Radiation exposure and leukaemia risk among cohorts of persons exposed to low and moderate doses of external ionising radiation in childhood.

BACKGROUND: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear. METHODS: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted. RESULTS: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards. DISCUSSION: We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy.

Cardiotoxicity in pediatric lymphoma survivors.

INTRODUCTION: Over the past five decades, the diagnosis and management of children with various malignancies have improved tremendously. As a result, an increasing number of children are long-term cancer survivors. With improved survival, however, has come an increased risk of treatment-related cardiovascular complications that can appear decades later. AREAS COVERED: This review discusses the pathophysiology, epidemiology and effects of treatment-related cardiovascular complications from anthracyclines and radiotherapy in pediatric lymphoma survivors. There is a paucity of evidence-based recommendations for screening for and treatment of cancer therapy-induced cardiovascular complications. We discuss current preventive measures and strategies for their treatment. EXPERT OPINION: Significant cardiac adverse effects occur due to radiation and chemotherapy received by patients treated for lymphoma. Higher lifetime cumulative doses, female sex, longer follow-up, younger age, and preexisting cardiovascular disease are associated with a higher incidence of cardiotoxicity. With deeper understanding of the mechanisms of these adverse cardiac effects and identification of driver mutations causing these effects, personalized cancer therapy to limit cardiotoxic effects while ensuring an adequate anti-neoplastic effect would be ideal. In the meantime, expanding the use of cardioprotective agents with the best evidence such as dexrazoxane should be encouraged and further studied.

Lymphoma and multiple myeloma in cohorts of persons exposed to ionising radiation at a young age.

There is limited evidence that non-leukaemic lymphoid malignancies are radiogenic. As radiation-related cancer risks are generally higher after childhood exposure, we analysed pooled lymphoid neoplasm data in nine cohorts first exposed to external radiation aged <21 years using active bone marrow (ABM) and, where available, lymphoid system doses, and harmonised outcome classification. Relative and absolute risk models were fitted. Years of entry spanned 1916-1981. At the end of follow-up (mean 42.1 years) there were 593 lymphoma (422 non-Hodgkin (NHL), 107 Hodgkin (HL), 64 uncertain subtype), 66 chronic lymphocytic leukaemia (CLL) and 122 multiple myeloma (MM) deaths and incident cases among 143,136 persons, with mean ABM dose 0.14 Gy (range 0-5.95 Gy) and mean age at first exposure 6.93 years. Excess relative risk (ERR) was not significantly increased for lymphoma (ERR/Gy = -0.001; 95% CI: -0.255, 0.279), HL (ERR/Gy = -0.113; 95% CI: -0.669, 0.709), NHL + CLL (ERR/Gy = 0.099; 95% CI: -0.149, 0.433), NHL (ERR/Gy = 0.068; 95% CI: -0.253, 0.421), CLL (ERR/Gy = 0.320; 95% CI: -0.678, 1.712), or MM (ERR/Gy = 0.149; 95% CI: -0.513, 1.063) (all p-trend > 0.4). In six cohorts with estimates of lymphatic tissue dose, borderline significant increased risks (p-trend = 0.02-0.07) were observed for NHL + CLL, NHL, and CLL. Further pooled epidemiological studies are needed with longer follow-up, central outcome review by expert hematopathologists, and assessment of radiation doses to lymphoid tissues.

Risk of Coronary Events 55 Years after Thymic Irradiation in the Hempelmann Cohort.

BACKGROUND: Studies of cancer survivors treated with older radiotherapy (RT) techniques (pre-1990s) strongly suggest that ionizing radiation to the chest increases the risk of coronary heart disease (CHD). Our goal was to evaluate the impact of more modern cardiac shielding techniques of RT on the magnitude and timing of CHD risk by studying a cohort exposed to similar levels of cardiac irradiation years ago. METHODS: Between 2004 and 2008, we re-established a population-based, longitudinal cohort of 2,657 subjects exposed to irradiation for an enlarged thymus during infancy between 1926 and 1957 and 4,388 of their non-irradiated siblings. CHD events were assessed using a mailed survey and from causes of death listed in the National Death Index. We used Poisson regression methods to compare incidence rates by irradiation status and cardiac radiation dose. Results were adjusted for the CHD risk factors of attained-age, sex, diabetes, dyslipidemia hypertension and smoking. RESULTS: Median age at time of follow-up was 57.5 years (range 41.2 - 88.8 yrs) for irradiated and non-irradiated siblings. The mean estimated cardiac dose amongst the irradiated was 1.45 Gray (range 0.17 - 20.20 Gy), with 91% receiving <3.00 Gy. During a combined 339,924 person-years of follow-up, 213 myocardial infarctions (MI) and 350 CHD events (MI, bypass surgery and angioplasty) occurred. After adjustment for attained age, gender, and other CHD risk factors, the rate ratio for MI incidence in the irradiated group was 0.98 (95%CI, 0.74 - 1.30), and for any CHD event was 1.07 (95%CI, 0.86 - 1.32). Higher radiation doses were not associated with more MIs or CHD events in this dose range, in either the crude or the adjusted analyses. CONCLUSIONS: Radiation to the heart during childhood of <3 Gy, the exposure in most of our cohort, does not increase the lifelong risk of CHD. Reducing cardiac radiation to this amount without increasing other cardiotoxic therapies may eliminate the increased CHD risk associated with radiotherapy for childhood cancer. By extension there is unlikely to be increased CHD risk from relatively higher dose imaging techniques, such as CT, because such techniques use much smaller radiation doses than received by our cohort.

Brief report of virtual clinician research tools for tobacco dependence or dyslipidemia.

Health avatars were created to deliver previously tested live interventions for tobacco dependence and cholesterol management. The exploratory aims were to develop and test whether the avatar can be reliably assessed for autonomy supportiveness using the Health Care Climate Questionnaire and estimate the mean changes in motivation variables and correlate the avatars' autonomy supportiveness with the motivation variables and health outcomes. The avatars were found to be reliably assessed for autonomy supportiveness on the Health Care Climate Questionnaire. Autonomy support was positively correlated with the change in motivations and reduction in low-density lipoprotein. These findings suggest that health avatars may be tested in clinical trials.

Willingness of Parkinson's disease patients to participate in research using internet-based technology.

BACKGROUND: Motor impairment and travel time have been shown to be important barriers to recruitment for Parkinson's disease (PD) clinical trials. This study determined whether use of Internet-based video communication for study visits would improve likelihood of participating in PD clinical trials. SUBJECTS AND METHODS: University of Utah PD clinic patients were invited to complete a survey asking if they would be willing to participate in a hypothetical research study under four different scenarios. McNemar's test was used to test the hypothesis that remote assessments would improve willingness to participate. RESULTS: Willingness to participate was 101/113 (87%) in the standard scenario. Willingness to participate was highest (93%; p=0.046) with most visits occurring via telemedicine at a local clinic, followed by some visits occurring via telemedicine at a local clinic (91%; p=0.157). Willingness to participate was lower with some (80%; p=0.008) or most (82%; p=0.071) visits occurring by home telemonitoring. CONCLUSIONS: Use of telemedicine may be an acceptable means to improve participation in clinical trials. This would need to be confirmed with the use of a larger-scale inquiry involving rural populations. Future research should assess subject or caregiver comfort and trainability with respect to computer-based technology in the home and systems barriers for wider implementation of telemedicine in neurology.

Radiation dose associated with renal failure mortality: a potential pathway to partially explain increased cardiovascular disease mortality observed after whole-body irradiation.

Whole-body and thoracic ionizing radiation exposure are associated with increased cardiovascular disease (CVD) risk. In atomic bomb survivors, radiation dose is also associated with increased hypertension incidence, suggesting that radiation dose may be associated with chronic renal failure (CRF), thus explaining part of the mechanism for increased CVD. Multivariate Poisson regression was used to evaluate the association of radiation dose with various definitions of chronic kidney disease (CKD) mortality in the Life Span Study (LSS) of atomic bomb survivors. A secondary analysis was performed using a subsample for whom self-reported information on hypertension and diabetes, the two biggest risk factors for CRF, had been collected. We found a significant association between radiation dose and only our broadest definition of CRF among the full cohort. A quadratic dose excess relative risk model [ERR/Gy(2) = 0.091 (95% CI: 0.05, 0.198)] fit minimally better than a linear model. Within the subsample, association was also observed only with the broadest CRF definition [ERR/Gy(2) = 0.15 (95% CI: 0.02, 0.32)]. Adjustment for hypertension and diabetes improved model fit but did not substantially change the ERR/Gy(2) estimate, which was 0.17 (95% CI: 0.04, 0.35). We found a significant quadratic dose relationship between radiation dose and possible chronic renal disease mortality that is similar in shape to that observed between radiation and incidence of hypertension in this population. Our results suggest that renal dysfunction could be part of the mechanism causing increased CVD risk after whole-body irradiation, a hypothesis that deserves further study.

Thyroid cancer risk 40+ years after irradiation for an enlarged thymus: an update of the Hempelmann cohort.

Although ionizing radiation is a known carcinogen, the long-term risk from relatively higher-dose diagnostic procedures during childhood is less well known. We evaluated this risk indirectly by assessing thyroid cancer incidence in a cohort treated with "lower-dose" chest radiotherapy more than 55 years ago. Between 2004 and 2008, we re-surveyed a population-based cohort of subjects treated with radiation for an enlarged thymus during infancy between 1926 and 1957 and their unexposed siblings. Thyroid cancer occurred in 50 irradiated subjects (mean thyroid dose, 1.29 Gy) and in 13 nonirradiated siblings during 334,347 person-years of follow-up. After adjusting for attained age, Jewish religion, sex and history of goiter, the rate ratio for thyroid cancer was 5.6 (95% CI: 3.1-10.8). The adjusted excess relative risk per gray was 3.2 (95% CI: 1.5-6.6). The adjusted excess absolute risk per gray was 2.2 cases (95% CI: 1.4-3.2) per 10,000 person-years. Cumulative thyroid cancer incidence remains elevated in this cohort after a median 57.5 years of follow-up and is dose-dependent. Although the incidence appeared to decrease after 40 years, increased risk remains a lifelong concern in those exposed to lower doses of medical radiation during early childhood.

Late effects of therapy for Hodgkin's lymphoma.

Hodgkin's lymphoma exemplifies a malignancy in which the benefits and risks of therapy are strikingly obvious: although 70% to 95% of patients survive (depending on disease stage), the late adverse health effects of therapy compromise quality of life and can be fatal. We review the broad range of these potential effects. Although secondary malignancies and cardiovascular disease are the most life-threatening sequelae, pulmonary, endocrine, and reproductive effects can also substantially compromise quality of life. Specific sequelae are not distributed evenly among survivors but depend on characteristics of the patient and treatment. Recent risk-adapted treatment protocols have eliminated or reduced the use of therapies most associated with adverse effects, such as alkylating agents, anthracyclines, and radiotherapy. Early studies suggest that these strategies reduce the frequency and severity of adverse effects, but additional follow-up of patients is necessary to confirm improved outcomes. Recognition of adverse effects has also led to recommendations for screening.