Long-term effects of radiation exposure among adult survivors of childhood cancer: results from the childhood cancer survivor study

In the last four decades, advances in therapies for primary cancers have improved overall survival for childhood cancer. Currently, almost 80% of children will survive beyond 5 years from diagnosis of their primary malignancy. These improved outcomes have resulted in a growing population of childhood cancer survivors. Radiation therapy, while an essential component of primary treatment for many childhood malignancies, has been associated with risk of long-term adverse outcomes. The Childhood Cancer Survivor Study (CCSS), a retrospective cohort of over 14,000 survivors of childhood cancer diagnosed between 1970 and 1986, has been an important resource to quantify associations between radiation therapy and risk of long-term adverse health and quality of life outcomes. Radiation therapy has been associated with increased risk for late mortality, development of second neoplasms, obesity, and pulmonary, cardiac and thyroid dysfunction as well as an increased overall risk for chronic health conditions. Importantly, the CCSS has provided more precise estimates for a number of dose-response relationships, including those for radiation therapy and development of subsequent malignant neoplasms of the central nervous system, thyroid and breast. Ongoing study of childhood cancer survivors is needed to establish long-term risks and to evaluate the impact of newer techniques such as conformal radiation therapy or proton-beam therapy.     

Apolipoprotein E genotyping in Turkish myocardial infarction survivors and healthy controls

The apolipoprotein (Apo) E gene is known to be polymorphic. Three common alleles determine six phenotypes which can easily be detected by restriction fragment length polymorphism. We performed apo E genotyping in myocardial infarction survivors and healthy controls for the first time in the Turkish population. DNA was amplified by polymerase chain reaction (PCR) and the PCR product was digested with restriction enzymesHhaI to detect apo E2, E3, E4 and withTaqI to detect apo E1. Relative allele frequency for the patient group was found to be 0.91 for E3, 0.07 for E2, 0.02 for E4 and for the control group 0.875 for E3, 0.067 for E2, 0.058 for E4.     

Obesity is underestimated using body mass index and waist-hip ratio in long-term adult survivors of childhood cancer

Objective

Obesity, represented by high body mass index (BMI), is a major complication after treatment for childhood cancer. However, it has been shown that high total fat percentage and low lean body mass are more reliable predictors of cardiovascular morbidity. In this study longitudinal changes of BMI and body composition, as well as the value of BMI and waist-hip ratio representing obesity, were evaluated in adult childhood cancer survivors.

Methods

Data from 410 survivors who had visited the late effects clinic twice were analyzed. Median follow-up time was 16 years (interquartile range 11–21) and time between visits was 3.2 years (2.9–3.6). BMI was measured and body composition was assessed by dual X-ray absorptiometry (DXA, Lunar Prodigy; available twice in 182 survivors). Data were compared with healthy Dutch references and calculated as standard deviation scores (SDS). BMI, waist-hip ratio and total fat percentage were evaluated cross-sectionally in 422 survivors, in who at least one DXA scan was assessed.

Results

BMI was significantly higher in women, without significant change over time. In men BMI changed significantly with time (ΔSDS = 0.19, P<0.001). Percentage fat was significantly higher than references in all survivors, with the highest SDS after cranial radiotherapy (CRT) (mean SDS 1.73 in men, 1.48 in women, P<0.001). Only in men, increase in total fat percentage was significantly higher than references (ΔSDS = 0.22, P<0.001). Using total fat percentage as the gold standard, 65% of female and 42% of male survivors were misclassified as non-obese using BMI. Misclassification of obesity using waist-hip ratio was 40% in women and 24% in men.

Conclusions

Sixteen years after treatment for childhood cancer, the increase in BMI and total fat percentage was significantly greater than expected, especially after CRT. This is important as we could show that obesity was grossly underestimated using BMI and waist-hip ratio.     

Nonsuicidal self-harm in youth: a population-based survey

Background

Nonsuicidal self-harm includes cutting, scratching, burning and minor overdosing. There have been few studies that have examined the rate of self-harm and mental-health correlates among community-based youth. We performed a population-based study to determine the prevalence of nonsuicidal self-harm, its mental-health correlates and help-seeking behaviour.

Methods

We used data from the Victoria Healthy Youth Survey, a population-based longitudinal survey of youth aged 14–21 in Victoria, British Columbia. The survey included questions about the history, method, frequency, age of onset and help-seeking for nonsuicidal self-harm. Youth were interviewed between February and June 2005. Univariable group differences were analyzed using students t test for continuous data and χ² for binary or categorical data. Multivariate analyses were conducted by use of multivariate analysis of variance and logistic regression.

Results

Ninety-six of 568 (16.9%) youth indicated that they had ever harmed themselves. Self-injuries such as cutting, scratching and self-hitting were the most common forms of nonsuicidal self-harm (83.2%). The mean age of onset was 15.2 years. Of those who reported nonsuicidal self-harm, 56% had sought help for this behaviour. Participants who reported 5 or more symptoms (out of 6) in a given symptom category were more likely than those who reported less than 5 symptoms to report nonsuicidal self-harm for the following categories: depressive mood (odds ratio [OR] 2.18, confidence interval [CI] 1.28–3.7) and problems with regulation of attention, impulsivity and activity (OR 2.24, CI 1.33–3.76).

Interpretation

We found a high lifetime prevalence of nonsuicidal self-harm. Many mental-health symptoms were associated with this behaviour, particularly those with depressive mood and attention-related problems. Just over half of youth reported seeking help for nonsuicidal self-harm. Clinicians who encounter youth should be vigilant to assess for this behaviour in youth who present with mental health issues.Nonsuicidal self-harm includes behaviours such as self-cutting, scratching and burning, done without the conscious intent to take one''s life. Onset typically occurs between 14 and 24 years of age.^1,2 The most common reasons for this type of harm are regulation of affect (e.g., to reduce tension or relieve dysphoric feelings), but reasons may also include self-punishment, interpersonal reasons, sensation seeking and anti-dissociation mechanisms.³ Factors associated with nonsuicidal self-harm include being female, awareness of self harm in peers, family members who self harm, drug misuse, depression, anxiety, impulsivity, disruptive disorders and low self-esteem.^4,5 Suicide ideation and attempts are more likely to be reported among those with repeated nonsuicidal self-harm.⁶A definition of “deliberate self-harm,” which does not distinguish between suicidal and nonsuicidal intent, has been proposed by the Child and Adolescent Self-Harm in Europe research group and has been used in several school-based surveys of adolescents.^4,7 The prevalence self-harm has been studied in school-based surveys of adolescents and young adults.^4–6,8 The results of these surveys are of limited generalizability because the samples were restricted to schools in large urban centres. Thus, we performed a population-based survey of youth in western Canada to investigate nonsuicidal self-harm. Our objectives were to determine the rate of nonsuicidal self-harm among Canadian youth; to determine the mental-health factors associated with nonsuicidal self-harm; and to examine the help-seeking patterns for this behaviour.     

Minor physical anomalies in patients with schizophrenia, unaffected first-degree relatives, and healthy controls: a meta-analysis

Background

Minor physical anomalies (MPAs) have been found to be more prevalent in schizophrenia than control participants in numerous studies and may index a potential endophenotype for schizophrenia.

Aim

To quantitatively define the magnitude of the difference in total MPA scores between patients with schizophrenia and healthy controls; to determine the degree of manifestation in unaffected first-degree relatives compared to patients and controls; and to investigate the degree of sensitivity among individual MPA items.

Methods

A systematic search was conducted on the literature pertaining to MPAs in patients with schizophrenia and unaffected relatives. Effect sizes (Cohen''s d and odds ratios) and corresponding confidence intervals were combined using the Comprehensive Meta-Analysis software package.

Results

A large difference was found when examining 14 studies comprising 1207 patients with schizophrenia and 1007 healthy controls (d = 0.95, 95% CI = 0.63, 1.27). Six studies involving relatives of individuals with schizophrenia showed a medium effect size (d = 0.45, 95% CI = 0.29,0.62) between patients and relatives, but a small and non-significant effect size (d = 0.32, 95% CI = −0.08, 0.73) between relatives and controls. The majority of MPAs items showed significant odds ratios (1.26–9.86) in comparing patients and controls.

Conclusions

The findings indicate that medium effect size of MPAs have been demonstrated in patients with schizophrenia as compared to healthy controls, and to a lesser extent in unaffected relatives. These findings are consistent with the idea that MPAs may represent a putative endophenotype for schizophrenia. However, more research including first-degree family members is warranted.     

Perceptions of e-cigarette harm among cancer survivors: Findings from a nationally representative survey

BackgroundThe growth in e-cigarette use may be driven by the perception that they are a safer, healthier alternative to conventional cigarettes. However, their long-term health implications are not well known and use is discouraged by most cancer societies. It is currently unclear how cancer survivors perceive the risks associated with e-cigarette and how this may influence use in this population.MethodsA cross-sectional analysis was conducted using the Health Information National Trends Survey (HINTS) (Years 2017–2019). Our primary study outcome was the perception of harm associated with e-cigarettes compared to traditional cigarettes among adults with and without a self-reported history of cancer. We used logistic regression analyses assessing the association of a cancer history with the perception that e-cigarettes are as much or more harmful than cigarettes.ResultsA total of 11,846 respondents (weighted population estimate 243,728,483) were included. Of these, 26.6% reported a history of cancer. The proportion of cancer survivors who perceived e-cigarettes to be as much or more harmful than conventional cigarettes was similar to non-cancer respondents (70.6% vs 68.3%, P = 0.35). There was no difference in perception of harm among cancer and non-cancer respondents, adjusted for sociodemographic factors (OR 0.82, 95% CI 0.6–1.1). Past (OR 9.06, 95% Cl 5.06–16.20) and never e-cigarette use (OR 23.40, 95% Cl 13.56–40.38) as well as having a history of cardiopulmonary disease (OR 1.28, 95% Cl 1.05–1.56) was associated with higher odds of perceiving e-cigarettes to be as much or more harmful.ConclusionCancer survivors commonly perceive e-cigarettes to be as much or more harmful than traditional cigarettes though these findings are similar to perceptions among adults without a history of cancer. There is a strong association with avoidance of e-cigarette products among those who perceive them to be harmful.     

Informal education and health promoting approaches in adult cancer survivors

This review looks at the available data relating to the informal education aspects and other health promoting approaches applied by adult cancer survivors to reduce the risk of cancer. The implications of such behavioral interventions on oncology practice are discussed. We also highlight areas of future research to pursue. Available data show that many cancer survivors remain engaged in risky health behaviors post-diagnosis, which are associated with an increased risk of disease's recurrence. However, over the last years patients seem to increasingly receive adequate risk-based medical care. The application of appropriate informal education approaches, such as diet, exercise, and cessation of former unhealthy habits, such as smoking and alcohol has facilitated behavioral changes in cancer survivors, thoroughly improving their well being and overall quality of life (QOL). Most of the research studies published to date have applied structured lifestyle interventions on intensive, individualized counseling sessions delivered by trained personnel or psychosocial-based mediations and reported that these approaches are largely effective in promoting the adoption of a healthier lifestyle in cancer survivors. These interventions have been reported to reduce the risk of cancer recurrence and thus to obtain an obvious positive impact on their well-being and overall QOL. However, there is still insufficient evidence to conclude and support with confidence the effectiveness of any of these behavioral interventions and therefore future interventions should be initiated to assess the long-term effects and validating outcomes of lifestyle and other psychosocial interventions.     

Upper extremity lymphatic function at rest and during exercise in breast cancer survivors with and without lymphedema compared with healthy controls.

Lymphoscintigraphy was used to measure lymphatic function at rest and during exercise in breast cancer survivors with lymphedema (BCRL, n = 10), breast cancer survivors (BC, n = 10), and controls (Cont, n = 10). After injection of (99m)Tc-antimony colloid to the hands, subjects rested or performed 12 repeated sets of arm cranking for 2.5 min at 0.6 W/kg followed by 2.5 min of rest. One-minute spot views were taken with a gamma-radiation camera immediately postinjection and every 10 min over 60 min to calculate clearance rate. As well, an upper body scan was taken at 65 min postinjection to measure radiopharmaceutical uptake in the axilla (Ax) and forearm (Fore). All groups displayed similar increases in clearance rate with exercise (P = 0.000). Ax significantly increased with exercise in Cont only [Cont: (mean +/- SD) 4.9 +/- 2.6 vs. 7.9 +/- 4.2%, P = 0.000; BCRL: 1.4 +/- 1.2 vs. 1.7 +/- 2.1%, P = 0.531; BC: 3.9 +/- 3.4 vs. 5.2 +/- 3.2%, P = 0.130], whereas Fore, indicating dermal backflow, significantly increased in BCRL only (BCRL: 2.4 +/- 0.87 vs. 4.4 +/- 2.0%, P = 0.004; BC: 1.1 +/- 0.25 vs. 1.1 +/- 0.31%, P = 0.784; Cont: 0.93 +/- 0.26 vs. 1.0 +/- 0.20%, P = 0.296). The results indicate that, in women with BCRL, exercise causes radiopharmaceuticals to clear from the hand at the same rate as BC and Cont, but, instead of reaching the axilla, a greater amount of activity gets trapped in the dermis of the forearm. BC, meanwhile, have similar lymphatic function as Cont; however, there is a highly variable response that may suggest that some BC subjects may be at risk for developing lymphedema.     

Comparison of racial differences in childhood cancer risk in case-control studies and population-based cancer registries

Introduction: Although selection bias in case-control studies has been studied extensively, little is known about selection of cases and controls among various ethnic groups. This study compares racial differences in childhood cancer rates as estimated by case-control studies with various design features. It also compares estimates of racial distribution among cases as reported by case-control studies to those observed for an ideal case series with complete ascertainment of cases for these studies or in population-based cancer registries in corresponding geographic regions and calendar periods. Methods: Peer-reviewed publications on childhood leukemia and brain tumors from North America, published between 1980 and 2007, were reviewed. Incidence data by race/ethnicity were compiled from research publications, federal cancer statistics, and cancer registries. Meta-analysis was conducted to assess racial/ethnic differences by study characteristics. Racial distributions of cases from published case-control studies were compared to those of a presumably noncensored case distribution (i.e. include both participating and non-participating cases in a case-control study) or cases recorded by cancer registries. Results: In interview-based case-control studies of childhood cancer, the proportion of Whites compared to non-Whites tended to be higher among controls than among cases; however, the opposite was true for record-based case-control studies. Additionally, the proportion of Whites tended to be higher among the participating cases in the published case-control studies compared to the proportion of Whites among the non-participating cases or in cancer registries. Conclusions: Investigators need to consider differential participation by racial group as a potential source of bias in the interpretation of case-control study results.     

Effects of childhood cancer on long-term survivors and their families.

Problems experienced by families of long-term survivors of acute lymphatic leukaemia and Wilms''s tumour were investigated to find out the best way of using limited resources to improve management of such patients. All patients had received treatment at Alder Hey Children''s Hospital, and all had completed treatment at least two years before the study. A social worker interviewed the parents of each child. The results showed that various aspects of management needed improvement, including: information given to parents at diagnosis of their child''s illness and during subsequent treatment; continuity of care and multidisciplinary teamwork among those caring for the child; greater understanding by school teachers that such children have the same educational needs as others; wider communication by hospital staff with the child''s other relatives, particularly grandparents; financial help for parents; and marital counselling. To help implement these proposals full-time social workers were attached to the hospital. Preliminary results were encouraging, though it is too early to evaluate the long-term effects of the changes.     

Reelin controls progenitor cell migration in the healthy and pathological adult mouse brain

Understanding the signals that control migration of neural progenitor cells in the adult brain may provide new therapeutic opportunities. Reelin is best known for its role in regulating cell migration during brain development, but we now demonstrate a novel function for reelin in the injured adult brain. First, we show that Reelin is upregulated around lesions. Second, experimentally increasing Reelin expression levels in healthy mouse brain leads to a change in the migratory behavior of subventricular zone-derived progenitors, triggering them to leave the rostral migratory stream (RMS) to which they are normally restricted during their migration to the olfactory bulb. Third, we reveal that Reelin increases endogenous progenitor cell dispersal in periventricular structures independently of any chemoattraction but via cell detachment and chemokinetic action, and thereby potentiates spontaneous cell recruitment to demyelination lesions in the corpus callosum. Conversely, animals lacking Reelin signaling exhibit reduced endogenous progenitor recruitment at the lesion site. Altogether, these results demonstrate that beyond its known role during brain development, Reelin is a key player in post-lesional cell migration in the adult brain. Finally our findings provide proof of concept that allowing progenitors to escape from the RMS is a potential therapeutic approach to promote myelin repair.     

Chromosomal abnormalities among offspring of childhood-cancer survivors in Denmark: a population-based study

Ionizing radiation and many cancer drugs have the potential to produce germ-cell mutations that might lead to genetic disease in the next generation. In a population-based study, we identified, from records in the Danish Cancer Registry, 4,676 children treated for cancer. Their 6,441 siblings provided a comparison cohort. The results of a search of the Central Population Register identified 2,630 live-born offspring of the survivors and 5,504 live-born offspring of their siblings. The occurrence of abnormal karyotypes diagnosed in these offspring and also in any pregnancies terminated following prenatal diagnosis of a chromosome abnormality was determined from the Danish Cytogenetic Registry. After exclusion of hereditary cases and inclusion of the prenatal cases, after correction for expected viability, the adjusted proportion of live-born children in survivor families with abnormal karyotypes (5.5/2,631.5 [0.21%]) was the same as that among the comparison sibling families (11.8/5,505.8 [0.21%]). There were no significant differences in the occurrence of Down syndrome (relative risk [RR]=1.07; 95% CI 0.16-5.47) or Turner syndrome (RR=1.32; 95% CI 0.17-7.96) among the children of cancer survivors, compared with the children of their siblings. These reassuring results are of importance to the survivors, to their families, and to genetic counselors.     

Genetic disease in offspring of long-term survivors of childhood and adolescent cancer.

Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P=.33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P=.49). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells.     

Level of daily physical activity in individuals with COPD compared with healthy controls

Background

Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality. COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue. Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults. COPD might worsen this scenario, but it is unclear to what degree. This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA). The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.

Results

A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar. After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA. Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA. The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%. Correlations of DPA and severity of the disease were low and/or not significant.

Conclusions

From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects. The intensity of DPA seems to be less affected by COPD than duration and counts. Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA. Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable.