Association between diabetes and subsequent malignancy risk among older breast cancer survivors.

Type II diabetes is associated with cancer risk in the general population but has not been well studied as a risk factor for subsequent malignancies among cancer survivors. We investigated the association between diabetes and subsequent cancer risk among older (66-84 years), 1-year breast cancer survivors within the linked Surveillance Epidemiology and End Results (SEER)-Medicare database using Cox regression analyses to quantify hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Among 133 324 women, 29.3% were diagnosed with diabetes before or concurrent with their breast cancer diagnosis, and 10 452 women developed subsequent malignancies over a median follow-up of 4.3 years. Diabetes was statistically significantly associated with liver (HR = 2.35, 95% CI = 1.48 to 3.74), brain (HR = 1.94, 95% CI = 1.26 to 2.96), and thyroid cancer risks (HR = 1.38, 95% CI = 1.01 to 1.89). Future studies are needed to better understand the spectrum of subsequent cancers associated with diabetes and the role of diabetes medications in modifying subsequent cancer risk, alone or in combination with cancer treatments.

Integrative assessment of brain and bone invasion in meningioma patients.

BACKGROUND: Various prognostic factors have been suggested in meningioma patients including WHO grading, brain invasion and bone involvement, for instance. Brain invasion was included as an independent criterion in the recent WHO classification. However, assessability of brain or bone involvement is often limited or varies between histopathologic, operative and imaging reports. Objective of our study was to investigate prognostic values including brain and bone involvement according to different clinical approaches. METHODS: A cohort of 111 patients was treated with primary, adjuvant or salvage irradiation between 2008 and 2017 using intensity-modulated radiotherapy. Positron-emission tomography (PET) was available for treatment planning in 81% of patients. Clinical data were extracted from the medical reports. Brain and bone involvement were stratified separately according to histopathologic, operative and imaging reports as well as judged in synopsis. RESULTS: WHO grade I tumours, lower estimated proliferation index, primary versus recurrence treatment and localization (i.e. skull base, optic nerve sheath) were beneficial prognostic factors for local control. Judgement of brain and bone invasion partly differed between diagnostic modalities. In synopsis, brain or bone invasion did not show a significant influence on local control rates. CONCLUSIONS: Several previously described prognostic factors could be reproduced. However, partly divergent histopathological, surgical and image-based judgements could be found in regard to brain and bone invasion and all methods imply limitations. Therefore, we suggest a particular, complemental synopsis judgement. In synopsis, brain or bone involvement did not coherently impair local control in our irradiated patients. This might be explained by elaborate radiation techniques and PET-based treatment planning.

Risk of developing radiogenic cancer following photon-beam radiotherapy for Graves' orbitopathy.

PURPOSE: The objective of this study was to estimate the probability for cancer development due to radiotherapy for Graves' orbitopathy with 6 MV x rays. METHODS: Orbital irradiation was simulated with the MCNP code. The radiation dose received by 10 out-of-field organs having a strong disposition for carcinogenesis was calculated with Monte Carlo methods. These dose calculations were used to estimate the organ-dependent lifetime attributable risk (LAR) for cancer induction in 30- and 50-yr-old males and females on the basis of the linear model suggested by the BEIR-VII report. Differential dose-volume histograms derived from patients' three-dimensional (3D) radiotherapy plans were employed to determine the organ equivalent dose (OED) of the brain which was partly exposed to primary radiation. The OED and the relevant LAR for brain cancer development were assessed with the plateau, bell-shaped and mechanistic models. The radiotherapy-induced cancer risks were compared with the lifetime intrinsic risk (LIR) values for unexposed population. RESULTS: The radiation dose range to organs excluded from the treatment volume was 0.1-91.0 mGy for a target dose of 20 Gy. These peripheral organ doses increased the LIRs for cancer development of unexposed 30- and 50-yr-old males up to 1.0% and 0.2%, respectively. The corresponding elevations after radiotherapy of females were 2.0% and 0.4%. The use of nonlinear models gave an OED range of the brain of 482.0-562.5 mGy depending upon the model used for analysis and the patient's gender. The elevation of the LIR for developing brain malignancies after radiotherapy of 30-yr-old males and females reached to 13.3% and 16.6%, respectively. The corresponding increases after orbital irradiation at the age of 50 yr were 6.7% and 8.3%. CONCLUSIONS: The level of the LIR increase attributable to radiation therapy for GO varied widely by the organ under examination and the age and gender of the exposed subject. This study provides the required data to quantify the elevation of these baseline cancer risks following orbital irradiation.

Effects of Radiation Exposure on the Cost-Effectiveness of CT Angiography and Perfusion Imaging in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: CT angiography and perfusion imaging is an important prognostic tool in the management of patients with aneurysmal subarachnoid hemorrhage. The purpose of this study was to perform a cost-effectiveness analysis of advanced imaging in patients with SAH, incorporating the risks of radiation exposure from CT angiography and CT perfusion imaging. MATERIALS AND METHODS: The risks of radiation-induced brain cancer and cataracts were incorporated into our established decision model comparing the cost-effectiveness of CT angiography and CT perfusion imaging and transcranial Doppler sonography in SAH. Cancer risk was calculated by using National Cancer Institute methodology. The remaining input probabilities were based on literature data and a cohort at our institution. Outcomes were expected quality-adjusted life years gained, costs, and incremental cost-effectiveness ratios. One-way, 2-way, and probabilistic sensitivity analyses were performed. RESULTS: CT angiography and CT perfusion imaging were the dominant strategies, resulting in both better health outcomes and lower costs, even when incorporating brain cancer and cataract risks. Our results remained robust in 2-way sensitivity analyses varying the prolonged latency period up to 30 years, with either brain cancer risk up to 50 times higher than the upper 95% CI limit or the probability of cataracts from 0 to 1. Results were consistent for scenarios that considered either symptomatic or asymptomatic patients with SAH. Probabilistic sensitivity analysis confirmed our findings over a broad range of selected input parameters. CONCLUSIONS: While risks of radiation exposure represent an important consideration, CT angiography and CT perfusion imaging remained the preferred imaging compared with transcranial Doppler sonography in both asymptomatic and symptomatic patients with SAH, with improved health outcomes and lower health care costs, even when modeling a significantly higher risk and shorter latency period for both cataract and brain cancer than that currently known.

InterCardioRisk: a novel online tool for estimating doses of ionising radiation to occupationally-exposed medical staff and their associated health risks.

Those working in interventional cardiology and related medical procedures are potentially subject to considerable exposure to x-rays. Two types of tissue of particular concern that may receive considerable doses during such procedures are the lens of the eye and the brain. Ocular radiation exposure results in lens changes that, with time, may progress to partial or total lens opacification (cataracts). In the early stages, such opacities do not result in visual disability; the severity of such changes tends to increase progressively with dose and time until vision is impaired and cataract surgery is required. Scattered radiation doses to the eye lens of an interventional cardiologist in typical working conditions can exceed 34 µGy min-1 in high-dose fluoroscopy modes and 3 µGy per image during image acquisition (instantaneous rate values) when radiation protection tools are not used. A causal relation between exposure to ionising radiation and increased risk of brain and central nervous system tumours has been shown in a number of studies. Although absorbed doses to the brain in interventional cardiology procedures are lower than those to the eye lens by a factor between 3.40 and 8.08 according to our simulations, doses to both tissues are among the highest occupational radiation doses documented for medical staff whose work involves exposures to x-rays. We present InterCardioRisk, a tool featuring an easy-to-use web interface that provides a general estimation of both cumulated absorbed doses experienced by medical staff exposed in the interventional cardiology setting and their estimated associated health risks. The tool is available at http://intercardiorisk.creal.cat.

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.

A three-dimensional point process model for the spatial distribution of disease occurrence in relation to an exposure source.

We study methods for how to include the spatial distribution of tumours when investigating the relation between brain tumours and the exposure from radio frequency electromagnetic fields caused by mobile phone use. Our suggested point process model is adapted from studies investigating spatial aggregation of a disease around a source of potential hazard in environmental epidemiology, where now the source is the preferred ear of each phone user. In this context, the spatial distribution is a distribution over a sample of patients rather than over multiple disease cases within one geographical area. We show how the distance relation between tumour and phone can be modelled nonparametrically and, with various parametric functions, how covariates can be included in the model and how to test for the effect of distance. To illustrate the models, we apply them to a subset of the data from the Interphone Study, a large multinational case-control study on the association between brain tumours and mobile phone use.

Assessment of the association between XRCC1 Arg399Gln polymorphism and glioma susceptibility.

The Arg399Gln polymorphism, located in the region of the BRCT-I interaction domain of XRCC1, has been extensively explored in its function and association with glioma risk. However, these studies generated contradictory instead of conclusive results. A meta-analysis was performed to derive a more precise evaluation of the relationship between XRCC1 Arg399Gln polymorphism and glioma risk. We searched the PubMed, EMBASE, and Web of Science and extracted 12 eligible studies with 4,062 glioma cases and 5,302 glioma-free controls for this meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association. In the overall analysis, we found that the XRCC1 Arg399Gln polymorphism was statistically associated with the risk of glioma (OR(GG vs. AG + AA) = 0.90, 95% CI = 0.84-0.97, P(heterogeneity) = 0.020; OR(allele G vs. allele A )= 0.96, 95% CI = 0.91-1.00, P(heterogeneity) = 0.110). We also observed significant association between this polymorphism and glioma risk in Asian populations. The results of the meta-analysis suggest a potential decreased susceptibility to glioma in association with the XRCC1 Arg399Gln polymorphism, especially in Asians. Yet, it is necessary to conduct future prospective explorations to gain a better insight into the impact of XRCC1 Arg399Gln polymorphism on glioma risk.

Possible health benefits from reducing occupational magnetic fields.

BACKGROUND: Magnetic fields (MF) from AC electricity are a Possible Human Carcinogen, based on limited epidemiologic evidence from exposures far below occupational health limits. METHODS: To help formulate government guidance on occupational MF, the cancer cases prevented and the monetary benefits accruing to society by reducing workplace exposures were determined. Life-table methods produced Disability Adjusted Life Years, which were converted to monetary values. RESULTS: Adjusted for probabilities of causality, the expected increase in a worker's disability-free life are 0.04 year (2 weeks) from a 1 microtesla (µT) MF reduction in average worklife exposure, which is equivalent to $5,100/worker/µT in year 2010 U.S. dollars (95% confidence interval $1,000-$9,000/worker/µT). Where nine electrosteel workers had 13.8 µT exposures, for example, moving them to ambient MFs would provide $600,000 in benefits to society (uncertainty interval $0-$1,000,000). CONCLUSIONS: When combined with the costs of controls, this analysis provides guidance for precautionary recommendations for managing occupational MF exposures.

Children's health and RF EMF exposure. Views from a risk assessment and risk communication perspective.

A review of the scientific literature published until August 2010, covering epidemiological studies on the effects of RF EMF exposure on the incidence of brain tumours and leukaemia in children as well as experimental studies on RF EMF effects on cognition and CNS in children, reveals no or only scant evidence for the assumption that RF EMF exposure poses a hazard to children. This result is at odds with public risk perceptions, i.e. prevailing concerns of (at least part of) the public about adverse health effect of RF EMF. Consequences for risk communication are discussed. A scientifically sound and easy-to-understand risk communication is especially exacerbated by the fact that current risk assessments cannot exclude that RF EMF might have adverse health effects due remaining knowledge gaps, but especially due to the impossibility to prove a non-effect.

Long-term health experience of jet engine manufacturing workers: IV. A comparison of central nervous system cancer ascertainment using mortality and incidence data.

PURPOSE: To compare ascertainment of central nervous system (CNS) neoplasms with the use of mortality and incidence data as part of an occupational epidemiology study. METHODS: Deaths were identified by matching the cohort of 223,894 jet engine manufacturing employees to the U.S. Social Security Administration death files and the National Death Index. Incident cancer cases were identified by matching the cohort to 19 state cancer registries. RESULTS: We identified 718 cases overall: 59% by the use of both mortality and cancer incidence tracing; 24% by the use of only mortality tracing, and 17% by the use of only cancer incidence tracing. Compared with state cancer registries, death certificates missed 38% of the malignant, more than six times the benign and nearly 1.5 times the unspecified CNS cases. The positive predictive value of death certificates, with cancer registry as gold standard, was 6% for unspecified, 35% for benign, and 86% for malignant histologies. CONCLUSIONS: Death certificates seriously underascertained benign and unspecified CNS tumors; analyses determined with mortality data would not accurately capture the true extent of disease among the cohort. Most state cancer registries have only collected nonmalignant CNS tumor information since 2004, which currently limits the usefulness of state cancer registries as a source of nonmalignant CNS tumor identification. Underascertainment of CNS deaths could seriously affect interpretation of results, more so if examining nonmalignant CNS.

Human exposure to selected animal neurocarcinogens: a biomarker-based assessment and implications for brain tumor epidemiology.

This review is based on the proceedings from the Second Lebow Conference, held in Chicago in 2007. The conference concentrated on developing a framework for innovative studies in the epidemiology of environmental exposures, focusing specifically on the potential relationship with brain tumors. Researchers with different perspectives, including toxicology, pharmacokinetics, and epidemiological exposure assessment, exchanged information and ideas on the use of biomarkers of exposure in molecular epidemiology studies and summarized the current knowledge on methods and approaches for biomarker-based exposure assessment. This report presents the state of science regarding biomarker-based exposure assessment of the four most common neurocarcinogens: acrylamide, 1,3-butadiene, N-nitroso compounds, and polycyclic aromatic hydrocarbons. Importantly, these chemicals are also carcinogenic in other organs; therefore, this discussion is useful for environmental epidemiologists studying all cancer types.

Setting prudent public health policy for electromagnetic field exposures.

Electromagnetic fields (EMF) permeate our environment, coming both from such natural sources as the sun and from manmade sources like electricity, communication technologies and medical devices. Although life on earth would not be possible without sunlight, increasing evidence indicates that exposures to the magnetic fields associated with electricity and to communication frequencies associated with radio, television, WiFi technology, and mobile cellular phones pose significant hazards to human health. The evidence is strongest for leukemia from electricity-frequency fields and for brain tumors from communication-frequency fields, yet evidence is emerging for an association with other diseases as well, including neurodegenerative diseases. Some uncertainty remains as to the mechanism(s) responsible for these biological effects, and as to which components of the fields are of greatest importance. Nevertheless, regardless of whether the associations are causal, the strengths of the associations are sufficiently strong that in the opinion of the authors, taking action to reduce exposures is imperative, especially for the fetus and children. Inaction is not compatible with the Precautionary Principle, as enunciated by the Rio Declaration. Because of ubiquitous exposure, the rapidly expanding development of new EMF technologies and the long latency for the development of such serious diseases as brain cancers, the failure to take immediate action risks epidemics of potentially fatal diseases in the future.

[French neurosurgical practice in neurooncology (national survey--part II). Census of current research protocols on brain tumors in France]. / Neurochirurgie et neuro-oncologie: état des lieux (ii). Recensement des protocoles de recherche sur les tumeurs cérébrales.

OBJECTIVE: This second part of the inquiry of the NeuroOncolgy Group of the French Neurosurgical Society was undertaken to evaluate the involvement of French neurosurgeons in brain tumor research. METHODS: In December 2003, A questionnaire called "Census of current and future research studies about brain tumors in your center" has been mailed to every French neurosurgical department. For each protocol, responders were asked to mention: the title of the protocol, its mono- or multi-centric design, the name of the principal investigator, the name of the neurosurgeon(s) involved in the study, the topic of the study (epidemiology, imaging, biology, genetics, therapy), tumor histology, financial support, and partners. RESULTS: Twenty-three centers responded. Sixty-three studies were described. There were 6 epidemiological studies, 7 imaging studies, 27 biological or genetic studies and 15 clinical trials concerning glial tumors, and 8 biological studies concerning non glial tumors. Each study is described in the text with the data previously mentioned. CONCLUSION: Despite the fact that several centers did not answer, this inquiry confirmed the strong involvement of French neurosurgeons in brain tumor research.

Occurrence of cancer among people with mental health claims in an insured population.

OBJECTIVE: The objective of this research is to determine whether people with mental disorders are at increased risk for the subsequent development of malignancies compared with people without mental disorders. METHODS: This is a retrospective cohort study of administrative claims data. The study population included 722,139 adults who filed at least one medical claim from 1989 to 1993. The mental disorder cohort included people with a) one psychiatric hospitalization, b) one outpatient psychiatrist visit, or c) two outpatient mental health claims occurring at least 6 months before a cancer claim. The controls were subjects filing claims for medical services who had no mental health visits. We calculated age-stratified odds ratios (ORs) for development of malignancy. RESULTS: People with mental disorders were no more or less likely to develop a malignancy than those without after adjusting for age (women: OR, 1.03; 95% confidence interval [CI], 0.95-1.12; men: OR, 1.10; 95% CI, 0.97-1.24). People with mental disorders, however, developed cancer at younger ages and had increased odds of primary central nervous system tumors (women: OR, 2.12; 95% CI, 1.40-3.21; men: OR, 2.09; 95% CI, 1.22-3.59) and respiratory system cancers (women: OR, 1.57; 95% CI, 1.13-2.19; men: OR, 1.52; 95% CI, 1.09-2.12). CONCLUSIONS: Insured people with mental disorder claims had an increased risk of certain malignancies and developed malignancies at younger ages. The increased odds of respiratory tumors are likely secondary to increased rates of smoking among people with mental disorders and support use of smoking cessation interventions in this population. The increased odds for brain tumors may reflect only the early presence of mental symptoms, or a true association between the two conditions. Further study of these findings is mandated.