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Complications of combined intraoperative radiation (IORT) and external radiation (ERT) of the upper abdomen: an experimental model.

An experimental model in the rabbit is presented which is suitable for analysis of clinically relevant, early side-effects of combined upper abdominal IORT and ERT. Fractionated ERT alone given through an upper abdominal a.-p. field including the entire stomach caused gastric ulcerations within < or = 58 days. Latent times decreased with increasing dose and the ED50 for occurrence of ulcers was 39 +/- 3.3 Gy. Single doses of IORT of 20-40 Gy alone administered through a 2-cm diameter field localized on the coeliac axis and carefully excluding any intestinal mucosa caused neither gastric ulcerations nor other clinical symptoms. When ERT with 40 Gy was preceded by IORT with 20-40 Gy or by sham IORT, 13 out of 15 animals developed ulcers after latent times which in a life-table analysis were shown to be significantly shorter than after ERT alone. However, a statistically significant IORT dose-dependence of latent time or incidence of ulcers could not be demonstrated in the present experiment. The most significant histological changes were observed in the areas of gastric ulcers. Already during ERT, the mucosal epithelium was depleted and regenerative activity was evident in spite of ongoing fractionated irradiation. However, profound irregularities in glandular structure and distribution, as well as number of proliferating epithelial cells were still present in healed ulcers at 80 days. In summary, IORT to the coeliac artery did precipitate the development of gastric ulcers induced by subsequent ERT. On the one hand, the data indicate that the surgical procedure of IORT did contribute to this effect. On the other hand, IORT to the coeliac artery could cause transient, functional alterations in blood supply to the depending organs, i.e. the stomach, and could thus precipitate the development of radiation-induced ulcers.

Animals↗

Uncertainties in radiation effect predictions for the natural radiation environments of space.

Future manned missions beyond low earth orbit require accurate predictions of the risk to astronauts and to critical systems from exposure to ionizing radiation. For low-level exposures, the hazards are dominated by rare single-event phenomena where individual cosmic-ray particles or spallation reactions result in potentially catastrophic changes in critical components. Examples might be a biological lesion leading to cancer in an astronaut or a memory upset leading to an undesired rocket firing. The risks of such events appears to depend on the amount of energy deposited within critical sensitive volumes of biological cells and microelectronic components. The critical environmental information needed to estimate the risks posed by the natural space environments, including solar flares, is the number of times more than a threshold amount of energy for an event will be deposited in the critical microvolumes. These predictions are complicated by uncertainties in the natural environments, particularly the composition of flares, and by the effects of shielding. Microdosimetric data for large numbers of orbits are needed to improve the environmental models and to test the transport codes used to predict event rates.

Cosmic Radiation↗

The radiation field characteristics of a 137Cs source used for calibration of radiation protection instruments.

In this work, an experimental study of the radiation beam characteristics of the photon beams produced by commercial irradiator that uses a single collimated 137Cs source is performed. A set of lead attenuators are placed at the exit window of the irradiator to vary the air Kerma that is required to cover the instrument scales at a particular calibration distance. The results strongly enhance the findings of previous studies that a single source with appropriate attenuation and collimation is a practical solution for calibration laboratories with an acceptable overall accuracy.

Brazil↗

A permanent breast seed implant as partial breast radiation therapy for early-stage patients: a comparison of palladium-103 and iodine-125 isotopes based on radiation safety considerations.

PURPOSE: A permanent breast seed implant (PBSI) technique has been developed as a new form of partial adjuvant radiation therapy for early-stage breast cancer. This study compares iodine-125 ((125)I) and palladium-103 ((103)Pd) isotopes by examining the exposure and effective dose (ED) to a patient's partner. METHODS AND MATERIALS: A low-energy survey meter was used to measure exposure rates as a function of bolus thickness placed over (103)Pd or (125)I seeds. A general mathematical expression for the initial exposure rate at 1 m (x(o,1m)) from the skin surface as a function of the implant size, R, and the distance between the skin surface and the implant, d, was derived. Also, a second general equation is proposed to calculate the ED to the patient's partner. RESULTS: The initial exposure rate at 1 meter and the ED are calculated as follows: x(o,1m) = 3alpha2R(3) ; ;beta(3) [e(-beta(2R+d))(betaR + 1) + e(-betad)(betaR - 1)], and ED = aR(b) [e(-c(2R+d)) (cR + 1) + e(-cd) (cR - 1)]. For (125)I, the parameters are: alpha = 0.154409, beta = 0.388460, a = 197, b = -0.95, and c = 0.38846. For (103)Pd, they are: alpha = 0.06877, beta = 0.421098, a = 18.6, b = -0.78, and c = 0.421098. For implant diameters varying from 2 to 6 cm and skin-to-implant distances varying from 0.7 to 4 cm, the ED is consistently below 2.6 mSv using the (103)Pd isotope, but more than 5 mSv in many instances and possibly up to 20 mSv using (125)I. CONCLUSIONS: PBSI using (103)Pd seeds appears safe because the patient's partner ED is consistently below 5 mSv. The(125)I isotope is not recommended for PBSI.

Algorithms↗

Dosimetric analysis and comparison of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy for patients with hepatocellular carcinoma and radiation-induced liver disease.

PURPOSE: This study compares the difference in dose-volume data between three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for patients with hepatocellular carcinoma (HCC) and previously documented radiation-induced liver disease (RILD) after 3D-CRT. MATERIALS AND METHODS: Between November 1993 and December 1999, 68 patients with HCC were treated with 3D-CRT at our institution. Twelve of them were diagnosed with RILD within 4 months of completion of 3D-CRT. RILD was defined as either anicteric elevation of alkaline phosphatase level of at least twofold and nonmalignant ascites, or elevated transaminases of at least fivefold the upper limit of normal or of pretreatment levels. Three-dimensional treatment planning using dose-volume histograms of normal liver was used to obtain the dose-volume data. These 12 patients with RILD were replanned with an IMRT planning system using the five-field (gantry angles 0 degrees, 72 degrees, 144 degrees, 216 degrees, and 288 degrees ) step-and-shoot technique to compare the dosimetric difference in targets and organs at risk between 3D-CRT and IMRT. Mean dose and normal tissue complication probability with literature-cited volume effect parameter of 0.32, curve steepness parameter of 0.15, and TD(50)(1) of 40 Gy, were used for the liver, whereas volume fraction at a given dose level was used for other critical structures. Paired Student t-test with 2-tailed p < 0.05 was used to assess the statistical difference between the two techniques. RESULTS: With comparable target coverage between 3D-CRT and five-field step-and-shoot IMRT, IMRT was able to obtain a large dose reduction in the spinal cord (5.7% vs. 33.2%, p = 0.007), and achieved at least similar organ sparing for kidneys and stomach. IMRT had diverse dosimetric effect on liver, with significant reduction in normal tissue complication probability (23.7% vs. 36.6%, p = 0.009), but significant increase in mean dose (2924 cGy vs. 2504 cGy, p = 0.009), as compared with 3D-CRT. CONCLUSIONS: IMRT is capable of preserving acceptable target coverage and improving or at least maintaining the nonhepatic organ sparing for patients with HCC and previously diagnosed RILD after 3D-CRT. The true impact of this technique on the liver remains unsettled and may depend on the exact volume effect of this organ.

Adult↗

[Radiation exposure and radiation risks from body scanners (author's transl)].

The exposure received during investigation with the Delta 50 FS body scanner was measured in 150 patients. On the basis of data in IRCP 26, the somatic and genetic risk from the absorbed dose was calculated. The somatic risk per examination varies between 1:40 000 and 1:310 000, depending on the part of the body examined. The genetic risk (probability of radiation induced malformation in off-springs) is of the order of 1:19 000 to 1:1 5 million.

Abnormalities, Radiation-Induced↗

Cellular origin of ionizing radiation-induced NF-kappaB activation in vivo and role of NF-kappaB in ionizing radiation-induced lymphocyte apoptosis.

PURPOSE: To investigate the cellular origin of ionizing radiation (IR)-induced NF-kappaB activation in vivo and the role of NF-kappaB in IR-induced lymphocyte apoptosis. MATERIALS AND METHODS: NF-kappaB activities were analysed by gel shift/supershift assay in isolated murine T- and B-cells, macrophages (MPhi) and tissues from normal and T- and B-cell-deficient Rag1 mice with or without exposure to IR. IR-induced lymphocyte apoptosis was determined by analysis of 3,3'-dihexyloxacarbocyanine iodide (DiOC(6)) uptake, annexin-V staining and the sub-G0/1 population, or by TUNEL assay. RESULTS: The results showed that IR activated NF-kappaB in lymphocytes, including both T- and B-cells, but failed to do so in MPhi. Furthermore, T- and B-cell-deficient Rag1 mice exposed to IR exhibited a significant reduction in NF-kappaB activation as compared with normal mice. Although NF-kappaB1 (p50) gene knockout or NF-kappaB decoy oligonucleotide treatment specifically inhibited IR-induced lymphocyte NF-kappaB activation, they had no significant effect on IR-induced lymphocyte apoptosis. CONCLUSIONS: This finding suggests that lymphocytes are the main cellular origin of IR-induced NF-kappaB activation in vivo. However, NF-kappaB activation has no significant effect on IR-induced lymphocyte apoptosis.

Animals↗

Human lymphocytes exposed to low doses of ionizing radiations become refractory to high doses of radiation as well as to chemical mutagens that induce double-strand breaks in DNA.

Human lymphocytes exposed to low doses of ionizing radiation from incorporated tritiated thymidine or from X-rays become less susceptible to the induction of chromatid breaks by high doses of X-rays. This response can be induced by 0.01 Gy (1 rad) of X-rays, and has been attributed to the induction of a repair mechanism that causes the restitution of X-ray-induced chromosome breaks. Because the major lesions responsible for the induction of chromosome breakage are double-strand breaks in DNA, attempts have been made to see if the repair mechanism can affect various types of clastogenic lesions induced in DNA by chemical mutagens and carcinogens. When cells exposed to 0.01 Gy of X-rays or to low doses of tritiated thymidine were subsequently challenged with high doses of tritiated thymidine or bleomycin, which can induce double-strand breaks in DNA, or mitomycin C, which can induce cross-links in DNA, approximately half as many chromatid breaks were induced as expected. When, on the other hand, the cells were challenged with the alkylating agent methyl methanesulfonate (MMS), which can produce single-strand breaks in DNA, approximately twice as much damage was found as was induced by MMS alone. The results indicate that prior exposure to 0.01 Gy of X-rays reduces the number of chromosome breaks induced by double-strand breaks, and perhaps even by cross-links, in DNA, but has the opposite effect on breaks induced by the alkylating agent MMS. The results also show that the induced repair mechanism is different from that observed in the adaptive response that follows exposure to low doses of alkylating agents.

Adult↗

A theoretical concept for measuring doses from external radiation sources in radiation protection.

A physically consistent concept is presented for monitoring individual exposures from external radiation, giving quantitative relations between 'fitted' dosemeters satisfying this relation, and 'non-fitted' dosemeters which do not. The calibration of both types is discussed in detail. For non-fitted dosemeters, procedures to determine the error limits are given. The application to accident dosimetry is briefly discussed.

Mathematics↗

Phase II study of radiation therapy combined with weekly nedaplatin in locally advanced uterine cervical carcinoma: Kitasato Gynecologic Radiation Oncology Group (KGROG 0501).

In order to evaluate the safety and efficacy of chemoradiotherapy using nedaplatin for locally advanced uterine cervical carcinoma in Japanese patients, we have started a single-institute phase II trial. Eligibility criteria include: (i) pathologically proven squamous cell carcinoma or adenocarcinoma, (ii) clinical FIGO stage Ib, IIa, or IIb with bulky tumor (> 40 mm) or pelvic lymph node swelling, or (iii) clinical FIGO stage IIIa, IIIb and IVa, (iv) no para-aortic lymph node swelling. A combination of external beam radiation and high dose rate intracavitary irradiation is given. Nedaplatin (30 mg/m2) is intravenously infused on a weekly basis for five times. The primary endpoint is 3-year overall survival, and the secondary endpoints are tumor response, 2-year overall survival, 3-year progression-free survival, acute adverse events, protocol treatment compliance, and late adverse events. We plan to recruit 45 patients within 3 years.

Adenocarcinoma↗

Can UV radiation-blocking soft contact lenses attenuate UV radiation to safe levels during summer months in the southern United States?

PURPOSE: Peak solar UV radiation (UVR) intensities are typically experienced in summer months. People living in the southern states of the United States, where the UVR frequently exceeds the recommended minimum erythema dose (MED), are at particular risk, especially outdoor workers. The present study analyzed summertime MED readings in Houston, TX, to assess the frequency of intensities regarded as unhealthy. The study also sought to assess whether UV-blocking hydrogel contact lenses provide ocular protection from these high doses. METHODS: Readings, taken at midday using a UVR biometer, were analyzed to assess the potential UVR risk. The spectral response of the meter, modified by the spectral transmission curves of the contact lenses, allowed us to mathematically assess the ocular protection provided. In addition, ambient UVR measurements were taken at midday, using a portable UVR radiometer. The detector was adapted so that a standard diameter hydrogel contact lens could be placed over it to quantify the UV-blocking capabilities of the lens. RESULTS: The MED readings showed that the recommended safety standards were exceeded approximately at local midday 90% of the time. Model calculations and empirical data demonstrated that contact lenses attenuated the MED readings by up to 90%, bringing them well within the recommended Environmental Protection Agency safety standards. CONCLUSION: The efficacy of the model used in this study was verified through direct comparison of the modeled and measured data. UV-blocking hydrogel soft contact lenses reduce the MED to the human eye and therefore limit the lifetime ocular dose. These lenses are highly recommended to prevent the development of UVR-related ocular pathologic conditions.

Contact Lenses, Hydrophilic↗

The influence of pre-radiation salivary flow rates and radiation dose on parotid salivary gland dysfunction in patients receiving radiotherapy for head and neck cancers.

Radiotherapy (RT) used for head and neck cancers causes permanent salivary gland dysfunction (SGD). Previous short-term studies have demonstrated that pre-RT salivary flow rates and the amount of radiation exposure to parotid glands influence the amount of RT-induced SGD. The purpose of this study was to determine which variables are related to the development of long-term post-RT SGD. Parotid flow rates (PFR) were assessed prior to and 1 year after completion of RT in spared parotid glands from 34 patients from 2 parotid-sparing protocols. The results reveal that spared PFR were not significantly higher 1 year post-RT in patients who had high pre-RT PFR, when compared with patients with low pre-RT PFR. However, patients who received higher doses of RT to spared parotid glands had lower PFR 1 year post-RT, compared with patients who had received lower doses of RT. These one-year findings suggest that high pre-RT PFR do not provide protection against RT-induced SGD. Conversely, reduced RT dosages to contralateral parotid glands are protective of PFR after completion of RT.

Adult↗

A new radiation shielding block material for radiation therapy.

In recent years, lead has been recognized as a source of environmental pollution; this includes lead use for radiation shielding in radiotherapy. We looked for a new material that could be a lead substitute. We chose a material composed of tungsten and resin. We compared the attenuation coefficient of the material with those of lead and Lipowitz's metal, and found the material has a higher attenuation coefficient than the other two. The material may be used as a substitute for lead because it is easy to fabricate and friendly to the environment.

Biocompatible Materials↗

Comparison of properties of spontaneous and radiation-induced mouse thymic lymphomas: role of Trp53 and radiation.

Mouse thymic lymphomas are readily induced by radiation and also arise without irradiation when the mice are null in Trp53 functions. In the present study, spontaneous thymic lymphomas in Trp53-/- mice were compared to those arising in irradiated Trp53+/- mice, revealing three features characteristic of the spontaneous lymphomas. (1) Mp53D2, a Trp53 modifier that affects the latent period of radiogenic thymic lymphomas in Trp53+/- mice, had no effect on the development of spontaneous lymphomas. (2) A sex difference in the latency was found. (3) A marked difference was noted in the frequency of allelic loss at the Ikaros gene on chromosome 11, encoding a transcription factor required for normal lymphocyte development and differentiation; 2% in the lymphomas of Trp53-/- mice and 78% in the radiogenic lymphomas of Trp53+/- mice, suggesting that loss of Trp53 may reduce the requirement for the loss of Ikaros for lymphomagenesis. Furthermore, allelic loss analysis on chromosome 19 localized a region that may harbor an unknown tumor suppressor gene. These results suggest intricate steps of lymphomagenesis influenced by the presence or absence of Trp53.

Animals↗

Potentiating effect of fetal thymus on fetal liver cells for the promotion of recovery from the radiation injury in murine allogenic radiation chimeras or a little bit of thymus goes a long, long way.

Lethally irradiated CBA (H-2k) mice were treated with small numbers of liver cells from strain-A (H-2a) fetal donors. Recovery from the radiation injury was dependent upon the dose of liver cells administered. Giving very small numbers of fetal thymus cells, in addition to liver cells, had a highly significant and salutary effect on survival. The results suggest that clinical transplantation of liver cells from a single fetus might succeed if thymus cells are added.

Animals↗

[Quantitative description of the process of radiation inactivation of cells. VII. Nature of primary radiation lesions leading to reproductive cell death].

The entity of radiation damage of viruses, bacteria and cells is defined by the organization of genetic structures. Asimmetrical chromosome exchanges have been proposed as the main reason of inactivation of di- and polyploid eukaryotic cells. If a single molecule of DNA is taken for the core of chromosome, the exchange is believed to be a consequence of cross-polymerization of two polypeptid strands of the single DNA molecule. Thus, the double strand break of DNA is necessary to produce aberration. A hypothesis is put forward on the identity of primary lesion of chromosome with the double strand break. The experimental survival curve is approximated according to the formula derived from the model. The yield of primary lesions of chromosomes is proposed to be equal to that of double strand breaks of chromosomes in order to examine the validity of the hypothesis. The optimal interaction distance of primary lesions in correspondence with parameters of the survival curve is equal to 0.8 mkm. This estimation is in good agreement with the microdosimetrical data, and the proposed hypothesis is not contradicted.

Cell Survival↗

[Mutagenic effect of different types of radiation on the sex cells of male mice. VIII. Frequency of development of reciprocal translocations in the spermatogonia of mice subjected to chronic gamma radiation].

The frequency of reciprocal translocations in mice spermatogonia after the exposure to chronic gamma-irradiation at doses of 100, 200, 300, 600, 920 r, at the dose rate of 4,2 r/day was investigated. It was shown that the mutation frequency increased insignificantly with the increase of the radiation dose (y=0,8+0,0011x). The comparison of the data obtained with earlier results revealed no changes in the yeild of translocations at the reduction of the dose rate from 10 r/day to 4,2 r/day. The investigation of the genetic radiosensitivity of mice spermatogonia after a chronic gamma-irradiation showed a tendency to increase in their radioresistance.

Animals↗

Ultraviolet radiation-induced murine tumors produced in the absence of ultraviolet radiation-induced systemic tumor immunosuppression.

Using micro-UV-irradiation versus whole-dorsal irradiation for inducing cutaneous carcinomas in Skh:HRI mice and an assay for UV radiation (UVR)-induced systemic tumor immunosuppression, the dependence upon systemic immunosuppression for the growth of UVR-induced carcinomas was examined. Squamous cell carcinomas were produced by repeated microirradiation of 0.8-cm2 middorsal skin with xenon are solar-simulated UVR. These tumors were excised from tumor-bearing animals who 7 days later were inoculated ventrally with a cloned UVR-induced squamous cell carcinoma cell line, the T51/6. This cell line only grows in UVR-induced immunosuppressed Skh:HRI mice. In two separate experiments T51/6 inocula failed to grow significantly in the previously tumor-bearing animals (1 of 13) and in unirradiated mice (0 of 19), whereas it grew in 100% (15 of 15) of animals given a whole-dorsal subcarcinogenic UVR dose from a filtered fluorescent tube solar simulator. No sinecomitant immune response to the T51/6 was found in previously UVR-induced tumor-bearing animals. In contrast to whole-dorsal UVR-induced tumors, microirradiation-induced squamous cell carcinomas, whose original growth environment lacked UVR-induced systemic tumor immunosuppression, did not grow preferentially in mice given an immunosuppressive dose of UVR. However both the whole-dorsal and microirradiation-induced tumors were shown to be poorly antigenic, since they lacked preferential growth in athymic nude mice. These observations provide evidence that UVR-induced systemic tumor immunosuppression is not necessary for the production of UVR-induced tumors. However, it does cause a positive selection pressure during tumor formation, independent of the carcinogenic effect of UVR, which affects the transplantation biology of a tumor.

Animals↗