Biokinetic model analysis with DTPA administration for a case of accidental inhalation of actinides in Japan.

Accidental inhalation intake of plutonium isotopes and 241Am occurred at a Pu research facility in Japan in 2017, and the five workers involved in this accident were treated by the administration of Ca/Zn-diethylenetriaminepentaacetic acid (DTPA). For the worker who was most internally exposed, the therapy was continued over 1 y after the accident. Urinary samples collected before and after each administration were subject to bioassay to evaluate the efficacy of the dose reduction. This study performed numerical analyses using a biokinetic model dealing with 241Am-DTPA with reference to the European Coordinated Network on Radiation Dosimetry approach, which assumes that the complex of actinides and Ca/Zn-DTPA is generated in the designated compartments in the biokinetic model. The results of the model prediction well captured the trend of the observed urinary excretion in the long-term bioassay and would be useful to evaluate the efficacy of the Ca/Zn-DTPA administration for the worker involved in the accident.

No evidence of thyroid consequences in seven nuclear workers at the Tokyo Electric Power Company Fukushima Daiichi Nuclear Power Plant accident: 10-year follow-up results of thyroid status.

Seven emergency nuclear workers, who had internal exposure due to an intake of radionuclides, mainly I-131, during the emergency response operation in March 2011, after the accident at the Tokyo Electric Power Company (TEPCO) Fukushima Daiichi Nuclear Power Plant (FDNPP), visited the National Institute of Radiological Sciences (NIRS) outpatient clinic for medical evaluation. They were followed up after their first visit for 10 years. The estimated committed equivalent doses to the thyroid were distributed between 3.2 to 1.2 × 10 Sv. This group thought to be received highest exposure at the accident. None of the workers had symptoms related to abnormal thyroid function. The examinations, including thyroid function tests and ultrasound, detected no abnormalities related to radiation exposure. However, there is a need for continuous monitoring of their thyroid status for longer periods in the future.

Radiation exposure to the lens of the eye for Japanese nuclear power plant workers.

In Japan, the radiation-dose limit for the lens of the eye was revised in April 2021. Consequently, for workers, the numerical values of the equivalent dose to the lens of the eye are equal to those of the effective dose. Radiation workers, radiation safety officers and licensees must comply with regulations related to radiation protection and optimize protection. The new guidelines on dose monitoring of the lens of the eye developed by the Japan Health Physics Society recommend for the dose to be estimated near the eye for accurate estimation, when the dose to the lens approaches or exceeds the management criteria. However, there is limited information regarding the non-uniform exposure of nuclear power plant workers. In this study, the dose equivalents of high-dose-rate workplaces and the personal doses of 88 workers were estimated at four Japanese commercial nuclear power plant sites (RWR: 3 units and BWR: 3 units) and the dose to the lens of the eye and the exposure situations of the workers were analyzed.

Reassessment of Internal Thyroid Doses to 1,080 Children Examined in a Screening Survey after the 2011 Fukushima Nuclear Disaster.

The dose reconstruction of populations potentially affected by the accident at the Fukushima Daiichi nuclear power plant in March 2011 is of great importance. However, it has been difficult to assess internal thyroid doses to Fukushima residents (mainly from their intake of I) due to the lack of direct measurements. For the residents, only about 1,300 data points related to I are available, and 1,080 of the data points were obtained from the screening campaign that was conducted by the Nuclear Emergency Response Local Headquarters at the end of March 2011 in Kawamata Town, Iwaki City, and Iitate Village. Here, we reassessed thyroid doses to 1,080 subjects aged ≤15 y old using new age-specific conversion factors to determine I thyroid contents from net signals of the devices used, with consideration for the possible uncertainty related to the measurements. The results demonstrated that thyroid equivalent doses to the subjects were <30 mSv (excluding outliers). We also demonstrate dose distributions of each age group from the above three municipalities and those of subjects from Minamisoma City and Fukushima City. One of the findings was that the I intake was similar among different age groups in each of the three municipalities. This was consistent with the assumption that ingestion was a dominant route of intake rather than inhalation. The range of thyroid doses to Iitate Village residents was similar to that to Iwaki City residents even though the I concentration in tap water was much higher in Iitate Village than Iwaki City. The range of thyroid doses to Minamisoma City residents was similar to that to Iitate Village and Iwaki City residents, and the range for Fukushima City residents was smallest among the five municipalities. Since the major route of intake has remained unclear, this paper presents the plausible upper and lower thyroid doses, between which the actual doses are thought to mostly exist, based on two intake scenarios: single inhalation and repeated ingestion. Further research is thus necessary to extract useful evidence from the individual evacuation behaviors for improving the present internal thyroid dose assessment.

Numerical Simulation Based on Individual Voxel Phantoms for a Sophisticated Evaluation of Internal Doses Mainly From 131I in Highly Exposed Workers Involved in the TEPCO Fukushima Daiichi NPP Accident.

As a response to the Tokyo Electric Power Company's Fukushima Daiichi nuclear power plant accident in 2011, seven TEPCO workers whose exposure doses were expected to be >250 mSv (a tentative dose limit stipulated by the Japanese central authority) attended Japan's National Institute for Radiological Sciences for additional internal dose measurements. The National Institute for Radiological Sciences examination revealed that these workers' internal doses came mainly from their intake of the radionuclide I during emergency operations. In this study, we performed numerical simulations based on individual volume-pixel (voxel) phantoms of six of the seven workers for a more sophisticated evaluation of their internal doses, taking into account the individual thyroid size and other specific parameters. The voxel phantoms were created from magnetic resonance imaging scan images. As a result, the individual thyroid volumes ranged from 6.5 to 28.2 cm and were considerably smaller than the reference value (~20 cm) adopted in the International Commission on Radiation Protection's dosimetric model for four of the six subjects. Compared to the original estimates of the thyroid absorbed dose, our preliminary evaluation revealed values that were increased by approximately 3-fold or decreased by 30% at maximum. A wide difference in the individual thyroid size would be one of the significant modifiers in the current dose estimation of subjects of the ongoing epidemiological study project. The present simulations also provided evidence that the direct thyroid measurements by the National Institute for Radiological Sciences to determine the workers' I thyroid contents were sufficiently accurate.

A SCREENING SURVEY EXERCISE FOR THYROID INTERNAL EXPOSURE FROM RADIOIODINE AFTER A NUCLEAR ACCIDENT.

In the aftermath of the 2011 Fukushima nuclear disaster, a screening survey for thyroid internal exposure from intake of radioiodine was performed on 1080 children using handheld NaI(Tl) survey meters. This article presents the design and results of a practical exercise conducted to develop the skills of personnel who would be potentially engaged in such a survey. Participants of this exercise were asked to measure manikin heads in which point sources were installed under normal (~0.05 µSv h-1) and elevated (~0.5 µSv h-1) background conditions. The results demonstrated that the measurements were less dependent on the background radiation level, and the deviation of net signals obtained by the participants were within 10-20% for dose rates above 0.2 µSv h-1. This result suggests that dose rates can be reliably obtained above a provisional operational intervention level for the device, 0.5 µSv h-1 under a real nuclear accident situation.

AN ACCIDENT OF INTERNAL CONTAMINATION WITH PLUTONIUM AND AMERICIUM AT A NUCLEAR FACILITY IN JAPAN: A PRELIMINARY REPORT AND THE POSSIBILITY OF DTPA ADMINISTRATION ADDING TO THE DIAGNOSIS.

This article introduces the first accident of internal contamination with plutonium (Pu) or americium (Am) in Japan for which treatment was carried out. An accident of internal contamination with Pu and Am occurred at a Pu research facility at Oarai-town of Ibaraki prefecture in Japan. A plastic bag containing these radionuclides ruptured when five workers were inspecting a storage container in a hood. As a consequence, these workers were internally contaminated with Pu and Am. Although contamination on the body surface was observed in all five workers, a positive nasal swab was detected in only three of them. A chelating agent, calcium diethylenetriaminepenta-acetate (CaDTPA), was administered to all of them including the two workers without a positive nasal swab. However, bioassay detected a significant amount of Pu and Am in urine after administration of DTPA in these two workers, whereas the levels of these nuclides were below minimum detectable levels in urine before the administration. Since the prevalence of adverse reactions in DTPAs is low, the present results suggest that administration of DTPA can be used for the diagnosis of internal contamination even when a nasal swab is negative or contamination around body orifices is not detected.

Current situations and discussions in Japan in relation to the new occupational equivalent dose limit for the lens of the eye.

Since the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens of the eye in 2011, there have been extensive discussions in various countries. This paper reviews the current situation in radiation protection of the ocular lens and the discussions on the potential impact of the new lens dose limit in Japan. Topics include historical changes to the lens dose limit, the current situation with occupational lens exposures (e.g., in medical workers, nuclear workers, and Fukushima nuclear power plant workers) and measurements, and the current status of biological studies and epidemiological studies on radiation cataracts. Our focus is on the situation in Japan, but we believe such information sharing will be useful in many other countries.

Mass Casualty Decontamination in a Chemical or Radiological/Nuclear Incident with External Contamination: Guiding Principles and Research Needs.

Hazardous chemical, radiological, and nuclear materials threaten public health in scenarios of accidental or intentional release which can lead to external contamination of people.  Without intervention, the contamination could cause severe adverse health effects, through systemic absorption by the contaminated casualties as well as spread of contamination to other people, medical equipment, and facilities.  Timely decontamination can prevent or interrupt absorption into the body and minimize opportunities for spread of the contamination, thereby mitigating the health impact of the incident.  Although the specific physicochemical characteristics of the hazardous material(s) will determine the nature of an incident and its risks, some decontamination and medical challenges and recommended response strategies are common among chemical and radioactive material incidents.  Furthermore, the identity of the hazardous material released may not be known early in an incident.  Therefore, it may be beneficial to compare the evidence and harmonize approaches between chemical and radioactive contamination incidents.  Experts from the Global Health Security Initiative's Chemical and Radiological/Nuclear Working Groups present here a succinct summary of guiding principles for planning and response based on current best practices, as well as research needs, to address the challenges of managing contaminated casualties in a chemical or radiological/nuclear incident.

The accident at the Fukushima Daiichi Nuclear Power Plant in 2011.

A huge earthquake struck the northeast coast of the main island of Japan on 11 March 2011, triggering a tsunami with more than 10-m-high waves hitting the area. The earthquake was followed by numerous sustained aftershocks. The earthquake and aftershocks left almost 16,000 people dead and more than 2,800 missing (as of 11 March 2014). The earthquake affected the Fukushima Daiichi Nuclear Power Plant (NPP) of Tokyo Electric Power Company (TEPCO), causing serious damage to the NPP and resulting in large amounts of radioactive materials being released into not only controlled areas but also the environment. Damage was caused to the cooling systems of the NPP, although they automatically shut down after the earthquake. The trouble with the cooling systems led to hydrogen explosions and core meltdown. The major nuclides released on land were ¹³¹I, ¹³4Cs, and ¹³7Cs. The release of these radioactive materials resulted in contamination of first responders and workers and also a high ambient dose of radiation around the NPP. The local hospital system, including that for radiation emergency medicine, was dysfunctional. Hospitals that had been designated as radiation emergency facilities were not able to function because the earthquake and tsunami had caused damage to their facilities; some of these were located within a 20-km radius of the NPP and in the evacuation areas. Local fire department personnel were also ordered to evacuate. Fukushima prefecture changed the screening level required for decontamination from 13,000 to 100,000 cpm, with decontamination by wiping being performed for over 13,000 cpm. However, as hospitals and fire departments had to abide by lower levels than that of the prefecture for receiving or transporting contaminated patients, these personnel could not accept or transport contaminated people from the NPPs. In addition, hospitals not designated as radiation emergency facilities would not receive patients from the NPPs because of concerns about the health effects of radiation. From this disaster, it was learned that basic knowledge of radiation and its effects is extremely important for health care providers.

Medical management of the consequences of the Fukushima nuclear power plant incident.

A huge earthquake struck the northeast coast of the main island of Japan on March 11, 2011, triggering a tsunami with 14-15 meter-high waves hitting the area. The earthquake was followed by numerous sustained aftershocks. The earthquake affected the nuclear power plant (NPP) in Fukushima prefecture, resulting in large amounts of radioactive materials being released into the environment. The major nuclides released on land were ¹³¹I, ¹³4Cs, and ¹³7Cs. Therefore, almost 170,000 people had to be evacuated or stay indoors. Besides the NPP and the telecommunications system, the earthquake also affected infrastructures such as the supplies of water and electricity as well as the radiation monitoring system. The local hospital system was dysfunctional; hospitals designated as radiation-emergency facilities were not able to function because of damage from the earthquake and tsunami, and some of them were located within a 20 km radius of the NPP, the designated evacuation zone. Local fire department personnel were also asked to evacuate. Furthermore, the affected hospitals had not established their evacuation plans at that time. We have learned from this "combined disaster" that the potential for damage to lifelines as well as the monitoring systems for radiation in case of an earthquake requires our intense focus and vigilance, and that hospitals need comprehensive plans for evacuation, including patients requiring life support equipment during and after a nuclear disaster. There is an urgent need for a "combined disaster" strategy, and this should be emphasized in current disaster planning and response.

Screening of Residents Following the Tokyo Electric Fukushima Daiichi Nuclear Power Plant Accident.

ABSTRACT: On 11 March 2011, the Great Eastern Japan Earthquake occurred, causing the accident at the Fukushima Daiichi Nuclear Power Plant of Tokyo Electric Power Co. Residents were surveyed for contamination, and hospitalized patients within a 30-km area were transferred. In this report, the authors review the results of the survey and the effects. The screening teams measured total body contamination of each person using a Geiger-Mueller survey meter. Decontamination level was set at 100 kcpm (100,000 cpm). For levels of 13 to <100 kcpm, decontamination by wiping was planned and took place. Contamination screening during 11-21 March 2011, was carried out for 72,660 people at 200 sites. From 12 March 2011 until 10 February 2012, a total of 244,281 people were screened. As a result, there were 110 cases exceeding 100 kcpm, and 901 cases with contamination levels of 13-100 kcpm. The number of contaminated individuals screened reached a peak from 16-18 March. In the accident, contamination screening of victims and residents was performed to deal with anxiety and discrimination toward the residents. Although there was some early delay, almost all of the evacuees were relatively promptly screened. There was no external contamination at levels thought to affect the health of residents. In addition, the detection of contamination levels over 13 kcpm peaked between 15-22 March. Considering factors such as the evacuation period, this suggests that even if iodine tablets had been administered during this time, they would not have been effective.

[Assessment, diagnosis and treatment of internal or body surface contamination].

Contamination with radioactive materials is classified into surface contamination and internal contamination. Measures for radiation protection to prevent dispersion of the radioactive materials and to protect the medical staffs are essential. Surface contamination is measured by surface survey meter such as a G-M counter. Washing or wiping is a choice for treatment. For internal contamination, direct(external) measurement and bioassay are the two methods for dose assessment. Estimation of the committed effective dose is necessary based on the activity inside the body. General treatment to reduce the absorption of radioactive materials, such as laxatives can be used. Stable iodine, Prussian Blue, and DTPA are three well-known and effective drugs for prophylaxis or de-cooperation against internal contamination.

Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial.

BACKGROUND: Several large randomised studies from western Europe and the USA have shown that accelerated fractionation of radiotherapy might be beneficial in the treatment of squamous-cell carcinoma of the head and neck (HNSCC). The aim of this study--the International Atomic Energy Agency (IAEA) ACC trial--was to determine whether accelerated fractionation could be applied in developing countries, where there are fewer therapeutic resources and where tumour burdens can be heavier. METHODS: Between Jan 6, 1999, to March 31, 2004, nine centres from Asia, Europe, the Middle East, Africa, and South America recruited patients with HNSCC of the larynx, pharynx, and oral cavity who were eligible for curative radiotherapy. Patients were randomly assigned in this open-label trial to receive an accelerated regimen of six fractions of radiotherapy per week (n=458) or to receive a conventional radiotherapy regimen of five fractions per week (n=450), receiving a total dose of 66-70 Gy in 33-35 fractions. Patients were stratified by tumour localisation, T classification, histopathological grade, and institution. Randomisation was done by a central computer-generated balanced randomisation algorithm. The primary endpoint was locoregional control, analysed for all eligible patients, irrespective of whether or not they had completed the course of radiotherapy. This trial is registered with ClinicalTrials.gov, number NCT00120211. FINDINGS: Six patients in the accelerated group and two in the conventional group were excluded from analyses because of withdrawal of consent or missing data. The planned total radiotherapy dose was received by 418 (92%) of the 452 eligible patients in the accelerated radiotherapy group and 413 (92%) of the 448 patients in the conventional radiotherapy group. Median treatment time was 40 days in the accelerated group and 47 days in the conventional group. The 5-year actuarial rate of locoregional control was 42% in the accelerated group versus 30% in the conventional group (hazard ratio [HR] 0.63, 95% CI 0.49-0.83; p=0.004). Acute morbidity in the form of confluent mucositis was noted in 45 patients in the accelerated group and 22 patients in the conventional group (2.15, 1.27-3.35); severe skin reactions were noted in 87 patients in the accelerated group and 50 patients in the conventional group (1.91, 1.31-2.79). There were no significant differences in late radiation side-effects. INTERPRETATION: An accelerated schedule of radiotherapy for HNSCC was more effective than conventional fractionation, and since it does not require additional resources, might be a suitable new worldwide standard baseline treatment for radiotherapy of HNSCC. FUNDING: International Atomic Energy Agency, Coordinated Research Project (IAEA-CRP E.3.30.18), the Danish Cancer Society, the Danish Strategic Research Council, and the Lundbeck Centre for Interventional Research in Radiation Oncology (CIRRO).

Regional hyperthermia combined with radiotherapy for locally advanced non-small cell lung cancers: a multi-institutional prospective randomized trial of the International Atomic Energy Agency.

BACKGROUND: An International Atomic Energy Agency (IAEA)-sponsored, multi-institutional prospective randomized trial was conducted to clarify whether the combination of hyperthermia and radiotherapy improves the local response rate of locally advanced non-small cell lung cancer (NSCLC) compared with that obtained by radiotherapy alone. METHODS: Between October 1998 and April 2002, 80 patients with locally advanced NSCLC were randomized to receive either standard radiation therapy alone (RT) or radiation therapy combined with hyperthermia (RT + HT). The primary endpoint was the local response rate. The secondary endpoints were local progression-free survival and overall survival. RESULTS: The median follow-up period was 204 days for all patients and 450 days for surviving patients. There were no significant differences between the two arms with regard to local response rate (P = 0.49) or overall survival rate (P = 0.868). However, local progression-free survival was significantly better in the RT+HT arm (P = 0.036). Toxicity was generally mild and no grade 3 late toxicity was observed in either arm. CONCLUSION: Although improvement of local progression-free survival was observed in the RT+HT arm, this prospective randomized study failed to show any substantial benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced NSCLC.

AK-2123 (Sanazol) as a radiation sensitizer in the treatment of stage III cervical cancer: results of an IAEA multicentre randomised trial.

PURPOSE: AK-2123, a nitrotriazole hypoxic cell sensitizer, has reportedly improved results in head and neck cancers, uterine cervical cancers and other solid tumours when added to radical radiotherapy. A prospectively randomised trial was initiated by the International Atomic Energy Agency (IAEA) evaluating AK-2123 and radiotherapy in treatment of uterine cervical cancer stage III and IV. PATIENTS AND METHODS: A total of 462 patients were randomised from 8 centres. Patients from four centres were excluded due to lack of accrual, closing of the centre and insufficient documentation and reporting. The final study population consisted of 333 patients who were randomised between May 1995 and December 1998. Patients were randomised to either standard radical treatment (radiation therapy alone, RT) or standard radical radiotherapy and additional administration of AK-2123 (RT+AK-2123). The total dose of 45-50.8 Gy was delivered by 20-28 fractions in an overall time of 4-5 1/2 weeks, with further dose escalation by brachytherapy or external beam. In the study arm, patients received 0.6 g/sqm AK-2123 by intravenous administration before external beam radiotherapy, treating with AK-2123 on alternate days (e.g. Monday-Wednesday-Friday) during the entire course of external beam therapy. Following exclusion of 7 patients who did not undergo treatment, a total of 326 patients remained for evaluation. RESULTS: The rate of local tumour control was significantly higher in the group after radiotherapy and additional administration of AK-2123. Local tumour control was 61% (95/155) after AK-2123 and 46% (79/171) after radiotherapy alone (p=0.006). The actuarial survival at 60 months was 57% after RT+AK-2123, compared to 41% after RT (Log Rank p=0.01). AK-2123 did neither increase gastro-intestinal toxicity nor was it attributed to any haematological toxicity. A mild peripheral toxicity (Grade 1: 13% and Grade 2: 2%) usually completely reversible was infrequently seen after AK-2123 administration. CONCLUSION: We conclude that the addition of AK-2123 to radical radiotherapy significantly increases local tumour control and survival in advanced squamous cell cancer of the uterine cervix without the addition of any major toxicity.

Regional hyperthermia combined with radiotherapy for uterine cervical cancers: a multi-institutional prospective randomized trial of the international atomic energy agency.

PURPOSE: Hyperthermia can be used to enhance the effects of radiation, and a combined treatment may, in some circumstances, be an advantage. Uterine cervical cancer is very common in developing countries. The control of locally advanced pelvic tumors is difficult with conventional treatment modalities. Based upon the biologic rationale and in view of the recent advances in heating and thermometry techniques, radiotherapy in combination with hyperthermia was investigated in a multi-institutional prospective randomized trial sponsored by the International Atomic Energy Agency. The primary purpose was to clarify whether the combination of hyperthermia and radiotherapy improves the rate of local control, compared with radiotherapy alone. METHODS AND MATERIALS: A total of 110 patients with biopsy-proven, locally advanced carcinoma of the uterine cervix were randomized to treatment by radiotherapy with or without hyperthermia. The patients were stratified by institution, stage, and histologic type. Each patient received external beam radiation therapy and brachytherapy. For the patients randomized to receive hyperthermia, a minimum of five sessions (60 min each, once per week) were administered, employing a radiofrequency (RF) capacitive heating device. Intratumoral temperature was measured at the first hyperthermic treatment, and at least once more during the course of treatment. The equipment and the policies and procedures at each participating institution except one (Pusan) were personally inspected at least once by the corresponding author, to ensure that quality assurance procedures were in place and were followed for treatment according to the protocol guidelines. The median follow-up period was 466 days for all the patients and 512 days for the surviving patients. RESULTS: The two arms were well balanced with regard to the patient factors, tumor factors, and treatment factors. The overall survival rate at 3 years was 73.2%, and the local control rate was 68.5%. There were no significant differences between the patients treated with or without hyperthermia, either with regard to the survival (p = 0.1893) or the rate of local control (p = 0.58). The survival was significantly worse among the patients with Stage IIb disease who received hyperthermia (p = 0.0162) although there was no difference in their rate of local control (p = 0.7988). Further analysis is necessary to determine if the difference in survival is due to a greater incidence of distant metastases or some other cause. Acute Grade 2-3 toxicity was seen in 10/55 patients (18%) treated by hyperthermia and in 2/55 of the patients (4%) treated without hyperthermia (p = 0.01). There was no significant difference in the late toxicity observed in the two arms. CONCLUSION: This prospective randomized study failed to show any benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced carcinoma of the uterine cervix. The acute toxicity was significantly greater among the patients receiving hyperthermia, and the survival was significantly worse among the Stage IIb patients receiving hyperthermia even though there was no difference in the local control rate.

AK-2123 (Sanazol) as a radiation sensitizer in the treatment of stage III cancer cervix: initial results of an IAEA multicentre randomized trial.

PURPOSE: AK-2123, a nitrotriazole hypoxic cell sensitizer has reportedly improved results in head and neck cancers, uterine cervical cancers and other solid tumours when added to radical radiotherapy. A prospectively randomised trial was initiated by the International Atomic Energy Agency (IAEA) evaluating AK-2123 and radiotherapy in treatment of uterine cervical cancer stage IIIA and IIIB. MATERIALS AND METHODS: A total of 333 patients were randomised between May 1995 and December 1998. Patients were randomised to either standard radical treatment (radiation therapy alone, RT) or standard radical radiotherapy and additional administration of AK-2123 (RT+AK-2123). The total dose of 45-50.8 Gy was delivered in 20 to 28 fractions over 4 to 5 1/2 weeks. The dose to the central disease was escalated to a radiobiologically equivalent dose of 70 Gy by external beam or brachytherapy, in accordance with each centres individual practice. In the study arm, patients received 0.6 g/sqm AK-2123 by intravenous administration before external beam radiotherapy, treating with AK-2123 on alternate days (e.g. Monday-Wednesday-Friday) during the entire course of external beam therapy. RESULTS: After a median follow up of 57 months (range 30-73 months) the rate of local tumour control was significantly higher in the group who received radiotherapy and additional administration of AK-2123. Local tumour control at the last follow up was 61% after combined radiotherapy and AK-2123 and 46% after radiotherapy alone (p = 0.005). AK-2123 neither increased gastro-intestinal toxicity nor gave any haematological toxicity. A mild peripheral neuropathy (Grade 1:11% and Grade 2:3%) was seen infrequently after AK-2123 administration and was usually completely reversible. Crude survival rates were 41% after radical treatment compared to 57% after combined therapy (p = 0.007). CONCLUSION: We conclude that the addition of AK-2123 to radical radiotherapy significantly increases response rates and local tumour control in advanced squamous cell cancer of the uterine cervix without any increase in major toxicity. Further analysis and follow up are needed to evaluate if this benefit will translate into prolonged survival. We strongly suggest that our initially very promising study should lead other centres to further studies of AK-2123 in randomised clinical trials.

Long-term changes in rabbit cornea after ionizing radiation.

PURPOSE: To investigate long-term changes in the cornea after ionizing irradiation in rabbits. METHODS: Mature albino rabbits (n = 4) were unilaterally irradiated with 20 Gy of x-rays. The contralateral eye served as a control. The rabbits were examined with slit-lamp biomicroscopy for 5 years. The eyes were then enucleated for histopathologic examinations with light microscopy and transmission electron microscopy. RESULTS: On biomicroscopy, there was no corneal abnormality during the 5-year follow-up period. On histopathology, no abnormality was observed in the corneal epithelium. In the endothelium, a vacuole-like structure was recognized by light microscopy, and transmission electron microscopy revealed marked enlargement of intercellular space and anamorphosis of the nuclei. CONCLUSION: Moderate x-ray irradiation to rabbit eye did not induce any long-term damage to the corneal epithelium, but the endothelium demonstrated persistent and irreversible damage, which was observed even 5 years after irradiation.

Radiotherapy with or without mitomycin c in the treatment of locally advanced head and neck cancer: results of the IAEA multicentre randomised trial.

BACKGROUND AND PURPOSE: Single agent mitomycin c (MMC) has been shown to improve the outcome of radiotherapy in single institution trials. In order to confirm these findings in a broader worldwide setting, the International Atomic Energy Agency (IAEA) initiated a multicentre trial randomising between radiotherapy alone versus radiotherapy plus MMC. MATERIAL AND METHODS: Patients with advanced head and neck cancer were treated with primary curative radiotherapy (66 Gy in 33 fractions with five fractions per week) +/-a single injection (15 mg/m(2)) of MMC at the end of the first week of radiotherapy. Stratification parameters were tumour localization, T-stage, N-stage, and institution. A total of 558 patients were recruited in the trial from February 1996 to December 1999. Insufficient accrual and reporting led to the exclusion of three centres. The final study population consisted of 478 patients from seven centres. Patients had stage III (n=223) or stage IV (n=255) squamous cell carcinoma of the oral cavity (n=230), oropharynx (n=140), hypopharynx (n=65) or larynx (n=43). Prognostic factors like age, gender, site, size, differentiation and stage were well balanced between the two arms. RESULTS: The haematological side effects of MMC were very modest (<5% grade 3-4) and did not require any specific interventions. Furthermore, MMC did not enhance the incidence or severity of acute and late radiation side effects. Confluent mucositis and dry skin desquamation was common, occurring in 56% and 62% of patients, respectively. The overall 3-year primary locoregional tumour control, disease-specific and overall survival rates were 19, 36 and 30%, respectively. Gender, haemoglobin drop, tumour site, tumour and nodal stage were significant parameters for loco-regional tumour control. There was no significant effect of MMC on locoregional control or survival, except for the 161 N0 patients, where MMC resulted in a better loco-regional control (3-year estimate 16% vs. 29%, P=0.01). CONCLUSIONS: The study did not show any major influence of MMC on loco-regional tumour control, survival or morbidity after primary radiotherapy in stage III-IV head and neck cancer except in N0 patients where loco-regional control was significantly improved.