Evaluation of Delivered Doses in Proton Beam Therapy for Prostate Cancer Using Positron Emission Tomography/Computed Tomography Imaging.

AIMS: Proton beams deposit energy along their paths and stop abruptly without penetrating the opposite side, making it difficult to detect their actual paths. However, confirming the path may lead to evaluating the actual doses to organs at risk in proton therapy for prostate cancer. As proton beams produce positron emitters through nuclear fragmentation reactions, theoretically, proton beam paths can be measured by positron emission tomography/computed tomography (PET/CT). Therefore, this study investigated whether conducting PET/CT examinations immediately after proton beam therapy helps to assess the doses delivered to the rectal and urinary bladder walls, which are the major sites of radiation-related toxicity. MATERIALS AND METHODS: Between June 2022 and June 2023, 51 consecutive patients with prostate cancer who underwent proton beam therapy were enrolled and imaged with PET/CT to measure these radioactive particles and validate the actual dose delivered to the rectal and urinary bladder walls. RESULTS: The delivered doses assessed using PET/CT after proton beam therapy strongly correlated with the planned volume for proton beam treatment. CONCLUSIONS: PET/CT exhibited potential as a valuable tool for validating the irradiated dose to organs at risk.

Dosimetric evaluation of compensator intensity modulation-based stereotactic body radiotherapy for Stage I non-small-cell lung cancer.

OBJECTIVE: To evaluate the dosimetry of compensator intensity modulation-based stereotactic body radiotherapy (SBRT) [non-coplanar intensity-modulated radiotherapy (ncIMRT)], its use was compared with that of three-dimensional conformation-based SBRT, for patients with Stage I non-small-cell lung cancer (NSCLC). METHODS: 21 consecutive patients with Stage I NSCLC were treated with ncIMRT or SBRT at Tokyo Medical University. To compare the two techniques, ncIMRT and SBRT plans for each patient were generated, where the planning target volume (PTV) coverages were adjusted to be equivalent to each other. The prescribed dose was set as 75 Gy in 30 fractions. PTV coverage, conformity index, conformation number (CN) and homogeneity index (HI) were used to compare the two strategies. RESULTS: There was no statistically significant difference between PTV coverage for the 100%, 95% and 90% dose levels in the SBRT plan and those in the ncIMRT plan. The CN values were 0.53 ± 0.13 in the SBRT plan and 0.72 ± 0.10 in the ncIMRT plan. These values were significantly better than those of the SBRT plan (p < 0.001). The HI in the ncIMRT plan was 1.04 ± 0.03%, which was also significantly better than that of SBRT. CONCLUSION: The ncIMRT plan provided superior conformity and reduced the doses to the lung for patients with Stage I NSCLC. ADVANCES IN KNOWLEDGE: The delivery technique with compensator intensity modulation-based SBRT was evaluated. Concerning target motion, this is thought to be more robust and safer than SBRT for early-stage NSCLC.

Patients with severe emphysema have a low risk of radiation pneumonitis following stereotactic body radiotherapy.

OBJECTIVE: To evaluate the risk of radiation pneumonitis (RP) after stereotactic radiotherapy (SBRT) for patients presenting with severe pulmonary emphysema. METHODS: This study included 40 patients with Stage I non-small-cell lung cancer who underwent SBRT, 75 Gy given in 30 fractions, at the Tokyo Medical University, Tokyo, Japan, between February 2010 and February 2013. The median age of the patients was 79 years (range, 49-90 years), and the male:female ratio was 24:16. There were 20 T1 and 20 T2 tumours. 17 patients had emphysema, 6 had slight interstitial changes on CT images and the remaining 17 had no underlying lung disease. The level of emphysema was classified into three groups according to the modified Goddard's criteria (severe: three patients, moderate: eight patients and mild: six patients). Changes in the irradiated lung following SBRT were evaluated by CT. RESULTS: On CT images, RP was detected in 34 (85%) patients, and not in 6 (15%) patients, during a median observation period of 313 days. Of the six patients, three had severe emphysema and three had no underlying lung disease. Patients with severe emphysema had lower risk of RP than those with moderate emphysema (p = 0.01), mild emphysema (p = 0.04) and no underlying lung disease (p = 0.01). CONCLUSION: Patients with severe emphysema had a low risk of RP following SBRT. ADVANCES IN KNOWLEDGE: Little is known about the association between RP and pulmonary emphysema. Patients with severe emphysema had lower risk of RP than those with no underlying lung disease.

Orbital lymphoproliferative disorders (OLPDs): value of MR imaging for differentiating orbital lymphoma from benign OPLDs.

BACKGROUND AND PURPOSE: Accurate discrimination of orbital lymphoma from benign orbital lymphoproliferative disorders is crucial for treatment planning. We evaluated MR imaging including DWI and contrast-enhanced MR imaging for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders. MATERIALS AND METHODS: Forty-seven histopathologically proved orbital lymphoproliferative disorders (29 orbital lymphomas and 18 benign orbital lymphoproliferative disorders) were evaluated. Two board-certified radiologists reviewed visual features on T1-weighted, fat-suppressed T2-weighted, diffusion-weighted, and contrast-enhanced MR images. For quantitative evaluation, ADC and contrast-enhancement ratio of all lesions were measured and optimal cutoff thresholds and areas under curves for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders were determined using receiver operative characteristic analysis; corresponding sensitivities and specificities were calculated. RESULTS: Multivariate logistic regression analysis showed that ill-defined tumor margin (P = .003) had a significant association with orbital lymphoma whereas the "flow void sign" (P = .005) and radiologic evidence of sinusitis (P = .0002) were associated with benign orbital lymphoproliferative disorders. The mean ADC and contrast-enhancement ratio of orbital lymphomas were significantly lower than those of benign orbital lymphoproliferative disorders (P < .01). An ADC of less than 0.612 × 10(-3) mm(2)/s and a contrast-enhancement ratio of less than 1.88 yielded areas under curves of 0.980 and 0.770, sensitivity of 94.1% and 95.5%, and specificities of 93.3% and 80.0% for predicting orbital lymphoma, respectively. CONCLUSIONS: Some characteristic MR imaging features and quantitative DWI and contrast-enhanced MR imaging are useful in further improving the accuracy of MR imaging for differentiation of orbital lymphoma from benign orbital lymphoproliferative disorders.

A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer.

This study investigated the maximum-tolerated dose of gemcitabine based on the frequency of dose-limiting toxicities of weekly gemcitabine treatment with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Fifteen patients with locally advanced pancreatic cancer that was histologically confirmed as adenocarcinoma were enrolled in this phase I trial of weekly gemcitabine (150-350 mg x m(-2)) with concurrent radiotherapy (50.4 Gy in 28 fractions). Gemcitabine was administered weekly as an intravenous 30-min infusion before radiotherapy for 6 weeks. Three of six patients at the dose of 350 mg x m(-2) of gemicitabine demonstrated dose-limiting toxicities involving neutropenia/ leukocytopenia and elevated transaminase, while nine patients at doses of 150 mg x m(-2) and 250 mg x m(-2) did not demonstrate any sign of dose-limiting toxicity. Of all 15 enrolled patients, six patients (40.0%) showed a partial response. More than 50% reduction of serum carbohydrate antigen 19-9 level was observed in 13 (92.9%) of 14 patients who had pretreatment carbohydrate antigen 19-9 levels of 100 U x ml(-1) or greater. The maximum-tolerated dose of weekly gemcitabine with concurrent radiotherapy was 250 mg x m(-2), and this regimen may have substantial antitumour activity for patients with locally advanced pancreatic cancer. A phase II trial of weekly gemcitabine at the dose of 250 mg x m(-2) with concurrent radiation in patients with locally advanced pancreatic cancer is now underway.

Immature glandular features in squamous cell carcinoma of the uterine cervix as an independent indicator of resistance to radiotherapy.

The aim of this study was to evaluate the significance of "immature glandular features" in cervical squamous cell carcinoma (SCC) as an indicator of tumor radioresistance. Pretreatment biopsied tissue specimens of cervical SCC from 100 patients who were uniformly treated with radiotherapy alone were classified into clinically radioresistant (cR) and radiosensitive (cS) groups. Seven histologic parameters comprising glassy cells, signet ring cells, squamous differentiation, recognizable gland, nuclear atypia, stromal response, and mitotic counts were examined. Glassy cells and signet ring cells were regarded as "immature glandular features". The correlation of these seven parameters with tumor response to radiotherapy and patient prognosis was analyzed by univariate and multivariate analyses. As objective indicators of glandular differentiation, alcian-blue staining and immunostaining of cytokeratins 7 and 20 were also performed. It was revealed that immature glandular features, absence of squamous differentiation, and low nuclear atypia were significant indicators of radioresistance of the tumor and of poorer patient prognosis. Combining those histological parameters, the present SCC cases were classified into 26 pathologically radioresistant (pR) and 74 radiosensitive (pS) groups. In the pR group, 54% (14 of 26) were clinically radioresistant, whereas 20% (15 of 74) of the pS group were clinically radioresistant (P = 0.002). The overall prognosis of the pR group was much poorer than that of the pS group (P < 0.0001). This correlation also held true in cases of identical stage and age. We could not show objectively glandular differentiation of "immature glandular features". Nonetheless, the identification of "immature glandular features" was effective in predicting the radiotherapy resistance of cervical SCC and poorer patient prognosis.

Lack of effectiveness of radiotherapy combined with cisplatin in patients with locally advanced pancreatic carcinoma.

BACKGROUND: Cisplatin has been reported to enhance the cell-killing effect of radiation. The current study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with cisplatin in patients with locally advanced pancreatic carcinoma. METHODS: Forty-one patients with pancreatic carcinoma that was unresectable but confined to the pancreatic region were treated with external beam radiation (50.4 grays [Gy] in 28 fractions over 5.5 weeks) and daily cisplatin (5 mg/m(2)/day as a 30-minute infusion just before each radiation fraction). Maintenance 5-fluorouracil (5-FU) (500 mg/m(2)) given once weekly was initiated 1 week after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. RESULTS: Of the 41 patients, 31 (76%) completed the scheduled course of chemoradiotherapy. The median survival time was 7.7 months, and the 1-year survival rate was 36%. The median progression free survival time was 5.8 months. The first site of failure was distant metastases in 25 patients, locoregional recurrence in 6 patients, and both sites in 1 patient. The major toxicity was leukocytopenia and nausea/emesis. CONCLUSIONS: Radiotherapy with daily cisplatin appears to be inferior to conventional chemoradiotherapy using 5-FU in patients with locally advanced pancreatic carcinoma.

Radiation pneumonitis in lung cancer patients: a retrospective study of risk factors and the long-term prognosis.

PURPOSE: To retrospectively evaluate the risk factors for acute radiation pneumonitis (RP) and long-term prognosis of patients with lung cancer treated by thoracic radiotherapy. METHODS AND MATERIALS: Of the 256 lung cancer patients who underwent definitive thoracic radiotherapy between June 1988 and May 1998, the 191 patients who were capable of being evaluated were divided into three groups according to the grade of RP. RP was defined as "severe," when it caused severe clinical symptoms, such as intractable cough, dyspnea at rest, and the need for oxygen or steroid therapy. The definition was made by using a modification of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer acute radiation morbidity scoring criteria. Factors that influenced the incidence of severe RP were assessed by using the Mantel-Haenszel chi(2) test in the univariate analysis and the logistic regression test in the multivariate analysis. Survival rates was calculated by using the Kaplan-Meier method, and the p values indicating the significance of differences between the RP groups were calculated by the log-rank test. RESULTS: Of the 94 patients (49%) who experienced clinical RP in this study, the RP was mild in 69 (36%) and severe in 25 (13%) patients. The 3-year survival rates of the patients who experienced no, mild, and severe RP were 33.4%, 38.2%, and and 0%, respectively, and the survival rate of the patients who experienced severe RP was significantly poorer than the other two groups combined (p = 0.0028). The incidence of severe RP did not correlate with any of the baseline patient characteristics, radiotherapeutic factors, or chemotherapeutic variables. Two clinical risk factors were identified from medical records before radiotherapy: low PaO2 (< 80 torr) and high C-reactive protein (CRP) (> 1.0 ng/mL). Both of them were significantly related to the development of severe RP in the univariate analysis (p = 0.004 and 0.013, respectively), and low PaO2 remained a significant risk factor in the multivariate analysis (p = 0.034). Multivariate analysis also revealed the occurrence of severe RP to be the most important factor determining poor survival (p = 0.0065). There was no significant difference in survival rate according to whether the patients had been treated with corticosteroids. CONCLUSION: Mild and severe RP occurred in 69 (36%) and 25 (13%), respectively, of 191 lung cancer patients who had undergone irradiation of the chest. Only severe RP was an adverse prognostic factor. Low PaO2 (< 80 torr) before radiotherapy was a significant risk factor predictive of severe RP. The role of corticosteroids in RP could not be accurately determined.

Prognostic factors in patients with locally advanced pancreatic carcinoma receiving chemoradiotherapy.

BACKGROUND: The combination of radiation therapy and chemotherapy (chemoradiotherapy [CRT]) has been accepted as standard therapy for patients with locally advanced pancreatic carcinoma (PC). This study investigated prognostic factors in patients with locally advanced PC receiving CRT. METHODS: Fifty-five consecutive patients with locally advanced PC, who received concurrent radiotherapy (50.4 grays) and chemotherapy using 5-fluorouracil or cisplatin, were analyzed retrospectively to investigate prognostic factors. RESULTS: Median survival time and overall survival rates at 1 and 2 years were 301 days, 35.1% and 2.4%, respectively. By multivariate analysis using the Cox proportional hazards model, performance status of 0-1 (P < 0.01), absence of regional lymph node swelling (P < 0.01), and serum CA 19-9 level of less than 1000 (P = 0.02) were independent favorable prognostic factors. A prognostic index based on the coefficients of those prognostic factors was used to classify patients into three groups with good, intermediate, and poor prognoses. The median survival times for these three groups were 410, 239, and 143 days, respectively (P < 0.01). CONCLUSIONS: The results may be helpful in predicting life expectancy, determining treatment strategies, and designing future clinical trials.

External radiotherapy for decompression of cholangiocellular carcinoma with obstructive jaundice: report of a case.

Percutaneous transhepatic catheter drainage (PTCD) is generally performed for the treatment of obstructive jaundice. However, in some cases it is difficult to perform insertion because of lack of dilatation of the intrahepatic bile duct. We report a patient who had been suffering from jaundice as a result of recurrent cholangiocarcinoma near the hilum and whose symptoms were relieved by external radiotherapy. We consider radiotherapy for cholangiocarcinoma effective palliative treatment for decompression of obstructive jaundice.

Fractionated stereotactic radiotherapy of brain metastases from renal cell carcinoma.

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for brain metastases from renal cell carcinoma (RCC). METHODS AND MATERIALS: From May 1983 to September 1998, 35 patients with brain metastases from RCC underwent radiotherapy at the National Cancer Center Hospital, Tokyo; 10 patients treated initially with FSRT (FSRT group); 11 with surgery followed by conventional radiotherapy (S/CR group); and 14 with conventional radiotherapy (CR group). Survival and local control rates were determined for patients who had an ECOG performance status of 0-2. RESULTS: Overall median survival rate was 18 months, and actuarial 1- and 2-year survival rates were 57.6% and 31.0%, respectively. Median survival rates were 25.6 months for the FSRT group, 18.7 months for the S/CR group, and 4.3 months for the CR group. Significant prognostic factors associated with survival were age less than 60 years and good performance status. In patients treated with FSRT, imaging studies revealed that 21 of 24 tumors (88%) were locally controlled during a median follow-up time of 5.2 months (range 0.5-68). Actuarial 1- and 2-year local control rates were 89.6% and 55.2%, respectively. No patient suffered from acute or late complications during and following FSRT. CONCLUSIONS: FSRT offers better tumor control and prolonged survival over the S/CR or CR groups, and should be considered as primary treatment for brain metastases from RCC. Patients under 60-years-old and those with a good performance status at the beginning of radiotherapy had a better prognosis.

Radiotherapy for hepatocellular carcinoma.

PURPOSE: To retrospectively evaluate the effectiveness of radiotherapy with or without transarterial embolization (TAE) and/or percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma who were ineligible for surgery. PATIENTS AND METHODS: From October 1984 to November 1997, 62 patients underwent radiotherapy receiving 50 to 70 Gy in 25 to 35 treatments with or without transarterial embolization and/or percutaneous ethanol injection and were followed for a median period of 8.6 months (1.5 to 92 months). RESULTS: Overall median survival rates were 9.5 months. Significant prognostic factors were the extent of pretreatment liver function impairment, radiation field size and the existence of tumor thrombosis. Six-month and 1-year local control rates were 67 and 54%, respectively. Seven of the 8 patients who suffered from hepatic failure had poor pretreatment liver functions. CONCLUSION: Radiotherapy with or without transarterial embolization and/or percutaneous ethanol injection appears effective in controlling hepatocellular carcinoma and prolonged survival. Individualized treatment strategies are presented depending on the tumor presentation and the degree of liver function impairment.

Long-term observations of a patient with choroidal melanoma following fractionated stereotactic radiotherapy: a case report.

A 60-year-old man with choroidal melanoma was treated with fractionated stereotactic radiotherapy and followed for 6 years. During this period, the tumor has not changed in size, and the patient has experienced only a slight decrease in visual acuity. In this case, stereotactic radiotherapy appears to have been safe and effective and may also be a cost-effective alternative to particle or plaque therapy.

The external radiotherapy with three-dimensional conformal boost after the neoadjuvant androgen suppression for patients with locally advanced prostatic carcinoma.

PURPOSE: To analyze the results in patients with locally advanced prostatic carcinoma treated by hormonal therapy followed by external radiotherapy using three-dimensional conformal radiation therapy (3D-CRT) boost. METHODS AND MATERIALS: From 1987 to 1995, 46 patients with histologically proven locally advanced adenocarcinoma of the prostate were treated with 3D-CRT at the National Cancer Center Hospital, Tokyo. The neoadjuvant androgen suppression started immediately after the diagnosis followed by radical radiation therapy, according to the prospective protocol. They were treated with photons of 6-14 MV for wide fields and the boost, of which a multiple-leaf collimator of 2-cm width was available. The boosted dose was delivered with the rotational 3D-CRT, after the delivery of whole pelvis 4-field box from a dose of 40-46 Gy up to 66 Gy. The planning target volume encompassed 1 cm outside throughout the clinical target volume, and the prostate and the seminal vesicles were included in the boost field. RESULTS: The 3D-CRT boost treatment completed as planned in all 46 patients. The median follow-up for all the patients was 60 months (range, 5-120 months). Nineteen of 46 patients died. Of these, 11 patients died of the intercurrent diseases. For all 46 patients, the 5- and 8-year overall survival rates were 61.3% and 42.4%, and the 5- and 8-year cause-specific survival rates were 82.4% and 64.4%, respectively. The prostate-specific antigen (PSA) relapse-free rates for 5- and 8-year were 64.6% and 52.5%, and the clinical local control rates for 5 and 8 years were 75.3% and 69.9%, respectively. The preradiation therapy PSA and the Gleason score were the factors that significantly associated with PSA relapse-free survival. Sixteen of 46 patients (35%) showed at least one form of late toxicities. Of these, 3 patients experienced late complications of Grade 3 (urinary, 2, proctitis, 1). CONCLUSION: The treatment results were fairly good and were consistent with those in Western countries, indicating that this study shows the preliminary status of 3D-CRT for the locally advanced prostate cancer in Japan. Preradiation therapy PSA seems to be a significant predictor of PSA relapse-free survival (p = 0.004) after neoadjuvant androgen suppression.

Brain involvement in Hodgkin's disease: case reports and review of the literature.

Hodgkin's disease involving in the central nervous system is extremely rare. It usually spreads contiguously, as visceral involvement is generally thought to occur secondary to involved adjacent lymph nodes. We report three such cases found in our institution in the last two decades. Based upon our limited experience together with reported data, whole brain irradiation combined with systemic chemotherapy remains the treatment of choice for these lesions.

Long-term survival after multimodality treatment for resectable pancreatic cancer.

BACKGROUND: The prognosis of pancreatic adenocarcinoma after radical pancreatectomy is poor, especially in advanced-stage disease. STUDY AIM: To determine the survival rates and evaluate the effectiveness of multimodality treatment for advanced pancreatic cancer. METHODS: From November 1983 to January 1993, 30 patients with pancreatic adenocarcinoma including 9 with carcinoma of the body and tail were treated by a multimodal approach consisting of extended pancreatectomy, intraoperative radiotherapy (IORT), and hepatic artery or portal vein infusion of mitomycin C (MMC) followed by systemic bolus injection. All surviving patients were followed for more than 8 yr and survival rates were calculated by the Kaplan-Meier method. RESULTS: There were no operative or hospital deaths. Eight patients survived for more than 5 yr, 3 of whom survived more than 10 yr. The 5-yr survival rate for 27 patients excluding 3 with metastasis to the liver, peritoneum, or lung was 31%, with a median survival of 31.1 mo. Among them, the 1-, 3-, and 5-yr survival rates for 19 patients with regional nodal metastasis were 95, 50, and 28%, respectively, with a median survival of 36.0 mo. CONCLUSION: The multimodality treatment combined with IORT and MMC chemotherapy appeared to have a benefit for prognosis of advanced pancreatic adenocarcinoma.

Comparison of radiation effects of gadolinium and boron neutron capture reactions.

PURPOSE: Cell survival assays were performed to evaluate the effects of radiations released during neutron capture reactions by gadolinium-157, boron-10 and by the combination of both. MATERIALS AND METHODS: Single cell suspensions with or without Gd-157 and/or B-10 were exposed to thermal neutrons produced by the Kyoto University reactor, and standard cell survival curves were obtained. RESULTS: Under the same molarity, cytocidal effects were 1.5 times greater for Gd-157 than for boron when compared at 10% survival levels. The presence of B-10 enhanced the radiation effect of Gd-157 neutron capture by 1.2-fold, suggesting that cells were not sufficiently irradiated as a result of neutron fluency attenuation by the presence of excess neutron capture agents in the medium. CONCLUSIONS: When an equal number of atoms were present, Gd-157 was effective as B-10 when exposed to an equal number of thermal neutrons. However, there was no benefit observed in the combination of Gd-157 and B-10 for neutron capture therapy. Further studies are needed to determine optimal Gd-157 and B-10 concentrations as a function of tumor dimension.

Preparation of lecithin microcapsules by a dilution method using the Wurster process for intraarterial administration in gadolinium neutron capture therapy.

Lecithin microcapsules containing gadolinium (Gd) were designed and prepared as a dosage form for intraarterial administration to accumulate Gd in tumors in neutron capture therapy. The microcapsules were composed of 1) a lactose core, 2) a layer of distearylamide of gadopentetic acid (Gd-DTPA-SAm) and polyvinylpyrrolidone (PVP) with or without soybean lecithin (SL) and 3) a membrane containing SL, cholesterol, stearic acid and PVP at three different compositions. A dilution method using the Wurster process was developed for small-scale preparation. In spite of using only 2 g of Gd-DTPA-SAm each, three types of microcapsules were obtained with a content of 24.9% as Gd-DTPA-SAm (3.66% as Gd) even at 150% coating level. The swelling type of microcapsules (MC-D1) did not release Gd at all for the entire 120 min of the experiment in a 0.9% saline solution. On the other hand, the rapid-erosion type (MC-D2) and the vesicle-dispersing type (MC-D3) released Gd with a lag time. The percent released depended on the coating level and the SL content in the Gd-fixing layer. A large number of droplet-like particles spouted out, and/or tubular vesicles formed with MC-D2 and MC-D3 in the saline solution. These phenomena implied that the water-insoluble Gd-DTPA-SAm would be entrapped in these particles/vesicles. When MC-D2 and MC-D3 were administered to normal rats via the hepatic artery, a Gd-accumulation as high as 70 and 71% of the injected dose was detected in the whole liver 2 h after administration. In addition, biochemical and histological evaluation of the liver after administration indicated that embolization of the microcapsules actually occurred in the blood vessels, and that necrosis induced by ischemia was not serious. These results suggested that administration of these microcapsules might be multiply repeated in order to accumulate the required amount of Gd in tumors.

Biodistribution of gadolinium incorporated in lipid emulsions intraperitoneally administered for neutron-capture therapy with tumor-bearing hamsters.

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).

Fractionated stereotactic radiotherapy of small intracranial malignancies.

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) in patients with small intracranial malignancies. METHODS AND MATERIALS: From July 1991 to March 1997, 80 patients with a total of 121 brain or skull-base tumors were treated with FSRT alone, and were followed for periods ranging from 3 to 62 months (median 9.8). The majority of patients received 42 Gy in 7 fractions over 2.3 weeks, but in July 1993, protocols using smaller fraction doses were introduced for patients whose radiation-field diameters were larger than 3 cm or whose tumors were close to critical normal tissues. RESULTS: For 64 patients with metastatic brain tumors the overall median survival was 8.3 months and 1-year actuarial survival rate was 33%. Significant prognostic factors were: the presence of extracranial tumors, pre-treatment performance status, and the lung as a primary site. Patients without extracranial tumors prior to FSRT had a median survival of 21.2 months. For seven patients with high-grade glioma, 1-year actuarial local control rate was 75%, with a median survival of 10.3 months. For patients with skull-base tumors the local control was achieved in 6 of 6 patients (100%), with a median survival of 30.7 months. No one suffered from acute complications, but three patients, two of whom had undergone FSRT as the third course of radiotherapy, developed late radiation injuries. CONCLUSION: Overall high local control and low morbidity rates suggest that FSRT is an effective and safe modality, even for those with a history of prior irradiation. However, patients with risk factors should be treated with smaller fraction doses.