The fungal metabolite wortmannin is a specific inhibitor of phosphatidylinositol-3 kinase (PI-3K) and an effective radiosensitizer. Both ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) exhibit sequences homologous to the catalytic domains of mammalian PI-3K. On the basis of these findings, it is assumed that ATM and DNA-PK are potential targets for the radiosensitizing effects of wortmannin. Recently, it has been reported that Nijmegen breakage syndrome protein (NBS1) is specifically phosphorylated by ATM in response to radiation exposure. In the present study, treatment with wortmannin enhanced the radiosensitivity of human tumor cells and reduced ATM-dependent phosphorylation of NBS 1 after X-irradiation. However, in tumor cells whose radiosensitivity was not enhanced by wortmannin, X-ray-induced phosphorylation of NBS 1 was reduced by the drug to a lesser degree than in those whose radiosensitivity was enhanced. The evidence presented here strongly suggests that, in addition to DNA-PKcs, ATM is a target protein involved in the radiosensitizing effect of wortmannin in human tumor cells.

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In the Remote After Loading System (RALS), the source position is reconstructed as a 3 dimensional position by X-ray catheter points on bi-plane X-ray films. There are several reconstruction methods. However, the geometrical accuracy of the source coordinate position is important to evaluate dose distribution in any case. Many institutions adopted a C-arm X-ray fluoroscopic system with a rotational mechanism due to the simplicity of handling. However, the I. I.-DR image by the C-arm system has image distortion that results from mechanical accuracy and fluorescence plane of I. I., and films are used to confirm the source position in RALS. Therefore, the RALS positioning system that corrected I. I. DR image distortion was reconstructed. RALS positioning system kept reconstruction accuracy of the source coordinate position within 1mm and this system also realized simplification of work and shortening in treatment time.

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By using three-dimensional conformal radiation therapy (3D-CRT) for lung tumors, one may increase the dose to the tumor without increasing the dose to the surrounding normal lungs, thus enhance local control rates even with patients in a poor condition. We have been conducting a 3D-CRT for lung tumors using a middle fraction size. The preliminary results were analyzed. Eighteen patients with 20 lung tumors were treated with 3D-CRT between September 1999 and May 2001 according to the criteria; Tumor size: 5 cm or smaller, V20: under 20%, Middle fraction size: 3-4 Gy, No limitations to patients' age and/or respiratory status unless patient's Performance Status (PS) was 4. The mean age was 75.4 years (range; 54-86). Of these, 14 tumors in 14 patients were primary lung cancer. Five tumors in 4 patients were metastatic lung cancer colon, esophagus, thymus and lung (primary tumor was also treated with 3D-CRT) and the other one was recurrent lung cancer. The median maximun tumor diameter was 35 mm (range; 10-50). As for the treatment techniques, 6 to 10 non-coplanar fixed ports (median: 10) were used. The mean total dose and fraction size were 62 Gy (range; 51-64) and 3-4 Gy, respectively. The mean overall treatment time was 28 days (range; 24-36). One-year local control and overall survival rates of all patients were 87.7%, 94.1%, respectively. As for primary lung cancer patients, I-year local control and overall survival rates were 90.9%, 92.3%, respectively. With respect to radiation toxicity for lungs, Grade 0 and I were recognized in 9 patients and in 11 patients, respectively. No patients experienced grade 2 or greater toxicity. The results of this preliminary study suggested that our 3D-CRT using a middle fraction size for lung tumors was promising with encouraging local control rates and little lung toxicity.

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Local effectiveness and complication of superselective intra-arterial infusion of high-dose cisdiamminedichloroplatinum (CDDP)(SIC) combined with radiation therapy (RT) were investigated. Between 1998 and 2000, 18 head and neck carcinomas including 10 maxillary carcinomas (T3; 1, T4; 9), 3 oral cavity carcinomas (T2; 1, T4; 2), and 5 oropharyngeal carcinomas (T2; 2, T4; 3) were treated with SIC and RT with or without surgery. CDDP of 100-150 mg/body was administered weekly in principle for 2-9 weeks (mean: 4.9) with the simultaneous administration of sodium thiosulfate. Radiation doses ranged from 40 Gy to 70 Gy (mean: 56.8 Gy). Complete response was obtained in 7 of 10 maxillary carcinomas, 2 of 3 oral-cavity carcinomas, and 2 of 5 oropharyngeal carcinomas, respectively. When surgical intervention was performed if necessary, 2-year local control rates for maxillary carcinoma, and other carcinoma including oral-cavity carcinoma and oropharyngeal carcinoma were 80% and 63% respectively. Two-year local control rates for T4 maxillary carcinoma, and other T4 carcinoma including oral-cavity carcinoma and oropharyngeal carcinoma were 78% and 40% respectively. Two-year overall survival rates for all cases, maxillary carcinoma, and oralcavity/oropharyngeal carcinoma were 88%, 90% and 86% respectively. All local recurrences occurred within 6 months from the initiation of treatment. The systemic toxicity of weekly SIC was comparatively mild; however, a total CDDP dose of 1, 000 mg or more and/or RT of 70 Gy induced complications of local soft tissue such as mucosal ulcer and fistula. SIC combined with RT is useful to improve the local control/survival rates and to avoid the aggressive surgery for locally advanced head and neck carcinoma. A high total dose of CDDP and/or RT of a comparatively high dose may be risk factors for local soft tissue complications.

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Intensity modulated radiation therapy (IMRT) for head and neck cancers and brain tumors was started in December 2000 at our hospital. Methods of quality assurance (QA) in IMRT at our hospital are reported. IMRT was given by 4 MV X-ray with a dynamic multi-leaf collimator (MLC) method. Treatment planning was obtained by an inverse planning method. It took two days to select an appropriate treatment plan among various plans obtained by inverse planning, and three days to perform dosimetry in phantoms for each beam and the total beams and to determine an isocenter of fields. The measured dose distribution in phantoms were consistent with the calculated dose distribution, although the measured doses were 2-4% lower than the calculated doses. The accuracy of MLC is the most important point in QA of IMRT. Beam profiles were obtained for all beams by a semiconductor profiler before IMRT every day. In addition, position of MLC was checked by a test pattern of a film method once a week. This method is very accurate and the slight deviation of MLC position as small as 0.2 mm could be detected by the method. A guideline of QA for IMRT should be established as soon as possible in Japan to perform IMRT safely and effectively.

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In high dose rate interstitial brachytherapy for prostate cancer, we compared a Geometrical optimization method and a Dose point optimization method in terms of coverage index (CI) and dose nonuniformity ratio (DNR) computed from dose volume histograms (DVHs) of respective dose distributions, under several different conditions of dose prescription points. In the Geometrical optimization method, we set the prescribed isodose curves as those crossing the prescription points placed at 3-, 5-and 10-mm distant from the applicators, respectively. When the distance was as close as 3mm, the CI was less than 90%. With 5 and 10mm, the CIs were large enough (97% and 100%); while in the case of 10 mm, the DNR was as high as 0.84, that is, yielding a too high dose volume. In the Dose point optimization method, when the prescription points were placed on the surface of CTV, the CI was as low as 72%, indicating that the Dose point optimization method failed to prescribe the given dose on CTV surface. When the dose points were placed at the distances of 5-and 10-mm outside of CTV, the CIs were 91%, and 100%; while the DNRs were as high as 0.64 and 0.85, respectively, indicating dose volumes their were too high. Whichever “optimization” program is used, it does not always ensure a good dose distribution, and so radiation oncologists should examine the dosedistribution carefully without overestimating the“computer-optimized” one.

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Purpose: To examine the late adverse effects of childhood hematological disorders treated with chemotherapy and radiotherapy including whole cranial irradiation at Sapporo Medical University Hospital.
Materials and Methods: Twenty-eight patients were treated with chemotherapy and 18-24 Gy of prophylactic cranial irradiation (PCI) for acute lymphoblastic leukemia (ALL), and 14 patients were treated with 3-12.8 Gy of total body irradiation (TBI) and bone marrow transplantation (BMT) for ALL, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), myelodysplastic syndrome (MDS), malignant lymphoma, and aplastic anemia (AA). Age at diagnosis ranged from 2 to 15 years old, and 28 were males and 14 were females. All patients were disease-free more than 2 years after diagnosis.
Results: Of 42 patients, 4 patients had decreased height (less than-2 S. D.), 3 patients required hormone replacement therapy, 2 patients had mental retardation, 3 patients had leukoencephalopathy, and I patient had a second malignancy. Except for the cases of decreased height, 3 of 7 late adverse effects were occurred in patients who had relapse of disease, and the risk of the adverse effects seemed to be higher for those patients whose doses of PCI were 22 Gy or more, or who received an additional craniospinal irradiation due to relapse of disease, and 18 Gy of PCI did not increase the risk of adverse effects.

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The regular survey on radiotherapy resources in Japan at the end of 2001 was performed as a regular activity of JASTRO Database Committee. The census was taken by mailing a questionnaire to 746 radiotherapy facilities and 637 (85%) questionnaires were returned.
The number of institutions which carried out radiotherapy in 2001 were estimated 707, and 603 (85%) answers were available for analysis.
The number of newly registered patients who received radiotherapy in 2001 were 118, 016, and it showed asteady increase.

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Purpose: The second questionnaire survey was carried out to describe the actual situation with respect to informed consent, especially written consent, at the radiation therapy department.
Methods and Materials: On April 2001, we sent the questionnaire to 167 institutes which had a radiation therapy department in the Kanto area. The results were compared with the first survey done in 1996.
Results: There were 88 eligible replies from 90 institutes. The average number of full-time radiation oncologists, that of full-time radiation technologists and that of radiation physicists did not increase. But the average annual number of patients who received radiation therapy in an institute was 286 (241 at the first survey), and there was a significant increase of the number between the second and the first surveys in the institutes that replied to both surveys. The number of institutes at which doctors told the truth about the diseases to equal or less than 50% of the patients decreased to 13%. This percentage significantly decreased compared to the first survey. Seventy five percent of institutes did not get written consent. But the percentage significantly decreased compared to the first survey. The content of explanation became detailed compared to the first survey, especially in the items of aim of treatment, method of treatment and possible toxicities.
Conclusion: The number of patients who received radiation therapy increased and more detailed explanations were carried out. But the number of radiation oncologists did not increase and it was still a small number of institutes whose radiation oncologists obtain written informed consent.

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As a result of efforts to improve information disclosure in medicine, an increasing number of patientsare actively seeking information on hyperthermia and/or wish to undergo hyperthermia therapy. To investigate interest among patients, we studied 12 patients who visited the Department of Radiation Oncology and Nuclear Medicine, Toranomon Hospital, Tokyo from April 2000 to December 2001 to seek second opinions on hyperthermia. The subjects consisted of 8 males and 4 females, and the median age was 53 years. Eight patients brought referral letters from their original doctors, and I I brought X-rays taken at their first hospital. The total number of consultations per patient was once or twice in all cases. The time spent with each patient was 0.5 hours to 3 hours per consultation (median: 1.5 hours). As a result, hyperthermia therapy was indicated for 2 patients. As sources of information on hyperthermia, 9 of the 12 patients had searched the internet before visiting Toranomon Hospital. Seven of the 9 searched Yahoo! Japan using the key word “on-netsuryouhou” rather than “hyperthermia”. This figure revealed that “on-netsuryouhou” was more often used, as ak ey word among patients, than “hyperthermia”. Within the scope of this study, it appeared that information on hyperthermia, including internet sources, is limited and/or difficult to access. This suggests the need for an educational campaign on hyperthermia.

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We have developed an exchange system of treatment planning data sets between multiple radiotherapy treatment planning systems (TPSs) used in our institution: a specially developed TPS for carbon ion therapy, and two commercial TPSs. The system allows mutual use of software utilities for the carbon ion treatment planning and its analyses. Data sets including tumor and treatment target volumes, anatomical structure contours and dose distributions are exchanged through RTOG data exchange format files. The implementation issues such as the coordinate matching to CT scan images as well as the import of dose distribution are described. Several test runs showed that the coordinates of the contours and dose distributions were unaltered within a pixel size of a CT image after the exchange. The system has proven to be useful in both clinical and research purposes such as image fusion and comparison of dose distributions in carbon ion treatment planning. It is also used to convert treatment planning data sets to and from DICOM RT information objects.

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