New Concerns for Neurocognitive Function during Deep Space Exposures to Chronic, Low Dose-Rate, Neutron Radiation.

As NASA prepares for a mission to Mars, concerns regarding the health risks associated with deep space radiation exposure have emerged. Until now, the impacts of such exposures have only been studied in animals after acute exposures, using dose rates ∼1.5×105 higher than those actually encountered in space. Using a new, low dose-rate neutron irradiation facility, we have uncovered that realistic, low dose-rate exposures produce serious neurocognitive complications associated with impaired neurotransmission. Chronic (6 month) low-dose (18 cGy) and dose rate (1 mGy/d) exposures of mice to a mixed field of neutrons and photons result in diminished hippocampal neuronal excitability and disrupted hippocampal and cortical long-term potentiation. Furthermore, mice displayed severe impairments in learning and memory, and the emergence of distress behaviors. Behavioral analyses showed an alarming increase in risk associated with these realistic simulations, revealing for the first time, some unexpected potential problems associated with deep space travel on all levels of neurological function.

Phase II trial evaluating the efficacy of sorafenib (BAY 43-9006) and correlating early fluorodeoxyglucose positron emission tomography-CT response to outcome in patients with recurrent and/or metastatic head and neck cancer.

BACKGROUND: The purpose of this study was to assess the efficacy and safety of sorafenib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) and to explore the predictive value of early metabolic responses. METHODS: Sorafenib was administered orally at 400 mg bid on a continuous basis. The primary endpoint was the response rate. Correlation of early (18)fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT response to time-to-event outcomes was a secondary objective. RESULTS: Twenty-three patients were included in this study. Grade 3 to 4 toxicities included fatigue (22%), hand-foot syndrome (9%), lymphopenia (17%), hyponatremia (39%), and hypophosphatemia (48%). One patient (5%) had a partial response (PR) and 12 patients (55%) had stable disease. Early metabolic response rate was 38%. Median progression-free survival (PFS) was 2.2 months in early metabolic nonresponders (13 of 21 patients) in comparison to 7.4 months in the 8 patients with class I early metabolic response (p = .006). CONCLUSION: Sorafenib showed a modest antitumor activity. Data suggest a possible role of (18)FDG PET metabolic response as an early predictor of a prolonged PFS.

Primary tumor standardized uptake value measured on fluorodeoxyglucose positron emission tomography is of prognostic value for survival in non-small cell lung cancer: update of a systematic review and meta-analysis by the European Lung Cancer Working Party for the International Association for the Study of Lung Cancer Staging Project.

INTRODUCTION: Few validated prognostic factors are available for survival in patients with lung cancer. [F]-fluoro-2-deoxy-d-glucose positron emission tomography has been shown to be of additional value to conventional imaging for staging lung cancer. The prognostic value of this lung tumor metabolic activity was studied in a first systematic review of studies published until 2006. METHODS: As further studies have appeared since 2006, this report has as objective to confirm and to estimate with less variability the prognostic value of primary tumor standardized uptake value (SUV) measured with [F]-fluoro-2-deoxy-d-glucose positron emission tomography on the basis of an updated search of eligible studies. RESULTS: Ten additional studies were eligible for the updated review and eight of them provided, in the publication, data allowing survival results aggregation. All together, 21 studies were analyzed. Comparing patients with low and high SUV, using preferentially the median SUV value of each study as threshold, we obtained a poor prognostic value for high SUV compared with low SUV with an overall combined hazard ratio of 2.08, significantly different from one with a 95% confidence interval ranging from 1.69 to 2.56. No interaction between older and newer studies was detectable (P = 0.60) as well as between studies having selected non metastatic patients or studies without selection criterion related to stage (P = 0.46). CONCLUSIONS: We confirmed the results of our previous review showing that SUV is potentially a very interesting factor for predicting patient outcome. We believe that a meta-analysis based on individual patient data would be of great value as allowing to assess the independent prognostic value, to take into account some factors responsible for heterogeneity between studies (SUV assessment method, disease stage, and histology), and to update survival data. We are planning to conduct such a meta-analysis on behalf of the International Association for the Study of Lung Cancer Staging Project.