Comparison and multi-model inference of excess risks models for radiation-related solid cancer.

In assessments of detrimental health risks from exposures to ionising radiation, many forms of risk to dose-response models are available in the literature. The usual practice is to base risk assessment on one specific model and ignore model uncertainty. The analysis illustrated here considers model uncertainty for the outcome all solid cancer incidence, when modelled as a function of colon organ dose, using the most recent publicly available data from the Life Span Study on atomic bomb survivors of Japan. Seven recent publications reporting all solid cancer risk models currently deemed plausible by the scientific community have been included in a model averaging procedure so that the main conclusions do not depend on just one type of model. The models have been estimated with different baselines and presented for males and females at various attained ages and ages at exposure, to obtain specially computed model-averaged Excess Relative Risks (ERR) and Excess Absolute Risks (EAR). Monte Carlo simulated estimation of uncertainty on excess risks was accounted for by applying realisations including correlations in the risk model parameters. Three models were found to weight the model-averaged risks most strongly depending on the baseline and information criteria used for the weighting. Fitting all excess risk models with the same baseline, one model dominates for both information criteria considered in this study. Based on the analysis presented here, it is generally recommended to take model uncertainty into account in future risk analyses.

Total body irradiation as part of conditioning regimens in childhood leukemia-long-term outcome, toxicity, and secondary malignancies.

BACKGROUND: Total body irradiation (TBI) is an established part of conditioning regimens prior to stem cell transplantation in childhood leukemia but is associated with long-term toxicity. We retrospectively analyzed survival, long-term toxicity, and secondary malignancies in a pooled cohort of pediatric patients (pts.) treated with the same TBI regimen. METHODS: Analyzed were 109 pts. treated between September 1996 and November 2015. Conditioning treatment according to EBMT guidelines and the ALL SCTped 2012 FORUM trial consisted of chemotherapy (CT) and TBI with 2 Gy b.i.d. on 3 consecutive days to a total dose of 12 Gy. Median follow-up was 97.9 months (2-228 months). RESULTS: Overall survival (OS) in our cohort at 2, 5, and 10 years was 86.1, 75.5, and 63.0%, respectively. Median survival was not reached. Long-term toxicity developed in 47 pts. After chronically abnormal liver and kidney parameters in 31 and 7 pts., respectively, growth retardation was the most frequent finding as seen in 13 pts. Secondary malignancies were rare (n = 3). CONCLUSION: TBI-containing conditioning regimens in pediatric stem cell transplantation (SCT) are highly effective. Efforts to replace TBI- with CT-containing regimens have only been successful in subgroups of pts. Although we could show long-term toxicity in 43% of pts., overall survival was 63% at 10 years. Still, long-term effects such as growth retardation can permanently impact the pts.' quality of life and functioning. Along with new substances, efforts should be undertaken to optimize TBI techniques and accompany the treatment by systematic follow-up programs beyond 5 years to improve detection of rare events.

Effect of prior radiation on stage, differentiation, and survival in bladder cancer.

PURPOSE: Clinically significant differences in radiation-related bladder tumors are not well-characterized, and survival analyses are needed. In this study, we aimed to utilize a national cancer database to evaluate the effect of prior radiation on tumor characteristics and survival in bladder cancer patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) 9 database was queried to identify patients diagnosed with bladder cancer as a second malignancy. Patients having undergone radiation prior to developing bladder cancer were selected for comparative analysis. Logistic regression was used to generate odds ratios to evaluate differences in differentiation, stage, grade, and tumor size. Kaplan-Meier analysis and Cox non-proportional hazards regression models were used to assess the association between previous radiation and bladder cancer survival. RESULTS: A total of 25,408 patients were identified, of which 14,570 patients had sufficient data for analysis. Of these, 5968 (41.0%) received radiation for their primary malignancy. Prior radiation conferred a lower risk of developing moderately- or poorly-differentiated bladder tumors and muscle invasive or node-positive disease. An increased risk of squamous cell carcinoma was noted (OR 1.43, CI 1.06-1.93). Prior radiation led to an increased risk of bladder cancer-specific (HR 1.13, CI 1.03-1.24) mortality at 5 years. The greatest effect of prior radiation was an increased risk of bladder cancer-specific mortality for carcinoma in situ at 5 years (OR 2.37, CI 1.45-3.86). CONCLUSION: Prior radiation is associated with lower grade and stage of bladder tumors in addition to worse cancer-specific survival.

Study on the radiation detriment.

Cancer incidence risks, lifetime effects and radiation detriments are determined for the whole population and various subpopulations as a result of acute and chronic exposure to low-LET radiation, taking into account the risk models, procedures and representative populations provided by ICRP. The results are given for solid cancers in different organs, as well as for soft tissue cancer in bone marrow. For most cancer sites a good agreement is obtained between the results of this study and the values published by the ICRP. The agreement with ICRP values is better for the whole population than for the working age population, where the results are systematically elevated. For chronic exposure, the years of life lost per radiation-induced cancer incidence are generally higher. In particular, this results in a radiation detriment for the whole population that is 30% higher than for acute exposure. The study reveals that risk quantities show a pronounced age dependence. The highest radiation risks are attributed to young persons; the lowest to persons in advanced ages. The total detriment imposed on people in different ages varies by a factor of about 30. The average values provided by the ICRP mask these variations and considerably underestimate radiation risks in childhood and adolescence. This also concerns the determination of the effective dose for persons in these age groups. Unlike the ICRP, which provides different nominal detriments for the whole population and the working age population, the results of this study do not support the use of different detriments for these populations.

Roles of Fibroblasts in Microenvironment Formation Associated with Radiation-Induced Cancer.

In tumor tissues, activated stromal fibroblasts, termed cancer-associated fibroblasts (CAFs), exhibit similar characteristics to myofibroblasts. CAFs promote cancer cell differentiation and invasion by releasing various factors, such as growth factors, chemokines, and matrix-degrading proteases, into neighboring tumor cells. However, the roles of tumor microenvironment in case of radiation-induced carcinogenesis remain poorly understood. We recently revealed that mitochondrial oxidative stress causes tumor microenvironment formation associated with radiation-induced cancer. Repeated low-dose fractionated radiation progressively damages fibroblast mitochondria and elevates mitochondrial reactive oxygen species (ROS) levels. Excessive mitochondrial ROS activate transforming growth factor-beta (TGF-ß) signaling, thereby inducing fibroblasts activation and facilitating tumor microenvironment formation. Consequently, radiation affects malignant cancer cells directly and indirectly via molecular alterations in stromal fibroblasts, such as the activation of TGF-ß and angiogenic signaling. This review summarizes for the first time the roles of mitochondrial oxidative stress in microenvironment formation associated with radiation-induced cancer. This review may help us understand the risks of exposure to low-dose radiation. The cross talk between cancer cells and stromal fibroblasts contributes to the development and progression of radiation-induced cancer.

Estimated risk of radiation-induced cancer following breast screening employing tomosynthesis and digital mammography.

The objective of this study was to estimate the risk of radiation-induced injury to the organs due to ionizing radiation following breast screening recommendations employing digital breast tomosynthesis (DBT) and digital mammography (DM). Using the Monte Carlo method, absorbed doses in the tissues and organs were calculated on an adult female phantom, considering two-view craniocaudal (CC) and mediolateral oblique (MLO) projections for each breast. The results showed differences in the total effective risk due to DM (CC + MLO) and DBT (CC + MLO) examinations in Brazil, ranging from 20.73 cases 10-5(DM) to 27.19 cases 10-5(DBT). Significant differences were also observed in the total effective risk of cancer incidence in the lungs due to DM (CC + MLO) and DBT (CC + MLO), ranging from 1.75×10-01cases 10-5(DM) to 1.76×10-01cases 10-5(DBT). The results indicate that the total effective risk of incidence should be considered as an additional parameter for the evaluation of DBT or DBT + DM program performance.

Protecting sensitive patient groups from imaging using ionizing radiation: effects during pregnancy, in fetal life and childhood.

The frequency of imaging examinations requiring radiation exposure in children (especially CT) is rapidly increasing. This paper reviews the current evidence in radiation protection in pediatric imaging, focusing on the recent knowledge of the biological risk related to low doses exposure. Even if there are no strictly defined limits for patient radiation exposure, it is recommended to try to keep doses as low as reasonably achievable (the ALARA principle). To achieve ALARA, several techniques to reduce the radiation dose in radiation-sensitive patients groups are reviewed. The most recent recommendations that provide guidance regarding imaging of pregnant women are also summarized, and the risk depending on dose and phase of pregnancy is reported. Finally, the risk-benefit analysis of each examination, and careful communication of this risk to the patient, is emphasized.

Long-Term Consequences of the Chernobyl Radioactive Fallout: An Exploration of the Aggregate Data.

Policy Points Policymakers should invest more on researching the long-term health effects of low-ionizing radiation exposure, as we are far from reaching a consensus on a topic that is of enormous importance for public health and safety. Public policies such as those limiting the import of contaminated food from areas hit by a radioactive disaster or those regulating the resident population's access to such areas should follow a precautionary approach. Neoplasm diagnosis and medical care should be designed in order to take into account the possible role of long-term, low-dose radiation exposure. Health care policies should provide effective screening and prevention strategies with a specific focus on the regions that were hit most severely by the Chernobyl nuclear fallout. Health care expenditure should be targeted, taking into account the geographical dispersion of the fallout in order to attenuate its possible effect on neoplasm incidence. CONTEXT: This study investigates the association between the radioactive 137 Cesium fallout originated by the 1986 Chernobyl nuclear accident and dispersed over Western Europe, as a result of a combination of radioactive cloud passage days and rainy days over a 10-day period, and long-term health patterns and related costs. Since the half-life of 137 Cesium is 30.17 years, part of the radioactivity in the affected regions is still present today, and it is usually still detected in the food chain, although at lower concentration levels. METHODS: We match longitudinal data on neoplasm incidence over the time span 2000-2013 in a number of European regions not immediately adjacent to Chernobyl with the randomly distributed levels of cesium deposition after the nuclear disaster in order to assess whether we can detect an association with the long-term health effects on the European population through a random effects model. FINDINGS: Considering 3 levels of fallout deposition-low, medium, and high-hospital discharges after treatment for neoplasms are, respectively, 0.36, 0.44, and 0.98 discharges over 100 inhabitants higher compared to regions with no fallout, with the population average being around 1.7 hospital discharges by neoplasms over 100 inhabitants. We checked the robustness of our findings to a number of tests including a placebo simulation and different model specifications. CONCLUSIONS: Radioactive fallout is positively associated with a higher incidence of hospital discharges after treatment for neoplasms almost 30 years after its release, with larger effects in regions where the radioactivity was more intense. Our estimates are comparable to the findings of the largest-scale study on the long-term health effects of continuous low levels of radiation exposure among workers in the nuclear industry and suggest that more research is needed on this topic, given its enormous importance for public health and safety.

Radiation burden and associated cancer risk for a typical population to be screened for lung cancer with low-dose CT: A phantom study.

OBJECTIVES: To estimate (a) organ doses and organ-specific radiation-induced cancer risk from a single low-dose CT (LDCT) for lung cancer screening (LCS) and (b) the theoretical cumulative risk of radiation-induced cancer for a typical cohort to be subjected to repeated annual LCS LDCT. METHODS: Sex- and body size-specific organ dose data from scan projection radiography (SPR) and helical CT exposures involved in LCS 256-slice LDCT were determined using Monte Carlo methods. Theoretical life attributable risk (LAR) of radiogenic cancer from a single 256-slice chest LDCT at age 55-80 years and the cumulative LAR of cancer from repeated annual LDCT studies up to age 80 years were estimated and compared to corresponding nominal lifetime intrinsic risks (LIRs) of being diagnosed with cancer. RESULTS: The effective dose from LCS 256-slice LDCT was estimated to be 0.71 mSv. SPR was found to contribute 6-12 % to the total effective dose from chest LDCT. The radiation-cancer LAR from a single LDCT study was found to increase the nominal LIR of cancer in average-size 55-year-old males and females by 0.008 % and 0.018 %, respectively. Cumulative radiogenic risk of cancer from repeated annual scans from the age of 55-80 years was found to increase the nominal LIR of cancer by 0.13 % in males and 0.30 % in females. CONCLUSION: Modern scanners may offer sub-millisievert LCS LDCT. Cumulative radiation risk from repeated annual 256-slice LDCT LCS examinations was found to minimally aggravate the lifetime intrinsic cancer risk of a typical screening population. KEY POINTS: • Effective dose from lung cancer screening low-dose CT may be <1 mSv. • Screening with modern low-dose CT minimally aggravates lifetime cancer induction intrinsic risk. • Dosimetry of lung cancer screening low-dose CT should encounter the radiation burden from the localizing scan projection radiography. • DLP method may underestimate effective dose from low-dose chest CT by 27 %.

Pediatric cleft palate patients show a 3- to 5-fold increase in cumulative radiation exposure from dental radiology compared with an age- and gender-matched population: a retrospective cohort study.

OBJECTIVE: The objective of the study was to compare estimates of pediatric cumulative exposure and lifetime attributable risk (LAR) of radiation-induced cancer from dental radiology between cleft palate (CP) subjects and age- and gender-matched controls (non-CP), with and without orthodontic treatment. MATERIALS AND METHODS: The radiation exposure frequency of CP subjects and non-CP controls with and without orthodontic treatment was compared for two-dimensional radiography (intra-oral, panoramic and cephalometric radiography), computed tomography (CT), and cone-beam CT (CBCT) using cumulative radiation dose as an estimate. From this dose estimate, the age- and gender-dependent risk for radiation-induced stochastic effects was calculated for each patient group. RESULTS: CP patients received more radiographic examinations than non-CP controls, with the exception of intra-oral radiographs. The cumulative dose to CP patients was considerably higher (1963 µSv at the age of 20 years) than non-CP patients with (597 µSv) and without (383 µSv) orthodontic treatment, primarily due to the higher frequency of CT scanning. Accordingly, CP patients had a three to five times higher LAR than non-CP patients. CONCLUSIONS: This study suggests a significantly higher lifetime radiation exposure to CP patients than non-CP controls from dental radiographic procedures. Diagnostic benefits from the use of CT and CBCT in children must be justified and appropriate dose optimization strategies implemented. CLINICAL RELEVANCE: The present study indicates the need for proper justification and optimization of pediatric exposures in dentistry, with a special focus on high-risk groups.

Incidence of second tumors after treatment with or without radiation for rectal cancer.

Background: The aim of this study was to analyze the association between radiation therapy (RT) for rectal cancer and the development of second tumors. Patients and methods: Data on all surgically treated non-metastatic primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from the Netherlands population-based cancer registry. Fine and Gray's competing risk model was used for estimation of the cumulative incidence of second tumors. Multivariable analysis was conducted using Cox regression. Results: The cohort consisted of 29 027 patients of which 15 467 patients had undergone RT. Median follow-up was 7.7 years (range 0-27). Among all 4398 patients who were diagnosed with a second primary tumor, 1030 had one or more pelvic tumors. The standardized incidence risk for any second tumor was 1.16 (95% confidence interval [CI] 1.12-1.19), resulting in 27.7/10 000 excess cancer cases per year in patients treated for rectal cancer compared with the general population. RT reduced the cumulative incidence of second pelvic tumors compared with patients who did not receive RT (subhazard ratio [SHR] 0.77, CI 0.68-0.88). Second prostate tumors were less common in patients who received RT (SHR 0.54, CI 0.46-0.64), gynecological tumors were more frequently observed in patients who received RT (SHR 1.49, CI 1.11-2.00). Conclusions: Patients with previous rectal cancer had a marginally increased risk of a second tumor compared with the general population. Gynecological tumors occurred more often in females who received RT, but this did not result in an overall increased risk for a second cancer. RT even seemed to have a protective effect on the development of other second pelvic tumors, pre-dominantly for prostate cancer. These findings are highly important and can contribute to improved patient counseling.

Investigation of DNA repair-related SNPs underlying susceptibility to papillary thyroid carcinoma reveals MGMT as a novel candidate gene in Belarusian children exposed to radiation.

BACKGROUND: Genetic factors may influence an individual's sensitivity to ionising radiation and therefore modify his/her risk of developing papillary thyroid carcinoma (PTC). Previously, we reported that common single nucleotide polymorphisms (SNPs) within the DNA damage recognition gene ATM contribute to PTC risk in Belarusian children exposed to fallout from the Chernobyl power plant accident. Here we explored in the same population the contribution of a panel of DNA repair-related SNPs in genes acting downstream of ATM. METHODS: The association of 141 SNPs located in 43 DNA repair genes was examined in 75 PTC cases and 254 controls from the Gomel region in Belarus. All subjects were younger than 15 years at the time of the Chernobyl accident. Conditional logistic regressions accounting for radiation dose were performed with PLINK using the additive allelic inheritance model, and a linkage disequilibrium (LD)-based Bonferroni correction was used for correction for multiple testing. RESULTS: The intronic SNP rs2296675 in MGMT was associated with an increased PTC risk [per minor allele odds ratio (OR) 2.54 95% CI 1.50, 4.30, P per allele = 0.0006, P corr.= 0.05], and gene-wide association testing highlighted a possible role for ERCC5 (P Gene = 0.01) and PCNA (P Gene = 0.05) in addition to MGMT (P Gene = 0.008). CONCLUSIONS: These findings indicate that several genes acting in distinct DNA repair mechanisms contribute to PTC risk. Further investigation is needed to decipher the functional properties of the methyltransferase encoded by MGMT and to understand how alteration of such functions may lead to the development of the most common type of thyroid cancer.

Radiation exposure in diagnostic imaging: wisdom and prudence, but still a lot to understand.

Since 2000, a series of scientific articles on CT have been raising increasing concern about the risk of radiation induced cancer in children. The alarming conclusions of some of these articles had international echo through global media, provoking widespread public concern. Actually, many of these alarming scientific publications appeared to be flawed by poor study design, but their conclusions were not openly contradicted. In US and Europe pediatric radiologists had to face a huge challenge, which brought to the Image Gently campaign and the Eurosafe initiative with the aim to rebut misinformation and to support medical radiation protection. The Linear No Threshold model-which is the base of contemporary radioprotection-is increasingly questioned by new recent studies suggesting that low dose radiation would decrease cancer risk thanks to the enhancement of immune system response. Actually, pediatric radiologists have to cope with many important issues and contradictory messages. Good medical practice includes good communication about the benefits and risks of health procedures, thus the communication of radiation risk is a key component for radiologists. When considering benefits and risks, an important risk is too often ignored: the risk that skipping a diagnostic exam may cause a misdiagnosis, and therefore, a poor outcome. We should emphasize that a risk from a radiological investigation is very small, if a risk at all, and we are not sure that there is a risk at very low doses, like those doses in the majority of X-ray procedures including CT.

Evaluation of radiotherapy techniques for radical treatment of lateralised oropharyngeal cancers : Dosimetry and NTCP.

AIM: The aim of this study was to investigate potential advantages and disadvantages of three-dimensional conformal radiotherapy (3DCRT), multiple fixed-field intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) in terms of dose to the planning target volume (PTV), organs at risk (OARs) and normal tissue complication probability (NTCP) for delivering ipsilateral radiotherapy. MATERIALS AND METHODS: 3DCRT, IMRT and VMAT were compared in patients with well-lateralised primary tonsillar cancers who underwent primary radical ipsilateral radiotherapy. The following parameters were compared: conformity index (CI); homogeneity index (HI); dose-volume histograms (DVHs) of PTVs and OARs; NTCP, risk of radiation-induced cancer and dose accumulation during treatment. RESULTS: IMRT and VMAT were superior to 3DCRT in terms of CI, HI and dose to the target volumes, as well as mandible and dose accumulation robustness. The techniques were equivalent in terms of dose and NTCP for the contralateral oral cavity, contralateral submandibular gland and mandible, when specific dose constraint objectives were used on the oral cavity volume. Although the volume of normal tissue exposed to low-dose radiation was significantly higher with IMRT and VMAT, the risk of radiation-induced secondary malignancy was dependant on the mathematical model used. CONCLUSION: This study demonstrates the superiority of IMRT/VMAT techniques over 3DCRT in terms of dose homogeneity, conformity and consistent dose delivery to the PTV throughout the course of treatment in patients with lateralised oropharyngeal cancers. Dosimetry and NTCP calculations show that these techniques are equivalent to 3DCRT with regard to the risk of acute mucositis when specific dose constraint objectives were used on the contralateral oral cavity OAR.

Imaging Radiation Doses and Associated Risks and Benefits in Subjects Participating in Breast Cancer Clinical Trials.

BACKGROUND: Medical imaging is commonly required in breast cancer (BC) clinical trials to assess the efficacy and/or safety of study interventions. Despite the lack of definitive epidemiological data linking imaging radiation with cancer development in adults, concerns exist about the risks of imaging radiation-induced malignancies (IRIMs) in subjects exposed to repetitive imaging. We estimated the imaging radiation dose and IRIM risk in subjects participating in BC trials. MATERIALS AND METHODS: The imaging protocol requirements in 10 phase III trials in the adjuvant and advanced settings were assessed to estimate the effective radiation dose received by a typical and fully compliant subject in each trial. For each study, the excess lifetime attributable cancer risk (LAR) was calculated using the National Cancer Institute's Radiation Risk Assessment Tool, version 3.7.1. Dose and risk calculations were performed for both imaging intensive and nonintensive approaches to reflect the variability in imaging performed within the studies. RESULTS: The total effective imaging radiation dose was 0.4-262.2 mSv in adjuvant trials and 26-241.3 mSv in metastatic studies. The dose variability resulted from differing protocol requirements and imaging intensity approaches, with computed tomography, multigated acquisition scans, and bone scans as the major contributors. The mean LAR was 1.87-2,410/100,000 in adjuvant trials (IRIM: 0.0002%-2.41% of randomized subjects) and 6.9-67.3/100,000 in metastatic studies (IRIM: 0.007%-0.067% of subjects). CONCLUSION: IRIMs are infrequent events. In adjuvant trials, aligning the protocol requirements with the clinical guidelines' surveillance recommendations and substituting radiating procedures with equivalent nonradiating ones would reduce IRIM risk. No significant risk has been observed in metastatic trials, and potential concerns on IRIMs are not justified. IMPLICATIONS FOR PRACTICE: Medical imaging is key in breast cancer (BC) clinical trials. Most of these procedures expose patients to ionizing radiation, and the risk of second cancer development after imaging has prompted recent concerns and controversy. Using accepted calculation models, the number of malignancies were estimated that were potentially attributable to the imaging procedures performed during a patient's participation in BC clinical trials. The results show that for patients participating in metastatic trials, the risk of imaging radiation-induced malignancies is negligible. In adjuvant trials, some second cancers due to imaging could be expected, and measures can be taken to reduce their risk.

Communicating Potential Radiation-Induced Cancer Risks From Medical Imaging Directly to Patients.

OBJECTIVE: Over the past decade, efforts have increasingly been made to decrease radiation dose from medical imaging. However, there remain varied opinions about whether, for whom, by whom, and how these potential risks should be discussed with patients. We aimed to provide a review of the literature regarding awareness and communication of potential radiation-induced cancer risks from medical imaging procedures in hopes of providing guidance for communicating these potential risks with patients. MATERIALS AND METHODS: We performed a systematic literature review on the topics of radiation dose and radiation-induced cancer risk awareness, informed consent regarding radiation dose, and communication of radiation-induced cancer risks with patients undergoing medical imaging. We included original research articles from North America and Europe published between 1995 and 2014. RESULTS: From more than 1200 identified references, a total of 22 original research articles met our inclusion criteria. Overall, we found that there is insufficient knowledge regarding radiation-induced cancer risks and the magnitude of radiation dose associated with CT examinations among patients and physicians. Moreover, there is minimal sharing of information before nonacute imaging studies between patients and physicians about potential long-term radiation risks. CONCLUSION: Despite growing concerns regarding medical radiation exposure, there is still limited awareness of radiation-induced cancer risks among patients and physicians. There is also no consensus regarding who should provide patients with relevant information, as well as in what specific situations and exactly what information should be communicated. Radiologists should prioritize development of consensus statements and novel educational initiatives with regard to radiation-induced cancer risk awareness and communication.

Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation.

A dramatic increase in the incidence of papillary thyroid carcinoma (PTC) after childhood exposure to ionizing radiation from the Chernobyl nuclear accident has been described as the largest number of tumors of one type due to one cause that have ever occurred. inter-individual variations in response to radiation have been documented and the role of genetics in sporadic PTC is well established, suggesting that genetic factors may also affect the risk of radiation-related PTC. To investigate how environmental and host factors interplay to modify PTC risk, we genotyped 83 cases and 324 matched controls sampled from children living in the area contaminated by fallout from the Chernobyl power plant accident for 19 polymorphisms previously associated with PTC, thyroid biology or radiation-induced second primary tumors. Significant association with PTC was found for rs1801516 (D1853N) in ATM (odds ratio (OR) = 0.34, 95% confidence interval (CI) 0.16, 0.73) and rs1867277 in the promoter region of FOXE1 (OR = 1.55, 95% CI 1.03, 2.34). Analysis of additional polymorphisms confirmed the association between these two genes and PTC. Our findings suggest that both DNA double-strand break repair pathway and thyroid morphogenesis pathway or dysregulation of thyroid differentiated state maintenance are involved in the etiology of PTC, and that the studied genetic polymorphisms and radiation dose appear to act as independent multiplicative risk factors for PTC.

Radiation-Induced Oropharyngeal Squamous Cell Carcinoma: Case Report and Review of the Literature.

BACKGROUND: Radiation therapy (RT) is a mainstay for the treatment of head and neck (HN) cancers, with 80% of patients receiving such treatment. Radiation-induced malignancies represent a life-threatening long-term effect of RT, with an incidence of 0.5% to 15%. CASE DESCRIPTION: After 13 years, a 33-year-old woman treated with chemo-radiotherapy for nasopharyngeal carcinoma developed a locally advanced, radiation-induced, p16-negative oropharyngeal squamous cell carcinoma (SCC) at the base of the tongue. Chemo/immunotherapy was administered as a first-line treatment. Given the optimal response and the feasibility of surgery, after three cycles, the patient underwent a total glossectomy, bilateral neck dissection, and reconstruction with a thoraco-dorsal free flap. A histological examination found SCC with a residual cancer burden of 70% and free margins. DISCUSSION: The mechanisms responsible for carcinogenesis after RT are still not completely clear. Diagnosis may be challenging due to the previous treatment; growth patterns are unusual, and lymphotropism is lower. Prognosis is usually poor since surgical resectability is often not achievable. CONCLUSIONS: Radiation-induced malignancies are difficult to treat. Patient management should always be discussed at a multidisciplinary level. Future research is needed to assess whether the promising results of clinical studies with pre-operative immunotherapy in locally advanced HN SCC patients may be translated into radiation-induced cancers.

Mathematical models of the solid cancer induced by atomic bomb and the spontaneous cancer in the daily life-Proposal of a new medical treatment for cancers.

BACKGROUND: A mathematical model of the radiation-induced cancer was devised to explain the change of incidence rates pursued by Radiation Effect Research Foundation for 25 years. AIM: The aim of this work is construction of mechanisms of radiation-induced cancer and cancers observed in the daily life. METHODS AND RESULTS: First, we found a way to separate spontaneous cancers from radiation-induced cancers observed among atomic-bomb victims in Hiroshima and Nagasaki districts by using a constructed algorithm. The isolated incidence rates of radiation-induced cancers were reproduced by a two-stage model mechanical collision of impinging radiation with cells and succeeding mutation of the damaged cell to cancer. This model satisfactorily reproduced observed solid cancer incidence rates. We further attempted to construct a mathematical model for the age-dependence of spontaneous cancers appearing in the daily life and concluded that the cancer should be generated at cell division. CONCLUSION: With these findings, we reached to a conclusion that cancers may be suppressed by eliminating damaged cells with mild-dose radiation.

What Would Become of Nuclear Risk if Governments Changed Their Regulations to Recognize the Evidence of Radiation's Beneficial Health Effects for Exposures That Are Below the Thresholds for Detrimental Effects?

The 1953 Atoms for Peace Speech to the United Nations proposed applying nuclear energy to essential needs, including abundant electrical energy. The widespread fear of ionizing radiation from nuclear facilities and medical procedures began after the United States National Academy of Sciences performed a study of radiation dangers to the human genome. This study, initiated and managed by an oil industry benefactor, recommended in 1956 that the risk of radiation-induced mutations be assessed using the linear no-threshold dose-response model instead of the threshold model. It was followed by a study that wrongly linked low radiation to cancer among the atomic bomb survivors. The ensuing controversy resulted in a compromise. The National Committee on Radiation Protection adopted the precautionary principle policy in 1959, justified by fear of cancer and lack of knowledge. The United States and all other countries followed this recommendation, which remains unchanged 62 years later. Its impact on nuclear energy and medicine has been profound. Many costly regulations have been enacted to prevent very unlikely human or equipment failures-failures that would lead to radiation exposures that are below the dose thresholds for lasting harmful effects. Potential low-dose radiation therapies, against inflammation, cancer, autoimmune, and neurodegenerative diseases, are shunned.