Biomarkers of exposure, sensitivity and disease

PURPOSE: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. OVERVIEW: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. OUTLINE: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.     

Biomarkers of exposure,sensitivity and disease

Purpose: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. Overview: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. Outline: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.     

The Impact of IMRT and Proton Radiotherapy on Secondary Cancer Incidence

BACKGROUND AND PURPOSE: There is concern about the increase of radiation-induced malignancies with the application of modern radiation treatment techniques such as intensity-modulated radiotherapy (IMRT) and proton radiotherapy. Therefore, X-ray scatter and neutron radiation as well as the impact of the primary dose distribution on secondary cancer incidence are analyzed. MATERIAL AND METHODS: The organ equivalent dose (OED) concept with a linear-exponential and a plateau dose-response curve was applied to dose distributions of 30 patients who received radiation therapy of prostate cancer. Three-dimensional conformal radiotherapy was used in eleven patients, another eleven patients received IMRT with 6-MV photons, and eight patients were treated with spot-scanned protons. The treatment plans were recalculated with 15-MV and 18-MV photons. Secondary cancer risk was estimated based on the OED for the different treatment techniques. RESULTS: A modest increase of 15% radiation-induced cancer results from IMRT using low energies (6 MV), compared to conventional four-field planning with 15-MV photons (plateau dose-response: 1%). The probability to develop a secondary cancer increases with IMRT of higher energies by 20% and 60% for 15 MV and 18 MV, respectively (plateau dose-response: 2% and 30%). The use of spot-scanned protons can reduce secondary cancer incidence as much as 50% (independent of dose-response). CONCLUSION: By including the primary dose distribution into the analysis of radiation-induced cancer incidence, the resulting increase in risk for secondary cancer using modern treatment techniques such as IMRT is not as dramatic as expected from earlier studies. By using 6-MV photons, only a moderate risk increase is expected. Spot-scanned protons are the treatment of choice in regard to secondary cancer incidence.     

Patient Radiation Exposure: Imaging During Radiation Oncology Procedures: Executive Summary of NCRP Report No. 184

The National Council on Radiation Protection and Measurements (NCRP) recently assessed patient radiation exposure in the United States, which was summarized in its 2019 NCRP Report No. 184. This work involved an estimation of the number of medical procedures using ionizing radiation, as well as the associated effective doses from these procedures. The NCRP Report No. 184 committee elected to not incorporate radiation dose from radiotherapy into its calculated population dose exposures, as the assessment of effective dose for the population undergoing radiotherapy is more complex than that for other medical radiation exposures. However, the aim of NCRP Report No. 184 was to raise awareness of ancillary radiation exposures to patients undergoing radiotherapy. Overall, it was estimated that annually, in 2016, approximately 800,000 patients received approximately 1 million courses of radiation therapy. Each of these treatments includes various types of imaging that may not be familiar to radiologists or others. Exposures from radiotherapy planning and delivery are reviewed in the report and summarized in this executive summary. The imaging techniques, use of this imaging, and associated tissue doses are described. Imaging can contribute a few percent to the planned treatment doses (which are prescribed to specified target volumes) as well as exposing patients to radiation outside of the target volume (in the imaging field of view).     

Dosimetric aspects of exposure of the population to ionizing radiation

Radiation carcinogenesis is generally considered to be the most important detrimental effect of exposure to ionizing radiation. The collective effective dose-equivalent values due to medical procedures amount to values between 10 and 20 per cent of the doses received from natural radiation. Risk factors have been derived up to the present from three large epidemiological studies, notably atomic bomb survivors, spondylitis patients and female patients treated for cancer of the cervix. The assessment of the absorbed doses received by the inhabitants of Hiroshima and Nagasaki has received continuous attention and the latest estimates are summarized. On the basis of original radiotherapy records the absorbed doses in organs adjacent to the primary treatment field can be derived from computerized dosimetry and this source of information should be further exploited. European co-operation has been established to investigate dosimetric problems for medical applications and radiation protection. The risk factors obtained up to the present are derived at relatively high dose levels (in excess of 0.3 Gy). The uncertainties in the extrapolation of these values to the area of low doses administered at low dose rates are discussed.     

Doses and population irradiation factors for Canadian radiation technologists (1978 to 1988)

Individual and collective radiation doses received by Canadian radiation technologists (RTs) working in diagnostic radiology, nuclear medicine and radiotherapy are summarized for the period 1978 to 1988. The data were obtained directly from the National Dose Registry, Department of National Health and Welfare. Over the 11-year study period the mean annual dose equivalent fluctuated around 0.2, 1.8 and 1.1 mSv for RTs working in diagnostic radiology, nuclear medicine and radiotherapy respectively. Over the same period the occupational collective dose equivalent decreased in diagnostic radiology (by 44%) and radiotherapy (by 35%) and increased in nuclear medicine (by 45%). Approximately 10,000 RTs are monitored each year, with an estimated total occupational collective dose equivalent of about 3.6 person-sieverts. Analysis of dose distribution data showed that only 1.3% of all monitored RTs received an annual whole-body dose equivalent greater than the current legal limit for members of the public (5 mSv). Approximately half of the RTs working in nuclear medicine and radiotherapy received an annual dose equivalent in excess of 0.5 mSv; only 7.3% of their diagnostic radiology counterparts exceeded this level. Demographic data showed a high preponderance of young women in all three RT classifications, and an analysis of the radiation risks to this occupational group revealed increases of up to 12% above the risk associated with a "standard" adult working population exposed to the same collective dose equivalent.     

Dosimetric Aspects of Exposure of the Population to Ionizing Radiation

Summary

Radiation carcinogenesis is generally considered to be the most important detrimental effect of exposure to ionizing radiation. The collective effective dose-equivalent values due to medical procedures amount to values between 10 and 20 per cent of the doses received from natural radiation. Risk factors have been derived up to the present from three large epidemiological studies, notably atomic bomb survivors, spondylitis patients and female patients treated for cancer of the cervix. The assessment of the absorbed doses received by the inhabitants of Hiroshima and Nagasaki has received continuous attention and the latest estimates are summarized. On the basis of original radiotherapy records the absorbed doses in organs adjacent to the primary treatment field can be derived from computerized dosimetry and this source of information should be further exploited. European co-operation has been established to investigate dosimetric problems for medical applications and radiation protection. The risk factors obtained up to the present are derived at relatively high dose levels (in excess of 0·3 Gy). The uncertainties in the extrapolation of these values to the area of low doses administered at low dose rates are discussed.     

External beam radiotherapy (EBRT) techniques used in breast cancer treatment to reduce cardiac exposure

Radiotherapy in breast cancer treatment has been shown to reduce local recurrence and improve survival rates. However, there is a concern that breast radiotherapy can cause an increase in cardiac mortality, particularly in patients being treated for left-sided breast cancer. This review aims to investigate how cardiac exposure is minimised in breast radiotherapy and determine an optimal method for reducing cardiac dose, using literature from ScienceDirect, Medline and CINAHL. IMRT and breathing-adapted radiotherapy both reduce cardiac exposure but IMRT also increases the irradiated volume at low dose. Several issues were reported with regards to the clinical implementation of these techniques. It is suggested that inspiration breath-hold radiotherapy, is the preferred solution to minimising cardiac exposure but more research is warranted to confirm this. Long-term follow-up is required to determine dose–response relationships. Research needs to focus on breast cancer treatment as a whole in order to effectively reduce cardiac mortality.     

2014-2018年江西省医用放射工作人员外照射个人剂量监测结果分析

目的 分析江西省医疗机构放射工作人员的外照射个人剂量情况,为放射防护工作提供参考.方法 以2014-2018年江西省医疗机构不同工种放射工作人员为调查对象,工种包括诊断放射学、放射治疗、核医学和介入放射学,统计分析江西医用放射工作人员的受照剂量水平.结果 本次共调查23 833人次,平均人均年有效剂量为0.316 mS...     

Resonancia magnética en la planificación de la braquiterapia intracavitaria para el tratamiento del cáncer de cérvix localmente avanzado

Cervical cancer is the third most common gynecological cancer. Its treatment depends on tumor staging at the time of diagnosis, and a combination of chemotherapy and radiotherapy is the treatment of choice in locally advanced cervical cancers. The combined use of external beam radiotherapy and brachytherapy increases survival in these patients. Brachytherapy enables a larger dose of radiation to be delivered to the tumor with less toxicity for neighboring tissues with less toxicity for neighboring tissues compared to the use of external beam radiotherapy alone. For years, brachytherapy was planned exclusively using computed tomography (CT). The recent incorporation of magnetic resonance imaging (MRI) provides essential information about the tumor and neighboring structures making possible to better define the target volumes. Nevertheless, MRI has limitations, some of which can be compensated for by fusing CT and MRI. Fusing the images from the two techniques ensures optimal planning by combining the advantages of each technique.     

A snapshot of patients' awareness of radiation dose and risks associated with medical imaging examinations at an Australian radiology clinic

BackgroundCumulative radiation exposure is linked to increasing the lifetime attributable risk of cancer. To avoid unnecessary radiation exposure and facilitate shared decision making, patients should be aware of these issues. This paper examines patients' awareness of radiation dose and risks associated with medical imaging examinations.MethodsConsecutive patients attending a private radiology clinic over a nine week period in 2014 in Metropolitan Melbourne were surveyed while waiting to undergo an imaging examination. Patients who were under 18 years of age, did not speak English and/or were referred for interventional imaging procedures were excluded from participation. Survey questions addressed patients' awareness of radiation dose associated with various imaging modalities' and patients' experience and preferences regarding communication of information about radiation. Data was analysed using SPSS (Ver 20.1).ResultsA total of 242 surveys were completed. Most participants were male (143/239, 59.8%) and aged between 33 and 52 years (109/242, 45%). Over half of participants were not concerned about radiation from medical imaging (130/238, 54.6%). Only a third of participants (80/234, 34.2%) correctly reported that CT has a higher radiation dose than X-ray. Very few participants correctly identified mammography, DEXA, PET and PET/CT as radiation emitting examinations. The majority of participants (202/236, 85.6%) indicated that they were not informed about radiation dose and risks by their referring doctor in advance.ConclusionThis paper provides information relevant to a single private radiology clinic in Australia. Nevertheless, our results have shown that patients presenting for medical imaging have little awareness of radiation dose and risks associated with these examinations and received little information by their referring physicians or staff at the radiology clinic.     

Assessment of effective dose from concomitant exposures required in verification of the target volume in radiotherapy

The requirement of the Ionising Radiation (Medical Exposure) Regulation 2000 [IR(ME)R] of justifying all exposures to ionizing radiation includes those from radiotherapy double exposure portal images resulting in exposure to normal tissues outside the treatment volume. Typical effective doses were calculated for a range of common sites using CT data to outline those parts of specific organs subject to concomitant radiation and generate dose-volume histograms. The product of the mean dose and the relative probability of inducing a fatal cancer in specific organs was used to determine a representative total effective dose in mSv per monitor unit for each site. A table of representative effective doses, ranging from 0.32 mSv to 2.56 mSv per monitor unit, was produced, which may be used to monitor cumulative effective doses of individual patients from double exposure portal images, in addition to those received from localization procedures.     

Evolution of radiation exposure to operator in diagnostic and interventional radiology procedures and reduction of radiation exposure to operator with protective device

A study was performed to evaluate operator dose during diagnostic and interventional radiology procedures (IVR) and to establish methods of operator dose reduction with a radiation protective device. Operator dose was measured by glass dosimeters worn on the neck and on the abdomen outside the lead apron. In addition, the dose of the primary beam at the collimator surface was measured, which made it possible to define the correlation between the entrance air kerma, measured with Skin Dose Monitor, and operator dose exposed during the monitored procedure. IVR protectors were developed to decrease the amount of scatter radiation received by operators performing the procedures, and their effects were evaluated in abdominal and cardiac angiography procedures. The average effective dose and doses of the neck and abdomen outside the lead apron, estimated for individual procedures, were as follows: abdominal angiography procedures: effective dose, 0.07 mSv; neck area, 0.18 mSv; abdominal area, 0.51 mSv; cardiac angiography procedures: effective dose, 0.07 mSv; neck area, 0.13 mSv; abdominal area, 0.68 mSv. Operator doses were well correlated with exposure dose in abdominal angiography procedures (diagnostic procedure r=0.84, IVR r=0.77). It was found that 68.0% of the effective dose in abdominal angiography procedures and 43.0% of the effective dose in cardiac angiography procedures could be reduced by the use of IVR protectors. Operator and patient doses in interventional radiology were interdependent. The minimization of operator doses is particularly important during interventional radiology, and it is necessary to be aware of practical radiation protection procedures. Measures that reduce patient dose will also reduce occupational exposure. Moreover, operator dose could be substantially reduced by the use of IVR protectors in addition to wearing a protective lead apron during IVR. It was suggested that IVR protectors are effective radiation protective devices in interventional radiology procedures.     

立体放射防护在介入治疗中的应用

目的:评价立体放射防护方法在介入治疗中的防护效果及其应用价值。方法:174例患者,介入治疗中分别采用床下铅橡胶帘、床边悬挂可活动式铅玻璃防护屏、医用铅防护服、铅防护围脖、铅防护眼镜及增加距离等X射线辐射防护措施,利用RAD60S个人报警剂量仪测量防护材料防护前后的X射线辐射剂量,并进行统计学分析。结果:铅玻璃防护屏、铅防护服、距离的增加可明显减少X射线辐射剂量,有显著性防护意义;X射线辐射剂量与透视和数字减影血管造影时间呈正相关,随着透视和减影造影时间的增加,医务人员和患者所接受的X射线辐射剂量明显增加。结论:立体防护在介入治疗中可有效减少X射线辐射剂量,保护医务人员和患者的身体健康。     

颅脑肿瘤放射治疗时射野外器官吸收剂量体模法测量与分析

目的 在是否使用楔形板和照射野面积不同的情况下,测量和分析颅脑肿瘤放射治疗时射野外器官的吸收剂量。 方法 使用中国成人男性仿真人体模型,模拟颅脑肿瘤放射治疗,采用不使用楔形板的普通方野照射技术组和使用楔形板的三维适形照射技术（3D-CRT）组,普通方野照射技术组分别用2 cm×2 cm野和4 cm×4 cm野进行照射,3D-CRT组分别按等效方野面积分为2 cm×2 cm野和4 cm×4 cm野进行照射;使用热释光剂量计测量射野外器官的吸收剂量并进行分析。 结果 颅脑肿瘤靶区处方剂量为100 cGy时,射野外各器官吸收剂量范围为0.13~2.83 mGy。头颈部器官4 cm×4 cm野照射时的吸收剂量与2 cm×2 cm野比较,差异有统计学意义（t=-5.023,P=0.004）;胸腹部器官4 cm×4 cm野照射时的吸收剂量与2 cm×2 cm野比较,差异无统计学意义（t=-1.438,P=0.171）。普通方野照射组头颈部器官、腹部器官的吸收剂量与3D-CRT组比较,差异均有统计学意义（t_头=-2.805,P=0.038;t_腹=-11.966,P=0.000）。 结论 接受颅脑肿瘤放射治疗的患者,射野外器官吸收剂量的大小与照射野面积、是否采用楔形板照射技术有关。接受大野照射的患者,靶区邻近器官吸收剂量越大;照射野面积和处方剂量相同时,使用楔形板的照射技术相对于不使用楔形板的射野外器官的吸收剂量增大。     

Dose and image quality in the comparison of analogue and digital techniques in paediatric urology examinations

In paediatric radiology it has been recognised that children have a higher risk of developing cancer from the irradiation than adults (two to three times); therefore, increased attention has been directed towards the dose to the patient. In this study the effect on patient dose and image quality in replacing the exposure in micturating cystourethrography (MCUG) examinations with the stored fluoroscopy image has been investigated. In the intravenous urography (IVU) examination we compared analogue and digital image quality, but the dose measurements were performed on a phantom. Standard clinical X-ray equipment was used. Sixty-eight patients in each of two centres were studied for the MCUG. Doses were measured with a dose-area product (DAP) meter and the image quality was scored. A non-parametric statistical analysis was performed. For the IVU, a phantom was used in the dose measurements but clinical images were scored in the comparison between analogue and digital images. For the MCUG, replacing the exposure with stored fluoroscopy images lowered the DAP value from 0.77 to 0.50 Gy cm². The image quality did not show any difference between the techniques; however, if reflux was to be graded, exposure was needed. For the IVU, the doses could be lowered by a factor of 3 using digital techniques. The image quality showed no statistical difference between the two techniques. There is a potential for a substantial dose reduction in both MUCG and IVU examinations using digital techniques.     

医学工作者的职业照射：剂量水平、辐射危害和个人剂量监测

辐射的医学应用是核能应用中最为活跃的领域，特别是近20年来介入放射学突飞猛进的发展，医学工作者是职业受照群体中增长最快的，也是最大的受照群体。由于辐射防护管理和培训的滞后，辐射防护意识和装备满足不了迅猛发展的需要，医学工作者（特别是介入放射学工作者）的职业性受照剂量较高，因此医学工作者是职业受照群体中最应受到关注的群体。为此。告诫职业受照的医学工作者，在用辐射技术造福于病人的同时，要关注自已的安全和健康，加强防护。接受完整的个人剂量监测。     

Three-dimensional conformal radiotherapy in the treatment of prostate cancer in Australia and New Zealand: Report on a survey of radiotherapy centres and the proceedings of a consensus workshop

There is an increasing use of 3-D conformal radiotherapy (3DCRT) in the radiotherapeutic management of prostate cancer. The Faculty of Radiation Oncology Genito-Urinary Group carried out a survey of Australian and New Zealand radiotherapy centres in the preparation of a consensus workshop. Of the 19 centres that were represented, there were 24 radiation oncologists, 16 radiation therapists and 12 medical physicists. The survey collected demographic information and data on the practices undertaken at those centres when delivering curative radiotherapy in the treatment of prostate cancer. There was much variation in the delivery of treatment in the areas of patient set-up, contouring of target volumes and organs of interest during computer planning, the techniques and the dose constraints used in these techniques, the use of adjuvant androgen deprivation therapy and the quality assurance processes used in monitoring effects of treatment. This variability reflects the range of data in the published literature. Emerging trends of practices were also identified. This is a first report on a multi-disciplinary approach to the development of guidelines in 3DCRT of prostate cancer.     

Assessment of the micronucleus assay as a biological dosimeter using cytokinesis-blocked lymphocytes from cancer patients receiving fractionated partial body-radiotherapy

Purpose

To assess the suitability of the cytokinesis block micronucleus assay as a biological dosimeter following in-vivo radiation using cancer patients undergoing radiotherapy.

Methods

Blood from 4 healthy donors was irradiated in vitro with γ-rays and the dose response of induced micronuclei in binucleate lymphocytes following cytokinesis block was determined. Micronucleus frequency was ascertained before and at intervals during radiotherapy treatment in 6 patients with various tumors in the pelvic region. Equivalent whole body doses (physical doses) at these times were calculated from radiation treatment plans and cumulative dose volume histograms.

Results

Linear dose response relationships were found for induced micronucleus frequency in lymphocytes resulting from both in-vitro and in-vivo irradiation. Doses resulting from in-vivo irradiation (biological doses) were estimated by substitution of micronucleus frequency observed in radiotherapy patients into the dose response curve from in-vitro irradiation of blood. The relationship between the biologically estimated dose (BD) and the calculated equivalent whole body dose (PD) was BD=0.868(±0.043)PD+0.117(±0.075).

Conclusion

The micronucleus assay appears to offer a reliable and consistent method for equivalent whole body radiation dose estimation, although our findings should be confirmed using lymphocytes from radiotherapy patients with tumors at anatomical sites other than the pelvis. Except at doses lower than about 0.4 Gy, the method yields dose estimates acceptably close to “true” physically determined doses. The assay can be performed relatively rapidly and can be used as a “first line” biological dosimeter in situations where accidental exposure to relatively high radiation doses has occurred.