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To present technical considerations and results of proton irradiation in a single fraction for hepatocellular carcinoma (HCC) patients with uncontrollable ascites. Three HCC patients with uncontrollable ascites underwent proton irradiation of 24 Gy in a single fraction. Hepatic tumors were solitary in two patients, and multiple in one, and tumor sizes were 30, 30, and 33 mm in maximum diameter. No patient had lymph node or distant metastases. The center position of radiation fields was determined and the beam range was adjusted, using CT data taken immediately before irradiation to compensate for changes in the volume of ascites. Adjustment of the beam range was within 6 mm in water-equivalent thickness. All irradiated tumors showed objective responses, and were controlled during the follow-up period. Of the three patients, two were alive with no evidence of disease at 13 and 30 months, respectively, after treatment. The remaining patient died of ruptured esophageal varices 6 months after treatment. No therapy-related toxicity of grade 3 or more was observed. Proton beams were successfully adjusted immediately before irradiation. Single-dose irradiation with precisely adjusted proton beams may be tolerable for HCC patients with uncontrollable ascites.

Treatment outcomes for patients with locally advanced cervical cancer are no better with neoadjuvant chemotherapy (NAC) combined with radiotherapy (RT) than with RT alone. We investigated the reason for this failure from the standpoint of the tumor regression rate (RR).A total of 48 patients with clinical stage IIB-IVA cervical squamous cell carcinoma were treated clinically with cisplatin-based NAC plus RT (n = 15) or RT alone (n = 33). The RR was defined as the slope of a tumor shrinkage curve derived with magnetic resonance images. The local control rate (LCR) and disease-free rate (DFR) were estimated by clinical stage (IIB vs. III-IVA), pretreatment volume (or = median vs.median), lymph node status (negative vs. positive), treatment type, overall treatment time (or =8 weeks vs.8 weeks), and RR (or = median vs.median) using univariate and multivariate analyses.RR during NAC or during NAC and RT (n = 15) was not significantly higher than RR by RT alone (n = 33). Low RR and positive nodal status were significantly powerful prognostic factors for both the LCR and DFR, whereas the others were not.Although effective in reducing tumor volume prior to RT, NAC showed no overall effect in increasing the RR, which was shown to be the most powerful prognostic factor.

This study was to clarify the long-term subjective functional state and the therapeutic factors that may influence the outcome and ADL of patients with intracranial germinoma. Subjects were 19 patients with an average age of 16.5 years. All patients received radiotherapy with a mean dose of 42.8 Gy, while 14 patients also received chemotherapies. After a median follow-up of 137 months (41–271), a written questionnaire was sent to each patient. Estimated 5- and 10-year event-free survival rates were 78% and 71%, respectively. Recurrence occurred in 5 patients, and 1 patient died of tumor. The extent of surgery did not affect the incidence of recurrence. Chemotherapy remained adjuvant. Radiotherapy administered to the field encompassing the whole ventricle was essential for long-term tumor control. Only one patient complained of a major treatment-related complication at the time of the questionnaire: radiation-induced cavernomas. Adverse effects related to treatment are not significant in this study. Radiotherapy of 24 Gy to the field encompassing the whole ventricle is essential, and elective use of chemotherapy and/or additional local boost radiotherapy may prevent recurrence and maintain quality of life (QOL) of the patients for a relatively long period.

症例は43歳のHBVキャリアの男性で，2004年3月に他院にて門脈腫瘍栓（Vp4）を伴う肝右葉の肝癌と診断された．その後陽子線治療（2Gy/回，計70Gy）を受け，治療後の経過観察中に肝左葉に多数の肝癌の出現を認めたため7月4日に当科に紹介入院となった．肝動脈造影では肝左葉に多数の結節状の濃染像を認めるも門脈左枝には腫瘍栓は認めなかった．肝左葉全体にchemolipiodolizationを施行した後より抗癌剤持続動注療法（low dose FP）を開始した．1コース終了後の血管造影検査上，腫瘍濃染像は消失し腫瘍マーカーも著明に低下した．その後薬剤を変更しながら動注療法，化学療法を継続し，2006年12月現在腫瘍の再発の徴候は認めていない．初発時門脈腫瘍栓を伴い，後に多発した肝癌でありながら集学的治療が著効した症例を経験したので報告する．

Purpose: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. Methods and Materials: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day −1 ) of the shrinkage curve by fitting to an exponential equation. Results: Early-assessed radioresponse ranged from 0.001 to 0.106 day −1 (median, 0.021 day −1 ) and late-assessed radioresponse from 0.009 to 0.091 day −1 (median, 0.021 day −1 ), with no significant difference between them ( p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse ( R 2 = 0.714, p = 0.0005). Conclusions: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness.

The purpose of this study was to develop an efficient method of determining gate-on and -off timing in respiration-gated radiotherapy. Gate-on and -off timing in a breathing cycle were defined as the respiratory signal level for the start of irradiation (Ls) in the expiration phase and that for the end of irradiation (Le) in the inspiration phase, respectively. Thirty subjects participated in this study. The diaphragm was used as the tracking target, and time-dependent changes in the position of the target were measured together with those in the respiratory signal level. For each subject, the following maps were created by varying the combination of Ls and Le: absolute target displacement (ATD) map, relative target displacement (RTD) map, and gate-on duty cycle (GDC) map. By classifying respiratory signal waveforms, three respiratory types were derived (A: the length of end-expiration level >40% of a breathing cycle, B: the length of end-expiration level ≤40% and that of end-inspiration level >20% of a breathing cycle, and C: the length of end-expiration level ≤40% and that of end-inspiration level ≤20% of a breathing cycle). For each respiratory type, average RTD and GDC maps were created. We presented an algorithm to obtain the optimal Ls and Le using the RTD (or ATD) and GDC maps, and this algorithm was verified by demonstrating that, in determining Ls and Le for a subject, the average RTD and GDC maps corresponding to the subject's respiratory type could be used effectively.

BACKGROUND Treatment modalities for patients with hepatocellular carcinoma (HCC) who have portal vein tumor thrombus (PVTT) are limited and controversial; furthermore, the prognosis for these patients is extremely poor. The authors conducted a retrospective review to determine the role of proton beam therapy in the treatment of patients who had HCC with PVTT. METHODS Twelve patients with HCC who had tumor thrombus in the main trunk or major branches of the portal vein (clinical T3–T4N0M0) were treated with proton beam therapy. At the time they received proton beam irradiation, patients ranged in age from 42 years to 80 years (median, 62 years), and their tumors ranged in size from 40 mm to 110 mm (median, 60 mm) in greatest dimension. A total dose of 50–72 gray (Gy) (median, 55 Gy) in 10–22 fractions was delivered to the tumors, including PVTT. RESULTS All tumors that were treated with proton beam therapy remained controlled at a median follow-up of 2.3 years (range, 0.3–7.3 years). Among 12 patients, 10 patients had new liver tumors outside the irradiated volume 0.1–2.4 years after proton beam therapy, and 3 patients also had distant metastases; consequently, 8 patients died of disease, and 2 patients were salvaged by further therapies. The remaining two patients were alive with no evidence of disease 4.3 years and 6.4 years after proton beam therapy. The progression-free survival rates were 67% at 2 years and 24% at 5 years. The median progression-free survival was 2.3 years. According to the Acute Radiation Morbidity Scoring Criteria (Radiation Therapy Oncology Group), therapy-related toxicity ≥ Grade 3 was not observed. CONCLUSIONS Proton beam therapy for patients with HCC who had PVTT was feasible and effective. It appeared to improve survival and local control significantly for these patients. Cancer 2005. © 2005 American Cancer Society.

Purpose To present the results of proton beam therapy for patients with esophageal cancer. Methods and materials This study reviewed 46 patients with esophageal cancer who were treated between 1985 and 1998 using proton beams with or without X-rays. All patients had locoregionally confined disease; all but one had squamous cell carcinoma. Of the 46 patients, 40 received combinations of X-rays (median, 48 Gy) and protons (median, 31.7 Gy) as a boost. The median total dose of combined X-ray and proton radiation for the 40 patients was 76.0 Gy (range, 69.1–87.4 Gy). The remaining 6 patients received only proton beam therapy (median, 82.0 Gy; range, 75–89.5 Gy). Results The 5-year actuarial survival rate for the 46 patients, patients with T1 ( n = 23), and those with T2–T4 ( n = 23) was 34%, 55%, and 13%, respectively. The 5-year disease-specific survival rate for the 46 patients, those with T1, and those with T2–T4 was 67%, 95%, and 33%, respectively. The 5-year local control rate for patients with T1 and T2–T4 lesions was 83% and 29%, respectively. The site of the first relapse was locoregional for 16 patients and distant organs for 2 patients. Conclusion The results suggest that proton beam therapy is an effective treatment for patients with locally confined esophageal cancer. Additional studies are required to determine the optimal total dose, fractionation schedule, and best combinations of protons and conventional X-rays with or without chemotherapy.

The purpose of this study was retrospectively to evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for patients who presented with intracranial metastases as the initial symptom of lung carcinoma. Fifteen patients with three or fewer brain metastases from lung carcinoma underwent FSRT receiving 42 Gy in 7 fractions or 40 Gy in 4 fractions from April 1999 to October 2002. Patients who developed new lesions were retreated with FSRT or whole brain radiotherapy (WBRT). Tumor control was obtained in 14 patients during a median period of 21.0 months (ranging from 11 to 34 months) with salvage radiotherapy whenever required. None died from brain metastasis. The median survival time was 7.0+/-3.0 months and 21.0+/-1.0 months for patients with or without extracranial metastases, respectively (p

Purpose The purpose of this study is to investigate the correlation between the respiratory waveform measured using a respiratory sensor and three-dimensional (3D) tumor motion. Methods and materials A laser displacement sensor (LDS: KEYENCE LB-300) that measures distance using infrared light was used as the respiratory sensor. This was placed such that the focus was in an area around the patient's navel. When the distance from the LDS to the body surface changes as the patient breathes, the displacement is detected as a respiratory waveform. To obtain the 3D tumor motion, a biplane digital radiography unit was used. For the tumor in the lung, liver, and esophagus of 26 patients, the waveform was compared with the 3D tumor motion. The relationship between the respiratory waveform and the 3D tumor motion was analyzed by means of the Fourier transform and a cross-correlation function. Results The respiratory waveform cycle agreed with that of the cranial-caudal and dorsal-ventral tumor motion. A phase shift observed between the respiratory waveform and the 3D tumor motion was principally in the range 0.0 to 0.3 s, regardless of the organ being measured, which means that the respiratory waveform does not always express the 3D tumor motion with fidelity. For this reason, the standard deviation of the tumor position in the expiration phase, as indicated by the respiratory waveform, was derived, which should be helpful in suggesting the internal margin required in the case of respiratory gated radiotherapy. Conclusion Although obtained from only a few breathing cycles for each patient, the correlation between the respiratory waveform and the 3D tumor motion was evident in this study. If this relationship is analyzed carefully and an internal margin is applied, the accuracy and convenience of respiratory gated radiotherapy could be improved by use of the respiratory sensor.Thus, it is expected that this procedure will come into wider use.

Purpose: To evaluate the clinical results of proton radiotherapy for patients with non–small-cell lung cancer (NSCLC). Methods and Materials: Between 1983 and 2000, 51 NSCLC patients were treated with proton beams at the University of Tsukuba. There were 28 patients in Stage I, 9 in Stage II, 8 in Stage III, 1 in Stage IV, and 5 with recurrent disease. Thirty-three patients had squamous cell carcinoma, 17 had adenocarcinoma, and 1 had large-cell carcinoma. Median fraction and total doses given were 3.0 Gy (range 2.0 – 6.0 Gy), and 76.0 Gy (range 49.0 –93.0 Gy), respectively. Results: The 5-year overall survival rate was 29% for all patients, 70% for 9 Stage IA patients, and 16% for 19 Stage IB patients, respectively (IA vs. IB: p < 0.05). The 5-year in-field local control rate was higher in patients with Stage IA (89%) when compared with those with Stage IB (39%). Forty-seven patients (92%) experienced acute lung toxicity of Grade 1 or less; 3 had Grade 2, 1 had Grade 3, and none experienced Grade 4 or higher. Patients in the present series showed very little late toxicity. Conclusion: Proton therapy is a very safe and effective treatment for patients with NSCLC, especially for those with early stages. The relative merit of proton therapy in comparison with stereotactic photon radiotherapy or three-dimensional conformal photon radiotherapy remains to be defined through future clinical trials. © 2003 Elsevier Inc.

Purpose: Lymph node metastasis is a major prognostic factor in the treatment of cervical cancer, but its nonsurgical assessment is not necessarily accurate, particularly in small nodes. We evaluated whether node-negative status could be accurately assessed using a low cutoff measure. Methods and Materials: The subjects were 84 patients with Stage IIB-IVA cervical squamous cell carcinoma treated by definitive radiotherapy. Nodal status was assessed by CT as negative ( 10 mm). Cause-specific survival and the disease-free rate, including the pelvic recurrence-free and distant metastasis-free rates, were estimated. Results: The cause-specific survival, disease-free rate, and pelvic recurrence-free rate at 5 years were significantly higher for the 32 patients with node-negative disease (83.5%, 86.1%, and 86.1%) and the 17 patients with possibly node-positive disease (59.2%, 93.8%, and 93.8%) than for the 35 patients with probably node-positive disease (32.6%, 22.0%, and 46.8%), respectively. No significant difference was found between negative and possibly node-positive status. In contrast, the distant metastasis-free rate differed significantly among node-negative (96.4%), possibly node-positive (59.3%), and probably node-positive (35.1%) status. Conclusion: Node-negative status assessed using a strict cutoff measure may be useful as a strong predictor of cervical cancer being confined to the pelvis.

Purpose The purpose of this study was to investigate the long-term imaging appearances of hepatic injury following proton beam irradiation. The time-attenuation curves, time of appearance and recovery, and 3D size reduction pattern are described in patients of different ages and genders with different irradiation doses, irradiated portals, and Child groups. Method Forty-six patients with hepatocellular carcinoma underwent 50 to 84 Gy proton beam irradiation in periods of 14-52 days. CT including noncontrast and dynamic study was performed every 3 months starting 3 weeks after the end of irradiation. The 3D volume measurement of areas of radiation-induced hepatic injury was performed through incremental dynamic CT images in every follow-up study. CT follow-up study of the patients was done for 12-76 months. Results Radiation-induced hepatic injury was observed as low attenuation areas on noncontrast CT and enhanced areas on dynamic study in the regions corresponding to the irradiation portals. Of our cases, 67.5% showed the appearance of radiation hepatitis in 3-4 weeks and 95.3% in 3-4 months after the end of irradiation. In both periods, there was a significant delay in the female patients. The time-attenuation curve showed an early and prolonged enhancement of the irradiated regions. The volume reduction pattern of the injured areas was found to be longstanding, exponential, and directed from periphery to the center. Conclusion Early appearance of radiation-induced hepatic injury was found only to be gender dependent, with a tendency to occur with higher irradiated doses; no other parameters affected this phenomenon in our cases. Disappearance of the injured areas, if present, takes a long time (at least 42 months).

AIM: The aim of this study was to describe persistence of hypervascularity in proton treated hepatocellular carcinoma at serial follow-up computed tomography (CT). METHODS: Four patients with unresectable solitary hypervascular hepatocellular carcinoma underwent 55–82 Gy proton-beam irradiation for a period of 15–47 days. Follow-up CT including plain, enhanced and dynamic imaging was performed for a period of 9–36 months. RESULTS: Good preservation of arterial blood supply while gradual decrease in tumour size was clearly depicted by dynamic CT. CONCLUSION: We believe that preservation of hypervascularity as judged by enhancement at CT and magnetic resonance imaging, does not necessarily mean that radiotherapy in hypervascular malignant tumours has been unsuccessful.

Emulsions containing a distearylamide (Gd-DTPA-SA) or a distearylester (Gd-DTPA-SE) of Gd (gadolinium)-diethylenetriaminepentaacetic acid (Gd-DTPA) were intraperitoneally injected in Greene's melanoma-bearing hamsters at a dose of 2.0 ml (3.0 or 6.0 mg Gd) per hamster. In the standard-Gd and high-Gd formulations used, the weight ratios of soybean oil, water, Gd-DTPA derivative (Gd-DTPA-SA or Gd-DTPA-SE), hydrogenated L-alpha-phosphatidylcholine from egg yolk (HEPC) and co-surfactant (HCO-60, Myrj 53, Myrj 59 or Brij 700) were 7.36:92:1:2:3 and 7.36:92:2:1:3, respectively. When the effects of the co-surfactants on the biodistribution of Gd from Gd-DTPA-SA-containing emulsions in the standard-Gd formulation were compared, the HCO-60 emulsion exhibited the highest Gd accumulation in tumors, possibly resulting from its fast and complete absorption, its small particle size (78 nm) and the stable coat on the particle surfaces with polyoxyethylene. Brij 700 emulsion kept the highest blood Gd concentration for a prolonged period, possibly due to particle properties similar to those of HCO-60. However, it exhibited a slower Gd accumulation in tumors, only reaching an identical level, in comparison with the HCO-60 emulsion. This suggested the tumor to be saturated with lipid particles. When Gd-DTPA-SE was used instead of Gd-DTPA-SA, its HCO-60 emulsion exhibited only very poor Gd-accumulation due to its easy degradation. The HCO-60 emulsion particles containing Gd-DTPA-SA in the high-Gd formulation (6.0 mg Gd in 2 ml) exhibited in vivo behavior identical to those in the standard-Gd formulation; then the Gd level in tumors reached 107 micrograms Gd/g tumor (wet), and the tumor:blood (T/B) and tumor:skin (T/Sk) Gd concentration ratios were 13.2 and 5.6, respectively, at 48 h after intraperitoneal administration. These results suggest that when intraperitoneally administered, this HCO-60 emulsion, and possibly also the corresponding Brij 700 emulsion, may be an excellent delivery system for accumulating Gd in tumors in neutron-capture therapy (NCT).

Gadolinium-containing lipid emulsions for neutron-capture therapy were designed to fulfill the following requirements : particle size smaller than 100 nm; gadolinium content as high as possible; surface of the emulsions modified with hydrophilic moieties to provide prolonged circulation in the blood. Emulsions containing soybean oil, water, Gd-diethylenetriaminepentaacetic acid-distearylamide (Gd-DTPA-SA), as an amphiphilic drug, and hydrogenated egg yolk phosphatidylcholine (HEPC), as an emulsifier, in a weight ratio of 7.36 : 92 : 1 : 2 were prepared without co-surfactants by the thin-layer hydration method using a bath-type sonicator. The mean particle size of the emulsions was 280.7 nm. In order to make the droplet size of the emulsions smaller than 100 nm, as well as to modify the emulsion surfaces, a co-surfactant, Tween[○!R] 80, HCO[○!R]-60, Pluronic[○!R] F68, polyoxyethylene alkyl ether (Brij[○!R]) or polyoxyethylene alkyl ester (Myrj[○!R]), was introduced into the standard system. Tween 80, HCO-60, Brij 76, 78 and 700 were effective in reducing the particle size to below 100 nm when the co-surfactant weight ratio (CWR), defined as co-surfactant/(HEPC+Gd-DTPA-SA) (w/w), was larger than 0.67; the particle size with Tween 80 and HCO-60 was reduced to 52.7 and 74.7 nm, respectively, at a CWR of 1.0 (w/w). In order to increase the gadolinium content, the weight ratio of Gd-DTPA-SA to HEPC was increased from 1 : 2 of the standard-Gd formulation to 2 : 1 of the high-Gd formulation. The measured particle size of the HCO-60 high-Gd emulsions was 78.7 nm when the CWR was 1.0 (w/w). In this case, the calculated gadolinium content reached 3.0 mg Gd/ml. These results indicate that HCO-60 is an effective co-surfactant not only in terms of particle size reduction but also with respect to gadolinium enrichment.

The results of conventional x-ray radiotherapy for loco-regionally advanced esophageal carcinoma have been disappointing because it is usually difficult to administer a sufficiently high radiation ...

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 : There is no consensus as to the best dose-fractionation regimen in high dose rate (HDR) brachytherapy for cervix cancer. Since 1983, two fractionation regimens have been used in different time periods at National Cancer Center Hospital, and their treatment results have been compared in terms of 5-year survival, local control, and complication rate to find the better therapeutic regimen. Methods and Materials : From November 1983 to October 1990, 130 patients with uterine cervix carcinoma were treated with HDR intracavitary brachytherapy using a remote afterloading system. There were 21 Stage Ib patients, 5 Stage IIa, 29 Stage IIb, 2 Stage IIIa, 68 Stage IIIb, and 5 Stage IVa. The median age was 64 years. The median follow-up time was 50 months. Radiotherapy consisted of external beam irradiation to the pelvis (mean dose of 50 Gy), combined with HDR brachytherapy (mean dose of 20 Gy to point A) given 5 Gy per session twice weekly (group A: 54 patients) or 6 Gy once weekly (group B: 76 patients). Results : The overall 5-year survival was 52% in group A and 72% in group B. Local recurrence rate was 11%, and distant failure rate was 21%, with no difference between the two groups. The complication rate was significantly lower in group B (37%) than in group A (55%). Multivariate analysis has shown that factors affecting survival were stage, brachytherapy dose, and local control status. No factor was predictive of local control, but the external beam radiation dose significantly influenced the risk of complications. Conclusion : The once-weekly HDR intracavitary applications combined with properly adjusted external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer.

Small-field radiotherapy based on a 6-MeV linac and a conventional head mold is investigated as an alternative to radiosurgery with stereotactic frames. The system requires no additional device and allows fractionated treatment. The dose distributions obtained are comparable to those reported with a Gamma Unit. Overall positioning errors are within 2 nun. Using this approach, seven patients with brain tumors who could not have been treated otherwise, underwent fractionated radiotherapy with total accumulated doses ranging from 70 to 108 Gy. The treatment was tolerated well with no acute toxicity or adverse effect encountered during the follow-up period of 8–14 months. All of the patients remained free from disease progression in the treated volumes. Although the follow-up is brief, the preliminary results suggest that this is a simple and inexpensive but effective system for the treatment of small intracranial malignancies.

Microcapsules of hygroscopic, highly water-soluble gadopentetate dimeglumine (Gd-DTPA-DM) for use in preliminary in vivo experiments for neutron-capture therapy were designed. They were prepared with such properties as a particle size small enough to be suspended and injected through a syringe, a negligible release of Gd-DTPA-DM, and a high drug content by means of the Wurster process, a spray coating method using a spouted bed with a draft tube. They were composed of lactose cores of 53-63 microm, an undercoat of ethyl cellulose (EC) and polyvinylpyrrolidone (PVP), a drug-layer of Gd-DTPA-DM, EC and PVP, a waterproof coat and a release-sustaining overcoat of EC and cholesterol (1:1), and a surface treated with hydrogenated egg lecithin. By curing at 110 degrees C for 30 min after mixing with 20% pulverized mannitol powder, the 20% overcoating suppressed the release of Gd-DTPA-DM from 75-106 microm microcapsules to less than 10% for the first 20 min, which was the period required to prepare a suspension, inject it and irradiate the neutron. The microcapsules could be used to confirm that the intracellular presence of Gd is not critical in gadolinium neutron-capture therapy.

application/pdf, The first experimental evidence of three-dimensional conformal irradiation is performed by using a new type of filter developed for charged particle radiotherapy. The new filter can yield a static irradiation field where the width of the spread-out Bragg peak is adjusted to the target as a two-dimensional continuous function in the transverse plane. The filter is made of many layers produced by using stereolithography. In the filter, a structure with two regions with different shaped miniaturized ridges is adopted to get a flat dose profile on the spread-out peak. A conformal field around a spherical target is realized by a filter that has a shape corresponding to the outward form of the target.

Malignant myoepithelioma of the head and neck usually arises in the salivary glands. We experienced a rare case with malignant myoepithelioma in the maxillary sinus. A 47-year-old woman with malignant myoepithelioma in the maxillary sinus underwent partial maxillectomy. However, local recurrence occurred 28 months after surgery and she was subsequently treated with radiation therapy with proton beams. The recurrent tumor showed complete response and the patient was alive with no evidence of disease 30 months after irradiation. No therapy-related severe toxicities were observed. A rare case with malignant myoepithelioma in the maxillary sinus was successfully treated with radiation therapy.

By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low-dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low-dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy.

Three patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) were treated using proton beam therapy at the University of Tsukuba, Japan. A total dose of 50-70 Gy in 10-35 fractions was given to the primary tumor and IVCTT. All the patients survived for more than 1 year from the beginning of proton beam therapy (13-55 months) and no treatment-related toxicity of grade 3 or higher was observed. These cases suggest that proton beam therapy is safe and effective for patients with HCC associated with IVCTT.

Purpose To investigate the safety and efficacy of proton beam therapy for aged patients with hepatocellular carcinoma (HCC). Methods and Materials Twenty-one patients aged ≥80 years with HCC underwent proton beam therapy. At the time of irradiation, patient age ranged from 80 to 85 years (median, 81 years). Hepatic tumors were solitary in 17 patients and multiple in 4. Tumor size ranged from 10 to 135 mm (median, 40 mm) in maximum diameter. Ten, 5, and 6 patients received proton beam irradiation with total doses of 60 Gy in 10 fractions, 66 Gy in 22 fractions, and 70 Gy in 35 fractions, respectively, according to tumor location. Results All irradiated tumors were controlled during the follow-up period of 6–49 months (median, 16 months). Five patients showed new hepatic tumors outside the irradiated volume, 2–13 months after treatment, and 1 of them also had lung metastasis. The local progression-free and disease-free rates were 100% and 72% at 3 years, respectively. Of 21 patients, 7 died 6–49 months after treatment; 2 patients each died of trauma and old age, and 1 patient each died of HCC, pneumonia, and arrhythmia. The 3-year overall, cause-specific, and disease-free survival rates were 62%, 88%, and 51%, respectively. No therapy-related toxicity of Grade ≥ 3 but thrombocytopenia in 2 patients was observed. Conclusions Proton beam therapy seems to be tolerable, effective, and safe for aged patients with HCC. It may contribute to prolonged survival due to tumor control.

We investigated whether conventional tandem-source dwelling to cover the entire uterus, classically regarded as the target volume, is necessary in modern intracavitary radiotherapy (ICRT) for cervical cancer.The study included 95 cervical squamous cell carcinoma patients treated by high-dose-rate ICRT (point A dose was 6.0 Gy, with three to five insertions per patient) after external beam radiotherapy (EBRT), with central pelvic doses of 12-50 Gy. The tandem-source dwell length was adjusted to the target volume specified by magnetic resonance (MR) imaging. A tandem applicator was inserted as far as the uterine fundus in accordance with the post-EBRT MR-assessed cavity length. The pre-EBRT MR-specified target volume was used for the dwell-length adjustment. The safety of the dwell-length adjustment was assessed in terms of treatment failure.The dwell-length adjustment was made in 248 of 366 total insertions with a dwell-length reduction of 5-55 mm (median 15 mm) at the corpus. Pelvic failure was identified in 22 patients with a 2-year pelvic disease-free survival rate of 75.6% but without evidence of failure at dwelling-skipped corpuses.Given after pelvic EBRT and ICRT of full-length dwelling in part, which may have eradicated possible subclinical extension, adjustment of the tandem-source dwell length to the MR-specified target volume appeared to be safe.

The treatment strategy for malignant liver tumors should be appropriately determined because post-treatment quality of life greatly depends on the patients' residual hepatic function. In this report, we present three patients with malignant liver tumors treated by proton beam therapy in whom pre- and post-therapeutic hepatic functional reserves were evaluated sequentially for more than a year by 99mTechnetium-galactosyl human serum albumin (99mTc-GSA) scintigraphy. All three patients exhibited the distinctive time course of 99mTc-GSA uptake efficiency, which suggested a transient decline in the ratio of liver activity to heart and liver activity at 15 minutes (LHL15) 3-6 months after proton beam therapy. This change was not in parallel with that expected from a functioning normal liver tissue volume. In a year after proton beam therapy, LHL15 recovered nearly to the pre-treatment level in all three patients. Our observations may be related to the up-regulation of receptor-mediated 99mTc-GSA uptake during hepatic regeneration after proton beam therapy.

Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non–small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6–29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade ≥3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

BACKGROUND. The authors conducted a retrospective review to define the usefulness of proton beam therapy for patients who had hepatocellular carcinoma (HCC) with limited treatment options. METHODS. Twenty-one patients with HCC for whom other treatment modalities either were contraindicative or were unfeasible because of coexisting diseases and unfavorable conditions received proton beam therapy. Four patients had renal failure, 2 patients had severe heart disease, 9 patients had severe cirrhosis, 1 patient had aplastic anemia, 1 patient had a dissecting abdominal aortic aneurysm before treatment, and 4 patients had bleeding tendency or unresectable tumors. Moreover, 2 of the latter 4 patients were allergic to iodine, and 2 other patients were unable to be catheterized for transcatheter arterial chemoembolization. Hepatic tumors were solitary in 14 patients and multiple in 7 patients, and the tumors ranged in greatest dimension from 25 mm to 100 mm (median, 40 mm). No patient had regional lymph node or distant metastasis. Total doses of 63 grays (Gy) to 84 Gy (median, 73 Gy) in 13 to 27 fractions (median, 18 fractions) were used for tumor treatments. RESULTS. All but 1 of the irradiated tumors were controlled at a median follow-up of 3.3 years. The objective response rate was 81%, and the primary site-control rate was 93% at 5 years. Eleven patients had intrahepatic recurrences, and 2 patients had distant metastases in the lungs. Four of 11 patients with intrahepatic recurrences received a second course of proton beam therapy, and all recurrent tumors were controlled. The overall and cause-specific survival rates were 62% and 82% at 2 years, respectively, and 33% and 67% at 5 years, respectively. Grade ≥3 therapy-related toxicities were not observed. CONCLUSIONS. Proton beam therapy was safe and effective for a variety of patients with HCC. The current results suggested that this method was tolerable and effective, even for patients with HCC who had limited treatment options. Cancer 2006. © 2006 American Cancer Society.

Purpose: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. Methods and Materials: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. Results: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently, proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3–4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. Conclusions: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.

Purpose: We present results of patients with hepatocellular carcinoma (HCC) treated with proton beam therapy. Experimental Design: We reviewed 162 patients having 192 HCCs treated from November 1985 to July 1998 by proton beam therapy with or without transarterial embolization and percutaneous ethanol injection. The patients in the present series were considered unsuitable for surgery for various reasons, including hepatic dysfunction, multiple tumors, recurrence after surgical resection, and concomitant illnesses. The median total dose of proton irradiation was 72 Gy in 16 fractions over 29 days. Results: The overall survival rate for all of the 162 patients was 23.5% at 5 years. The local control rate at 5 years was 86.9% for all 192 tumors among the 162 patients. The degree of impairment of hepatic functions attributable to coexisting liver cirrhosis and the number of tumors in the liver significantly affected patient survival. For 50 patients having least impaired hepatic functions and a solitary tumor, the survival rate at 5 years was 53.5%. The patients had very few acute reactions to treatments and a few late sequelae during and after the treatments. Conclusions: Proton beam therapy for patients with HCC is effective, safe, well tolerable, and repeatable. It is the useful treatment mode for either cure or palliation for patients with HCC irrespective of tumor size, tumor location in the liver, insufficient feeding of the tumor with arteries, presence of vascular invasion, impaired hepatic functions, and coexisting intercurrent diseases.

Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at the University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3–79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A.

We preliminarily estimated the treatment effect on cervical cancer in terms of the tumor regression rate (TRR) achieved with chemoradiotherapy and radiotherapy alone.The study included cervical squamous cell carcinomas treated by radiotherapy alone (n=45) or chemoradiotherapy (concurrent once-a-week cisplatin 30 mg/m2, n=13). Tumors were measured three-dimensionally on pre- and mid-treatment magnetic resonance images. TRR was defined as the slope of the exponential regression curve of tumor volume (day(-1)) on the assumption that tumors regressed exponentially with time.TRR ranged widely (0.004-0.090 day-(-1)) and did not significantly differ between treatment with chemoradiotherapy (median, 0.032 day(-1)) and with radiotherapy alone (median, 0.024 day(-1)) (p = 0.361). TRR0.05 day(-1) was seen in four chemoradiotherapy tumors (30.8%) and in six radiotherapy-alone tumors (15.0%) (p = 0.207), whereas TRR0.01 day(-1) was seen in no chemoradiotherapy tumors (0.0%) and in five radiotherapy-alone tumors (11.1%) (p = 0.180). TRR for tumors5.0 cm in diameter was greater with chemoradiotherapy (n=5) than with radiotherapy alone (n=12) (p = 0.065).Although the difference did not reach a statistically significant level, our TRR data suggest that concurrent chemotherapy heightens the radioresponse of large-size cervical cancer.

We report a case of a woman with a metastatic liver tumor from gastric carcinoma, who has been successfully treated with concurrent proton beam therapy and systemic chemotherapy. A 76-year-old woman underwent distal gastrectomy with regional lymph node dissection for advanced gastric carcinoma on January 17, 2002. She received five courses of sequential chemotherapy with methotrexate-5-fluorouracil after the surgical resection. A metastatic liver tumor was detected in the caudate lobe of the liver by computed tomography at 6 months after the surgical resection. We employed concurrent proton beam therapy and systemic chemotherapy which consisted of 5-fluorouracil (250 mg/body per day, as a 24-h intravenous injection for 4 weeks) and low dose cisplatin (10 mg/body on days 1-5 every week for 4 weeks). Proton beam therapy targeting the metastatic liver tumor was performed in a daily fraction of 3 Gy, 5 days per week, with a total dose of 66 Gy over 30 days. The tumor disappeared 3 months after the treatment and no recurrence has been observed for 2 years after termination of the treatment. Throughout the entire course of treatment, the patient received injections of granulocyte stimulating factor subcutaneously for grade 3 leukopenia. She never complained of abdominal symptoms, such as epigastralgia, nausea or diarrhea. Liver failure related to proton irradiation has not been observed. This concurrent proton beam radiotherapy with systemic chemotherapy could be an effective treatment modality for metastatic liver tumor from gastric carcinoma.

Purpose: To evaluate the feasibility of real-time monitoring of a fiducial marker in/near the digestive tract and to analyze the motion of organs at risk to determine a reasonable internal margin. Methods and Materials: We developed two methods to insert a fiducial marker into/near the digestive tract adjacent to the target volume. One method involves an intraoperative insertion technique, and the other involves endoscopic insertion into the submucosal layer of the normal digestive tract. A fluoroscopic real-time tumor-tracking radiotherapy system was used to monitor the marker. Results: Fourteen markers (2 in the mediastinum and 12 in the abdomen) were implanted intraoperatively in 14 patients with no apparent migration. Seventeen of 20 markers (13/14 in the esophagus, 1/2 in the stomach, and 3/4 in the duodenum) in 18 patients were implanted using endoscopy without dropping. No symptomatic adverse effects related to insertion were observed. The mean/standard deviation of the range of motion of the esophagus was 3.5/1.8, 8.3/3.8, and 4.0/2.6 mm for lateral, craniocaudal and anteroposterior directions, respectively, in patients with intrafractional tumor motion less than 1.0 cm. Conclusion: Both intraoperative and endoscopic insertions of a fiducial marker into/near the digestive tract for monitoring of organs at risk were feasible. The margin for internal motion can be individualized using this system.

Background. We have reported that proton radiotherapy for hepatocellular carcinoma (HCC) is a safe and effective therapeutic option. However, it is difficult to evaluate its effect in certain cases. Recently, it has been reported that the usage of contrast-enhanced color Doppler ultrasonography (CECDU) can improve diagnostic accuracy, both in terms of the presence of hepatic tumor and in the evaluation of treatment. The aim of this study was to determine the usefulness of CECDU in assessing the therapeutic response of HCC treated with proton radiotherapy. Methods. Twenty-two patients treated with the proton radiotherapy were studied. We inspected HCC lesions by CECDU, before and after the irradiation, over time. The magnitude of blood flow in the HCC was quantified on still images by CECDU. The ratio of the number of color pixels against that of the total number of pixels in the tumor area was defined as the tumor blood flow ratio (TBFR). Results. Immediately after the proton treatment, a transient increase of blood flow in the tumor was recognized in more than half of the patients, while the TBFR was unchanged or decreased in the remaining patients. At longer periods after irradiation, the TBFR in all HCCs gradually decreased, and this reduction of TBFR was statistically significant from 9 months after irradiation. These findings are consistent with those obtained previously by computed tomography (CT) as well as magnetic resonance imaging (MRI). Conclusions. We propose CECDU as a useful diagnostic option for the evaluation of HCC treated with proton radiotherapy.

To present the initial experience with proton beam therapy at the new Proton Medical Research Center (PMRC) of the University of Tsukuba.The new facility has a synchrotron with maximum energy of 250MeV and two rotational gantries. We treated 105 patients with 120 lesions with proton beams in the first year, beginning in September 2001. The most common lesion treated was primary liver cancer (40 lesions) followed by lung cancer, head and neck cancers, and prostate cancer. Concurrent X-ray radiotherapy was given for 38 of the 120 lesions.The median follow-up period was 11 months (range, 1-19 months). Of the 105 patients, 97% had Grade 0-2 RTOG/EORTC acute morbidities, while the remaining 3% had Grade 3. Tumor response after irradiation was CR for 35% of the lesions, PR for 25%, SD for 22%, PD for 9%, and not evaluated for 9%.The proton beam therapy conducted at the new facility of the University of Tsukuba was safe and effective.

To determine retrospectively whether radical surgery plus postoperative radiotherapy (RT) is superior to definitive RT from the standpoint of disease control and adverse events in the treatment of stages IB-IIA and stage IIB cervical squamous cell carcinoma.The study included 143 patients treated by definitive RT (stages IB-IIA, n = 15; stage IIB, n = 27) or postoperative RT (stages IB-IIA, n = 67; stage IIB, n = 34). Cause-specific survival (CSS) and recurrence-free rate (RFR) were estimated. Late adverse events (proctitis, cystitis, lymphedema, and ileus) were graded, and the incidences were estimated.Overall, 5-year CSS and RFR did not differ significantly between patients treated with definitive RT (80.4% and 69.7%, respectively) and those treated with postoperative RT (80.6% and 79.1%, respectively). Rates according to clinical stage also did not differ significantly between the two types of treatment. Grades 1-3 adverse events occurred. Grades 2-3 lymphedema and Grades 2-3 ileus, but not Grades 2-3 cystitis, occurred significantly often with postoperative RT.Despite no difference in survival or patterns of recurrence, adverse events were significantly more frequent with postoperative RT than with definitive RT for both stages IB-IIA and stage IIB disease.

We investigated whether a small pelvic (SP) field that covers primarily the pericervical regions in postoperative radiotherapy for cervical squamous cell carcinoma is adequate for a subgroup of node-negative patients. Of 84 patients with stage I–II disease treated with postoperative radiotherapy due to pathologic risk factors, 42 node-negative patients received SP-field radiotherapy, whereas remaining 42 node-positive patients were treated with a conventional whole pelvic (WP) field that also covered pelvic lymph nodes, both with 50.0–50.4 Gy/25–28 fractions. The pathologic risk factors included positive nodes, deep stromal invasion (≥2 /3 thickness), parametrial extension, and positive or close surgical margin. Recurrence was identified for 20 patients: three in the SP group and 17 in the WP group. Intrapelvic recurrence accounted for all three recurrences in the SP group and for four in the WP group; 5-year pelvic-control rate did not differ significantly between the SP (93%) and WP (90%) groups. Extrapelvic recurrence (n = 11) was identified exclusively in the WP group. Patterns of recurrence indicate that use of an SP field instead of a WP field may be adequate in postoperative radiotherapy for a subgroup of node-negative, high-risk patients.

Purpose To determine the role of proton therapy in patients with carcinoma of the uterine cervix. Methods and materials Between 1983 and 1991, 25 patients with squamous cell carcinoma of the uterine cervix (stages IIB–IVA) were treated with a curative intent by external photon irradiation to the pelvis, followed by proton irradiation to the primary tumor, delivering a median total tumor dose of 86 Gy (range 71 Gy/26 Fr–101 Gy/46 Fr), and were followed for a median period of 139 months (range 11–184 months). Results Ten-year overall survival rates for stages IIB and IIIB/IVA patients were 89% and 40%, respectively. Five-year local control rates for stages IIB and IIIB/IVA patients were 100% and 61%, respectively. Four percent of patients experienced severe (Grade 4 or more) late complications in the intestine or urinary bladder at 5 years. Conclusions External photon and proton therapy is effective for those who are not eligible for intracavitary irradiation, and who otherwise have a poor prognosis. The results show that tumor control, survival, and morbidity are similar to those after conventional therapy.

To evaluate clinical results of proton beam therapy for patients with skull base chordoma.Thirteen patients with skull base chordoma who were treated with proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The patients were followed for a median period of 69.3 months (range, 14.6-123.4 months).The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors30 mL. Partial or subtotal tumor removal did not yield better local control rates than for patients who underwent biopsy only as the latest surgery.Proton beam therapy is effective for patients with skull base chordoma, especially for those with small tumors. For a patient with a tumor of30 mL with no prior treatment, biopsy without tumor removal seems to be appropriate before proton beam therapy.

To evaluate the effectiveness and feasibility of proton therapy for head and neck cancers. From 1983 to 2000, 33 patients with head and neck malignancies but no history of surgical resection were treated with 250-MeV protons with or without X-ray irradiation. This study retrospectively evaluated local control, survival, and treatment sequelae of these patients. The median total target dose using protons with or without X-rays was 76 Gy (range: 42–99 Gy) and the median proton dose per fraction 2.8 Gy (range: 1.5–6.0 Gy). Overall 5-year survival and local control rates were 44% and 74%, respectively. One (3%) and six patients (18%) suffered from treatment-related acute and late toxicity > grade 3 (RTOG/EORTC acute and late radiation morbidity scoring criteria). One patient with a history of radiotherapy suffered from acute toxicity > grade 3. Proton therapy appeared to offer high local control rates with few toxicities relative to conventional radiotherapy. However, late toxicity was seen in areas where large radiation doses had been given.

In Proton Medical Research Center (PMRC), we have performed the respiration-gated irradiation for treating the tumor in the body trunk. In the conventional method, patients must hold their expiration during CT scanning. The phase of holding expiration is different from the end-expiration phase. This results in difference of anatomical location in the body between CT scanning and the respiration-gated irradiation. For the sake of highly-accurate irradiation, a respiration gated CT scanning system is introduced. In case of natural respiration, it has been difficult to achieve the gated CT scanning because a stable period of end-expiratory is not so long as CT scanning time (1 second in our case). In this study, we developed a guided respiration method, which leads a patient to maintain the end-expiratory phase during required time. The respiration gated CT scanning is performed by using this. The phase of the acquired CT image can be approximated to that of respiration-gated irradiation.

VX-2 tumors growing in hind legs of New Zealand White rabbits (n = 4) were exposed to thermal neutrons for 40 min (2.1 x 10(12) neutrons cm-2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5-6 fold higher than that in the contralateral tumor. Growth of gadolinium-infused tumors was significantly inhibited compared to that of control tumors (P < 0.05) between the 16th and 23rd days after treatment.

After the shutdown of the former JRR2, which had been used for boron neutron capture therapy (BNCT) in clinical cases, in summer 1998 a new neutron irradiation facility (JRR4) was installed as a medical reactor for BNCT at the Japan Atomic Energy Institute (JAERI), Tokai, Ibaraki. This JRR4 facility is a conversion of the former high-fuel uranium-loaded nuclear reactor to low-fuel uranium-loaded reactor. This facility is designed mainly for BNCT. There are medical facilities and equipment including an operating room and fully installed anesthetic apparatus to allow safe and effective intraoper-ative BNCT. An outline of this facility is presented in this chapter.