 post-Chernobyl. The previously noted excess in Cumbria was entirely confined to females (Cumbrian females: RR for post-Chernobyl compared with pre-Chernobyl=10.8; 95% CI: 1.4-85.3). These findings may be consistent with sex-specific differences in susceptibility to an environmental exposure, such as fallout from the Chernobyl nuclear accident.