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We have developed a practical dose verification method for radiotherapy treatment planning systems by using only a Farmer ionization chamber in inhomogeneous phantoms. In particular, we compared experimental dose verifications of multi-layer phantom geometries and laterally inhomogeneous phantom geometries for homogeneous and inhomogenous dose calculations by using the fast-Fourier-transform convolution, fast-superposition, and superposition in the XiO radiotherapy treatment-planning system. We applied the dose verification method to three kernel-based algorithms in various phantom geometries with water-, lung- and bone-equivalent media of different field sizes. These calculations were then compared with experimental measurements by use of the Farmer ionization chamber. The fast-Fourier-transform convolution algorithm overestimated the dose by about 8% in the lung phantom geometry. The superposition algorithm and the fast-superposition algorithm were both accurate to better than 2% when compared to the measurements even for complex geometries. Our dose verification method was able to clarify the differences and equivalences of the three kernel-based algorithms and measurements with use only of commonly available apparatus. This will be generally useful in commissioning of inhomogeneity-correction algorithms in the clinical practice of treatment planning.

Dosimetric characteristics of a metal oxide-silicon semiconductor field effect transistor (MOSFET) detector are studied with megavoltage photon beams for patient dose verification. The major advantages of this detector are its size, which makes it a point dosimeter, and its ease of use. In order to use the MOSFET detector for dose verification of intensity-modulated radiation therapy (IMRT) and in-vivo dosimetry for radiation therapy, we need to evaluate the dosimetric properties of the MOSFET detector. Therefore, we investigated the reproducibility, dose-rate effect, accumulated-dose effect, angular dependence, and accuracy in tissue-maximum ratio measurements. Then, as it takes about 20 min in actual IMRT for the patient, we evaluated fading effect of MOSFET response. When the MOSFETs were read-out 20 min after irradiation, we observed a fading effect of 0.9% with 0.9% standard error of the mean. Further, we applied the MOSFET to the measurement of small field total scatter factor. The MOSFET for dose measurements of small field sizes was better than the reference pinpoint chamber with vertical direction. In conclusion, we assessed the accuracy, reliability, and usefulness of the MOSFET detector in clinical applications such as pinpoint absolute dosimetry for small fields.

Quality assurance and quality control of delivered dose are important in proton therapy. The delivered proton dose is controlled using a dose monitor system which consists of two ionization chambers filled with free air. Response of the monitor for the delivered dose changes under the influence of temperature and pressure of surrounding air. In the dose monitor system at the National Cancer Center Hospital East, the monitor is near an X-tray tube which operates at a high temperature and is frequently used in every patient setup. Therefore the response of the dose monitor changes a lot with the temperature of the X-ray tube. In this report, temperature and pressure influence on the dose monitor was investigated in detail. Furthermore, a new method was presented to correct the monitor response using the real-time data of temperature and pressure at any time for each patient. This method improved the accuracy of delivered dose from 1% to 0.5%.

Proton therapy is a form of radiotherapy that enables concentration of dose on a tumor by use of a scanned or modulated Bragg peak. Therefore, it is very important to evaluate the proton-irradiated volume accurately. The proton-irradiated volume can be confirmed by detection of pair-annihilation gamma rays from positron-emitting nuclei generated by the nuclear fragmentation reaction of the incident protons on target nuclei using a PET apparatus. The activity of the positron-emitting nuclei generated in a patient was measured with a PET-CT apparatus after proton beam irradiation of the patient. Activity measurement was performed in patients with tumors of the brain, head and neck, liver, lungs, and sacrum. The 3-D PET image obtained on the CT image showed the visual correspondence with the irradiation area of the proton beam. Moreover, it was confirmed that there were differences in the strength of activity from the PET-CT images obtained at each irradiation site. The values of activity obtained from both measurement and calculation based on the reaction cross section were compared, and it was confirmed that the intensity and the distribution of the activity changed with the start time of the PET imaging after proton beam irradiation. The clinical use of this information about the positron-emitting nuclei will be important for promoting proton treatment with higher accuracy in the future.

Purpose: The utility of positron emitter nuclei generated by photonuclear reactions was verified for X-ray beam monitoring in a phantom., Materials and Methods: Positron emission tomography-computed tomography (PET-CT) images of a gelatinous water phantom (H(2)O target) and a polyethylene phantom (CH(2) target) were acquired 5 min after delivering a dose of 17 Gy with an X-ray beam energy of 21 MV. Reconstructed PET images and the calculated half-life showed that the positron emitters of (15)O (half-life 122.2 s) in the H(2)O target and (11)C (half-life 20.4 min) in the CH(2) target were generated by photonuclear reactions., Results: A comparison was made between measured activity and dose distributions for each target. The measured times of annihilation gamma rays from the positron emitter nucleus were 10 and 30 min for the (15)O nucleus in the H(2)O target and the (11)C nucleus in the CH(2) target, respectively. The activity distributions of the (15)O and (11)C positron emitter nuclei were similar to the measured dose distributions for both depth and lateral directions except for dose buildup and collimator edge regions. It was confirmed that no activity was detected at an X-ray energy of 14 MV, which was far below the energy threshold for both photonuclear reactions., Conclusion: It was estimated that the PET-CT image acquired from the activity of the (15)O and (11)C positron emitter nuclei might provide the area of X-ray beam irradiation in a phantom.

Objective: The relationship was studied between the timing of assessment of complete response and ultimate cure rate in the chemoradiotherapy of advanced head and neck cancer., Methods: A retrospective review was conducted regarding tumor responses at 4 weeks, 3 months, and 6 months after concomitant chemoradiotherapy using cisplatin and 5-FU for 70 patients with stage III/IV squamous cell carcinoma of the oropharynx, hypopharynx and supraglottic larynx. Predictive values of tumor responses at these three time points for survival and tumor control at 2 years were tested using the chi-square test., Results: Twelve (17%) patients achieved complete response (CR) at 4 weeks. Because of late regression or early recurrence, the CR rate changed to 18/70 (26%) and 24/70 (34%) at 3 and 6 months, respectively. CR or not at 6 months was significantly correlated with all survival endpoints (P < 0.001), but not those at 4 weeks and 3 months (P > 0.100). Kaplan-Meier estimate of overall survival at 5 years was 63% (95% CI 43-84%) for 24 CR patients at 6 months., Conclusion: CR rate at 6 months was a better surrogate endpoint than that at 4 weeks or 3 months in this series of patients.

Background/aims: Hypofractionated radiotherapy can shorten the irradiation period and allow systemic chemotherapy with full-dose gemcitabine to be started earlier. The purpose of this study was to determine the feasible dose of hypofractionated radiotherapy that could be followed by full-dose gemcitabine in patients with locally advanced pancreatic cancer., Methodology: Nine patients with unresectable locally advanced pancreatic cancer were enrolled in this study. Three patients received radiotherapy at 45Gy in 15 fractions (level 1) and six at 40 Gy in 8 fractions (level 2). Systemic chemotherapy with gemcitabine was started 3 months after the start of irradiation and was administered as a 30-minute intravenous infusion of a dose of 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle., Results: No patients experienced dose-limiting toxicity at either level of radiotherapy. Gemcitabine was started in two of the three patients treated at the level 1 on schedule. At level 2, grade 3 nausea, vomiting and anorexia was observed in all 6 patients, and gemcitabine could not be started on schedule in 4 of the 6 patients. Two (22%) of the 9 patients achieved a partial response. The median time to progression was 5.8 months and the median overall survival time was 9.5 months., Conclusions: Hypofractionated radiotherapy with 40 Gy in 8 fractions was not feasible in patients with locally advanced pancreatic cancer.

Objective: To evaluate the advantage of accelerated fractionation radiotherapy for patients with hypopharyngeal cancer requiring total laryngectomy., Methods: Seventy patients with previously untreated, technically resectable hypopharyngeal cancer who received larynx-preserving treatment with radiotherapy between April 1992 and June 2004 were analyzed. No patients had previous history of other malignancy or poor performance status that would possibly affect the outcomes. A total RT dose of > or = 60 Gy/6 weeks was determined depending on the tumor clearance during treatment before December 1998, and fixed to 70 Gy in all patients thereafter. Accelerated fractionation (70 Gy/<49 days) was completed in 35 patients during the latter period. Concomitant platinum-based chemotherapy was used in 41 patients after May 1998., Results: Local control rates at 2 years were 72 and 68% for patients with T2 and T3/T4 disease, respectively. Patients who had received 70 Gy/<49 days achieved a better local control rate than those who had received other, more conservative total dose/overall treatment time with statistical significance (91% versus 50% at 2 years, P < 0.001). Multivariate analysis involving 70 Gy/<49 days of radiotherapy, T-classification (T2 versus T3/4), and use of chemotherapy revealed that administering 70 Gy/<7 weeks was the only independent prognostic factor (P = 0.007) for better local control., Conclusions: Our experience in radiotherapy for hypopharyngeal cancer mirrored the results of previously conducted large randomized trials for various head and neck cancers. Encouraging local control in this study warrants prospective study to test the long-term oncological and functional outcome of larynx-preserving treatment in patients with advanced but resectable volume of this disease.

Respiratory-gated (RG) radiotherapy is useful for minimizing the irradiated volume of normal tissues resulting from the shifting of internal structures caused by respiratory movement. The present study was conducted to evaluate the treatment field in RG radiotherapy using a phantom system simulating patient respiration. A phantom system consisting of a 3-cm ball-shaped dummy tumor and film placed in a cork lung phantom was used (THK Co., Ltd.). RG radiotherapy was employed in the expiratory phase. The phantom movement distance was set to 2 cm, and the gating signals from a respiratory-gating system (AZ-733V, Anzai Medical) were varied. The settings used for irradiation were an X-ray energy of 6 MV (PRIMUS, Toshiba Medical Systems), treatment field of 5 cm x 7 cm, and X-ray dose of 100 MU. Images were acquired using an electric portal-imaging device (EPID, OPTIVUE 500), and the X-ray dose distribution was measured by the film method. In images acquired using the EPID, the tumor margins became less clear when the gating signals were increased, and the ITVs were determined to be 3.6 cm, 3.7 cm, 4.2 cm, and 5.1 cm at gating rates of 10%, 25%, 50%, and no gate, respectively. With regard to the X-ray dose distribution measured by the film method, the dose profile in the cephalocaudal direction was shifted toward the expiratory phase, and the degree of shift became greater when the gating signals were increased. In addition, the optimal treatment fields in the cephalocaudal direction were determined to be 5.2 cm, 5.2 cm, 5.6 cm, and 7.0 cm at gating rates of 10%, 25%, 50%, and no gating, respectively. Although RG radiotherapy is useful for improving the accuracy of radiotherapy, the characteristics of the RG radiotherapy technique and the radiotherapy system must be clearly understood when this method is to be employed in clinical practice. Image-guided radiotherapy (IGRT) is now assuming a central role in radiotherapy, and properly identifying internal margins is an important issue for ensuring optimal treatment. The results of this study confirmed that it is necessary to ensure the optimal treatment field in radiotherapy of the trunk and that it is essential to confirm tumor position on the basis of image evaluation.

Respiratory-gated (RG) radiotherapy is useful for minimizing the irradiated volume of normal tissues resulting from the shifting of internal structures caused by respiratory movement. In this technique, although improvement in the dose distribution of the target can be expected, the actual absorbed dose distribution is not clearly determined. Therefore, it is important to clarify the absorbed dose at the tumor and at the evaluation points according to the patient's respiration. We have developed a phantom system that simulates patient respiration (TNK Co., Ltd.), to evaluate the absorbed dose and ensure precise RG radiotherapy. Actual patient respiratory signals were obtained using a respiratory synchronization and gating system (AZ-733V, Anzai Medical). The acquired data were then transferred to a phantom system driven by a ball screw to simulate the shifting of internal structures caused by respiratory movement. We measured the absorbed dose using a micro-ionization chamber dosimeter and the dose distribution using the film method for RG irradiation at expiratory phase by using Linac (PRIMUS, Toshiba Medical Systems Corp.) X-rays. When the distance of phantom movement was set to the average patient respiratory movement distance of 1.5 cm, we first compared absorbed dose with RG irradiation with a gating signal of 50% or less, and without RG irradiation. The absorbed dose at the iso-center was improved by 6.0% and 4.4% at a field size of 4x4 cm2, and by 1.3% and 0.7% at a field size of 5x5 cm2 with an X-ray energy of 6 MV and 10 MV, respectively. There was, however, no dose change at a field size of 10x10 cm2 and 15x15 cm2. When the gating signal was reduced to 25% and 10%, absorbed dose was also improved. With regard to the flatness of the dose profile, no changes in dose distribution were observed in the lateral direction, e.g., beam flatness was within 1.4% and 1.6% at field sizes of 5x5 cm2 and 10x10 cm2, respectively, with an X-ray energy of 6 MV. In the cranial-caudal direction, the dose profile was relatively large even if a gating signal of 50% was applied, i.e., 8.1% and 10.4% at field sizes of 5x5 cm2 and 10x10 cm2, respectively. Beam flatness without RG was much worse, i.e., 37.8% and 38.2%, at field sizes of 5x5 cm2 and 10x10 cm2, respectively. In both cases, the dose was insufficient in the expiratory direction. Although RG radiotherapy is quite useful, the margins in the inspiratory and expiratory phases should be considered based on the level of gating signal and field size in order to formulate appropriate radiotherapy planning in terms of the shifting of internal structures. To ensure accurate radiotherapy, the characteristics of the RG irradiation technique and the radiotherapy equipment must be clearly understood when this technique is to be employed in clinical practice.

Proton beam therapy (PBT) has made it possible to deliver a higher concentration of radiation to the tumor by its Bragg-peak, and is easy to utilize due to the fact that its biological characteristics are identical with X-rays. PBT has a half-century history, and more than 40,000 patients have been reported as having had treatments with proton beams worldwide. The historic change to this therapy occurred in the 1990s, when the Loma Linda University Medical Center began its clinical activity as the first hospital in the world to utilize a medically dedicated proton therapy facility. Since then, similar hospital-based medically dedicated facilities have been constructed. Results from around the world have shown the therapeutic superiority of PBT over alternative treatment options for ocular melanoma, skull base sarcoma, head & neck cancer, lung cancer,esophageal cancer, hepatocellular carcinoma, and prostate cancer. PBT is expected to achieve further advancement both clinically and technologically.

It is very important for proton therapy to make and carry out a quality assurance (QA) program. Operators and medical personnel have to avoid any trouble during treatment and provide patients with high quality and reliable treatment. A proton therapy machine consists of an accelerator, gantry and various beam modifying devices. Although QA for proton therapy is complicated and difficult, we tried to realize daily QA for proton therapy. Two main purposes in daily QA are stable operation of the accelerator and reliable control of the irradiation system. In order to determine the daily QA issues, past problems were considered. We made a daily QA program and used it for one year. In this paper, we show the daily QA program and report our results. The daily QA was clearly effective for stable operation of the accelerator and for controlling quality of the irradiation system.

Objective: To assess the feasibility of high-dose radiotherapy for prostate cancer using proton boost therapy following photon radiotherapy., Methods: The primary endpoint was acute grade 3 or greater genitourinary (GU) and gastrointestinal (GI) toxicities. The study included patients with clinical stage T1-3N0M0 prostate cancer. Radiotherapy consisted of 50 Gy/25 fx photon irradiation to the prostate and the bilateral seminal vesicles followed by proton boost of 26 Gy(E)/13 fx to the prostate alone. Hormonal therapy was allowed before and during the radiation therapy., Results: Between January 2001 and January 2003, 30 patients were enrolled in this study. Acute grade 1/2 GU and GI toxicities were observed in 20/4 and 17/0 patients, respectively. With the median follow-up period of 30 months (range 20-45), late grade 1/2 GU and GI toxicities occurred in 2/3 and 8/3 patients, respectively. No grade 3 or greater acute or late toxicities were observed. All patients were alive, but six patients relapsed biochemically after 7-24 months., Conclusions: Proton boost therapy following photon radiotherapy for prostate cancer is feasible. To evaluate the efficacy and safety of proton beam therapy, a multi-institutional phase II trial is in progress in Japan.

Background: With the development of chemoradiotherapy for esophageal cancer, the complete response (CR) rate would become an important surrogate end-point. However, the Response Evaluation Criteria in Solid Tumors (RECIST) do not provide criteria for a response at the primary site of esophageal cancer. The objective of this study was to assess the validity of the endoscopic CR criteria for the primary site of esophageal cancer treated with chemoradiotherapy., Methods: We reviewed 139 patients with T1-T4, N0-1, M0-1a esophageal cancer treated with definitive chemoradiotherapy from August 1992 to April 1999. CR was tentatively defined upon endoscopic observation of the entire esophagus as: (i) disappearance of the tumor lesion; (ii) disappearance of ulceration (slough); and (iii) absence of cancer cells in biopsy specimens., Results: CR at the primary site (primary-CR) was achieved in 80 patients (58%). Of these, 71 (89%) were evaluated as having primary-CR within 6 months from the start of therapy. With a median follow-up of 53 months, a remarkable difference in the 5-year survival rate was observed between patients evaluated as having primary-CR and having non-CR (46 and 6%, P < 0.0001). Local failure was observed in 15 patients and the local control rate in patients with primary-CR was 78% at 5 years., Conclusions: These criteria appear to represent an appropriate surrogate end-point because they are convenient to apply, require only a short time before a primary-CR can be declared and their fulfillment can predict long-term survival. It is recommended that RECIST include precise endoscopic findings for primary lesions in esophageal cancer in the CR criteria.

In proton radiotherapy, the irradiation dose can be concentrated on a tumor. To use this radiotherapy efficiently in the clinical field, it is necessary to evaluate the proton-irradiated area and condition. The proton-irradiated area can be confirmed by coincidence detection of pair annihilation gamma rays from beta+ decayed nuclei generated by target nuclear fragment reaction of irradiated proton nuclei and nuclei in the irradiation target. In this study, we performed experiments of proton irradiation to a polyethylene (PE:CH2) target containing 12C nuclei, which is a major component of the human body, and a gelatinous water (H2O) target containing 16O nuclei at different proton irradiation energy levels under different beam conditions of mono-energetic Bragg peak and spread-out Bragg peak. The distribution of the activity in the target after proton irradiation was measured by a positron emission tomography (PET) apparatus, and compared with the calculated distribution. The temporal dependence of the activity distribution during the period between the completion of proton irradiation and the start of measurement by the PET apparatus was examined. The activity by clinical proton irradiation was 3 kB/cc in the PE target and 13 kB/cc in the water target, indicating that the intensity was sufficient for the evaluation of the distribution. The range of the activity distribution against the physical range was short (several millimeter water equivalent length), indicating the presence of target dependence. The range difference in the water target was slightly large with time dependence until the start of measurement. The difference of the lateral widths with full width half at maximum in the distributions of the measured irradiated dose and activity was within 1 mm.

Purpose: To evaluate the safety and efficacy of proton beam radiotherapy (PRT) for hepatocellular carcinoma., Patients and Methods: Eligibility criteria for this study were: solitary hepatocellular carcinoma (HCC); no indication for surgery or local ablation therapy; no ascites; age >/= 20 years; Zubrod performance status of 0 to 2; no serious comorbidities other than liver cirrhosis; written informed consent. PRT was administered in doses of 76 cobalt gray equivalent in 20 fractions for 5 weeks. No patients received transarterial chemoembolization or local ablation in combination with PRT., Results: Thirty patients were enrolled between May 1999 and February 2003. There were 20 male and 10 female patients, with a median age of 70 years. Maximum tumor diameter ranged from 25 to 82 mm (median, 45 mm). All patients had liver cirrhosis, the degree of which was Child-Pugh class A in 20, and class B in 10 patients. Acute reactions of PRT were well tolerated, and PRT was completed as planned in all patients. Four patients died of hepatic insufficiency without tumor recurrence at 6 to 9 months. Three of these four patients had pretreatment indocyanine green retention rate at 15 minutes of more than 50%. After a median follow-up period of 31 months (16 to 54 months), only one patient experienced recurrence of the primary tumor, and 2-year actuarial local progression-free rate was 96% (95% CI, 88% to 100%). Actuarial overall survival rate at 2 years was 66% (48% to 84%)., Conclusion: PRT showed excellent control of the primary tumor, with minimal acute toxicity. Further study is warranted to scrutinize adequate patient selection in order to maximize survival benefit of this promising modality.

We examined energy metabolism and amino acid content in the hippocampus of amygdaloid-kindled rats using (1)H NMR spectroscopy. Three weeks after the last stage 5 seizure, kindled rats were killed by microwave irradiation. The hippocampus was dissected out and subjected to MeOH/CHCl(3) extraction. All (1)H spectra were analyzed to quantify absolute concentrations using a non-linear least squares method, combined with a prior knowledge of chemical shifts. Saturation effects were compensated for by the T1 measurement of each component. Levels of energy metabolism-related compounds, phosphocreatine, creatine, glucose and succinate were the same in both kindled rats and sham controls. Lactate concentration had a tendency to increase, although this was not statistically significant. When compared with sham controls, levels of aspartate, glutamate, glycine and glutamine, as well as GABA and inositol, were increased in the ipsilateral but not the contralateral hippocampus. In contrast, levels of taurine, alanine and threonine were unchanged. Finally, N-acetylaspartylglutamate content was elevated, whereas N-acetyl-l-aspartate content was unaltered in the ipsilateral hippocampus of kindled animals. Our results suggest that amygdala kindling may affects amino acid metabolism, but not energy metabolism.

The (31)P NMR localised method was used to study the metabolism of phospholipid and high energy phosphate in the prefrontal cortex. The spectra were taken from patients with schizophrenia (11 males) receiving neuroleptic medication, and were compared to normal controls (15 males). Their spectral intensities were analysed using a non-linear least-squares method with a prior knowledge of the fixed chemical shifts and linewidths, leading to further resolution into resonances of glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite concentrations were calculated referring to the spectral intensities of phosphate phantoms with known concentrations. T1 values of phantom and cerebrum were estimated from a series of localised inversion recovery spectra to correct for the signal saturation effects. The schizophrenic patients showed an increased concentration of GPC but not GPE, PE or PC. Furthermore, no difference was observed regarding the concentration of high-energy phosphates such as phosphocreatine, inorganic phosphate and ATP. The patients did not show any differences in mitochondrial function such as phosphorylation potential and the ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the prefrontal cortex could be characteristic of the pathophysiology of schizophrenia with mild negative symptoms.

Background/aims: To examine the efficacy and safety of a combined modality therapy consisting of hepatic arterial infusion of 5-fluorouracil and external-beam radiotherapy in patients with advanced pancreatic carcinoma., Methodology: Hepatic arterial infusion chemotherapy consisted of 5-FU 1000mg/m2 administrated as a 5-hr continuous infusion once weekly. External-beam radiotherapy (total dose, 50Gy; 2Gy/day) was delivered to the pancreas tumor concurrently for 5-6 weeks. Seventeen patients with no distant metastases except to the liver were enrolled in this study., Results: Patients received a median of 13 cycles of chemotherapy. Sixteen of 17 patients received a total radiotherapy dose of 50Gy. In one patient, treatment was discontinued after 24Gy of radiotherapy and 2 cycles of chemotherapy because of progressive disease. Nausea and vomiting were the most common types of toxicity. Grade 3 or worse toxicity was observed in 2 patients. Four patients developed gastroduodenal ulcers. Of the 16 patients, 7 (41%) showed a partial response, and 9 (53%) showed no change. The median overall survival was 4.5 months and 1-yr overall survival of 11.8% was observed., Conclusions: The combined therapy is active and well tolerated, but results in a poorer prognosis, in spite of its high initial response rate.

Proton beam therapy (PBT) makes it possible to deliver a higher concentration of radiation to the tumor by its Bragg-peak, and is easy to utilize due to its identical biological characteristics with X-rays. PBT has a half-century history, and more than 35,000 patients have been reported as having had treatments with proton beams worldwide. The historic change to this therapy occurred in the 1990s, when the Loma Linda University Medical Center began clinical activity as the first hospital in the world to utilize a medically dedicated proton therapy facility. Since then, similar hospital-based medically dedicated facilities have been constructed. Results from around the world have shown the therapeutic superiority of PBT over alternative treatment options for ocular melanoma, skull base sarcoma, head and neck cancer, lung cancer, esophageal cancer, hepatocellular carcinoma, and prostate cancer. PBT is expected to achieve further advancement both clinically and technologically.

Purpose: To assess the long-term toxicity after definitive chemoradiotherapy (CRT) for squamous cell carcinoma (SCC) of the esophagus., Patients and Methods: Patients newly diagnosed with SCC of the esophagus and treated with definitive CRT between 1992 and 1999 in our institution were recruited from our database on the basis of the following criteria: age

Relatively little is known about how recirculation of lymphocytes through the inflamed intestinal mucosa is regulated. The aim of this study was to investigate the dynamic process of T lymphocyte-endothelial cell adhesion in TNF-alpha-challenged murine colonic mucosa by intravital microscopy. T lymphocytes from spleen (SPL) and intestinal lamina propria (LPL) were fluorescence labeled, and their adhesion to microvessels in the colonic mucosa was observed. In TNF-alpha (25 microg/kg)-stimulated colonic venules, an enhanced adhesion of SPL and LPL was demonstrated, with dominant recruitment of LPLs. The magnitude of the increased LPL adhesion was more significant in the colon than in the small intestine. These T lymphocyte interactions in the colonic mucosa were significantly reduced by blocking MAbs against either mucosal addressin cell adhesion molecule-1 (MAdCAM-1), VCAM-1, alpha(4)-integrin, or beta(7)-integrin but not by anti-ICAM-1. Immunohistochemistry revealed significant MAdCAM-1 expression in the lamina propria and VCAM-1 expression in the submucosa of TNF-alpha-treated colon. Spatial heterogeneity of MAdCAM-1 and VCAM-1 activation following TNF-alpha challenge may promote specific T lymphocyte recruitment in the inflamed colonic mucosa.

Background: The majority of patients with non-small cell lung cancer have inoperable disease that is already too advanced for radical treatment at the initial diagnosis. But patients who suffer from symptoms caused by intrathoracic tumor often require palliative treatment to relieve the symptoms. We investigated, retrospectively, the outcome of short-course palliative radiotherapy for airway stenosis in non-small cell lung cancer., Methods: Between October 1997 and June 2001, 24 patients were treated by palliative radiotherapy to relieve airway stenosis caused by intrathoracic tumor. The short-course radiotherapy consisted of a total dose of 30 Gy given in ten fractions over 2 weeks. The effect of treatment was assessed by improvement of radiographic findings. The duration of palliation and this duration as a percentage of the remaining survival time were also investigated., Results: Palliation of airway stenosis was achieved in 13 (54.2%) patients. The time until palliation was achieved ranged from 11 to 44 days (median, 24 days). The duration of palliation ranged from 44 to 351 days (median, 116 days). In the palliated patients, the median survival time was 192 days, while that of the non-responders was 43 days. The duration of palliation as a percentage of the remaining lifetime ranged from 41% to 96% (median, 66%)., Conclusions: Short-course palliative radiotherapy of 30 Gy in ten fractions over 2 weeks achieved good palliation without severe acute toxicities in over half of the patients. It is suggested that, in the palliated patient, the airway can be, potentially, maintained over the long term.

Purpose: To evaluate the efficacy and toxicity of high-dose thoracic radiotherapy (TRT) alternating with chemotherapy (CH) for unresectable stage III non--small-cell lung cancer (NSCLC)., Patients and Methods: Forty-one patients received TRT with 1.5 Gy twice daily, 5 days a week, on weeks 1, 2, 5, 6, and 9, up to a total dose of 66 to 72 Gy, alternating with cisplatin 80 mg/m(2) on day 1 and vindesine 3 mg/m(2) on days 1 and 8, repeated every 4 weeks, for two or three courses beginning on week 3., Results: The median (range) total dose of TRT and number of CH courses were 72 Gy (16.5 to 72 Gy) and three (zero to three), respectively. Delay in TRT > or = 5 days was observed in 24 (75%) of 32 patients who completed the projected treatment, due to leukopenia in 12, esophagitis in seven, infection in two, and other causes in three patients. Partial responses were obtained in 36 patients (88%). The median survival time and 3- and 5-year survival rates were 18.4 months, 24%, and 10%, respectively. Grade 3 or 4 leukopenia and esophagitis developed in 32 and seven patients, respectively. Grade 3 or 4 late esophageal toxicity developed in two patients., Conclusion: Alternating high-dose TRT and CH for stage III NSCLC produced a high response rate with median and long-term survival comparable to prior trials utilizing standard approaches in this population. Acute and late esophageal toxicity was observed and interruption of TRT was required in most of the patients.