[en] The very high temperature gas-cooled reactors (VHTGRs) are those concepts that have average coolant temperatures above 900 degrees C or operational fuel temperatures above 1250 degrees C. These concepts provide the potential for increased energy conversion efficiency and for high-temperature process heat application in addition to power generation and nuclear hydrogen generation. While all the High Temperature Gas Cooled Reactor (HTGR) concepts have sufficiently high temperatures to support process heat applications, such as desalination and cogeneration, the VHTGR's higher temperatures are suitable for particular applications such as thermochemical hydrogen production. However, the high temperature operation can be detrimental to safety following a loss-of-coolant accident (LOCA) initiated by pipe breaks caused by seismic or other events. Following the loss of coolant through the break and coolant depressurization, air from the containment will enter the core by molecular diffusion and ultimately by natural convection, leading to oxidation of the in-core graphite structures and fuel. The oxidation will release heat and accelerate the heatup of the reactor core. Thus, without any effective countermeasures, a pipe break may lead to significant fuel damage and fission product release. The Idaho National Engineering and Environmental Laboratory (INEEL) has investigated this event for the past three years for the HTGR. However, the computer codes used, and in fact none of the world's computer codes, have been sufficiently developed and validated to reliably predict this event. New code development, improvement of the existing codes, and experimental validation are imperative to narrow the uncertainty in the predictions of this type of accident. The objectives of this Korean/United States collaboration are to develop advanced computational methods for VHTGR safety analysis codes and to validate these computer codes

[en] The heat transfer boundary conditions used in the RELAP5-3D computer program have evolved over the years. Currently, RELAP5-3D has the following options for the heat transfer boundary conditions: (a) heat transfer correlation package option, (b) non-convective option (from radiation/conduction enclosure model or symmetry/insulated conditions), and (c) other options (setting the surface temperature to a volume fraction averaged fluid temperature of the boundary volume, obtaining the surface temperature from a control variable, obtaining the surface temperature from a time-dependent general table, obtaining the heat flux from a time-dependent general table, or obtaining heat transfer coefficients from either a time- or temperature-dependent general table). These options will be discussed, including the more recent ones

[en] Purpose: To report the results of a Phase II study of hyperfractionated craniospinal radiation therapy, with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs) and malignant ependymomas. Methods and Materials: Newly diagnosed PNET or malignant ependymomas were treated with hyperfractionated craniospinal radiation therapy. The primary tumor site was treated to a dose of 72 Gy, with 30 Gy given to the rest of the craniospinal axis. The fraction size was 1.0 Gy, given twice a day. Patients with poor risk factors also received adjuvant chemotherapy with CCNU, cisplatin, and vincristine. Patients had follow-up for survival, time to tumor progression, and patterns of relapse. Results: A total of 39 patients (21 males/18 females) were treated between March 12, 1990 and October 29, 1992. The median age was 16 years (range 3-59 years). Tumor types included 25 medulloblastomas, 5 pineoblastomas, 5 cerebral PNETs, 1 spinal cord PNET, and 3 malignant ependymomas. Twenty cases were staged as poor-risk and received adjuvant chemotherapy following radiation. Three-year progression-free survival (PFS) was 60% and 63% for poor-risk and good-risk patients, respectively. Overall 3-year survival for these groups was 70% and 79%, respectively. For the 25 patients with medulloblastoma, there were 16 good-risk and 9 poor-risk patients. Three-year PFSs were 63% and 56%, respectively. The 5-year survival for good-risk medulloblastoma was 69% with 43.7% of these patients having failures outside the primary site. Conclusions: Survival in patients with good-risk medulloblastoma was no better than that seen in previous studies with single-fraction radiation, and the rate of failure outside the primary site is excessive. Those with poor-risk features had comparable survival to that seen in patients with good risk factors, but these patients were treated with chemotherapy, and the role that hyperfractionated radiation played in their outcome is uncertain

[en] Purpose: To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors. Methods and Materials: Between 1983 and 1987, study patients received 1.7-1.8 Gy radiation once a day, Monday through Friday, to a total dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m²/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. Results: One-hundred thirty eight patients (median age, 43 years) were evaluable for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum (n 116) is 46%. For the astrocytoma (ASTRO) stratum (n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate (p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age (p < 0.001), Karnofsky performance score (p = 0.04), and extent of surgery (p = 0.04); limited-field irradiation was not significant (p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Grade ≥III leukopenia in 18%, and Grade ≥III thrombocytopeni in 9%. Conclusion: The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO patients can lead to substantial increases in survival compared to published survival data

[en] Background: Gadolinium (Gd)-containing MRI contrast agents (GdCA) are widely used in studies of brain tumors, and a number of reports suggest that under certain conditions, such as renal failure, Gd may be released from GdCA into patient's tissues. Whether this may happen in abnormal tissues in the absence of renal failure has not been studied. Purpose: To test the hypothesis that the local retention of GdCA resulting from brain tumor-associated alterations in the blood-brain barrier (BBB) may result in the deposition of Gd released from the GdCA, depending on stability. Material and Methods: In this retrospective study, 30 selected brain tumor biopsies from 28 patients (taken before and after an institutional switch from a less stable to an intermediate stable GdCA) were searched for Gd-containing deposits using scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS). Relevant histories and laboratory results were obtained through institutional electronic records. Associations between the presence of deposits and other variables were tested for statistical significance using the two-tailed Fisher's exact test. Results: Insoluble deposits containing Gd associated with phosphorus and calcium were found in seven biopsies from five patients. These deposits were found in patients with estimated GFRs above 53 ml/min, and were detected more often in those receiving GdCA before the switch from a less stable to an intermediate stable GdCA (P = 0.04), and may be more frequent in patients receiving more than one contrast-enhanced MR scan (P = 0.15). Conclusion: Gd-containing deposits are present in brain tumors following contrast-enhanced MR scans in patients without severe renal disease. Further studies are needed to assess the clinical importance of the deposits we observed and to determine whether they are also found in other conditions that alter the integrity of the BBB

[en] Purpose: Various measures of the rate of tumor cell proliferation have been found to predict survival in patients with intracerebral gliomas. We correlated the bromodeoxyuridine labeling index (BrdUrd LI) with the response to radiation therapy, survival, and known prognostic factors in a series of patients with glioblastoma multiforme (GM) to test its utility as a prognostic factor. Methods and Materials: The BrdUrd LI was determined in 200 newly diagnosed intracranial GMs. Age and sex were known for all patients. The response to radiation therapy was determined in 116 patients by comparing neuroimaging studies obtained before and after external beam radiation therapy. Survival was analyzed in 64 patients who were treated according to two consecutive prospective clinical protocols. Results: The median BrdUrd LI was 6.5% (mean, 7.2%; range, 1.1-25.4%). The BrdUrd LI did not correlate significantly with age, sex, radiation response, or survival. Age and Karnofsky performance score were independent prognostic factors in our cohort. Conclusion: The proliferative rate as measured by BrdUrd LI was not a prognostic factor in our GM cohort. The BrdUrd LI did not correlate significantly with known prognostic factors in GM. There was no significant relationship between the BrdUrd LI and radiation response

[en] Purpose: This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy. Methods and Materials: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment. Results: As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in the two arms seem to be due to early deaths in the BUdR arm, not related to toxicity of the treatment. Conclusions: Despite encouraging Phase 2 results with BUdR, it is unlikely that a survival benefit will be seen. A final study analysis will not be done for at least 3 more years

[en] Purpose: To determine if adjuvant interstitial hyperthermia (HT) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy. Methods and Materials: Adults with newly-diagnosed, focal, supratentorial glioblastoma ≤ 5 cm in diameter were registered postoperatively on a Phase II/III randomized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea. Those patients whose tumor was still implantable after teletherapy were randomized to brachytherapy boost (60 Gy at 0.40-0.60 Gy/h) ± HT for 30 min immediately before and after brachytherapy. Time to progression (TTP) and survival from date of diagnosis were estimated using the Kaplan-Meier method. Results: From 1990 to 1995, 112 eligible patients were entered in the trial. Patient ages ranged from 21-78 years (median, 54 years) and KPS ranged from 70-100 (median, 90). Most commonly due to tumor progression or patient refusal, 33 patients were never randomized. Of the patients, 39 were randomized to brachytherapy ('no heat') and 40 to brachytherapy + HT ('heat'). By intent to treat, TTP and survival were significantly longer for 'heat' than 'no heat' (p = 0.04 and p = 0.04). For the 33 'no heat' patients and 35 'heat' patients who underwent brachytherapy boost, TTP and survival were significantly longer for 'heat' than 'no heat' (p = 0.045 and p = 0.02, respectively; median survival 85 weeks vs. 76 weeks; 2-year survival 31% vs. 15%). A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with randomization to 'heat' (p = 0.008; hazard ratio 0.51). There were no Grade 5 toxicities, 2 Grade 4 toxicities (1 on each arm), and 7 Grade 3 toxicities (1 on 'no heat' and 6 on the 'heat' arm). Conclusion: Adjuvant interstitial brain HT, given before and after brachytherapy boost, after conventional radiotherapy significantly improves survival of patients with focal glioblastoma, with acceptable toxicity

[en] In mid-2010, the World Energy Council published a comprehensive report on shale gas. Given the slow pace of change and long lead-times typical to the energy sector, it is amazing to note how different the global outlook for shale gas is today compared to last year. A widely anticipated global gas market revolution has not happened outside of the United States. Moreover, a number of important issues which need to be addressed sooner rather than later have emerged and obscured the rising star of shale gas. One year on, the following key findings are emerging: - In general, the new estimates of shale gas resources are more conservative than those reported in 2010, mainly due to the differences in the methodology used by the data publishers. - Shale gas development can have a significant impact on the dynamics and prices on the natural gas market, and on gas-fired power generation. - Implications of increased use of shale gas will not be the same in all regions. In the short to medium term, however, no other region is likely to be able to emulate the success of shale gas in North America supported by its large and well-developed gas transport infra-structure and gas market structures. - Regulatory uncertainties slow down shale gas development in many countries. - Notwithstanding the environmental moratoriums in some countries, use of shale gas will continue to grow, keeping pressure on natural gas prices and the LNG market. - Development of shale gas in Europe can help diversify its gas supply sources moving away from the current heavy dependence on Russian gas. - Lower natural gas prices may lead to a significant shift toward the increasing use of gas in power generation and transport. - The policy discussion around the Energy- Water Nexus and Security and Sustainability is crucial for the future of shale gas

[en] Purpose: This study was designed to evaluate a combined modality treatment for malignant gliomas using radiation therapy with a radiosensitizer and an adjuvant chemotherapy regimen designed to modify resistance to BNCU. Methods and Materials: Patients were eligible if they were 15 years of age or older, and had newly diagnosed glioblastoma multiforme (GBM), or anaplastic glioma (AG). Treatment consisted of external beam radiotherapy given to a dose of 60 Gy using a single daily fraction Monday to Friday. Concurrent hydroxyurea at a dose of 300 mg/m² every 6 h every other day was given during radiation. Following radiotherapy, patients were then treated with BCNU and 6-Thioguanine (6TG). The 6-TG was given by mouth every 6 h for 12 doses prior to BCNU. Patients were initially treated with 60 mg/m²/dose of 6TG, with escalation to a maximum dose of 100 mg/m²/dose. The primary study end points were time to tumor progression and survival. Results: A total of 245 eligible patients were enrolled from 1/18/88 to 12/26/91. The histologic subtypes included 135 GBM, and 110 with AG (103 with anaplastic astrocytoma, 7 with high-grade mixed oligoastrocytoma). For the GBM group, the median time to tumor progression (TTP) and median survival were 33 (95% CI 26, 39) and 56 (95% CI 49, 69) weeks, respectively. For the AG group the median TTP was 282 weeks (95% lower confidence bound = 155 weeks). Median survival for this group has not been reached (95% lower confidence bound = 284 weeks) with a median follow-up for surviving patients of 298 weeks. A proportional hazards model was used to look at potential prognostic factors for survival, including initial Karnofsky Performance Scale (KPS), age, and extent of surgery, as well as dose of 6TG. Higher KPS, and lower age, predicted for longer survival (p < 0.01, < 0.001) in GBM patients; lower age was significant (p = 0.05) for AG cases. A higher (greater than 95 mg/m²) or lower dose of 6TG was not statistically significant in this model. Conclusions: This therapy was no more effective in patients with GBM than other reported series. In patients with malignant gliomas other than GBM, prolonged progression-free and overall survival is noted, without a median survival reached at the time of this report. In this subset of AG patients, survival is comparable to recent studies using halogenated prymidines during radiation and Procarbazine, CCNU, and Vincristine (PCV) as adjuvant chemotherapy