Thermal stress and radiation protection principles

Exposure to radiofrequency (RF) fields can occur in residential, occupational and medical settings. Since many technologies use RF fields, it is important to fully investigate their effects on the human body. Since the demonstrated effect of RF exposure is heating, it is important to critically evaluate studies of elevated temperature effects on the human body, from the cellular and tissue level to the whole body level, including potential effects on the susceptible groups such as the very young and the very old. WHO convened a Workshop in the Spring of 2002 on the subject of Adverse Temperature Levels in the Human. The goal of the workshop was to evaluate most recent data useful for the development of science-based RF exposure limits. This paper outlines radiation protection principles that underline such an evaluation. It discusses the quality of literature needed for sound scientific reviews, provides the hierarchy of scientific evidence used to establish effects, distinguish between biological effects and adverse health consequences and indicates how evidence is evaluated. In addition, criteria for determining the most sensitive effects, the value of an effect that has a dose-response and methods of extrapolation are also described. Finally, the need to account for scientific uncertainty in the formulation of guidance on exposure is discussed.     

Application of radiobiologic principles to radiation therapy

Oxygen remains one of the most potent sensitizers of mammalian cells yet studied and, most important, it is maximumly sensitizing at physiologic concentrations. There is very good evidence that solid tumors of both experimental animals and man contain hypoxic and viable cells. In experimental animals hyperbaric oxygen does result in improvement of radiation therapy even when the treatment is highly fractionated and protracted over periods of up to 3 to 4 1/2 weeks. This represents strong evidence that--at least in some human tumors--results of fractionated irradiation will be significantly improved by the addition of hyperbaric oxygen. At the same time it is admitted that results of clinical trials of hyperbaric oxygen and radiation therapy do not indicate any marked improvement by the addition of hyperbaric oxygen. However, the trials are early and based on small numbers; they may well show a modest but clinically important improvement as they mature. It is essential that the trials cover several tumor types. Hyperbaric oxygen may not be useful in radiotherapy for all tumors. Evidence from the tests of tourniquet hypoxia and radiotherapy indicate that, at least for osteosarcoma, the hypoxic cell per se may not be the dominant factor in deciding results of standard fractionated therapy.     

Assessment of secondary radiation and radiation protection in laser-driven proton therapy

This work is a feasibility study of a radiation treatment unit with laser-driven protons based on a state-of-the-art energy selection system employing four dipole magnets in a compact shielded beamline. The secondary radiation emitted from the beamline and its energy selection system and the resulting effective dose to the patient are assessed. Further, it is evaluated whether or not such a compact system could be operated in a conventional treatment vault for clinical linear accelerators under the constraint of not exceeding the effective dose limit of 1 mSv per year to the general public outside the treatment room. The Monte Carlo code Geant4 is employed to simulate the secondary radiation generated while irradiating a hypothetical tumor. The secondary radiation inevitably generated inside the patient is taken into account as well, serving as a lower limit. The results show that the secondary radiation emanating from the shielded compact therapy system would pose a serious secondary dose contamination to the patient. This is due to the broad energy spectrum and in particular the angular distribution of the laser-driven protons, which make the investigated beamline together with the employed energy selection system quite inefficient. The secondary radiation also cannot be sufficiently absorbed in a conventional linear accelerator treatment vault to enable a clinical operation. A promising result, however, is the fact that the secondary radiation generated in the patient alone could be very well shielded by a regular treatment vault, allowing the application of more than 100 fractions of 2 Gy per day with protons. It is thus theoretically possible to treat patients with protons in such treatment vaults. Nevertheless, the results show that there is a clear need for alternative more efficient energy selection solutions for laser-driven protons.     

Spinal cord protection during radiation therapy

Treating intrathoracic malignancies to high doses, particularly those of lung and esophagus, requires limiting the radiation dose delivered to the spinal cord. Several factors are important in determining the cord dose. These are: The distance from the block or collimator edge to the cord, the variation of dose with distance from the block or collimator edge and, the expected variation of this distance for clinical set-up from day-to-day. When treating with an oblique beam, the position of the cord may be difficult to identify. A technique for localizing the spinal cord on a simulator film at an arbitrary gantry angle is presented. The technique requires determination of distances from the central axis of the beam to the medial aspect of the pedicle and posterior vertebral body. These can readily be obtained from measurements on orthogonal, AP/PA and lateral isocentric simulator radiographs. A mathematical transformation is applied to determine the corresponding cord locations on the oblique radiographs for any arbitrary gantry angle. The accuracy of cord localization was within 2-3 mm with a precision of 2 mm for five physicians who used this technique. The beam edge characteristics for 60Co, 6 MV, and 10 MV teletherapy unit were measured for various depths and field sizes. For the 6 and 10 MV units, the beam penumbra is nearly independent of the field size, depth and field defining devices (inner and outer collimator jaws, trimmer bars, and shielding blocks). Because the beam penumbra is dependent on the design of the linear accelerator, its measurement should be made individually for each linear accelerator. Our preliminary data on patient positioning uncertainty did not exceed the 6-8 mm limit documented in the literature.     

痰热清注射液对放射性肺炎的预防作用

目的：观察痰热清注射液对急性放射性肺炎的预防作用。方法：90例不能手术的非小细胞肺癌病人随机分入治疗组44人与对照组46人。采用适形放射治疗技术,总剂量56—64Gy,V20限制在20％-30％;治疗组从放疗开始到放疗结束应用痰热清注射液每天20ml静脉点滴,每连用5天,停用2天。对照组单纯放疗。结果：治疗组和对照组放射性肺炎发生例数（率）分别是5（11．3％）和14（30．4％）,两组之间有显著差别（P〈0．05）,且治疗组无2级及以上放射性肺炎的发生。放射性肺炎发病时间分别是放疗开始后62．2天和54．3天,差异显著（P〈0．05）。结论：接受放射治疗的非小细胞肺癌患者放疗期间应用痰热清注射液能有效预防放射性肺炎的发生。     

Radioguided surgery of breast cancer: radiation protection survey

The aim of this study was to estimate the radioactive risk for surgical staff performing radioguided sentinel lymph node (SN) biopsy and to calculate the contamination level in the operating room for assessment of the possible need for specific radiation protection procedures. We studied 20 patients who were selected for quadrantectomy and SN biopsy. The day before surgery a volume of 0.15 mL of 99mTc-nanocoll was injected: the activity was 3.11 +/- 0.85 MBq in group A (15 pts) and 11.6 +/- 0.6 MBq in group B (5 pts). External radiation to staff was evaluated by measuring the exposure rate in air one hour after radiopharmaceutical administration. The air KERMA rate during surgery was estimated considering the physical decay of 99mTc. Contamination of disposable materials and surgical instruments in the operating room was measured using a contamination monitor, whereas the residual activity in the SN and the injection site was measured with a gamma probe. The exposure rate at 20 cm from the injection site was 0.75 microSv/h when the most radioactive patients (group B) were treated. Contamination in the operating room proved to be negligible. Considering the number of radioguided treatments carried out by a surgeon in one year, an equivalent effective dose of 0.075 mSv was estimated; the recommended dose limit according to the relevant Italian law, DL 230/95, is 1 mSv/yr. Surgical staff therefore do not require a classification of "exposed workers" and there is no need to supply the operating room with special containers for radioactive waste.     

痰热清注射液对放射性肺炎的预防作用

目的:观察痰热清注射液对急性放射性肺炎的预防作用.方法: 90例不能手术的非小细胞肺癌病人随机分入治疗组44人与对照组46人.采用适形放射治疗技术,总剂量56-64 Gy,V20 限制在20%-30%;治疗组从放疗开始到放疗结束应用痰热清注射液每天20ml静脉点滴,每连用5天,停用2天.对照组单纯放疗.结果: 治疗组和对照组放射性肺炎发生例数(率)分别是5(11.3%)和14(30.4%),两组之间有显著差别(P<0.05),且治疗组无2级及以上放射性肺炎的发生.放射性肺炎发病时间分别是放疗开始后62.2天和54.3天,差异显著(P<0.05).结论: 接受放射治疗的非小细胞肺癌患者放疗期间应用痰热清注射液能有效预防放射性肺炎的发生.     

Localization and protection of kidneys in radiation treatment planning using computed tomography

Irradiation treatment portals of the upper abdomen must limit the dose to the kidneys. Sparing one-third of the parenchyma of each kidney will prevent late clinical sequelae. One hundred CT scans of the abdomen were studied to evaluate using the vertebrae as landmark for treatment planning. In lateral fields, using the anterior border of the vertebral column as a landmark for the posterior high isodose line will limit treatment to less than 60% (mean 22%) of a single kidney. Placing the edge of an anterior/posterior field 2 cm lateral to the vertebral column will limit the dose to less than 44% of a single kidney (mean 11%).     

Prostate brachytherapy with iodine-125 seeds: radiation protection issues

AIMS AND BACKGROUND: Brachytherapy for prostate cancer by means of permanently implanted 125I sources is a well established procedure. An increasing number of patients all over the world are treated with this modality. When the technique was introduced at our institution, radiation protection issues relative to this technique were investigated in order to comply with international recommendations and national regulations. Particular attention was paid to the need for patient shielding after discharge from hospital. METHODS: The effective and equivalent doses to personnel related to implantation, the effective dose to patient relatives as computed by a developed algorithm, the air kerma strength values for the radioactive sources certified by the manufacturer compared with those measured by a well chamber, and the effectiveness of lead gloves in shielding the hands were evaluated. RESULTS: The effective dose to the bodies of personnel protected by a lead apron proved to be negligible. The mean equivalent doses to the physician's hands was 420 microSv for one implant; the technician's hands received 65 microSv. The mean air kerma rate measured at the anterior skin surface of the patient who had received an implant was 55 microGy/h (range, 10-115) and was negligible with lead protection. The measured and certified air kerma strength for125I seeds in RAPID Strand corresponded within a margin of +/- 5%. The measured attenuation by lead gloves in operative conditions was about 80%. We also defined the recommendations to be given to the patient at discharge. CONCLUSIONS: The exposure risks related to brachytherapy with 125I to operators and public are limited. However, alternation of operators should be considered to minimize exposure. Patient-related measurements should verify the dose rate around the patient to evaluate the need for shielding and to define appropriate radiation protection recommendations.     

Lens epithelial cell protection by aminothiol WR-1065 and anetholedithiolethione from ionizing radiation

Lens epithelium disorganization, glutathione (GSH) depletion, and epithelial cell death have been incriminated in the cytopathogenic mechanisms that lead to cataract formation following UVB and x-ray exposures. The objective of this study was to determine the in vitro capacity of the aminothiol WR-1065, the active metabolite of amifostine, and anetholedithiolethione (ADT or Sulfarlem®) to protect bovine lens epithelial cells against x-ray irradiation. WR-1065 and ADT were used at a concentration of 20 μM. A single dose of 10 Gy was delivered at a rate of 2 Gy/min. Fluorimetric assays were then performed using a neutral red probe to evaluate cell viability, a Hoechst 33342 probe (HO) to evaluate nuclear condensation and apoptosis, and a monobromobimane probe to estimate the intracellular GSH pool. Twenty-four hours after x-ray exposure, cells pretreated with WR-1065 showed increased GSH levels, improved cell viability, and decreased HO fluorescence in addition to a lesser proportion of cells with apoptotic nuclear modifications. Between 72 and 120 hr postirradiation, ADT-pretreated cells also showed increased intracellular GSH levels and cell viability and decreased HO fluorescence and apoptotic cell morphology. This in vitro study demonstrates that WR-1065 and ADT protects lens epithelial cells from x-ray injury; thus, ADT and amifostine are appropriate candidates for clinical trials in humans. They are currently used in preventing radiation-induced xerostomia and should be further tested in the prevention of late radiation-induced ocular complications such as sicca syndrome and cataract. © 2002 Wiley-Liss, Inc.     

Synthesis of nanosilver using a vitamin C derivative and studies on radiation protection

Silver nanoparticles were prepared from silver nitrate using a vitamin C derivative, 6-palmitoyl ascorbic acid-2-glucoside (PAsAG), via a sonochemical experiment. The resultant golden yellow solution that contained silver nanoparticle-PAsAG complex (SN-PAsAG) of about 5?nm particle sizes was explored for its potential to offer protection to DNA from γ-radiation-induced damages. The presence of SN-PAsAG during irradiation inhibited the disappearance of covalently closed circular (ccc) form of plasmid pBR322 with a dose modifying factor of 1.78. SN-PAsAG protected cellular DNA from radiation-induced damage as evident from comet assay study on mouse spleen cells, irradiated ex vivo. When orally administered with SN-PAsAG at 1 hour prior to whole-body radiation exposure, cellular DNA was found protected from radiation-induced strand breaks in various tissues (spleen cells, bone marrow cells, and blood leucocytes) of animals. Also, SN-PAsAG could enhance the rate of repair of cellular DNA in blood leucocytes and bone marrow cells when administered immediately after radiation exposure. The studies, under in vitro, ex vivo, and in vivo radiation exposure conditions, showed effective radiation protection.     

Negligible radiation protection of endothelial cells by vascular endothelial growth factor

Glioblastoma multiforme (GBM) is a radioresistant tumor. Tumor neoangiogenesis is an important mechanism for tumor sustenance. Angiogenesis is primarily mediated by vascular endothelial growth factor (VEGF), and earlier studies have suggested that VEGF protects human umbilical vein endothelial cells (HUVECs) against high doses of radiation. We tried to extend these findings to other endothelial cell lines and clinically relevant irradiation doses. Therefore, four different endothelial cell lines (HUVEC-C, primary HUVEC-P, an immortalized HUVEC cell line: EC-RF24, and bovine retina endothelial cells: BREC) were cultured without or with recombinant human VEGF165 (rhVEGF165). Cells were irradiated with gamma-rays from a 137Cs-source. Radiosensitivity was determined by proliferation or clonogenic assay. Apoptosis was assayed by flow cytometric determination of the sub-G1 population or by counting nuclear fragmentation. We found that the biologically active rhVEGF165 was able to improve clonogenic survival of HUVEC-C after 2 and 5 Gy. However, rhVEGF165 could not significantly alter the radiosensitivity of all cell lines studied in proliferation assays. rhVEGF165 only slightly reduced apoptosis in HUVEC-C after 3 Gy. In conclusion, the radioprotective effect from rhVEGF165 was found on different endothelial cell lines after clinically relevant radiation doses was negligible. We therefore hypothesize that the high VEGF-levels found in GBM in vivo do not reduce the radiosensitivity of endothelial cells, which is thought to contribute to the strong radioresistance of the tumor vasculature.