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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.

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.

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.

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

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.

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.

Summary 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).

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 45–50.8Gy 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 0.6g/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.

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 ( 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.

Purpose : To provide recommendations for the implementation of high dose rate (HDR) 192 Ir brachytherapy technology in developing countries. Methods : An Advisory Group Meeting of the International Atomic Energy Agency (IAEA) met to address the implementation of HDR 192 Ir brachytherapy technology in developing countries. These recommendations reflect only the personal opinions of the authors and do not necessarily represent the opinion of the IAEA. Results : An HDR treatment system should be purchased as a complete unit that includes the 192 Ir radioactive source, source loading unit, applicators, treatment planning system, and control console. Infrastructure support may require additional or improved buildings and procurement of or access to new imaging facilities. A supportive budget is needed for quarterly source replacement and the annual maintenance necessary to keep the system operational. The radiation oncologist, medical physicist, and technologist should be specially trained before HDR can be introduced. Training for the oncologist and medical physicist is an ongoing process as new techniques or sites of treatment are introduced. Procedures for quality assurance (QA) of patient treatment, and the planning system must be introduced. Emergency procedures with adequate training of all associated personnel must be in place. Conclusions : The decision to select HDR in preference to alternate methods of brachytherapy is influenced by the ability of the machine to treat a wide variety of clinical sites. In departments with personnel and budgetary resources to support this equipment appropriately, economic advantage becomes evident only if large numbers of patients are treated. Intangible benefits of source safety, personnel safety, and easy adaptation to fluctuating demand for treatments also require consideration when evaluating the need to introduce this treatment system.

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.

Although tumor clearance is a common criterion in assessing the impact of radiotherapy (RT), it is not always reliable. Patterns of tumor clearance were determined using 91 metastatic lymph nodes (LNs) from 51 patients with head and neck tumors treated by definitive RT (61-80 Gy) or preoperative RT (43-65 Gy). Clearance rate (CR) was estimated as a daily volume decrement expressed as a ratio to the pre-RT LN volume. CR was greater for the so-called radioresponsive nasopharyngeal subgroups and more poorly differentiated than those of oral cavity and well-differentiated, respectively. Histologically, LNs that were removed following RT consisted mainly of fibrous tissues, necrotic tissues, and few cancer cells. There was no difference in CR between the cancer-cell-positive group (n = 21) and the cancer-cell-negative group (n = 31). Although the CR may reflect inherent radiosensitivity of tumor cells, tumor persistence predicts the amount of oncologically inactive materials rather than that of remaining cancer cells.

Patterns of radiologic response of 10 thymomas treated by preoperative radiotherapy (RT) (18-20 Gy/2 weeks) were determined in conjunction with histologic response. Changes in tumor volume were evaluated with CT scans obtained 5 to 36 days before and 14 to 24 days after the initiation of RT and before surgery. The extent of tumor volume reduction (TR) varied widely (40-78%), while the mean daily volume decrement expressed as a percentage of the pre-RT tumor volume correlated significantly with the pre-RT tumor volume. Histologically, the tumors, all of which were resected 17 to 33 days after RT initiation, generally consisted of predominant fibrous tissues, rare necrotic foci, and few epithelial cells. The TR did not correlate with pre-RT tumor volume, observation period, histologic subtype, or quantity of remaining epithelial cells. The TR of thymomas does not predict RT impact on tumor cells but does reflect the quantity of inherent tumor stroma.

Purpose : To determine the preserved functional capacity of the liver as a probable determinant of radiation tolerance in patients with cirrhosis and hepatocellular carcinoma, who underwent proton beam radiotherapy. Materials and Methods : We reviewed computed tomographic (CT) scans of 26 patients with cirrhosis and hepatocellular carcinoma during a period of 12–27 months after proton beam radiotherapy. Tumors were treated with focused proton beams with target doses of 140–186 TDF (time, dose, and fractionation). We measured the degree of hypertrophy of the untreated liver volume by measuring the total liver volume and the treated liver volume which was radiologically identified on contrast-enhanced CT scans. The risk of radiation-induced liver failure was estimated using the prediction score (PS) originally used for estimating posthepatectomy liver failure, substituting the planned treated liver volume for the resection liver volume. Results : The degree of hypertrophy ranged from —19% to 51%, and was significantly positively correlated with the ratio of the planned treated liver volume to the functional liver volume. The PS agreed well with observed radiation tolerance in 21 patients, but underestimated the tolerance in 5. This underestimation was diminished when the PS was recalculated using the identified untreated liver volume in lieu of the planned untreated liver volume. Conclusion : As in surgical treatment, radiation tolerance of the cirrhotic liver after focused treatement is closely related to the preserved functional capacity of the identified untreated liver volume, which shows compensatory hypertrophy following radiotherapy.

Purpose : To determine the capacity of biological clearance in tumor regression following radiotherapy by using metastatic brain tumors as a clinical model in which mechanical clearance is negligible. Methods and Materials : Thirty-eight tumors (19 nonsmall cell lung cancer, 11 small cell lung cancer, and 8 nonlung cancer) in 23 patients were followed with computed tomography (CT) scans over 3 months or more following initiation of radiotherapy, with doses ranging between 34 and 66 Gy. The tumor regression rate (RR ; mm 3 /day), which represented the capacity of biological clearance, was calculated for each CT observation period. The complete response (CR) rate was calculated. The relationship between RR and tumor diameter was determined with regression analysis in conjunction with the pattern of contrast enhancement and the type of primary disease. The change of the RR also was examined. Results : The CR rate was 60.5% for the total group ; it was lower for ring-enhanced tumors (41.7%) than diffusely enhanced tumors (69.2%), which included mostly small cell lung cancer metastases. The RR correlated significantly with the tumor diameter (D), with a regression curve of exponential function (RR = 0.035 *D 2.5 ). The RR varied widely and was rather large until 40 days following initiation of radiotherapy, especially for the subgroups of diffusely enhanced tumors and the small cell lung cancer tumors, and became rather constant thereafter. Conclusion : A tumor diameter exponent in the regression curve of smaller than 3.0 indicates that the larger the tumor volume is, the smaller the capacity of biological clearance. The capacity of biological clearance also is dependent on vascularity and cellularity of the tumor components expressed by the pattern of contrast enhancement.

The purpose of this investigation was to compare the biological effects of a 135 MeV/u carbon-ion beam and 13 MeV fast neutron beam using human osteosarcoma cells. We have studied the clonogenic cell survival, recovery of potentially lethal damage (PLD) in plateau phase cells, and spheroid cure in multicellular spheropid after irradiation at various positions in the plateau and spread out Bragg peak (SOBP) of a 135 MeV/u carbon-ion beam and with 13 MeV neutrons. The carbon beam had a 4-cm range in water and a range filter was used to produce a 3-cm extended-peak region. The reference radiation was {sup 137}Cs {gamma}-rays. The relative biological effectiveness (RBE) values for 10% survival level of plateau phase cells for carbon-ions at the position of plateau, proximal peak, midpeak, and distal peak within the SOBP, and neutrons were 1.71, 2.48, 2.63, 3.47, and 2.29, respectively. Corresponding RBE values at 1% level were 1.64, 1.93, 2.06, 2.49, and 2.05. The extent of recovery from PLD was reduced after carbon-ions at proximal peak, midpeak, and distal peak, and neutrons, although not substantially reduced after carbon-ions at plateau. The RBE values for 50% spheroid cure level of spheroids for carbon-ions at the position of plateau,more » proximal peak, midproximal peak, middistal peak, and distal peak within the SOBP, and neutrons were 1.69, 1.88, 1.87, 1.94, 2.03, and 1.90, respectively. The biological parameters measured all indicate an approximately comparable biological effectiveness between 75-80 KeV/{mu}m carbon-ions of the SOBP and 13 MeV neutrons in the human tumor model studied in vitro. 34 refs., 5 figs., 2 tabs.« less

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.

To assess the usefulness of proton beams for treatment of patients with rectal cancer, we have performed comparative 3D treatment planning for proton beam and x-ray beam therapy. Three common x-ray techniques (AP-PA, 3-field, and 4-field box), a proton beam only plan, and a proton boost plan were compared. The plan which would have been treated without the aid of the 3D planning system was also simulated. Dose distributions were analyzed and dose-volume histograms computed for the target volumes and critical normal tissues. Analyses of these plans demonstrate that the proton beam techniques reduce the volume of small bowel irradiated. This may allow higher doses to be delivered to the tumor, with a probable increase in local control, or a reduction in normal tissue complications probability. All the plans developed with the 3D planning system treated significantly less bowel than the one planned without it.

The low tolerance of the central nervous system (CNS) limits the radiation dose which can be delivered in the treatment of many patients with brain and head and neck tumors. Although there are many reports concerning the tolerance of the CNS, few have examined individual substructures of the brain and fewer still have had detailed dose information. This study has both. A three dimensional planning system was used to develop the combined proton beam/photon beam treatments for 27 patients with skull-base tumors. The cranial nerves and their related nuclei were delineated on the planning CT scans and the radiation dose to each was determined from three dimensional dose distributions. In the 594 CNS structures (22 structures/patient in 27 patients), there have been 17 structures (in 5 patients) with clinically manifest radiation injury, after a mean follow-up time of 74 months (range 40–110 months). From statistical analyses, dose is found to be a significant predictor of injury. Using logistic regression analysis, we find that, for each cranial nerve, at 60 Cobalt Gray Equivalent (CGE) the complication rate is 1% (0.5–3% with 95% confidence) and that the 5% complication rate occurs at 70 CGE (64–81 CGE with 95% confidence). The slope of the dose response curve (at 50%) is 3.2 (2.2–5.4 with 95% confidence). No significant relationship between dose and latency period for nerve injury was found.

Fifteen patients with invasive bladder cancer were treated with selective intra-arterial cisplatin and external beam radiotherapy (30.6 Gy over 3 weeks) prior to a planned cystectomy. Cisplatin, in total 200 mg, was administered via bilateral internal iliac artery infusion during the course of radiotherapy. Seven patients were evaluated for local response. Partial response (PR) was revealed in 4, and minor response (MR) in 3. Ten patients received total cystectomy, and pathological effects by the criteria adipted by Japanese Urological Association and The Japanese Society of Pathology, were as follows: Ef. 3 in 1 case, Ef. 2 in 6. Ef. 1b in 1 and Ef. 1a in 2. Down staging was observed in 8 patients from the clinical to the pathological stage. Thirteen patients are alive for 21 months. Two patients have died (1 lung infarction, 1 pancreatic cancer). Though nausea and sciatica-like pain were observed in some cases, there was no severe systemic side effects such as bone marrow suppression and renal toxicity. From these results it is concluded that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated.

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 May1995 and December1998. 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.

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.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.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.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, is a nitrotriazole with a potential to sensitize hypoxic tissue to radiation. Cancer of cervix in advanced stages are predominantly treated with radiation. These are the tumours which harbour a large hypoxic core. This is an Indian experience of the multicentric trial. Patients were randomized to control and AK-2123 arm. 49 patients were randomized to each group. Patients received external radiation with telecobalt to a dose of 50 Gy in five weeks. Those in the study arm received 600 mg/m2, on alternate days. The patients were further treated with intracavitory radiation a dose of 20 Gy. The total dose of 70 Gy was achieved. Patients in the study arm had a complete response of 71.43% (35 of 49) while only 21 of 49 (42.86%) responded in the control group. The overall survival at two years was 72.2% for the study group and 32.43% for control. Neuropathy, a drug related toxicity was transient except, in one patient, which has persisted. AK-2123, has shown significant radiation sensitizing potential.

Background and purpose : The acquisition of radiotherapy by countries in transition (CITs) is an evolutionary process from having no resources whatsoever, to meeting the standards adopted by well-developed countries. The influence of the economic ability of a country to acquire and sustain this technology has intuitively been accepted as a major factor but has not before been subjected to analysis for a large group of countries. This information has been analysed to provide guidance to countries commencing and expanding radiotherapy services. Material and methods : The number of linear accelerators and 60 Co megavoltage teletherapy machines in 72 CITs, those with gross national income per capita (GNI/cap) $12 000 pa were expressed as machines per million population (MEV/mil) and used as an index of the ability of the country to provide a service. This figure was related to GNI/cap. The average populations of 24 further countries without radiotherapy were compared with 21 countries with radiotherapy facilities having the same range of GNI/cap. Results : The relationship log 10 MEV/mil=−2.90+0.85 log 10 GNI/cap was identified between the machines and income. Also verified was that small low income countries were less likely to have the technology than those with large populations. Conclusions : The increase in the number of teletherapy machines is closely linked to the GNI/cap of a country. Our sample of well developed countries failed to demonstrate a levelling off of equipment acquisition with income. In the lower income group, smaller countries were less likely to have radiotherapy services than those with large populations.

Purpose : Resources for radiation therapy in Asian and Pacific countries were analyzed to obtain a better understanding of the status of radiation oncological practice in the region. Methods and Materials : The data were obtained mainly through surveys on the availability of major equipment and personnel which were conducted through an International Atomic Energy Agency regional project. The study included 17 countries in South Asia, South East Asia, East Asia and Australasia. Data were related to national populations and economic and a general health care indices. Results : Large differences in equipment and personnel among countries were demonstrated. The availability of both teletherapy and brachytherapy was related to the economic status of the countries. The shortage of teletherapy machines was evident in more countries than that of brachytherapy. Many departments were found to treat patients without simulators or treatment planning systems. The number of radiation oncologists standardized by cancer incidence of a country did not correlate well with economic status. Conclusions : There were significant deficiencies in the availability of all components of radiation therapy in the analyzed countries. The deficiencies were linked predominantly to the economic status of the country. Cognisance should be taken of the specific shortfalls in each country to ensure that expansion or any assistance offered appropriately match its needs and can be fully utilized. The information on the resources currently available for radiation oncological practice in the region presented in this paper provides a valuable basis for planning of development aid programs on radiation therapy.

Clearance of a parenchymal tumor following radiotherapy was determined by using follow-up CT scans of 18 hepatocellular carcinoma tumors treated with focused proton beams. Regression analysis of the daily decrement ( DD ) and the diameter ( D ) of a tumor mass in each CT observation interval, DD=a∗Db, showed that the exponent b was 3.0 or larger in early periods and 2.0 or smaller in late periods. This suggests that the clearance depends initially on the tumor volume, subsequently on the tumor surface area, and then it becomes much more moderate, possibly due to radiation damage to the parenchymal tissues.

The radiation tolerance of the liver was investigated in 12 patients, 11 of them with liver cirrhosis, treated for hepatocellular carcinoma by partial liver irradiation with doses between 50 and 77 Gy. The tolerance was assessed by the complication probability (Lyman's model), which concerned the injured tissue itself, and by a prediction score used for postsurgical liver failure, which concerned the preserved functional capacity, assuming that the > or = 30 Gy volume was equivalent to the resected volume. The prediction score corresponded better with the observed risk of fatal liver failure than the complication probability. The liver volume after radiotherapy correlated largely with the untreated volume and the low-dose volume. Thus the preserved functional capacity gives a better expression of the radiation tolerance than direct measures of the extent of injured tissue.

The survival of patients with glioblastoma multiforme is extremely poor, the 5-year survival rate being almost zero. The cause of failure is almost exclusively local progression of tumor, the remainder is due to complications of treatment. Although this tumor is clearly radiation resistant, there is evidence of a dose response relationship. Using a thin slice CT scan of the entire head of a patient with glioblastoma multiforme, 3-dimensional radiation treatment plans were developed for treatment to a dose of 90 cobalt-Gray-equivalent (CGE). Dose distributions using protons were compared to those using x-rays. The results showed advantages for the proton beam technique. Namely the proton plan irradiated less non-target brain than the x-ray plan; this was especially so in the decrease of coverage of deep-seated structures. The volume of non-target brain that received more than 70 CGE was 175 ml for the x-ray plan and 94 ml for the proton plan. This study indicates that for a subpopulation of patients with glioblastoma multiforme, at least 90 CGE could be delivered with proton beam techniques to the target with only small volumes of normal brain structures receiving more than 70 CGE.

Using proton beam therapy, high doses have been delivered to chordomas and chondrosarcomas of the base of skull and cervical spine. Dose inhomogeneity to the tumors has been accepted in order to maintain normal tissue tolerances, and detailed attention to patient immobilization and to precise positioning has minimized the margins necessary to ensure these dose constraints. This study examined the contribution of precise positioning to the better dose localization achieved in these treatments. Three patients whose tumors represented different anatomic geometries were studied. Treatment plans were developed which treated as much of the tumor as possible to 74 Cobalt-Gray-Equivalent (CGE) while maintaining the central brain stem and central spinal cord at less than or equal to 48 CGE, the surface of the brain stem, surface of the spinal cord, and optic structures at less than or equal to 60 CGE, and the temporal lobes at less than or equal to 5% likelihood of complication using a biophysical model of normal tissue complication probability. Two positioning accuracies were assumed: 3 mm and 10 mm. Both proton beam plans and 10 MV X ray beam plans were developed with these assumptions and dose constraints. In all cases with the same positioning uncertainties, the proton beam plans delivered more dose to a larger percentage of the tumor volume and the estimated tumor control probability was higher than with the X ray plans. However, without precise positioning both the proton plans and the X ray plans deteriorated, with a 12% to 25% decrease in estimated tumor control probability. In all but one case, the difference between protons with good positioning and poor positioning was greater than the difference between protons and X rays, both with good positioning. Hence in treating these tumors, which are in close proximity to critical normal tissues, attention to immobilization and precise positioning is essential. With good positioning, proton beam therapy permits higher doses to significantly more of the tumor in these sites than do X rays.