Masatsugu Takahashi

Bevacizumab Treatment for Symptomatic Radiation Necrosis Diagnosed by Amino Acid PET

Bevacizumab is effective in treating radiation necrosis; however, radiation necrosis was not definitively diagnosed in most previous reports. Here we used amino acid positron emission tomography to diagnose radiation necrosis for the application of bevacizumab in treating progressive radiation necrosis. Lesion/normal tissue ratios of <2.5 on (18)fluoride-labeled boronophenylalanine-positron emission tomography were defined as an indication of effective bevacizumab treatment. Thirteen patients were treated with bevacizumab at a dose of 5 mg/kg every 2 weeks. Two patients were excluded because of adverse events. The median reduction rate in perilesional edema was 65.5%. Karnofsky performance status improved in six patients after bevacizumab treatment. Lesion/normal tissue ratios on (18)fluoride-labeled boronophenylalanine-positron emission tomography (P = 0.0084) and improvement in Karnofsky performance status after bevacizumab treatment (P = 0.0228) were significantly associated with reduced rates of perilesional edema. Thus, (18)fluoride-labeled boronophenylalanine-positron emission tomography could be useful for diagnosing radiation necrosis and predicting the efficacy of bevacizumab in progressive radiation necrosis.

Stereotactic radiosurgery (SRS) for multiple metastatic brain tumors : effects of the number of target tumors on exposure dose in normal brain tissues

AbstractBackground. This study was carried out to clarify the practical limit of the number of stereotactic radiosurgery (SRS)-targeted tumors based on the irradiation dose of normal brain tissues. Methods. Twenty-five patients with multiple brain metastases who received SRS from October 1998 to May 2002 were enrolled in the study. In each patient, the treatment options were thoroughly studied before deciding upon a course of treatment. The number of irradiated targets was increased one by one until all of the targets were included in a treatment plan. Given a surface dose of 25 Gy, we calculated the dose volume histogram (DVH) for the entire brain in each treatment plan and compared it with those of other treatment plans. Ultimately, only 5 of the 25 patients received irradiation for all of their tumors; the others received selective irradiation targeting only those tumors that were causing symptoms. Results. When the number of targets increased, the DVH curve shifted to the right. The volume of the brain irradiated at a dose of 5 Gy or higher was 25.7% or less for 4 or fewer targets, 45.7% for 5–6 targets, 81.0% for 7–8 targets and 100% for 9–11 targets. When the number of the targets exceeded 8, more than 50% of the entire brain was irradiated at levels of at least 8.7 Gy. The dose distribution became very complex as the number of targets increased. Although the survival time of the group in which tumors were selectively targeted was longer than that in the group in which all tumors were irradiated, the difference between the two groups was not statistically significant (P = 0.2537). Conclusion. In SRS for multiple brain metastases, risks of both acute and late sequelae may increase because the exposure dose to normal brain tissues increases with increased numbers of target tumors. Dose distribution becomes more complex according to the increase in the number of targets. Based on our DVH curves, we conclude that the exposure dose to normal brain tissues is acceptable when the number of targets is less than 7. Importantly, our study also reveals that it may not be necessary or desirable to irradiate all metastatic tumors.

Sivelestat sodium hydrate reduces radiation-induced lung injury in mice by inhibiting neutrophil elastase

The aim of this study was to investigate whether sivelestat, a neutrophil elastase (NE) inhibitor, mitigates radiation-induced lung injury in mice. C57BL/6J mice were administered a dose of 20 Gy to the bilateral whole lungs. Sivelestat was administered immediately before and 1 h after irradiation in group RE2, and immediately before and 1, 3 and 6 h after irradiation in group RE4. Group R received irradiation without sivelestat injection. Mice that did not receive sivelestat injection or irradiation were used as controls. NE activity was measured 24 and 48 h after irradiation, and the mice were sacrificed 24 h, 48 h and 15 weeks after irradiation for histopathological examination. In groups RE2 and RE4, NE activity was significantly suppressed until 48 h after irradiation compared to group R. The degree of lung damage in each group was scored during histopathological examination. Results showed that the scores of groups RE2 and RE4 were significantly lower compared to those of group R 15 weeks after irradiation. In conclusion, sivelestat reduced radiation‑induced lung injury in the mice by suppressing NE activity and excessive inflammatory reactions.