Estimation of cancer risks due to chest radiotherapy treatment planning computed tomography (CT) simulations.

The objective of our study was to determine organ doses to estimate the lifetime attributable risk (LAR) of cancer incidence related to chest tomography simulations for Radiotherapy Treatment Planning (RTTP) using patient-specific information. Patient data were used to calculate organ doses and effective dose. The effective dose (E) was calculated by two methods. First, to calculate effective dose in a standard phantom, the collected dosimetric parameters were used with the ImPACT CT Patient Dosimetry Calculator and E was calculated by applying related correction factors. Second, using the scanner-derived Dose Length Product, LARs were computed using the US National Academy of Sciences (BEIR VII) model for age- and sex-specific risks at each exposure. DLP, CTDIvol, and scan length were 507 ± 143 mGy.cm, 11 ± 4 mGy, and 47 ± 7 cm, respectively. The effective dose was 10 ± 3 mSv using ImPACT patient dosimetry calculator software and 9 ± 2 mSv using the scanner-derived Dose Length Product. The LAR of cancer incidence for all cancers, all solid cancers and leukemia were 65 ± 29, 62 ± 27, 7 ± 2 cases per 100,000 individuals, respectively. Radiation exposure from the usage of CT for radiotherapy treatment planning (RTTP) causes non-negligible increases in lifetime attributable risk. The results of this study can be used as a guide by physicians to implement strategies based on the As Low As Reasonably Achievable (ALARA) principle that lead to a reduction dose without sacrificing diagnostic information.

Epstein-Barr Virus History and Pathogenesis.

Epstein-Barr virus (EBV) is the first identified human oncogenic virus that can establish asymptomatic life-long persistence. It is associated with a large spectrum of diseases, including benign diseases, a number of lymphoid malignancies, and epithelial cancers. EBV can also transform quiescent B lymphocytes into lymphoblastoid cell lines (LCLs) in vitro. Although EBV molecular biology and EBV-related diseases have been continuously investigated for nearly 60 years, the mechanism of viral-mediated transformation, as well as the precise role of EBV in promoting these diseases, remain a major challenge yet to be completely explored. This review will highlight the history of EBV and current advances in EBV-associated diseases, focusing on how this virus provides a paradigm for exploiting the many insights identified through interplay between EBV and its host during oncogenesis, and other related non-malignant disorders.

Effects of green tea on prostate carcinogenesis in rat models and a human prostate cancer xenograft model.

BACKGROUND: There is evidence to suggest that green tea soy may have protective effects against prostate cancer, but there are several epidemiologic and clinical studies that did not identify such an effect. We tested the notion of protective effects in a rat model of prostate carcinogenesis that has been predictive of the effects of selenium and vitamin E in randomized clinical trials and a human prostate cancer xenograft model in nude mice and rat prostate tumor cells transplanted in immune-competent syngeneic animals. METHODS: Prostate cancer was induced in rats with methylnitrosourea and testosterone and tumor incidence was determined. Subcutaneous tumor growth was measured resulting from injected cells isolated from rat prostate cancers grafted in syngeneic animals and from the prostate-specific antigen (PSA)-producing human prostate cancer PC346 xenografted in nude mice. Brewed decaffeinated green tea infusion or caffeinated green tea extract and the same 300 mg/ml concentration of caffeine were provided in drinking water of the rats and nude mice. RESULTS: Caffeinated green tea extract and caffeine provided in drinking water did not modify the induction of prostate cancer in the rat model compared with control rats. The same drinking water treatments also did not affect the growth and PSA production of PC346 human prostate cancer xenografts in nude mice and the growth of two transplantable rat prostate cancer tumor lines in Wistar Firth rats. Brewed green tea infusion as drinking water did also not affect tumor growth in these xeno- and allograft models. CONCLUSION: These animal studies with drinking water exposure to green tea and caffeine do not support the idea that green tea is protective against prostate cancer.

Novel Insights into Potential Cannabis-Related Cancerogenesis from Recent Key Whole Epigenome Screen of Cannabis Dependence and Withdrawal: Epidemiological Commentary and Explication of Schrott et al.

Whilst the cannabis-cancer link has been traditionally described as controversial recent whole nation and whole continent studies have demonstrated that well documented laboratory-based multimodal cannabinoid genotoxicity is indeed reflected in numerous cancer types in larger epidemiological series. A recent longitudinal human sperm epigenome-wide DNA methylation screen in both cannabis dependence and cannabis withdrawal has revealed remarkable insights into the manner in which widespread perturbations of DNA methylation may lead to cancerogenic changes in both the exposed and subsequent generations as a result of both cannabis exposure and withdrawal. These results therefore powerfully strengthen and further robustify the causal nature of the relationship between cannabinoid exposure and cancerous outcomes well beyond the previously published extensive mechanistic literature on cannabinoid genotoxicity. The reported epigenomic results are strongly hypothesis generating and call powerfully for further work to investigate oncogenic mechanisms in many tissues, organs and preclinical models. These epigenomic results provide an extraordinarily close predictive account for the epidemiologically observed pattern of cannabis-related malignant disease and indicate that malignant and multigenerational cannabinoid epigenotoxicity is potentially a significant and major public health concern.

Epstein-Barr virus: Current questions and challenges.

Epstein-Barr virus (EBV) infects most people worldwide and persists for life due to complicated interplay between lytic infection and multiple types of latent infections. While usually asymptomatic, EBV is a causative agent in several types of cancer and has a strong association with multiple sclerosis. Exactly how EBV promotes these diseases and why they are rare consequences of infection are incompletely understood. Here I will discuss current ideas on disease induction by EBV, including the importance of lytic protein expression in the context of latent infection as well as the possible importance of specific EBV variants in disease induction.

Effect of multiple doses of N-methyl-N-nitrosourea, an end product of methylguanidine (found in processed food), on the fertility of female Swiss albino mice.

Methylguanidine, an originator of carcinogenic methylnitrosourea, has been found in many animal meats and processed stored food often in high concentration. The present study was designed to understand the multiple dose effect of N-methyl-N-nitrosourea (MNU), an end product of methylguanidine, in Swiss albino mice fertility as well as cancer induction. Accordingly, a total of five experimental groups of animal (female Swiss albino mice) were taken, considering group-I as vehicle control and group-II-V as treatment groups (whereas group-II-Vwere treated with single to quadruple doses of 50 mg/kg of MNU respectively in a three weeks interval). After accomplishment of MNU injection, each female mice was mated with male mice to check the fertility efficiency. The results of the study indicated that, mice treated with highest number of MNU doses were 42.85% less efficient in getting pregnant than the control mice. There were noted changes in body weight, food and water intake upon MNU-exposure compared to control group. A significant increase in cumulative weight of vital female organs like uterus and ovary were also observed in mice injected with quadruple doses of MNU (50 mg/kg) compared to control mice. The findings of the study suggest the direct effect of MNU in pregnancy, without any cancer incidence in the vital female organs of Swiss albino mice.

The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case.

BACKGROUND: Recently, low dose radiotherapy delivered to the whole lung has been proposed as treatment for the pneumonia due to COVID-19. Although there is biological plausibility for its use, the evidence supporting its effectiveness is scarce, and the risks associated with it may be significant. Thus, based on a virtual case simulation, we estimated the risks of radiation-induced cancer (RIC) and cardiac disease. METHODS: Lifetime attributable risks (LAR) of RIC were calculated for the lung, liver, esophagus, and breast of female patients. The cardiovascular risk of exposure-induced death (REID) due to ischemic heart disease was also calculated. The doses received by the organs involved in the treatment were obtained from a simulation of conformal radiotherapy (RT) treatment, delivering a dose of 0.5 Gy-1.5 Gy to the lungs. We considered a LAR and REID <1% as acceptable, 1-2% cautionary, and >2% unacceptable. RESULTS: The lung was at the highest risk for RIC (absolute LAR below 5200 cases/100,000 and 2250 cases/100,000 for women and men, respectively). For women, the breast had the second-highest LAR, especially for young women. The liver and esophagus had LARs below 700/100,000 for both sexes, with a higher incidence of esophageal cancer in women and liver cancer in men. Regarding the LAR cutoff, we observed an unacceptable or cautionary LAR for lung cancer in all women and men <60 years with an RT dose >1 Gy. LAR for lung cancer with an RT dose of 1 Gy was cautionary for women >60 years of age and men <40 years of age. No LAR estimation was unacceptable for the RT dose ≤0.7 Gy in all groups irrespective of sex or age at exposure. Only 0.5 Gy had an acceptable REID. CONCLUSIONS: A RT dose ≤0.5 Gy provides an acceptable LAR estimate (≤1%) for RIC and REID, irrespective of sex and age. The current ongoing trials should initially use doses ≤0.5 Gy to maintain the risks at an acceptable level and include only patients who fail or do not have any other treatment option.

Estimating lung cancer and cardiovascular mortality in female breast cancer patients receiving radiotherapy.

By integrating data of the PLCO cancer screening trial, SCORE-risk charts and radiotherapy excess ratios, we were able to create risk charts estimating radiotherapy-induced lung cancer and cardiovascular mortality in female breast cancer patients. These risk models might be useful to individualize radiotherapy and optimize lung cancer and cardiovascular prevention and screening.

Low Preoperative Prolactin Levels Predict Non-Organ Confined Prostate Cancer in Clinically Localized Disease.

INTRODUCTION: To evaluate the association between preoperative serum prolactin (PRL) levels and risk of non-organ confined prostate cancer (PCa) in clinically localized disease. MATERIALS AND METHODS: From December 2007 to December 2011, 124 patients with clinically localized PCa were retrospectively evaluated. Non-organ confined disease in the surgical specimen was defined according to extra-capsular extension, seminal vesicle invasion, positive surgical margins, and lymph node invasion. The association between clinical factors and serum levels of pituitary-testis hormones with the risk of non-organ confined disease was evaluated. RESULTS: Perioperative factors associated with non-organ confined disease include prostatic-specific antigen (OR 1.144; p = 0.025), proportion of biopsy positive cores (BPC, OR 36.702; p = 0.007), bioptical Gleason Score > 6 (OR 2.785; p = 0.034), and PRL (OR 0.756, p < 0.0001). The association was strong for BPC (area under the curve [AUC] 0.704; p < 0.0001) and PRL (AUC 0.299; p < 0.0001). When we dichotomized according to median value, PRL ≤7.7 µg/L was an independent predictor of extraprostatic disease (OR 6.571; p < 0.0001) with fair discrimination power (AUC 0.704; p < 0.0001). CONCLUSION: Low preoperative PRL levels predict the risk of non-organ confined PCa in clinically localized disease.

Estimating cancer induction risk from abdominopelvic scanning with 6- and 16-slice computed tomography.

PURPOSE: The biological effects of ionizing radiation (BEIR VII) report estimates that the risk of getting cancer from radiation is increased by about a third from current regulation risk levels. The propose of this study was to estimate cancer induction risk from abdominopelvic computed tomography (CT) scanning of adult patients using 6- and 16-slice CT scanners. MATERIALS AND METHODS: A cross-sectional study on 200 patients with abdominopelvic CT scan in 6- and 16-slice scanners was conducted. The dose-length product (DLP) and volume CT Dose Index (CTDIvol) values from the scanners as well as the effective dose values from the ImPACT CT patient dosimetry calculator with the biological effects of ionizing radiation (BEIR VII) method were used to estimate the cancer induction risk. RESULTS: The mean (and standard deviation) values of CTDIvol and DLP were 6.9 (±1.07) mGy and 306.44 (± 60.57) mGy.cm for 6-slice, and 5.19 (±0.91) mGy and 219.7 (±49.31) mGy.cm for 16-slice scanner, respectively. The range of effective dose in the 6-slice scanner was 2.61-8.15 mSv and, in the 16-slice scanner, it was 1.47-4.72 mSv. The mean and standard deviation values of total cancer induction risk in abdominopelvic examinations were 0.136 ± 0.059% for men and 0.135 ± 0.063% for women in the 6-slice CT scanner. The values were 0.126 ± 0.051% for men and 0.127 ± 0.056% for women in the 16-slice scanner. CONCLUSIONS: The cancer induction risk of abdominopelvic scanning was noticeable. Therefore, radiation dose should be minimized by optimizing the protocols and applying appropriate methods.

Rescue of Moribund Chicken Embryos by Extremely Low-Frequency Electric Fields.

BACKGROUND: Modern living is awash with low-frequency electromagnetic radiation raising concern over health effects, birth defects, and infant cancers especially leukemias. Medical/scientific opinion is ambivalent, especially regarding possible mechanisms of action despite our bodies׳ many electric currents. AIMS: Are some cancers induced by morphogenetic changes rather than direct mutation? We wished to see if morphogenetic effects of weak, extremely low-frequency electric (ELF) fields in embryonated hen׳s eggs could induce cancers, knowing that such treatment is usually deleterious. We report a pilot study intended to reveal a promising cell source in which to search for cancer cells by established methods and then to check for DNA damage. METHODS: Stored (5°C for 1-36 days) fresh, fertile hens׳ eggs were incubated (38°C, total five or six days) in presence or absence of a weak ELF oscillating electric field (1-40V/cm, 1-50Hz and two to six days). Separated embryos were assessed for development stage. RESULTS: Storage of untreated eggs (>12 days, 5°C) allows a steady loss of normal embryo formation at 38°C (few viable by 25 days, half-life ~18 days). Surprisingly, incubation in a weak ELF field during the period of declining viability significantly (P: 0.03-0.0001) improved viability and condition of the embryos (new half-life ~21 days), rather than the expected converse. Thus for a few days, the field could keep viable some embryos that would otherwise not have survived. CONCLUSIONS: The rescued embryos and their untreated controls seem the most promising place to seek any carcinogenic effects of ELF fields. The nature of the presumed critical component keeping them viable during 5°C storage is at least of equal interest.

Accuracy of out-of-field dose calculation of tomotherapy and cyberknife treatment planning systems: a dosimetric study.

PURPOSE: Late toxicities such as second cancer induction become more important as treatment outcome improves. Often the dose distribution calculated with a commercial treatment planning system (TPS) is used to estimate radiation carcinogenesis for the radiotherapy patient. However, for locations beyond the treatment field borders, the accuracy is not well known. The aim of this study was to perform detailed out-of-field-measurements for a typical radiotherapy treatment plan administered with a Cyberknife and a Tomotherapy machine and to compare the measurements to the predictions of the TPS. MATERIALS AND METHODS: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The measured dose distributions from 6 MV intensity-modulated treatment beams for CyberKnife and TomoTherapy machines were compared to the dose calculations from the TPS. RESULTS: The TPS are underestimating the dose far away from the target volume. Quantitatively the Cyberknife underestimates the dose at 40 cm from the PTV border by a factor of 60, the Tomotherapy TPS by a factor of two. If a 50% dose uncertainty is accepted, the Cyberknife TPS can predict doses down to approximately 10 mGy/treatment Gy, the Tomotherapy-TPS down to 0.75 mGy/treatment Gy. The Cyberknife TPS can then be used up to 10 cm from the PTV border the Tomotherapy up to 35 cm. CONCLUSIONS: We determined that the Cyberknife and Tomotherapy TPS underestimate substantially the doses far away from the treated volume. It is recommended not to use out-of-field doses from the Cyberknife TPS for applications like modeling of second cancer induction. The Tomotherapy TPS can be used up to 35 cm from the PTV border (for a 390 cm(3) large PTV).