Dietary quality, caloric intake, and adiposity of childhood cancer survivors and their siblings: an analysis from the cardiac risk factors in childhood cancer survivors study.

Childhood cancer survivors are at increased risk of cardiovascular disease, in part because of adiposity. Whether survivors have healthy diets and whether dietary quality is associated with adiposity among survivors are not known. Survivors and siblings from the Cardiac Risk Factors in Childhood Cancer Survivors Study completed 3-day food records that were used to estimate daily caloric intake relative to recommended and dietary quality using the Healthy Eating Index-2005 (HEI). Medical records were reviewed for cancer therapies. Body composition was measured by dual-energy x-ray absorptiometry. Of 91 childhood cancer survivors and 30 sibling controls, there were no marked differences in mean daily caloric intakes (98% vs. 100% of recommended) or HEI total scores (55.5 vs. 53.3), respectively, with both groups scoring worst for the consumption of dark green vegetables and whole grains. Survivors exposed to cranial irradiation had lower total HEI scores (-6.4, P = 0.01). Among survivors, better dietary quality, as reflected by the total HEI score, was associated with decreasing percent body fat (ß = -0.19, P = 0.04). Survivors consume diets similar to their siblings although these diets are only moderately adherent to current guidelines. Decreased dietary quality is associated with higher body fat and receipt of cranial irradiation in survivors.

Cranial irradiation as an additional risk factor for anthracycline cardiotoxicity in childhood cancer survivors: an analysis from the cardiac risk factors in childhood cancer survivors study.

Anthracycline-treated childhood cancer survivors experience cardiac damage that results in decreased left ventricular (LV) mass, leading to increased LV wall stress, which underlies their greater risk of cardiomyopathy. Many of these survivors also are at risk of growth hormone (GH) abnormalities from cranial irradiation exposure, although it is unknown whether such exposure is associated with cardiotoxicity. Echocardiograms and insulin-like growth factor-1 (IGF-1), a marker of GH, were measured in 130 anthracycline-treated childhood cancer survivors, 59 of whom had been exposed to cranial irradiation, a mean 10 years after their cancer diagnosis. Echocardiographic parameters and IGF-1 were standardized relative to age or body surface area using data from sibling control subjects and expressed as the percentage difference from normal values. The results showed that after adjustment for other risk factors, survivors exposed to cranial irradiation had an additional 12 % decrease in LV mass compared with unexposed survivors (P < 0.01) and an additional 3.6 % decrease in LV dimension (P = 0.03). Survivors exposed to cranial irradiation also had a 30.8 % decrease in IGF-1 relative to normal values, which was greater than the 10.5 % decrease in unexposed survivors (P < 0.01). The above findings led us to conclude that in anthracycline-treated childhood cancer survivors a mean 10 years after their diagnosis, those with cranial irradiation exposure had significantly greater decreases in LV mass and dimension. Because cranial irradiation also was associated with decreased IGF-1, it is possible that GH deficiencies mediated this effect, suggesting that GH replacement therapy may help to prevent the development of cardiotoxicity.

Aggregating traditional cardiovascular disease risk factors to assess the cardiometabolic health of childhood cancer survivors: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study.

BACKGROUND: Childhood cancer survivors are at increased risk of cardiovascular disease (CVD), which may be associated with traditional CVD risk factors. We used CVD risk aggregation instruments to describe survivor cardiometabolic health and compared their results with sibling controls. METHODS: Traditional CVD risk factors measured in 110 survivors and 31 sibling controls between 15 and 39 years old were aggregated using Pathobiological Determinants of Atherosclerosis in Youth (PDAY) scores and the Framingham Risk Calculator (FRC) and expressed as ratios. The PDAY odds ratio represents the increased odds of currently having an advanced coronary artery lesion, and the FRC risk ratio represents the increased risk of having a myocardial infarction, stroke, or coronary death in the next 30 years. Ratios are relative to an individual of similar age and sex without CVD risk factors. RESULTS: The median PDAY odds ratio for survivors was 2.2 (interquartile range 1.3-3.3), with 17% >4. The median FRC risk ratio was 1.7 (interquartile range 1.0-2.0), with 12% >4. Survivors and siblings had similar mean PDAY odds ratios (2.33 vs 2.29, P = .86) and FRC risk ratios (1.72 vs 1.53, P = .24). Cancer type and treatments were not associated with cardiometabolic health. There was a suggested association for physical inactivity with PDAY odds ratios (r = 0.17, P = .10) and FRC risk ratios (r = 0.19, P = .12). CONCLUSIONS: Cardiometabolic health is poor in childhood cancer survivors but not different than that of their siblings, highlighting the importance of managing traditional CVD risk factors and considering novel exposures in survivors.

Racial disparities in traumatic stress in prostate cancer patients: secondary analysis of a National URCC CCOP Study of 317 men.

INTRODUCTION: African American men have the highest rates of prostate cancer of any racial group, but very little is known about the psychological functioning of African American men in response to prostate cancer diagnosis and treatment. PURPOSE: In this secondary analysis of a national trial testing a psychological intervention for prostate cancer patients, we report on the traumatic stress symptoms of African American and non-African American men. METHODS: This analysis includes 317 men (African American: n = 30, 9%; non-African American: n = 287, 91%) who were enrolled in the intervention trial, which included 12 weeks of group psychotherapy and 24 months of follow-up. Using mixed model analysis, total score on the Impact of Events Scale (IES) and its Intrusion and Avoidance subscales were examined to determine mean differences in traumatic stress across all time points (0, 3, 6, 12, 18, and 24 months). In an additional analysis, relevant psychosocial, demographic, and clinical variables were added to the model. RESULTS: Results showed significantly higher levels of traumatic stress for African American men compared to non-African American men in all models independently of the intervention arm, demographics, and relevant clinical variables. African Americans also had a consistently higher prevalence of clinically significant traumatic stress symptoms (defined as IES total score ≥ 27). These elevations remained across all time points over 24 months. CONCLUSIONS: This is the first study to show a racial disparity in traumatic stress specifically as an aspect of overall psychological adjustment to prostate cancer. Recommendations are made for appropriate assessment, referral, and treatment of psychological distress in this vulnerable population.

Exercise, sleep quality, and mediators of sleep in breast and prostate cancer patients receiving radiation therapy.

Cancer patients often report impaired sleep quality. Impaired sleep quality may be due to increased levels of sleep-mediating cytokines resulting from cancer treatment. Exercise may have a positive influence on sleep-mediating cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and soluble tumor necrosis factor-alpha receptor (sTNF-R), which may improve sleep quality. This two-arm pilot study compared the influence of a home-based exercise intervention with standard care/control on sleep quality and mediators of sleep. Breast and prostate cancer patients (n = 38) beginning radiation therapy were randomized to a 4-week exercise program or no exercise arm. Global sleep quality, subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction were assessed with the Pittsburgh Sleep Quality Index. IL-6, TNF-α, and sTNF-R were measured before and after intervention. There was a greater improvement in sleep quality in the exercise group from pre- to postintervention, although the difference was not significant. Additionally, there were associations between IL-6 and sleep efficiency and duration, suggesting that regulation of sleep-mediating cytokines by exercise may mediate improvements in sleep-quality components.

Strategies to prevent anthracycline-induced cardiotoxicity in cancer survivors.

Cancer diagnostics and therapies have improved steadily over the last few decades, markedly increasing life expectancy for patients at all ages. However, conventional and newer anti-neoplastic therapies can cause short- and long-term cardiotoxicity. The clinical implications of this cardiotoxicity become more important with the increasing use of cardiotoxic drugs. The implications are especially serious among patients predisposed to adverse cardiac effects, such as youth, the elderly, those with cardiovascular comorbidities, and those receiving additional chemotherapies or thoracic radiation. However, the optimal strategy for preventing and managing chemotherapy-induced cardiotoxicity remains unknown. The routine use of neurohormonal antagonists for cardioprotection is not currently justified, given the marginal benefits and associated adverse events, particularly with long-term use. The only United States Food and Drug Administration and European Medicines Agency approved treatment for preventing anthracycline-related cardiomyopathy is dexrazoxane. We advocate administering dexrazoxane during cancer treatment to limit the cardiotoxic effects of anthracycline chemotherapy.

Leukaemia and myeloid malignancy among people exposed to low doses (<100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies.

BACKGROUND: Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less certain, although this is the dose range most relevant to the general population. We aimed to estimate the risk of leukaemia associated with low-dose radiation exposure in childhood (age <21 years). METHODS: In this analysis of historical cohort studies, we pooled eligible cohorts reported up to June 30, 2014. We evaluated leukaemia and myeloid malignancy outcomes in these cohorts with the relevant International Classification of Diseases and International Classification of Diseases for Oncology definitions. The cohorts included had not been treated for malignant disease, had reported at least five cases of the relevant haematopoietic neoplasms, and estimated individual active bone marrow (ABM) doses. We restricted analysis to individuals who were younger than 21 years at first irradiation who had mean cumulative ABM doses of less than 100 mSv. Dose-response models were fitted by use of Poisson regression. The data were received in fully anonymised form by the statistical analyst. FINDINGS: We identified nine eligible cohorts from Canada, France, Japan, Sweden, the UK, and the USA, including 262 573 people who had been exposed to less than 100 mSv enrolled between June 4, 1915, and Dec 31, 2004. Mean follow-up was 19·63 years (SD 17·75) and mean cumulative ABM dose was 19·6 mSv (SD 22·7). 154 myeloid malignancies were identified (which included 79 acute myeloid leukaemias, eight myelodysplastic syndromes, and 36 chronic myeloid leukaemias, in addition to other unspecified myeloid malignancies) and 40 acute lymphoblastic leukaemias, with 221 leukaemias (including otherwise unclassified leukaemias but excluding chronic lymphocytic leukaemia) identified overall. The fitted relative risks at 100 mSv were 3·09 (95% CI 1·41-5·92; ptrend=0·008) for acute myeloid leukaemia and myelodysplastic syndromes combined, 2·56 (1·09-5·06; ptrend=0·033) for acute myeloid leukaemia, and 5·66 (1·35-19·71; ptrend=0·023) for acute lymphoblastic leukaemia. There was no clear dose-response for chronic myeloid leukaemia, which had a relative risk at 100 mSv of 0·36 (0·00-2·36; ptrend=0·394). There were few indications of between-cohort heterogeneity or departure from linearity. For acute myeloid leukaemia and myelodysplastic syndromes combined and for acute lymphoblastic leukaemia, the dose-responses remained significant for doses of less than 50 mSv. Excess absolute risks at 100 mSv were in the range of 0·1-0·4 cases or deaths per 10 000 person-years. INTERPRETATION: The risks of acute myeloid leukaemia and acute lymphoblastic leukaemia were significantly increased after cumulative doses of ionising radiation of less than 100 mSv in childhood or adolescence, with an excess risk also apparent for cumulative radiation doses of less than 50 mSv for some endpoints. These findings support an increased risk of leukaemia associated with low-dose exposure to radiation and imply that the current system of radiological protection is prudent and not overly protective. FUNDING: National Cancer Institute Intramural Research Program, National Cancer Institute, and US National Institutes for Health.

Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts.

Context: The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and the radiosensitive thyroid gland. Objectives: Evaluation of relative risk (RR) trends for thyroid radiation doses <0.2 gray (Gy); evidence of a threshold dose; and possible modifiers of the dose-response, e.g., sex, age at exposure, time since exposure. Design and Setting: Pooled data from nine cohort studies of childhood external radiation exposure and thyroid cancer with individualized dose estimates, ≥1000 irradiated subjects or ≥10 thyroid cancer cases, with data limited to individuals receiving doses <0.2 Gy. Participants: Cohorts included the following: childhood cancer survivors (n = 2); children treated for benign diseases (n = 6); and children who survived the atomic bombings in Japan (n = 1). There were 252 cases and 2,588,559 person-years in irradiated individuals and 142 cases and 1,865,957 person-years in nonirradiated individuals. Intervention: There were no interventions. Main Outcome Measure: Incident thyroid cancers. Results: For both <0.2 and <0.1 Gy, RRs increased with thyroid dose (P < 0.01), without significant departure from linearity (P = 0.77 and P = 0.66, respectively). Estimates of threshold dose ranged from 0.0 to 0.03 Gy, with an upper 95% confidence bound of 0.04 Gy. The increasing dose-response trend persisted >45 years after exposure, was greater at younger age at exposure and younger attained age, and was similar by sex and number of treatments. Conclusions: Our analyses reaffirmed linearity of the dose response as the most plausible relationship for "as low as reasonably achievable" assessments for pediatric low-dose radiation-associated thyroid cancer risk.

Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies.

Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.

Cardiovascular status in long-term survivors of Hodgkin's disease treated with chest radiotherapy.

PURPOSE: Cardiovascular status was assessed in 48 Hodgkin's disease (HD) survivors at a median of 14.3 years (range, 5.9 to 27.5 years) after diagnosis because they may be at increased risk for cardiovascular abnormalities. PATIENTS AND METHODS: Patients completed the Short-Form 36 quality-of-life instrument and were screened by echocardiography, exercise stress testing, and resting and 24-hour ECG. RESULTS: All patients received mediastinal irradiation (median, 40.0 Gy; range, 27.0 to 51.7 Gy) at a median age of 16.5 years (range, 6.4 to 25.0 years). Four patients received an anthracycline. Although every patient described their health as good or better, and none had symptomatic heart disease at screening, all but one had cardiac abnormalities on screening. Restrictive cardiomyopathy was suggested by reduced average left ventricular (LV) dimension (P < .001) and mass (P < .001), without increased LV wall thickness. Significant valvular defects were present in 42%; 75% had conduction defects. One survivor developed complete heart block shortly after the study visit. Autonomic dysfunction was suggested by a monotonous heart rate in 57%, persistent tachycardia in 31%, and blunted hemodynamic responses to exercise in 27%. Peak oxygen uptake (VO2max) during exercise, a predictor of mortality in heart failure, was significantly reduced (< 20 mL/kg/m2) in 30% of survivors. VO2max was correlated with increasing fatigue, increasing shortness of breath (both, r = -0.35; P =. 02), and decreasing physical component score on the SF-36 (r = 0.554; P = .00017). CONCLUSION: A variety of unsuspected, clinically significant cardiovascular abnormalities are common in long-term survivors of HD who are treated at a young age with mediastinal irradiation. We recommend serial, comprehensive cardiac screening of HD survivors who fit this profile.

Radiation-associated cardiovascular disease.

As the number of cancer survivors grows because of advances in therapy, it has become more important to understand the long-term complications of these treatments. This article presents the current knowledge of adverse cardiovascular effects of radiotherapy to the chest. Emphasis is on clinical presentations, recommendations for follow-up, and treatment of patients previously exposed to irradiation. Medline literature searches were performed, and abstracts related to this topic from oncology and cardiology meetings were reviewed. Potential adverse effects of mediastinal irradiation are numerous and can include coronary artery disease, pericarditis, cardiomyopathy, valvular disease and conduction abnormalities. Damage appears to be related to dose, volume and technique of chest irradiation. Effects may initially present as subclinical abnormalities on screening tests or as catastrophic clinical events. Estimates of relative risk of fatal cardiovascular events after mediastinal irradiation for Hodgkin's disease ranges between 2.2 and 7.2 and after irradiation for left-sided breast cancer from 1.0 to 2.2. Risk is life long, and absolute risk appears to increase with length of time since exposure. Radiation-associated cardiovascular toxicity may in fact be progressive. Long-term cardiac follow-up of these patients is therefore essential, and the range of appropriate cardiac screening is discussed, although no specific, evidence-based screening regimen was found in the literature.

Radiation-associated cardiovascular disease: manifestations and management.

Irradiation of the heart incidental to the treatment of malignancies can cause a spectrum of cardiovascular complications. These include pericarditis, myocardial fibrosis, muscular dysfunction, valvular abnormalities, and conduction disturbances. Survivors of Hodgkin's disease and breast cancer survivors treated with radiotherapy after mastectomy appear to be the groups at highest risk for radiation-associated cardiovascular disease. Although modern techniques of chest radiotherapy have decreased its frequency by reducing the dose and volume of radiation exposure to the heart, survivors treated with radiation remain at increased risk of cardiovascular disease. The risk of fatal cardiovascular disease increases with younger age at treatment, longer follow-up, and higher dose volumes of exposure to the heart. Certain chemotherapeutic agents, such as anthracyclines, also increase the risk of damage to the heart. Cardiac damage associated with radiotherapy may be progressive. Screening of survivors may help identify those at highest risk for serious cardiovascular disease. The broad range of radiation-associated cardiovascular disease makes it necessary for survivors to be examined with multiple screening modalities, although data do not exist to support definitive recommendations on test frequency.

Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy.

PURPOSE: To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status. METHODS: We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls. RESULTS: The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 µU/mL, respectively, v 8.2 µU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons). CONCLUSION: Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.

A pooled analysis of thyroid cancer incidence following radiotherapy for childhood cancer.

Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors.

Characteristics and determinants of adiposity in pediatric cancer survivors.

BACKGROUND: Adiposity and the diseases associated with it, including cardiovascular disease, are emerging long-term complications of pediatric cancer survivors. Direct evaluations of adiposity and comparisons to contemporary controls that can differentiate recent trends in obesity from cancer-related treatments and sequelae are limited. METHODS: We evaluated demographic, treatment, lifestyle, and endocrine factors at the time of dual-energy X-ray absorptiometry testing in 170 non-Hispanic white survivors and 71 sibling controls, and compared three measures of adiposity [body mass index (BMI), total body fat, and trunk fat]. For the survivors alone, we determined factors independently associated with BMI and body fat. RESULTS: Survivors were at 12 years since diagnosis; 58% had leukemia or lymphoma. BMI did not differ between groups. Among males, body fat was greater in survivors than in controls (25.8% versus 20.7%; P = 0.007), as was trunk fat (26.7% versus 21.3%; P = 0.008). Total or trunk fat did not differ among females. Cholesterol, triglycerides, low-density lipoprotein cholesterol, and television viewing hours were higher among male survivors than in controls. Independent factors associated with higher BMI and total and trunk fat included any cranial radiation and television viewing hours, whereas prior treatment with cyclophosphamide was associated with lower BMI and body fat measures. CONCLUSIONS: Compared with siblings, male survivors have greater body fat and metabolic risks. Cranial irradiation and television hours are important risk factors for adiposity in pediatric cancer survivors. IMPACT: Pediatric cancer survivors should be carefully monitored for cardiovascular risk factors and sedentary lifestyles.

Breast cancer risk 55+ years after irradiation for an enlarged thymus and its implications for early childhood medical irradiation today.

BACKGROUND: Radiotherapy during childhood increases long-term cancer risk, but the risk from radiation as a result of relatively higher dose diagnostic procedures remains less well known. This study, which evaluates breast cancer incidence in a cohort treated with "lower dose" chest radiotherapy over 50 years ago, can assist with estimating lifetime breast cancer risk in young children exposed to radiation from procedures such as chest computed tomography (CT) or treatment with recent "lower dose" chest radiotherapy protocols. METHODS: A population-based, longitudinal cohort of subjects exposed to thymic irradiation during infancy from 1926 to 1957 and of their unexposed siblings was re-established. Previously followed until 1987, we resurveyed cohort members from 2004 to 2008. Poisson regression models compared breast cancer incidence rates between women in the cohort by treatment and dose category groups. RESULTS: Breast cancer occurred in 96 treated (mean breast dose, 0.71 Gy) and 57 untreated women during 159,459 person-years of follow-up. After adjusting for attained age and treatment/birth cohort, the rate ratio was 3.01 (2.18-4.21). The adjusted excess relative risk per Gy was 1.10 (95% confidence interval, 0.61-1.86). Traditional breast cancer risk factors did not contribute significantly to multivariate model fit. CONCLUSION: Our results show that at radiation doses between those received by the breast from chest CT and cancer therapy during early childhood, breast cancer incidence rates remain elevated >50 years after exposure. This implies that increased breast cancer risk will remain a lifelong concern in females treated during childhood with currently reduced radiotherapy doses and for infants receiving multiple chest CTs.

A population-based cohort study of occupational exposure to magnetic fields and cardiovascular disease mortality.

PURPOSE: This cohort study aims to examine cardiovascular disease (CVD) mortality risks among workers in occupations potentially exposed to magnetic fields (MF). METHODS: Risks for major CVD mortality by potential job-related MF exposure were examined in a sample of U.S. workers from the National Longitudinal Mortality Study using multivariate proportional hazards models. RESULTS: After adjustment for demographic factors, there were no significant excess risks between individuals with medium (0.15 to <0.20 microT), high (0.20 to < 0.30 microT), or very high (>/= 0.30 microT) exposure levels as compared with individuals with background exposure levels of MF (<0.15 microT) for the CVD mortality outcomes. Indirect adjustment for potential confounding by current smoking prevalence did not change the pattern of these results. CONCLUSION: Our study does not provide evidence for an association between occupational MF exposure and CVD mortality risk.

The effect of modafinil on cognitive function in breast cancer survivors.

BACKGROUND: The authors conducted a randomized clinical trial examining the effects of modafinil in reducing persistent fatigue in patients after treatment for cancer and performed secondary analyses to assess the effect of modafinil on cognitive function. METHODS: Breast cancer patients who reported a score of >or=2 on the Brief Fatigue Inventory were enrolled in the study. In phase 1 (P1), patients received 200 mg modafinil open-label once daily for 4 weeks. In phase 2 (P2), patients with a positive response after P1 were randomized either to an additional 4 weeks of modafinil or to placebo. Tests of memory and attention selected from the Cognitive Drug Research (CDR) computerized cognitive assessment were performed at baseline (before modafinil) and after completing phases 1 and 2. The paired differences for each test score were subjected to a Wilcoxon signed rank test. RESULTS: Of the 82 women who were enrolled, 76 completed P1, and 68 completed all assessments in the study. Modafinil had a significant effect on the Speed of Memory (P = .0073) and Quality of Episodic Memory (P < .0001) during P1 of the study. After randomization at Week 8, those patients who continued modafinil demonstrated significantly greater improvement in Speed of Memory (P = .029), Quality of Episodic Memory (P = .0151), and mean Continuity of Attention (P = .0101) relative to the group that was switched to placebo. CONCLUSIONS: The authors found that modafinil improved cognitive performance in breast cancer survivors by enhancing some memory and attention skills. Although confirmation is needed, these findings suggest that modafinil may enhance quality of life in this patient population.