Cancer risks for relatives of children with cancer.

We determined the extent and distribution of cancers in relatives of 379 children newly diagnosed with cancer. Family history was collected from 1,337 first-degree and 3,399 second-degree relatives and incidence compared with national age- and gender-specific rates. Overall, 14 children (3.7%) had a relative with a history of childhood cancer and 26 children (6.9%) had a first-degree relative with a history of cancer, with only one of these having an identifiable familial cancer syndrome. There was a higher than expected incidence of childhood cancer among first-degree relatives (parents and siblings) (standardized incidence ratio (SIR) 1.43; 95% CI 0.54-5.08). There was also a higher than expected incidence of adult cancers among first-degree relatives (SIR 1.45; 95% CI 0.93-2.21), particularly in females (SIR 1.82; 95% CI 1.26-3.39). The increased family cancer history in first-degree females was largely attributable to an effect in mothers (SIR 1.78; 95% CI 1.27-3.33). The gender-specific association was reflected in higher than expected incidence rates of breast cancer in both mothers (SIR 1.92; 95% CI 0.72-6.83) and aunts (SIR 1.64; 95% CI 0.98-2.94). These findings support the hypothesis that previously undetected familial cancer syndromes contribute to childhood cancer.

Childhood and parental diagnostic radiological procedures and risk of childhood brain tumors.

PURPOSE: Childhood brain tumors (CBT) are the second most common type of childhood cancer and the leading cause of childhood cancer mortality. Few causes of CBT are known, but parental, fetal, and early life exposures are likely to be important given the early age at diagnosis of many cases. We aimed to investigate whether parents' diagnostic radiological procedures before conception, in the mother during pregnancy or the child's procedures were associated with an increased risk of CBT. METHODS: This population-based case-control study was conducted between 2005 and 2010. Cases were identified through all ten Australian pediatric oncology centers, and controls via nationwide random-digit dialing; frequency-matched to cases on age, sex and state of residence. Information on radiological exposures in the time periods of interest was obtained for 306 case and 950 control families through mailed questionnaires. Analysis used unconditional logistic regression, adjusting for matching variables and potential confounders. RESULTS: We found no evidence of positive associations between risk of CBT overall and childhood or parental pre-pregnancy radiological procedures. Increased ORs for high-grade gliomas associated with childhood radiological procedures were based on small numbers and may be due to chance. CONCLUSIONS: Given the evidence for an increased risk of CBT in cohort studies of computed tomography (CT) in childhood, the lack of such an association in our study may be due to the reduced intensity of CTs after 2001. Future research to investigate the safety of fetal exposure to more intense procedures like CT scans is needed.

Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia.

Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs). A meta-analysis of our findings with the published findings of previous studies was also conducted. The ORs for any professional pest control treatments were 1.19 (95% CI 0.83, 1.69) in the year before pregnancy, 1.30 (95% CI 0.86, 1.97) during pregnancy and 1.24 (95% CI 0.93, 1.65) for those done after the child's birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre-B than T cell ALL and for t(12;21) (ETV6-Runx-1) than other cytogenetic sub-types. The pooled OR from a meta-analysis of our study with three previous studies of professional pest control treatments during pregnancy was 1.37 (95% CI 1.00, 1.88). Our results, and those of our meta-analysis, provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the child's early years. The analysis of pooled data from international collaborations may provide more certainty regarding these potentially important associations.

Exercise echocardiography in asymptomatic survivors of childhood cancer treated with anthracyclines: a prospective follow-up study.

BACKGROUND: Exercise echocardiography reveals abnormalities in asymptomatic childhood cancer survivors who previously have been treated with anthracyclines. We determined the added value of monitoring childhood cancer survivors with exercise echocardiography compared to monitoring with resting echocardiography alone to predict anthracycline-induced cardiotoxicity. Secondary aims were to evaluate change in resting cardiac function over 10 years and to determine risk factors for late cardiotoxicity. PROCEDURE: We invited a cohort of 110 originally asymptomatic anthracycline-treated childhood cancer survivors, who had undergone cardiac tests including exercise echocardiography 10.5 years earlier, for new cardiac evaluation. Each subject underwent a resting echocardiogram at both evaluations. At first evaluation a repeat echocardiogram was performed following peak exercise. Resting echocardiographic parameters were converted to z-character. RESULTS: Ninety-two of 110 survivors (mean anthracycline dose 307 mg/m(2), mean follow-up time from start of treatment 8.2 years at first and 18.8 years at second evaluation) were evaluated prospectively. Mean resting fractional shortening z-character (RFSz) decreased from -0.18 to -0.93. Higher cumulative anthracycline dose was a risk factor for a lower RFSz at late follow-up (P = 0.0002). Adding exercise fractional shortening (XFS) to a model containing RFSz did not improve prediction of abnormal RFSz at late follow-up. CONCLUSIONS: Monitoring with exercise echocardiography has no added value to monitoring with resting echocardiography alone in predicting late anthracycline-induced cardiotoxicity in childhood cancer survivors. RFSz deteriorates over time, even in originally asymptomatic patients. Previous treatment with higher cumulative anthracycline dose is the main risk factor for a lower RFSz at late follow-up.

Impairments of attention following treatment with cranial irradiation and chemotherapy in children.

Neurobehavioral impairments are frequently reported following treatment for childhood cancers, with cranial irradiation (CRT). This study investigated attention and information processing skills, predicting that these skills would be impaired due to the vulnerability of cerebral white matter in early childhood. Three treatment groups were studied: (i) CRT+chemotherapy (n = 35); (ii) chemotherapy alone (n = 19); (iii) healthy children (n = 35). All children were aged 9 to 16 years at time of assessment, with no pre-diagnosis history of neurologic, developmental, or psychiatric disorder. Children were administered a series of task measuring processing speed and sustained, selective, and shifting attention. For children treated with CRT + chemo, results identified residual deficits in processing speed for complex tasks, selective and shifting attention. In contrast, processing speed was intact for simple tasks, and there was no clear evidence of deterioration in performance over time, as might be expected in the presence of a sustained attention deficit. Children treated with chemotherapy alone demonstrated generally intact attentional skills. However, this group did record an increasing number of attentional lapses over time on tasks tapping sustained attention skills.

Exercise echocardiography reflects cumulative anthracycline exposure during childhood.

BACKGROUND: Low and moderate dose anthracycline therapy used in current treatment protocols, may be associated with subclinical abnormalities of cardiac function and late presentation with congestive heart failure. Exercise echocardiography is a useful and non-invasive means of uncovering latent cardiac dysfunction in other settings. The purpose of this study is to determine whether exercise echocardiography has the potential to detect subclinical abnormalities of cardiac function in children treated with anthracyclines. PROCEDURE: One hundred ten children previously treated with anthracycline, in remission and off treatment for >12 months were assessed, together with 31 control subjects. Each subject had a resting ECG and echocardiogram performed, and following exercise on a treadmill according to the Bruce protocol, a repeat echocardiogram was performed. RESULTS: Cumulative anthracycline dose was the only patient variable related to any of the outcome measures. Resting fractional shortening was normal in the majority of treated patients but was inversely related to cumulative anthracycline dose (rate of decline 1.2%/100 mg/m(2)). Following peak exercise, the inverse relationship between fractional shortening and anthracycline dose was more pronounced (rate 2.7%/100 mg/m(2)). CONCLUSIONS: Higher anthracycline doses are associated with a greater difference in peak fractional shortening between treated subjects and controls. Exercise echocardiography is a simple, relatively inexpensive tool that may enhance the detection of latent cardiac dysfunction after anthracycline administration during childhood.

Health-related quality of life of children with acute lymphoblastic leukaemia: comparisons and correlations between parent and clinician reports.

The improving prognosis for children with cancer refocuses attention to long-term outcomes with an emphasis on quality of life. Few studies have examined relationships and differences in reported results between the parent, child and clinician. We examined parent-proxy and clinician-reported functional status and health-related quality of life for children and adolescents with acute lymphoblastic leukemia (ALL). Children and adolescents, 5-18 years, in the maintenance phase of treatment for ALL attending the Haematology/Oncology outpatient clinic at the Royal Children's Hospital, Melbourne, were eligible. Measures included: 1) parent-reported functional health and well-being (Child Health Questionnaire [CHQ]); 2) parent-reported condition specific quality of life (Pediatric Cancer Quality of Life inventory [PCQL]); 3) clinician ratings of physical and psychosocial health; and 4) clinical indicators. Insufficient numbers of older patients prohibited collection of adolescent self-reports. We had a 94% response and 31 participants. Mean time since diagnosis: 1.5 (SD 0.4) years. Parents reported significantly lower functioning and well-being than population norms for all CHQ scales, whereas cancer-specific quality of life was comparable to PCQL norms. Clinician reports of the child's global physical and psychosocial health were moderately associated with each other (r(s) = 0.56, p < 0.001), and with the parent-reported physical (r(s) = 0.47, p < 0.01) and psychosocial (r(s) = 0.56, p < 0.001) CHQ summary scores. Clinician reports of the child's psychosocial health were not associated with any clinical indicators reported regularly. The results demonstrate that the social, physical and emotional health and well-being of children with ALL is significantly poorer than the health of their community-based peers. Routinely collected indicators of clinical progress conceal the psychosocial burden of ALL. Data on health, well-being and quality of life can easily be incorporated into clinical care.