Published papers

Background: The prognosis for advanced gastric cancer is poor, with surgery as the only treatment for resectable advanced gastric cancer. Therefore, treatment options that might improve the prognosis are needed. To that end, neoadjuvant chemoradiotherapy with S-1 and cisplatin (CDDP) was investigated. Patients and Methods: The chemotherapy schedule included one cycle repeated after 6 weeks. S-1 was administered orally every day on days 1-21 and CDDP was infused on days 1, 8 and 15. Radiation therapy was started concurrently with chemotherapy and repeated daily on days 1-5, 8-12, 15-19, and 22-26. Results: A total of 10 patients were recruited. The first four patients were entered into level 1 (CDDP, 20 mg/m2). The next six patients were entered into level 0 (15 mg/m2), because of dose-limiting toxicity (delaying the second course of chemotherapy in two patients) that had been observed at level 1. The maximum tolerated dose (MTD) of CDDP was 20 mg/m2. Seven patients underwent surgery and all had an R0 (no residual tumor) resection without surgical complications. Conclusion: Neoadjuvant chemoradiotherapy with S-1 and CDDP may cause surgery to be delayed, but shows promise for resectable advanced gastric cancer.

Purpose: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m2]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade ≥3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC. © 2010 Elsevier Inc. All rights reserved.

We analysed the repositioning accuracy of bite-plate fixations from serial QA-CT (quality-assurance CT) taken during the course of stereotactic radiotherapy. A total of 72 series of CT examinations from 15 consecutive patients, who underwent stereotactic radiotherapy for various intracranial tumours, were examined. Three or four CT scans were obtained for the purpose of QA for the right and left incus, as well as the crista galli. The stereotactic coordinates of the centres of the incus and the top of the crista galli were semi-automatically obtained for each QA-CT scan. Positional displacements for these anatomical reference points and the centre of the points were obtained. The mean displacements for these points in the 3D directions ranged from -0.10 to 0.08 mm (standard deviations: 0.44-0.94). The absolute positional displacement ranged from 0.93 to 1.09 mm (standard deviations: 0.52-0.88 mm). The rotations of the head were 0.49 0.36°. Our 3D measurement technique using anatomical landmarks revealed excellent stability of the mouthpiece fixation system in terms of translational and rotational displacements. This technique can also be used as a QA method for other fixation devices. © 2009 Institute of Physics and Engineering in Medicine.

Background: One of the most important factors in stereotactic radiosurgery (SRS) for intracranial arteriovenous malformation (AVM) is to determine accurate target delineation of the nidus. However, since intracranial AVMs are complicated in structure, it is often difficult to clearly determine the target delineation. Purpose: To investigate the usefulness of principal component analysis (PCA) on intra-arterial contrast enhanced dynamic CT (IADCT) images as a tool for delineating accurate target volumes for stereotactic radiosurgery of AVMs. Materials and Methods: IADCT and intravenous contrast-enhanced CT (IVCT) were used to examine 4 randomly selected cases of AVM. PCA images were generated from the IADCT data. The first component images were considered feeding artery predominant, the second component images were considered draining vein predominant, and the third component images were considered background. Target delineations were first carried out from IVCT, and then again while referring to the first and second components of the PCA images. Dose calculation simulations for radiosurgical treatment plans with IVCT and PCA images were performed. Dose volume histograms of the vein areas as well as the target volumes were compared. Results: In all cases, the calculated target volumes based on IVCT images were larger than those based on PCA images, and the irradiation doses for the vein areas were reduced. Conclusion: In this study, we simulated radiosurgical treatment planning for intracranial AVM based on PCA images. By using PCA images, the irradiation doses for the vein areas were substantially reduced.

Purpose: We previously reported that most of axillary regions could be irradiated by the modified tangential irradiation technique (MTIT). The purpose of this study was to determine whether the three-dimensional conformal radiotherapy (3D-CRT) with a field-in-field technique improves dosimetry for the breast and axillary nodes. Methods and Materials: Fifty patients with left-sided breast cancer were enrolled. With MTIT, we planned the radiation field to be wider in the cranial direction than the standard tangential fields to include the axillary regions. With 3D-CRT, a field-in-field technique was used to spare the heart and contralateral breast to the extent possible by applying the multileaf collimator manually. Dose-volume histograms were compared for the breast, axillary region, heart, lung, and other normal tissues. Results: There were no significant differences in the percent volume of the breast receiving >90% of the prescribed dose (V90) between MTIT and 3D-CRT. The mean V90 of the level I to III axillary regions were increased from 93.7%, 48.2%, and 41.3% with MTIT to 97.6%, 85.8%, and 82.8% with 3D-CRT. 3D-CRT significantly reduced the volume of the heart receiving >30 Gy (mean, 7.6 vs. 15.9 mL), the percent volume of the bilateral lung receiving >20 Gy (7.4% vs. 8.9%), and the volume of other normal tissues receiving >107% of the prescribed dose (0.1 vs. 2.9 mL). Conclusion: The use of 3D-CRT with a field-in-field technique improves axillary node coverage, while decreasing doses to the heart, lungs, and the other normal tissues, compared with MTIT. © 2009 Elsevier Inc. All rights reserved.

Chemoradiotherapy improves therapeutic outcome in many different types of cancer. However, there is concern about the occurrence of delayed complications, as patients are surviving longer. Because patients with esophageal cancer receive a wide range of irradiation field to the mediastinum and the heart, they may have delayed complications of heart and lung functions as previously reported in Hodgkin's disease. We presented a case of death related to uncontrollable pleural and pericardial effusions in a patient with advanced cancers of the esophagus and stomach who achieved a complete remission following chemoradiotherapy and salvage gastric resection, focusing on detailed pathophysiological conditions related to concurrent chemoradiotherapy.

Purpose: To investigate how the delineations of the internal target volume (ITV) made from 'slow' CT alter with reference to 'thin-slice' CT. Materials and methods: Thin-slice CT images taken under breath-holding conditions and slow CT images taken under shallow-breathing conditions (8 s/image) of 11 lung cancers were used for this study. Five radiation oncologists delineated ITV of the 11 lesions using slow CT images (ITV1), and then redefined them with reference to thin-slice CT images (ITV2). SD-images (standard deviation image) were created for all patients from ITV images in order to visualize the regional variation of the ITVs. Results: The mean value of ITV2 was smaller than that initially defined by ITV1. There was no significant change in ITV1 and ITV2 between operators with regard to standard deviation in volume. There was a significant difference in the distribution of the ratio of ITV1 to ITV2 obtained on thin-slice CTs between cases with and without ground glass opacity. In cases without ground glass opacity there was a tendency for ITV2 to have a smaller volume than ITV1. Conclusions: Combined use of slow CT and thin-slice CT in delineation of ITV contours appeared to be useful in making adjustments for obscured tumor images caused by respiratory movement. © 2007 Elsevier Ireland Ltd. All rights reserved.

The authors critically reviewed previous articles concerning the significance of breast irradiation following breast-conserving surgery in terms of the following subject items: indications for breast-conserving therapy, the significance and complications of breast irradiation, the timing of the start of breast irradiation, the significance of boost irradiation, the potential improvement of survival with systemic therapy plus breast irradiation, the significance of axillary dissection, indications and the significance of regional nodal irradiation, accelerated hypofractionated radiotherapy, omission of breast irradiation in low-risk patients, and future directions. In addition, our previously reported results of breast irradiation following breast-conserving surgery at the Keio University Hospital are outlined. Our newly developed tangential irradiation technique directed to the axilla and a recently introduced three-dimensional simulation technique for radiotherapy treatment planning are also presented. © Japan Radiological Society 2006.

PURPOSE: To prospectively use long-scan-time computed tomography (CT) to visualize the trajectory of tumor movements or the internal target volume. MATERIALS AND METHODS: The study was approved by the institutional review board. Written informed consent was obtained from participants after the study and the role of procedures were explained fully. During the planning of stereotactic radiation therapy for 10 patients (nine men, one woman; mean age, 77 years; range, 69-89 years) with small lung tumors (mean volume, 9.0 cm3; range, 3.6-24.9 cm3), fluoroscopic imaging, long-scan-time CT, and thin-section CT were performed. The tumor and the partial-volume-averaging effects that resulted from tumor movement were delineated on each section at long-scan-time CT performed during the patient's steady breathing with scan time of 8 seconds per image. Visualized internal target volume was defined by integrating the sections. A simple model was examined for estimating internal target volume on the basis of respiratory motion and gross target volume delineated on thin-section CT images. Visualized internal target volume and estimated internal target volume were compared quantitatively and graphically. The Mann-Whitney test was used to analyze the relation between gross target volume delineated on thin-section CT images and the ratio of visualized internal target volume to the defined gross target volume. RESULTS: The correlation coefficient between visualized internal target volume and estimated internal target volume was r = 0.98 (P < .001). The mean relative error ± standard deviation was 1.9% ± 19.0 (range, -11.0% to 56.4%). Excluding one case with an irregularly shaped tumor (56.4%), the mean relative error was -4.1% ± 4.1. In patients with small tumors (defined gross target volume, ≤10 cm3), the ratio of the visualized internal target volume to the defined gross tumor volume was significantly larger than that in patients with larger tumors (1.2-2.0 vs 1.0-1.2; P < .05). In some cases in which marginal spiculation depicted on thin-section CT images was blurred on long-scan-time CT images, the blurred area was erroneously excluded from the target volume. CONCLUSION: In most cases, values for visualized internal target volume and estimated internal target volume were similar and long-scan-time CT depicted virtually the entire tumor trajectory. © RSNA, 2005.

The purposes of this study were to investigate the feasibility of drip infusion cholangiography computed tomography (CTCh) for choledocholithiasis and to compare the detection of the stone on CTCh with that of MR cholangiopancreatography (MRCP). CTCh examinations were performed after infusion of intravenous biliary contrast material (iotroxic acid meglumine, 100 ml) for patients with suspected biliary diseases and were reconstructed to maximum intensity projection (MIP) and multiplanar reformation (MPR). Of 432 patients who underwent CTCh, we identified 15 who underwent surgery or cholangioscopic removal for choledocholithiasis and 32 patients who underwent cholecystectomy due to cholecystolithiasis. Their MRCP images were compared with the CTCh images. The sensitivity and specificity of CTCh for detecting choledochal stones were 87% and 96% whereas those of MRCP were 80% and 88%. The sensitivity and specificity of CTCh for detecting gallstones were 78% and 100% whereas those of MRCP were 94% and 88%. CTCh allowed high sensitivity and specificity for detecting choledochal stones but diminished the detection for cholecystolithiasis compared with MRCP. © Springer-Verlag 2005.

Purpose: We report here our experience of brachytherapy using I-125 seeds for localized prostate cancer in 100 patients. Materials and Methods: We carried out brachytherapy with I-125 seed permanent implants in 100 patients with localized prostate cancer between September 2003 and October 2004. Preplanning dosimetry was done using transrectal ultrasonic images obtained three or four weeks prior to treatment Using transrectal ultrasound, we inserted I-125 seeds in the prostate through needles according to the preplanning diagram. We then examined the results on prostate CT performed one month later. Results: It was necessary to describe transrectal ultrasonic image such as preplanning. There were several cases in which the source arrangement of the schedule was corrected immediately before the operation. In the examination after one month, the numerical value at the start of treatment initially was not satisfactory, but we eventually obtained a result that could to be evaluated. Conclusion: We carried out permanent implant brachytherapy for localized prostate cancer using I-125 seeds and reported our experience.

Purpose: To evaluate long-term pulmonary toxicity of stereotactic radiotherapy (SRT) by pulmonary function tests (PFTs) performed before and after SRT for small peripheral lung tumors. Methods and Materials: A total of 17 lesions in 15 patients with small peripheral lung tumors, who underwent SRT between February 2000 and April 2003, were included in this study. Twelve patients had primary lung cancer, and 3 patients had metastatic lung cancer. Primary lung cancer was T1-2N0M0 in all cases. Smoking history was assessed by the Brinkman index (number of cigarettes smoked per day multiplied by number of years of smoking). Prescribed radiation doses at the 80% isodose line were 40-60 Gy in 5-8 fractions. PFTs were performed immediately before SRT and 1 year after SRT. Test parameters included total lung capacity (TLC), vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and diffusing capacity of lung for carbon monoxide (DLCO). PFT changes were evaluated in relation to patient- and treatment-related factors, including age, the Brinkman index, internal target volume, the percentages of lung volume irradiated with >15, 20, 25, and 30 Gy (V15, V20, V25, and V30, respectively), and mean lung dose. Results: There were no significant changes in TLC, VC, or FEV1.0 before vs. after SRT. The mean percent change from baseline in DLCO was significantly increased by 128.2%. Univariate and multivariate analyses revealed a correlation between DLCO and the Brinkman index. Conclusions: One year after SRT as compared with before SRT, there were no declines in TLC, VC, and FEV1.0. DLCO improved in patients who had been heavy smokers before SRT, suggesting a correlation between DLCO and smoking cessation. SRT seems to be tolerable in view of long-term lung function. © 2005 Elsevier Inc.

One year has passed since we started brachytherapy with radioactive iodine-125 seeds for carcinoma of the prostate. During the follow-up of patients, we have relatively frequently found migrated seeds in the lungs. Migrated seeds are reported to reach mainly the pulmonary artery and cause embolization without clinical symptoms. We counted the embolized seeds and determined the proportion of migrating seeds on chest X-ray exam. We found 47 cases of pulmonary embolization in our initial 100 cases. Less than half of the embolization were found in the chest X-ray exam performed on the next day after the implantation. We found more migrated seeds in the lower lung fields than in the upper and middle lung fields. Pulmonary embolization of implanted iodine-125 seeds is not unusual, and cases of prostate brachytherapy are likely to increase in Japan. We will have increased opportunities to observe chest X-ray films with migrated seeds in the future.

We took a routine conservative approach for hypopharyngeal carcinoma. This retrospective study analyzes the outcome of treatment with this policy. Between 1993 and 2002, 36 patients with hypopharyngeal carcinoma received radiotherapy with or without chemotherapy at our institution. Doses ranged from 60 Gy to 72 Gy given to the involved fields. Fourteen patients received CDDP and 5FU, either inductive or concurrent with radiotherapy. The overall five-year survival was 38% and the two-year local control rate was 69%. The local control rate was dependent on the size of primary tumor. Two-year local control rates were 60% with radiotherapy alone and 88% with chemoradiotherapy. Neck dissections combined with radiotherapy were all successful for 12 patients with N1-2. In 14 patients with N0, 3 patients were salvaged successfully after nodal recurrence. Ultimate conservation rate of laryngo-pharynx was 67%. This non-surgical therapy provided survival comparable with that achieved with the standard approach of surgery and postoperative radiotherapy.

Purpose: Ir-192 thin wires were used in our hospital since December 1997 for low dose rate brachytherapy for prostatic carcinoma. Since February 2000, we used the therapeutic planning system which created a pattern of dose distribution from a transrectal echogram, however, there were difficulties associated with this treatment which we tried to improve. However, a technical problem with the Ir-192 low dose rate brachytherapy became obvious. Improvements to the method have been tried since October 2001, and are reported here. Method: We performed brachytherapy for localized prostatic carcinoma on 105 patients from February 2000 to February 2003. We defined the period from February 2000 to September 2001 as the early phase (47 cases). The period from October 2001 to February 2003 was defined as the late phase in which technical improvements were introduced (58 cases). We compared the late phase with the early phase. The early phase treatment procedure is as follows. We did centesis with a plastic needle for the prostate gland using transrectal ultrasound as a guide through the aperture of a template by a transperineal approach. The position of the paracentesis needle was checked by CT and also obtained a pattern of dose distribution in 2 dimensions from the maximal profile of the prostate gland. This was analysed and dose rate calculated and radiation source halt time. We set the clinical target volume around the circumferential part of the prostate gland. We inserted radiation source in a pallium needle and then fixed them in situ. However, the next points were modified. 1) We changed the posture of a patient into extended lithotomy. 2) We invested the position of the transrectal ultrasound probe in a part of infraversion/dorsum. 3) A metal marker was inserted into the apex of the prostate gland and was maintained. 4) We contrasted the urethra by means of transrectal ultrasound. 5) The calculated dose distribution from the transrectal ultrasound for therapeutic planning could be obtained in 3 dimensions. The dose volume histogram was calculated in relation to the prostate, urethra and rectum from which we decided the dose rate. Each technical improvement was evaluated. Result: 1) The loading of the needle, which avoided the pubic arch by taking the extended lithotomy was enabled. 2) Visualization enabled a good amount of the border area of the prostate gland by positioning of the transrectal ultrasound probe moving towards the dorsum. 3) We inserted a metal marker at the gland apex part in order to aim the radiation source displacement and maintain it. 4) It became easy to identify the urethra by contrasting it. 5) We devised a configuration of paracentesis needle. It became technically clear that the dosage to the urethra and the rectum could be decreased by these improvements. Conclusion: We evaluated the problem of brachytherapy for localized prostatic carcinoma with a low dose rate Ir-192 thin wire. We introduced technical improvements to improve treatment. This has provided a reference point for further technical improvements for brachytherapy for prostatic carcinoma.

OBJECTIVE. We studied the serial changes and CT manifestations of pulmonary radiation injury after hypofractionated stereotactic radiation therapy for peripheral small lung tumors. SUBJECTS AND METHODS. Hypofractionated stereotactic radiation therapy was applied to 20 patients with proven primary (n = 11) or metastatic (n = 9) lung cancer, for a total of 22 lesions of 3 cm or less in diameter located within 3 cm from the parietal pleural surface. Follow-up CT was scheduled at 1 and 3 months, and every 3 months thereafter. RESULTS. Ground-glass opacities were observed around four (18%) of 22 lesions at 3-6 months. The opacities nearly corresponded to the planned target volume, but half of them were unevenly distributed. Ground-glass opacities gradually disappeared or evolved into dense consolidation while shrinking. Dense consolidations developed in 16 (73%) of 22 lesions, including seven in the center of the planned target volume and nine in the periphery of the planned target volume. Dense consolidations moved in six of these 16 lesions and gradually shrank, becoming fixed as solid or linear opacities approximately 12 months later. CONCLUSION. The pulmonary opacities observed after hypofractionated stereotactic radiation therapy for peripheral small lung tumors may not precisely correspond to the planned target volume (unlike those with conventional radiation therapy) and may change in shape and location dynamically during the first year. Knowledge of these findings is necessary to avoid misunderstandings concerning tumor regrowth or new tumors.

There is good evidence that radiotherapy is effective in relieving bone pain due to metastatic tumor. For localized bone pain, external beam treatment will be successful in reducing pain in some 80% of patients. Many prospected randomized trials show single fractions as effective as more prolonged regimens both in terms of incidence and duration of pain relief. For scattered painful metastases, wide-field hemibody irradiation or the systemic administration of radioisotopes is effective.