Hepatic Gene Expression Changes in Rats Internally Exposed to Radioactive 56MnO2 Particles at Low Doses.

We have studied the biological effects of the internal exposure to radioactive manganese-56 dioxide (56MnO2), the major radioisotope dust found in soil after atomic bomb explosions. Our previous study of blood chemistry indicated a possible adverse effect of 56MnO2 on the liver. In the present study, we further examined the effects on the liver by determining changes in hepatic gene expressions. Male Wistar rats were exposed to 56MnO2 particles (three groups with the whole-body doses of 41, 90, and 100 mGy), stable MnO2 particles, or external 60Co γ-rays (2 Gy), and were examined together with the non-treated control group on postexposure day 3 and day 61. No histopathological changes were observed in the liver. The mRNA expression of a p53-related gene, the cyclin-dependent kinase inhibitor 1A, increased in 56MnO2 as well as in γ-ray irradiated groups on postexposure day 3 and day 61. The expression of a stress-responsive gene, nuclear factor κB, was also increased by 56MnO2 and γ-rays on postexposure day 3. However, the expression of cytokine genes (interleukin-6 or chemokine ligand 2) or fibrosis-related TGF-ß/Smad genes (Tgfb1, Smad3, or Smad4) was not altered by the exposure. Our data demonstrated that the internal exposure to 56MnO2 particles at less than 0.1 Gy significantly affected the short-term gene expressions in the liver in a similar manner with 2 Gy of external γ-irradiation. These changes may be adaptive responses because no changes occurred in cytokine or TGF-ß/Smad gene expressions.

DNA damage in hair root cells as a biomarker for gamma ray exposure.

The purpose of the present research is to examine whether human hair root cells can be used for dose assessment after in vitro exposure to ionizing radiation. Hair root samples plucked from random head regions were collected from 5 healthy human subjects. Some of these hair samples were used as control and some were irradiated with 0.5-5Gy of gamma ray using a Cs-137 gamma irradiator at a dose rate of 0.14Gy/s. DNA damage (single-strand breaks) was determined in hair root cells of these samples using the comet assay technique. The comet assay parameters, tail length (TL) and tail moment (TM), showed a significant increase (p<.05) in single-strand DNA breaks in hair roots cells of the exposed samples compared to control. A linear dose-effect relationship was observed when tail moment or tail length was plotted against the log of the radiation dose. This research suggests a possible use of human hair root cell DNA damage as a biomarker especially for low dose radiation.

[The mechanism of the antitumor effect of total/subtotal radiotherapy with non-tumoricidal doses of radiation].

The myelodepression at therapy for solid malignancies is considered as a mediating element of common antineoplastic activity on the basis of ability of stem cells of hemapoietic system to participate in regeneration of the various tissues of the body, including tumor. The equivalence of the therapeutic benefit mediated by both mild myelodepression due to total/subtotal radiation exposure and conventional chemotherapy with cytotoxic drugs is argued.

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells.

BACKGROUND: The aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles. MATERIAL/METHODS: Mice were subjected to whole-body exposure with 60Co gamma rays with a dose range of 0-8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR). RESULTS: Of the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2-8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges. CONCLUSIONS: The results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.

Quality assurance tool for determination of position and transit time of a Co-60 source in high dose rate brachytherapy.

In this study, three holders were designed, constructed and characterized to perform quality assurance on the source position and transit time in remote afterloading systems with Co-60 sources for high dose rate brachytherapy. The holders design focused on achieving accuracy, low cost, and a time efficient tool for use in clinical settings. Sensitivities greater than 0.6%/mm and maximum precisions better than 0.14 mm for the source position were obtained. The transit time was determined for the holders with a relative precision better than 19%.

Borosilicate glass 60Co high dose rate brachytherapy thermoluminescence dosimetry.

Brachytherapy is commonly used in treatment of cervical, prostate, breast and skin cancers, also for oral cancers, typically via the application of sealed radioactive sources that are inserted within or alongside the area to be treated. A particular aim of the various brachytherapy techniques is to accurately transfer to the targeted tumour the largest possible dose, at the same time minimizing dose to the surrounding normal tissue, including organs at risk. The dose fall-off with distance from the sources is steep, the dose gradient representing a prime factor in determining the dose distribution, also representing a challenge to the conduct of measurements around sources. Amorphous borosilicate glass (B2O3) in the form of microscope cover slips is recognized to offer a practicable system for such thermoluminescence dosimetry (TLD), providing for high-spatial resolution (down to < 1 mm), wide dynamic dose range, good reproducibility and reusability, minimal fading, resistance to water and low cost. Herein, investigation is made of the proposed dosimeter using a 1.25 MeV High Dose Rate (HDR) 60Co brachytherapy source, characterizing dose response, sensitivity, linearity index and fading. Analysis of the TL glow curves were obtained using the Tmax-Tstop method and first-order kinetics using GlowFit software, detailing the frequency factors and activation energy.

Establishment and multiparametric-cytogenetic validation of 60Co-gamma-ray induced, phospho-gamma-H2AX calibration curve for rapid biodosimetry and triage management during radiological emergencies.

Exposure to ionizing radiation is unavoidable to our modern developing society as its applications are widespread and increasing with societal development. The exposures may be planned as in medical applications or may be unplanned as in occupational work and radiological emergencies. Dose quantification of planned and unplanned exposures is essential to make crucial decisions for management of such exposures. This study aims to establish ex-vivo dose-response curve for 60Co-gamma-ray induced gamma-H2AX-foci by immunofluorescence using microscopy and flowcytometry with human lymphocytes. This technique has the potential to serve as a rapid tool for dose estimation and triage application during small to large scale radiological emergencies and clinical exposures. Response curves were generated for the dose range 0-4 Gy (at 1, 2, 4, 8, 16, 24, 48, 72 and 96 h of incubation after irradiation) with microscopy and 0-8 Gy (at 2, 4, 8, 16 and 24 h of incubation after irradiation) with flow cytometry. These curves can be applied for dose reconstruction when post exposure sampling is delayed up to 96 h. In order to evaluate Minimum Detection Limit (MDL) of the assay, variation of background frequency of gamma-H2AX-foci was measured in 12 volunteers. To understand the application window of the assay, gamma-H2AX foci decay kinetics has been studied up to 96 h with microscopy and response curves were generated from 1 to 96 hours post exposure. Gamma-H2AX fluorescence intensity decay kinetics was also studied up to 96 h with flow cytometry and response curves were generated from 2 to 24 hours post irradiation. Established curves were validated with dose blinded samples and also compared with standard cytogenetic assays. An inter-comparison of dose estimates was made among gamma-H2AX assay, dicentric aberrations and reciprocal translocations for application window in various dose ranges and time of blood collection after exposures.

Estimation and comparison of integral dose to target and organs at risk in three-dimensional computed tomography image-based treatment planning of carcinoma uterine cervix with two high-dose-rate brachytherapy sources: 60Co and 192Ir.

BACKGROUND: Iridium-192 (192Ir) has been a widely accepted radioisotope for high-dose-rate (HDR) brachytherapy. Recently, Cobalt-60 (60Co) radioisotope with a longer half-life (5.26 years) has been gaining popularity due to economic and logistical reasons as compared with the traditional 192Ir. AIM: This study aimed to evaluate and compare the integral dose (ID) to the target and organs at risk (OARs) with two HDR brachytherapy sources in brachytherapy treatment of carcinoma uterine cervix to find appropriate HDR radioisotopes for clinical benefit. MATERIALS AND METHODS: This is a retrospective analysis of 52 computed tomography image-based brachytherapy plans of 52 patients who have received intracavitary treatment with 192Ir HDR source. For each patient plan, one additional set of plan was created using 60Co source in place of 192Ir source keeping the same dwell position, and again dose was optimized. The volume and mean dose for target, OARs, and volume structures of 400%, 200%, 150%, 100%, and 50% were recorded for the estimation and comparison of ID. RESULTS: The mean ID to high-risk clinical target volume was significantly higher by 5.84% in 60Co plan than that in 192Ir plan. For OARs, the mean ID to the rectum was significantly higher by 2.60% in 60Co plan as compared to 192Ir plan, whereas for bladder and sigmoid colon, it was lower in 60Co plan than that in 192Ir plan. The mean ID of central dose volume structures of 400%, 200%, 150%, 100%, and 50% was higher by 12.97%, 9.77%, 8.16%, 6.10%, and 3.22%, respectively, in 60Co plan than that of 192Ir plan. CONCLUSION: The results of our study concluded that 192Ir HDR radioisotope should be preferred for intracavitary brachytherapy due to its ideal physical characteristics for better clinical outcomes.

Acute Radiation-induced GI-ARS and H-ARS in a Canine Model of Mixed Neutron/Gamma Relative to Reference Co-60 Gamma Radiation: A Retrospective Study.

Studies performed decades ago in the canine and nonhuman primate established the dose response relationships for the hematopoietic acute radiation syndrome in response to mixed neutron/gamma, x-radiation, and Co gamma radiation. There were no published studies that determined the dose response relationships for the gastrointestinal acute radiation syndrome in response to either noted radiation quality. This analysis of a retrospective, unpublished study provided the dose response relationships in a canine model for the acute gastrointestinal syndrome relative to the acute hematopoietic syndrome due to mixed neutron/gamma radiation. Canines were exposed to total-body, steady state, bilateral, 0.40 Gy min, mixed neutron/gamma (5.4:1) radiation from a TRIGA reactor. The average neutron/gamma energy (MeV) was 0.85/0.9, and exposure was reported as midline tissue dose. Medical management was not administered. The mixed neutron/gamma exposure resulted in an estimated LD50/6 of 2.83 Gy [2.76, 2.94] and LD50/30 of 2.16 Gy [2.01, 2.24] for the GI- and H-ARS respectively. The mean survival times for decedents after mixed neutron/gamma exposure approximate to the LD50/6 were 8.5 d, 10.5 d, and 4 d for 2.75 Gy, 2.80 Gy, 3.00, and 3.12 Gy exposures, respectively. The mean survival times for decedents for mixed neutron/gamma exposure approximate to the LD50/30 were 21.3 d and 15.6 d for 2.00 Gy and 2.25 Gy, respectively. Furthermore, the dose response relationships for the acute hematopoietic syndrome due to mixed neutron/gamma exposure (0.85/0.9 MeV; 5.4:1) resulted in an estimated relative biological effectiveness of 1.2 as compared with reference Co gamma radiation.

Fatting parameters after duck egg exposure to γ-radiation.

In our experiment, we deal with the phenomenon of radiation hormesis and improvements based on this phenomenon to different growing characteristics of the fast-growing, very feed-efficient, and with a high-yielding carcass hybrid of the Peking duck (Cherry Valley SM3 medium). In the first phase of the project, we exposed hatching duck eggs to low and middle doses of gamma radiation 60Co (0.06-2.00 Gy) before placing them into a setter in the hatchery. We then followed the standards of artificial incubation. The treatment of our chosen doses of gamma radiation has no significant influence on the history and results of hatching (from 85.5% to 92.6%); it was influenced only by the basic management and husbandry of the parent stock. From our observations we confirm that the Peking duck, despite genetic progress, retained its vitality and robustness. Its embryos are not damaged even with a dose of 2 Gy, which is over the deterministic effect of ionizing radiation for vertebrates. At the end of the fatting period a significant drop in plasma phosphorus levels was measured in the ducks; however, it was dependent on the radiation dose to which the hatching eggs were exposed (r = -0.965). A positive effect of radiation hormesis may be expected in the case of 1 Gy dose where the highest values of mean corpuscular hemoglobin, mean corpuscular hemoglobin, combined hemoglobin, and drake weight were measured. Lower and higher doses of ionizing radiation used did not display these effects.

Dosimetric comparison of 60Co and 192Ir high dose rate source used in brachytherapy treatment of cervical cancer.

PURPOSE: The study purpose included dosimetric comparison of cobalt 60 (60Co) and iridium 192 (192Ir) high dose rate (HDR) source used in brachytherapy treatment of cervical cancer. MATERIALS AND METHODS: Computed tomography (CT) scans for 15 patients of carcinoma of uterine cervix using 3-mm slice thickness were considered for the study The contouring of high-risk clinical target volume (HRCTV), bladder, and rectum on CT images was done as per the GEC ESTRO guidelines with the help of magnetic resonance imaging images in the treatment planning system. All parameters were kept the same for 60Co (3.5 mm active length, 0.5 mm active dia, Bebig) and 192Ir (3.5 mm active length, 0.6 mm active dia, Bebig) HDR source with 2.5-mm step size and dose prescription to Point A. As per the International Commission on Radiation Unit (ICRU)-89 guidelines, the dose-volume parameters such as D50(Gy), D90(Gy), and D98(Gy) for HRCTV and D0.1cc (Gy), D1cc (Gy), D2cc (Gy), and D5cc (Gy) to the bladder and rectum were calculated for both the HDR sources. RESULTS: The difference in dose-volume histogram parameters such as D50,D90,and D98 of HRCTV was 3.19%, 1.13%, and 0.50%, respectively, for the two radioisotopes. The difference in dose values of D0.1cc, D1cc, D2cc, D5cc, and ICRU reference points of bladder was -0.58%, -0.67%, -0.99%, -0.94%, and -1.75%, respectively. On the other hand, dose difference for D0.1cc, D1cc, D2cc, D5cc, and ICRU reference points of rectum was 0.67%, 0.26%, 0.56%, 0.63%, and -0.33%, respectively. CONCLUSIONS: The present study results show that all the dose parameters of HRCTV, bladder, and rectum with 60Co were comparable with those of 192Ir HDR source. The isodose distribution is more bulge out for 60Co in cranial-caudal direction compared to that of 192Ir. However, these differences can be reduced by treatment planning optimization techniques. The clinical plan evaluation in each slice and plane is necessary to explore the logistic and financial benefits of miniaturized 60Co source over 192Ir HDR source.

Irradiation does not compromise or exacerbate the innate immune response in the brains of mice that were transplanted with bone marrow stem cells.

Microglia and invading macrophages play key roles in the brain immune response. The contributions of these two populations of cells in health and diseases have yet to be clearly established. The use of chimeric mice receiving bone marrow-derived stem cell grafts from green fluorescent protein (GFP)-expressing mice has provided an invaluable tool to distinguish between local and blood-derived monocytic populations. The validity of the method is questioned because of the possible immune alterations caused by the irradiation of the recipient mouse. In this experiment, we compared the brain expression of innate immune markers Toll-like receptor 2, interleukin-1 beta, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 in C57BL/6, GFP, and chimeric mice following an intracerebral injection of lipopolysaccharide. The endotoxin caused a marked transcriptional activation of all these innate immune genes in microglial cells across the ipsilateral side of injection. The expression patterns and signal intensity were similar in the brains of the three groups of mice. Consequently, the chimera technique is appropriate to study the role of infiltrating and resident immune cells in the brain without having immune compromised hosts. Disclosure of potential conflicts of interest is found at the end of this article.

Optimal (57)Co flood source activity and acquisition time for lymphoscintigraphy localization images.

UNLABELLED: We evaluated different (57)Co flood source activities and acquisition times to obtain an optimal localization image for breast lymphoscintigraphy that would adequately outline the body and allow detection of nodes seen on the emission scan while minimizing unnecessary radiation exposure to the patient. METHODS: An anthropomorphic thorax breast phantom representing an average-size patient was used to simulate nodes on a breast lymphoscintigraphy scan. The activities in the nodes at the time of acquisition ranged from 37 to 185 kBq (1-5 microCi). Four experiments were performed, consisting of 10-min emission and 3-min localization images. Anterior, posterior, and right and left lateral views of the thorax phantom were acquired, using each of 5 different (57)Co flood sources with activities ranging from 37 to 269 MBq (1.0-7.26 mCi). Ten 1-min localization images for each source were acquired and compared for quality. Three-minute localization images for 2 phantom thicknesses of 10 and 20 cm were acquired to determine the contrast-to-noise ratio for each (57)Co source. The total exposure was measured using an ion chamber survey meter. RESULTS: All sources allowed visualization of the lymphatic nodes in acquisitions as short as 3 min. Images using the 126-MBq (3.41-mCi) source demonstrated an adequate body outline along with visualization of all nodes seen on the emission image. The 37-MBq (1.0-mCi) source did not provide sufficient definition of the body outline, whereas the hotter sources decreased node visualization by increasing the background around the nodes at the same time that they increased the patient exposure. Node activity of 37 kBq (1 microCi) became undetectable on the anterior localization images yet was still visible on the lateral image because of greater attenuation of (57)Co photons. The estimated dose rate from the (57)Co sheet sources was 0.641 microSv/MBq/h. CONCLUSION: Acquiring a 3-min localization scan using a 126-MBq (3.41-mCi) source provided the best combination of clear-body outline and visualization of all nodes seen on the emission image. The estimated dose to the patient from the 126-MBq (3.41-mCi) sheet source was very low (8.7 microSv for unilateral and 13.1 microSv for bilateral). Node detectability decreased in localization images acquired using (57)Co sources of higher activity. This effect would be more pronounced in lymphoscintigrams of thin patients compared with those of patients of average thickness.

A revised dosimetric characterization of 60Co BEBIG source: From single-source data to clinical dose distribution.

PURPOSE: Although the dosimetric characterization of 60Co BEBIG source can be found in several literature studies, the data sets show major discrepancies and the lack of uncertainty analyses. This study tried to determine an accurate dosimetric data set for this source using Monte Carlo (MC) simulations along with detailed uncertainty analysis. To explore how different dosimetric data sets can make changes in practical situations, clinical dose distributions based on our results were compared with the dose distributions derived from Granero et al. and consensus data sets. METHODS AND MATERIALS: The MC simulations were performed with Monte Carlo N-Particle eXtended code (MCNPX) version 2.6.0 and the TG-43 parameters were estimated adhering to the American Association of Physicists in Medicine (AAPM) and European SocieTy for Radiotherapy and Oncology (ESTRO) 229 report. The dose rate distributions for single-source and two typical clinical cases, including one intracavitary and one interstitial, were calculated using an in-house code on the basis of the TG-43 formalism. RESULTS: The total uncertainties for water dose rate on source transverse axis at 1 cm and 5 cm, air kerma strength, and dose rate constant were evaluated to be 0.10%, 0.09%, 0.04%, and 0.11%, respectively. Meaningful differences were found for the interstitial case in which 22% of clinical target volume (CTV) showed differences from ±1% to ±10% or even larger. CONCLUSIONS: The MC uncertainty was derived about 16 times smaller than the typical MC component stated in TG-138, partly because of large number of histories and partly because the spectra of 60Co and also its photons' attenuation coefficients are adequately accurate. The results showed that in the clinical situations, the applicator geometry and the superposition of single-source dose distributions can reduce the differences observed between several data sets.

Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy.

A novel photosensitizer with magnetic resonance imaging (MRI) activity was designed from fullerene (C(60)) for efficient photodynamic therapy (PDT) of tumor. After chemical conjugation of polyethylene glycol (PEG) to C(60) (C(60)-PEG), diethylenetriaminepentaacetic acid (DTPA) was subsequently introduced to the terminal group of PEG to prepare PEG-conjugated C(60) (C(60)-PEG-DTPA). The C(60)-PEG-DTPA was mixed with gadolinium acetate solution to obtain Gd(3+)-chelated C(60)-PEG (C(60)-PEG-Gd). Following intravenous injection of C(60)-PEG-Gd into tumor-bearing mice, the PDT anti-tumor effect and the MRI tumor imaging were evaluated. The similar O(2)(*-)generation was observed with or without Gd(3+) chelation upon light irradiation. Both of the C(60)-PEG-Gd and Magnevist(R) aqueous solutions exhibited a similar MRI activity. When intravenously injected into tumor-bearing mice, the C(60)-PEG-Gd maintained an enhanced MRI signal at the tumor tissue for a longer time period than Magnevist(R). Injection of C(60)-PEG-Gd plus light irradiation showed significant tumor PDT effect although the effect depended on the timing of light irradiation. The PDT efficacy of C(60)-PEG-Gd was observed at the time when the tumor accumulation was detected by the enhanced intensity of MRI signal. This therapeutic and diagnostic hybrid system is a promising tool to enhance the PDT efficacy for tumor.

Evaluation of treatment results and toxicity in cases of repeated radiation therapy of spinal metastasis.

The study evaluates retrospective results and toxicity in repeated radiation therapy in patients with recurrent pain caused by backbone metastasis, having undergone previous radiotherapy in the same body region. Fifty-seven patients were analyzed: 24 women and 33 men, aged 45-74 years (median = 59 years). They underwent a second radiation therapy treatment of the spinal column, between March 2002 and May 2004, performed due to recurrent pain in the previously irradiated region. The radiation used cobalt isotope 60 ((60)Co), to include the metastatically changed vertebrae and the margin of the adjusting healthy upper and lower vertebra. The radiated skin area measured 84-104 cm(2). Patients were divided into 3 groups depending on their treatment schemas: 12 patients -- first course of radiotherapy 4 Gy x 5, second 4 Gy x 5; 16 patients -- first course of radiotherapy 4 Gy x 5, second 8 Gy x 1; 29 patients -- first course of radiotherapy 8 Gy x 1, second 8 Gy x 1. The time delay between the first and the second radiation therapies was between 11 and 766 days (median = 135 days). An analgesic effect was achieved with most treated patients -- 41/57 (71.9%) with the use of second radiotherapy and with an insignificant percentage of complications, unimportant from the clinical point of view. No serious complications such as paralysis, paresis, spinal cord necrosis, neurological dysfunction of urethral or sigmoidorectal sphincters were noted in any of the treated patients. Based on our experience, this retrospective analysis shows usefulness of the second radiotherapy treatment as a safe method of palliative treatment in cases of painful bone metastasis appearing after a previous radiation therapy.

Dose distributions around selectron applicators.

Measured and calculated dose distributions around selectron applicators, loaded with 60Co high dose rate pellets, are presented. The effect of the stopping screw, spacers, pellets themselves and the applicator wall on the dose distribution is discussed. The measured dose distribution is in almost perfect agreement with the calculated distribution in planes perpendicular to the applicator axis and containing a source. On the applicator axis directly below the applicator the measured dose amounts to about 75% of the calculated value, when only the stopping screw attenuates the beam from a pellet. When the beam is attenuated by spacers in addition to the stopping screw, the discrepancy between the calculated and measured dose may exceed 50%. Clinically relevant source geometries are also discussed. It is shown that for most regions around the applicator the method of a simple addition of dose contributions from individual point sources is an acceptable approximation for the calculation of dose distributions around the selectron applicators.

Treatment of carcinoma of the uterine cervix by remotely controlled afterloading intracavitary radiotherapy with high-dose rate: a comparative study with a low-dose rate system.

From September, 1974 through December, 1979, a total of 249 patients with carcinoma of the cervix uteri Stage IIb and III were randomly allocated to either remotely controlled high-dose-rate intracavitary radiotherapy or manual afterloading low-dose-rate therapy, with radiotherapy of 20 Gy in 2 weeks to Point A to whole pelvis and 40 Gy in 4 weeks to the parametria. The dose to Point A by intracavitary radiotherapy was 40-60 Gy with one or two fractions in the low-dose-rate group and 30 Gy for the high-dose-rate group by 3 fractions with a once a week schedule. The purpose of this paper is to compare the results between the groups and to clarify the problems in the high-dose-rate group clinically. The local control rate was higher in the high-dose-rate group; however, the complication rate was also higher in this group than in the low-dose-rate group. The dose schedule and the place of rectal dose measurement is discussed. The overall cumulative survival rate was nearly the same in both groups (55% at 5 years), although some difference was noted in each stage. The most common cause of death was distant metastasis outside the pelvis and the second most common was intercurrent disease in Stage IIb and local failure in Stage III.

Hyperthermia enhances thermal-neutron-induced cell death of human glioblastoma cell lines at low concentrations of 10B.

PURPOSE: To examine the ability of pre- vs. post-irradiation hyperthermia to enhance the effectiveness of thermal neutrons to kill human glioblastoma cells. METHODS AND MATERIALS: Human glioblastoma cell lines, T98G, A7, A172, and U 87MG, were exposed to thermal neutrons from the Kyoto University Research (KUR) reactor or to 60Co gamma-rays. Hyperthermia was tested before and after irradiation of T98G (44 degrees C, 15 min) and A7 cells (44 degrees C, 40 min), and with different concentrations (0-30 ppm) of 10B-boric acid. The biological end point of all experiments was cell survival measured by a colony formation assay. RESULTS: The relative biological effectiveness (RBE) values of thermal neutrons for these cell lines compared with 60Co gamma-rays were 1.8-2.0 at their D(0) values. When T98G and A7 cells were heated after thermal neutron irradiation, there was a synergistic effect at low 10B concentrations (up to 5 ppm for T98G and up to 10 ppm for A7 cells). With high concentrations of boron (10-30 ppm for T98G and 20-30 ppm for A7 cells), hyperthermia and neutron irradiation interact additively rather than synergistically. There was no enhancement when cells were heated before thermal neutron irradiation. These results suggest that the radiosensitizing effect of hyperthermia may be attributed to partial inhibition of the repair of the potentially lethal damage caused by neutron irradiation.

Radiotherapy versus surgery in the treatment of cervix stage Ib cancer.

In the years 1971-77 we have treated 250 Stage Ib patients with cancers of the cervix. One hundred twenty-three (49.2%) underwent a radical surgery, 37 had a classical Wertheim-Meigs operation, and 86 had a lymphadenectomy that was extended to the lumbar-aortic region. When feasible, all patients received postoperative radium therapy on the vaginal vault. The remaining 127 patients received a complete course of radiotherapy. This was not a randomized clinical trial. In fact surgery was preferred for patients who were younger (mean age: 49.6 years) and more physically fit, while radiotherapy was the treatment chosen for those who were older (mean age: 57.7) and generally less fit or obese. The 5 year NED survival was 89.3% in the surgical group and 90.9% in the radiotherapy group (P less than .05). Four fatal complications were observed in the surgical group (3.2%). Rate and causes of failures or complications are analyzed in detail.