Search

Edaravone has been reported to have a radioprotective effect at high concentrations. We now report that a lower dose of edaravone enhanced X-ray-induced apoptosis of some cell lines harboring p53 wild-type status, such as MOLT-4, Nalm-6, and HepG2. The knock-down of p53 using siRNA in MOLT-4 cells abolished the radiosensitizing effect of edaravone. Enhanced phosphorylations of p53 at Ser 15 and Ser 20 and up-regulation of PUMA, a p53 target protein, were observed after X-irradiation in the presence of edaravone. We conclude that the low dose of edaravone sensitized cells to X-irradiation by promoting the p53-dependent apoptotic signaling pathway.

To investigate the efficacy and toxicity of definitive chemoradiotherapy (CRT) for elderly patients with locally advanced esophageal cancer. Twenty-two patients aged over 75 that performed definitive CRT were retrospectively reviewed. The regimen included concurrent CRT consisting of two cycles of chemotherapy (CTx) of platinum and 5-fluorouracil, and radiation therapy (RT) of 50-50.4 Gy (actual range: 45.4-71.4 Gy), and additional CTx where possible. Both CTx and RT were reduced in dose and field where necessary. The disease-free survival rate and the overall survival rate at 3 years were 33.3% ± 11.4% and 25.9% ± 10.8%. Grade 4 leukocytopenia and thrombocytopenia occurred in three (14%) and four (18%) patients. Treatment-related death was suspected in up to four (18%) patients at the most. Univariate analyses for disease-free survival showed that neither total radiation dose nor number of total cycles of CTx was significant. The pattern of relapse was predominantly more frequent in the intra-RT field than outside the RT field. For elderly patients, adverse events are frequent, and decreased organ reserve may cause treatment-related death. Reduction in CTx dose or RT field, appropriate only for two cycles of CTx, and careful monitoring may help to minimize toxicity. Physicians should not be too afraid of adverse events or be negative about CRT for elderly patients, as long as comorbidities and complications are managed carefully.

Objective To evaluate Japanese tolerability to pilocarpine of 5 mg t.i.d. Methods From January 2006 to July 2006, 39 patients with xerostomia received 5 mg t.i.d. pilocarpine for at least for 12 weeks unless they had experienced unacceptable adverse effects. All patients received radiotherapy that included the parotid glands in the radiation field >50 Gy. The body weights of the patients ranged from 42 to 73 kg (median 60 kg). Results Thirty-six of the 39 patients were evaluable. The tolerated rate was only 47%. Of the 25 patients whose body weights were less than 65 kg, the tolerated rate was 36%, whereas the rate of the 11 patients whose body weights were 65 kg or above was 72% (p = 0.050). The most common adverse effect was sweating with an incidence of 64%. Response rate, which was defined as the total number of patients with an increase of at least 25 mm from the baseline in the VAS score divided by the number of maintaining patients among those who started pilocarpine after more than 4 months from the start of radiotherapy, was 40% at 12 weeks (n = 15). Conclusion For Japanese, 5 mg t.i.d. pilocarpine caused a high incidence of unacceptable adverse effects. A lower dose of pilocarpine needs to be considered.

The latest linear accelerator equipped with a kilovoltage (kV) cone-beam CT (CBCT) unit is useful for registration at the time of treatment, and thus reduces the setup error [1 4]. But in the case of intracranial or abdominal tumors, the contours of the tumors are difficult to determine on the CT images without contrast media, since such tumors are located next to normal soft tissue whose Hounsfield unit is close to those of the tumors themselves. Image registration by CBCT is performed based on the bony structures or soft tissue around the tumor. But this process does not necessarily guarantee that the position of the isocenter at treatment is identical with that at the time of planning CT, since bone or soft-tissue registration is based on a volume-matching process. It is difficult to know the exact tumor location for a low-contrast tumor even if on-board registration of the tumor is intended, since the tumor contour is not well visualized even on planning CT images without contrast media. We attempted to visualize metastatic brain

Aim: This study was conducted to evaluate the effect of external radiation therapy on lymph node metastases from hepatocellular carcinoma (HCC). Methods: A total 28 patients with cytopathologically proven HCC were subjected to radiation therapy over a 5-year period, and treatment was continued in all cases. All patients underwent irradiation with a total dose ranging between 46 and 60 Gy in daily 2.0-Gy fractions, five times a week. Results: Among the metastatic lesions treated, 18 (64%) and five (18%) patients achieved partial responses and complete responses, respectively. The 1- and 2-year overall survival rates and the median survival time were 53% and 33%, respectively, and 13 months in patients given external beam radiation therapy (EBRT) for a non-palliative, near-cure intent (n = 21). Conclusions: Although lymph node metastasis from HCC is sensitive to EBRT, the intent of EBRT should be limited to palliation. For palliative purposes, it is useful in treatment with 50 Gy in 25 fractions for these patients.

X-ray-induced apoptosis/Edaravone/MOLT-4 cells/Radioprotective effect/Free radical scavenger. Edaravone, a clinical drug used widely for the treatm ent of acute cerebral infarction, is reported to scavenge free radicals. In the present study, we investigated the radioprotective effect of edaravone on Xray-induced apoptosis in MOLT-4 cells. Apoptosis was determined by the dye exclusion test, Annexin V binding assay, cleavage of caspase, and DNA fragmentation. We found that edaravone significantly suppressed the X-ray-induced apoptosis. The amount of in tracellular ROS production was determined by the chloromethyl-2’,7’-dichlorodihydro-fluorescein diacetate system. We found that the intracellular ROS production by X-irradiation was completely suppressed b y the addition of edaravone. The accumulation and phosphorylation of p53 and the expression of p21 WAF1 , a target protein of p53, which were induced by Xirradiation, were also suppressed by adding edaravone. We conclude that the free radical scavenger edaravone suppresses X-ray-induced apoptosis in MOLT-4 cells by inhibiting p53.

Aim: We describe the clinical presentation, evaluation, management and outcome of patients experiencing small bowel perforation following radiation therapy for cervical cancer. Methods and Materials: A database consisting of 95 Japanese women with stage 0–4 A cervix cancer treated between 1991 and 2004 contained seven patients (7.4%) with small bowel perforation. Results: The median age at the time of perforation was 72.5 years (range 62–78). The median time from completion of radiotherapy to perforation was 6 months (range 2–58). Surgery (one small bowel resection and anastomosis with diversion; six small bowel resection and anastomosis) was performed immediately in all seven patients. One of seven patients died of small bowel perforation (i.e. mortality rate was 14%). Bowel adhesion was detected during the operation in only three cases (43%). Signs of peritonitis were absent in six cases (86%). Severe abdominal pain was seen in all seven patients. The perforation site was ileum in all seven cases. In all patients, pathological changes were compatible with postirradiation injury of the gastrointestinal tract. Conclusions: The presenting complaints of patients with bowel perforation following radiotherapy vary, and signs of peritonitis may be absent. Emergency physicians must be alert for these complications in patients who have been treated with radiotherapy.

Purpose: To evaluate the treatment outcome of concurrent chemoradiation therapy (cCRT) for 13 clinically confirmed T1 esophageal cancer patients. Methods: Between June 2000 and February 2004, patients with T1 esophageal cancer (tumor invading lamina propria or submucosa) received cCRT (50.4 Gy; CDDP: 75 mg/m2, day 1, bolus; 5-FU: 1000 mg/m2, days 1 to 4, continuous) (n = 13, T1 group). This treatment regimen was compared with the following 2 other groups treated during the same period: one was treated with radiation therapy alone for T1 disease (n = 5, RT-alone group); and the other group of patients consisted of those with T2 disease (tumor invading muscularis propria) who received the same cCRT regimen as the first T1 group (n = 9, T2 group). Results: The overall survival rates at 1 and 3 years were in the T1 group, 75% and 75%; in the T2 group, 75% and 45% (P =0.2890); and in the RT-alone group, 60% and 40% (P = 0.2978). No treatment-related mortalities occurred in the T1 and RT-alone groups, but one patient in the T2 group died of radiation-induced pneumonitis. Conclusions: Although this study was not randomized, the results showed that cCRT is a safe and effective method for treating patients with superficial esophageal cancer.

Background: Hepatocellular carcinoma with inferior vena cava invasion is a rare but fatal condition of disease progression. The aim of this study was to analyze the results of treatment for hepatocellular carcinoma with inferior vena cava invasion by three-dimensional conformal radiation therapy. Methods: From 1990 to 2006, 18 histopathologically confirmed hepatocellular carcinoma patients with inferior vena cava invasion who were unsuitable for surgery were treated by three-dimensional conformal radiation therapy at our hospital with two to four static or dynamic conformal arc fields. Results: A median total tumor dose of 50 Gy (range 30‐60 Gy) was delivered. The progression-free rate was 91.6% among the patients in whom follow-up computed tomography was obtained. Actuarial survival at 1 year was 33.3%, and the median survival period was 5.6 months. Conclusions: Three-dimensional conformal radiation therapy might offer a chance of long survival for a part of the hepatocellular carcinoma patients with inferior vena cava invasion, since a third of such patients survived more than a year. Additional treatments should be considered to prevent distant metastases and hepatic functional deterioration after threedimensional conformal radiation therapy.

Background To determine the usefulness of dose volume histogram (DVH) factors for predicting the occurrence of radiation pneumonitis (RP) after application of stereotactic radiation therapy (SRT) for lung tumors, DVH factors were measured before irradiation. Methods From May 2004 to April 2006, 25 patients were treated with SRT at the University of Tokyo Hospital. Eighteen patients had primary lung cancer and seven had metastatic lung cancer. SRT was given in 6–7 fields with an isocenter dose of 48 Gy in four fractions over 5–8 days by linear accelerator. Results Seven of the 25 patients suffered from RP of symptomatic grade 2–5 according to the NCI-CTC version 3.0. The overall incidence rate of RP grade2 or more was 29% at 18 months after completing SRT and three patients died from RP. RP occurred at significantly increased frequencies in patients with higher conformity index (CI) (p = 0.0394). Mean lung dose (MLD) showed a significant correlation with V5–V20 (irradiated lung volume) (p < 0.001) but showed no correlation with CI. RP did not statistically correlate with MLD. MLD had the strongest correlation with V5. Conclusion Even in SRT, when large volumes of lung parenchyma are irradiated to such high doses as the minimum dose within planning target volume, the incidence of lung toxicity can become high.

Objective To evaluate the therapeutic effects of radiotherapy on spinal bone metastases from hepatocellular carcinoma (HCC). Methods A retrospective review was conducted on 24 ambulatory patients with spinal bone metastases from HCC treated by radiotherapy from 1995 to 2004. Ambulatory rate and local progression-free rate after radiotherapy were analyzed. Eight (33%) of 24 patients had radiographic spinal cord compression from the spinal bone metastases before the treatment. Two (8.3%) of the 24 patients had some spinal deficits before the treatment. Biological equivalent dose (BED) with alpha/beta ratios of 10 ranged from 39 to 50.7 Gy (median 44.8 Gy). Results The median observation period was 5.1 months ranging from 0.9 to 36.0 months. Among the 24 patients, five (21%) underwent salvage therapies, while of the remaining 19 patients four (21%) became nonambulatory by the last follow-up. The ambulatory rates at 3 months and 6 months were 85 and 63%, respectively. The local progression-free rates at 3 months and 6 months were 53 and 47%, respectively. Conclusions Radiotherapy with a BED of 39-50.7 Gy (median 44.8 Gy) is not sufficiently effective for the patients with spinal bone metastases from HCC to prevent paralysis. Dose escalation with a highly precise radiation technique will need to be evaluated.

Background: Radiofrequency ablation (RFA) is an alternative to percutaneous ethanol injection therapy (PEIT) for single non-surgical hepatocellular carcinoma. However, the risk of seeding along the needle track has been reported. Methods: Seven patients presenting with neoplastic seeding after RFA or PEIT were treated with external beam radiotherapy using conventional fractionation. All patients underwent irradiation with a total dose in the range of 44–61 Gy (median and mode value: 50 Gy). Results: An objective response to treatment was achieved in six of seven patients (86%). A complete response was obtained in two patients (29%). The median survival time was 14.7 months and the actuarial 1- and 2-year survivals were 67% and 50%, respectively. Conclusions: The response to treatment was relatively good without serious complications. Seeding from hepatocellular carcinoma is sensitive to external beam radiotherapy. It is useful in the treatment of these patients with 50 Gy in 25 fractions.

Taste loss is a major cause of morbidity in patients undergoing head-and-neck irradiation. The relationship between the time course and the degree of taste disorder was studied in both acute and late phases.Taste ability was measured by the taste threshold for the four basic tastes using a filter paper disc method in patients before, during, and after radiotherapy. The subjects were divided into two groups. In Group A, the radiation fields included most of the tongue (n = 100), and in Group B the radiation fields did not include the tip of the tongue (n = 18).In Group A, there was a significant impairment of the threshold of all four basic tastes at 3 weeks after starting radiotherapy (RT), and this impairment remained at 8 weeks (p0.05). This was not seen in Group B. In Group A, there was no significant difference in the patterns of taste sensitivity change between the high-dose (20 Gy) and low-dose (or =20 Gy) groups. In the late phase, recovery of taste loss was seen in both groups since 4 months after completing RT.Unless the anterior part of the tongue was irradiated, taste loss was not observed during RT. When the anterior part of the tongue was irradiated, a difference by radiation dose was not observed in the taste loss pattern. Additionally, radiation-induced taste dysfunction appears to be a temporal effect.

We describe the clinical presentation, evaluation, management and outcome of patients experiencing small bowel perforation following radiation therapy for cervical cancer.A database consisting of 95 Japanese women with stage 0-4 A cervix cancer treated between 1991 and 2004 contained seven patients (7.4%) with small bowel perforation.The median age at the time of perforation was 72.5 years (range 62-78). The median time from completion of radiotherapy to perforation was 6 months (range 2-58). Surgery (one small bowel resection and anastomosis with diversion; six small bowel resection and anastomosis) was performed immediately in all seven patients. One of seven patients died of small bowel perforation (i.e. mortality rate was 14%). Bowel adhesion was detected during the operation in only three cases (43%). Signs of peritonitis were absent in six cases (86%). Severe abdominal pain was seen in all seven patients. The perforation site was ileum in all seven cases. In all patients, pathological changes were compatible with postirradiation injury of the gastrointestinal tract.The presenting complaints of patients with bowel perforation following radiotherapy vary, and signs of peritonitis may be absent. Emergency physicians must be alert for these complications in patients who have been treated with radiotherapy.

The objective of the current study was to investigate the effects and the morbidities of single-fraction stereotactic radiation therapy (SRT) for lung tumors.A Microtron device was modified to deliver stereotactic irradiation under respiratory gating. Between August 1998 and December 2004, 59 malignant lung tumors (11 primary tumors, 48 metastases) that measured40 mm in greatest dimension were treated by single-fraction SRT. Nine tumors received a minimal dose of30 grays (Gy), and 50 tumors received a minimal dose ofor = 30 Gy. The macroscopic target volume ranged from 1 cc to 19 cc (mean, 5 cc).The 1-year and 2-year local progression-free rates (LPFRs) were 93% and 78%, respectively. The overall survival rate was 76.5% at 1 year and 41% at 2 years. Local regrowth of the irradiated tumor was a direct cause of death in two patients. Only the minimal radiation dose to the reference target volume tended to have an influence on the LPFR (P = 0.068). The 2-year LPFRs for patients who received irradiation doses ofor = 30 Gy and30 Gy were 83% and 52%, respectively. With regard to morbidities, Grade 3 respiratory symptoms (according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme) were noted in one patient.The results from the current study suggested that single-fraction SRT was tolerable and was capable of attaining excellent local control in patients who had malignant lung tumors that measured4 cm in greatest dimension.

To evaluate the treatment outcome of radiotherapy combined with cis-diammine-glycolatoplatinum (nedaplatin) plus 5-fluorouracil (5-FU) for esophageal cancer. From January 2000 to December 2004, a total of 12 esophageal cancer patients with locally advanced and metastatic esophageal cancer (stages II-IVB) were treated with radiation therapy (50.4 Gy) combined with nedaplatin (80 mg/m(2), bolus infusion) and 5-FU (800 mg/m(2)/24 h, continuous infusion for 4 days) (NDP group). We compared the data with those of patients during the same period receiving a different chemotherapy regimen consisting of cisplatin (75 mg/m(2), bolus infusion) and 5-FU (1000 mg/m(2)/24 h, continuous infusion for 4 days) (n = 29, CDDP group) combined with the same radiation therapy. The median survival period was 11.5 months in the NDP group and 13.1 months in the CDDP group. The overall survival rates at 1-, 2-, and 3-years were 40%, 13%, and 13% in the NDP group and 56%, 42%, and 8% in the CDDP group (P = 0.2472), respectively. Grade III and IV leukocytopenia was observed in six (50%) and none of the patients in the NDP group and 14 (48%) and seven (24%) in the CDDP group, respectively. Grade III thrombocytopenia was observed in three (25%) in the NDP group and four (14%) in the CDDP group. Radiation combined with nedaplatin and 5-FU is a safe and effective method for treating esophageal cancer. We recommend that NDP should be used rather than dose-reduction of CDDP combined with 5-FU in patients with impaired renal function as indicated by low creatinine clearance value (40-60 mL/min).

The clinical experiences of 12 patients with non-hepatic abdominal tumors who underwent stereotactic hypofractionated radiotherapy are presented.Ten lesions were metastatic, one was a primary pancreatic cancer, and the remaining one was irradiated postoperatively for a positive margin of extrahepatic bile duct cancer. In one patient, single fractional stereotactic radiotherapy was employed, while the remaining 11 patients were treated with 3 fractions. Gross tumor volume of the 10 ranged from 2 cc to 32 cc (mean: 11 cc), and the minimal dose enclosing 95% of the planning target volume (D95) was between 28.6 Gy and 35 Gy. The minimal number of portals was 6. In 8 patients, radiotherapy was performed under respiratory gating. Mean follow-up time was 10 months (5-51 months).Local regrowth was seen in 9 months in only 1 of the 12 tumors, and the patient died of the disease. Four patients died because of tumor growth in other sites. The remaining 7 patients are alive without disease. As for morbidity, NCI-CTC grade 3 gastritis was seen in one patient, grade 2 gastritis in 2 patients, and grade 2 duodenitis in one patient. These patients all improved with non-surgical therapy.Stereotactic hypofractionated radiotherapy is effective for the treatment of selected non-hepatic abdominal tumors. However, the optimal radiation dose for tumor control and the tolerance dose of the gastrointestinal tract in hypofractionated irradiation must be studied further.

Purpose: 131I radionuclide therapy is widely performed in a thyroid cancer treatment, but there has been almost no evaluation of the dose distribution. The aim of this work is to develop the calculation system using the data of SPECT‐CT and to examine the effects of their image resolutions on the dose distribution. Methods: We designed and constructed an acrylic phantom for measurement. A radioactive iodine capsule and glass dosimeters can be set in the layer structure of the phantom. We put iodine capsules (37MBq, 111MBq, 185MBq) in the middle of the phantom and acquired SPECT‐CT (Infinia Hawkeye4 (GE))images. Both the CT value data (image resolution: 1.1 mm) and the intensity map data of SPECT(image resolution: 4.4 mm) were independently used for the estimation of the cumulative dose distribution generated from the radioactive iodine in the phantom. We adopted Monte Carlo program PHITS2.0 as the simulation of the dose calculation. The absolute dose was measured by glass dosimeters.Results: The measurement result by glass dosimeters was very similar to the Monte Carlo simulation result, in which the difference was about 0.3 %. We obtained the dose distributions reconstructed by the radioactive iodine distribution using CT value data and SPECT data, respectively. The iodine distribution from CT could be finer than that of SPECT data because of its higher image resolution. As a result, the difference was found to be factor two in the middle of the iodine distribution. On the other hand, both of the dose distribution was almost same above 2.2 cm distance from the center. Conclusions: We can reconstruct the 131I dose distribution using SPECT‐CT data. For more accurate calculation of the dose distribution, it would be crucial to increase the resolution of SPECT data.