Nakashi Sasano

Exceptionally high incidence of symptomatic grade 2-5 radiation pneumonitis after stereotactic radiation therapy for lung tumors.

BackgroundTo 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.MethodsFrom 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.ResultsSeven 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.ConclusionEven 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.

Radiotherapy for lymph node metastases in patients with hepatocellular carcinoma: Retrospective study

Aim:  This study was conducted to evaluate the effect of external radiation therapy on lymph node metastases from hepatocellular carcinoma (HCC).

Oral pilocarpine (5 mg t.i.d.) used for xerostomia causes adverse effects in Japanese

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, 5mg t.i.d. pilocarpine caused a high incidence of unacceptable adverse effects. A lower dose of pilocarpine needs to be considered.

Esophageal cancer: definitive chemoradiotherapy for elderly patients

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.

Small bowel perforation without tumor recurrence after radiotherapy for cervical carcinoma: Report of seven cases

Aim:  We describe the clinical presentation, evaluation, management and outcome of patients experiencing small bowel perforation following radiation therapy for cervical cancer.

Edaravone, a known free radical scavenger, enhances X-ray-induced apoptosis at low concentrations.

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.

Contrast media-assisted visualization of brain metastases by kilovoltage cone-beam CT

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

The experience of concurrent chemoradiation for Japanese patients with superficial esophageal squamous cell carcinoma: a retrospective study.

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.

Three-dimensional Conformal Radiotherapy for Hepatocellular Carcinoma with Inferior Vena Cava Invasion

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 three-dimensional conformal radiation therapy.

External beam radiotherapy to treat intra‐ and extra‐hepatic dissemination of hepatocellular carcinoma after radiofrequency thermal ablation

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.