We evaluated the treatment outcome of stereotactic radiosurgery (SRS) alone, allowing for salvage with repeat SRS or fractionated radiotherapy, for managing patients with brain metastases from non-small cell lung cancer (NSCLC). From October 1998 through November 2008, 84 patients with NSCLC metastatic to the brain were treated with linac SRS. The marginal dose of SRS ranged from 12 to 20 Gy. Twenty-one patients underwent salvage radiotherapy and repeat SRS was used for 12. The 1- and 5-year overall survival rates were 38% and 11%, respectively, and the median survival time was 9 months. The 1- and 2-year local control rates were 77% and 52%, respectively, and the median time of local control was 9 months. The most common cause of death was active extracranial disease, and central nervous system (CNS) failure was determined in 16%. Chronic CNS toxicity of grade 4 was observed in 2 patients. Uni- and multivariate analyses revealed that factors significantly affecting overall survival were the presence of active extracranial disease (P < 0.0001 and P = 0.003, respectively), performance status (P = 0.001 and P = 0.009, respectively), and number of brain metastases (P = 0.0003 and P = 0.019, respectively). There were 15 long-term survivors, surviving more than 2 years. A large proportion (87%) had a single brain metastasis initially and few intracranial distant metastases afterwards (20%). SRS alone allowing for salvage radiotherapy was effective for managing brain metastases and avoiding CNS failure from NSCLC. In consideration of appropriate prognostic factors and the so-called oligometastases situation for patient selection, the use of upfront whole brain radiotherapy might improve outcome.

Enhanced cell lethality, also known as hyper-radiosensitivity, has been reported at low doses of radiation (≤0.5 Gy) in various cell lines, and is expected to be an effective cancer therapy. We conducted this study to examine the impact of time interval and dose rate of low-dose fractionated exposures with a short time interval. We evaluated the cell-survival rates of V79 and A549 cells using clonogenic assays. We performed fractionated exposures in unit doses of 0.25, 0.5, 1.0 and 2.0 Gy. We exposed the cells to 2 Gy of X-rays (i) at dose-rates of 1.0, 1.5 and 2.0 Gy/min at 1-min intervals and (ii) at a dose-rate of 2.0 Gy/min at 10-s, 1-min and 3-min intervals by fractionated exposures. Apoptosis and cell cycle analyses were also evaluated in the fractionated exposures (unit dose 0.25 Gy) and compared with single exposures by using flow cytometry. Both cell-type survival rates with fractionated exposures (unit dose 0.25 Gy) with short time intervals were markedly lower than those for single exposures delivering the same dose. When the dose rates were lower, the cytotoxic effect decreased compared with exposure to a dose-rate of 2.0 Gy/min. On the other hand, levels of apoptosis and cell cycle distribution were not significantly different between low-dose fractionated exposures and single exposures in either cell line. These results indicate that a stronger cytotoxic effect was induced with low-dose fractionated exposures with a short time interval for a given dose due to the hyper-radiosensitivity phenomenon, suggesting that dose rates are important for effective low-dose fractionated exposures.

Radionuclide concentrations in environmental samples such as surface soils, plants and water were evaluated by high purity germanium detector measurements. The contribution rate of short half-life radionuclides such as 132I to the exposure dose to residents was discussed from the measured values. The highest values of the 131I/137Cs activity ratio ranged from 49 to 70 in the environmental samples collected at Iwaki City which is located to the south of the F1-NPS. On the other hand, the 132I/131I activity ratio in the same environmental samples had the lowest values, ranging from 0.01 to 0.02. By assuming that the 132I/131I activity ratio in the atmosphere was equal to the ratio in the environmental samples, the percent contribution to the thyroid equivalent dose by 132I was estimated to be less than 2%. Moreover, the contribution to the thyroid exposure by 132I might be negligible if 132I contamination was restricted to Iwaki City.

Exposure to high-doses of ionizing radiation (IR) leads to development of a strong acute radiation syndrome (ARS) in mammals. ARS manifests after a latency period and it is important to develop fast prognostic biomarkers for its early detection and assessment. Analysis of chromosomal aberrations in peripheral blood lymphocytes is the gold standard of biological dosimetry, but it fails after high doses of IR. Therefore, it is important to establish novel biomarkers of exposure that are fast and reliable also in the high dose range. Here, we investigated the applicability of miRNA levels in mouse serum. We found significantly increased levels of miR-375-3p following whole body exposure to 7 Gy of X-rays. In addition, we analyzed their levels in various organs of control mice and found them to be especially abundant in the pancreas and the intestine. Following a dose of 7 Gy, extensive cell death occurred in these tissues and this correlated negatively with the levels of miR-375-3p in the organs. We conclude that high expressing tissues of miR-375-3p may secrete this miRNA in serum following exposure to 7 Gy. Therefore, elevated miR-375-3p in serum may be a predictor of tissue damage induced by exposure to a high radiation dose.

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