B. Miller

OBJECTIVE: Glucocorticoid analogues are often administered to patients with intracranial space-occupying lesions. Clinical response can be dramatic, but the neurophysiological response is not well documented. This study sought to investigate the blood-lesion barrier, blood-brain barrier, and cerebral perfusion characteristics of patients who have undergone such therapy using magnetic resonance imaging. METHODS: Seventeen patients with intracranial mass-enhancing lesions underwent magnetic resonance imaging before and after 3 days of high-dose dexamethasone therapy. Assessments of blood-lesion barrier and blood-brain barrier integrity were based on a dynamic T1-weighted exogenous contrast technique that yielded the normalized maximal change in contrast uptake (T1-uptake). Perfusion was assessed using a dynamic T2*-weighted exogenous contrast technique to yield relative regional cerebral blood volume and first-moment mean transit time. Comparisons were made in T1-uptake, regional cerebral blood volume, and first-moment mean transit time of both enhancing lesion and contralateral normal-appearing white matter (CNAWM) obtained before and after dexamethasone. RESULTS: Significant reduction in T1-uptake was observed (19% decrease, P < 0.005) within enhancing pathological tissue, whereas no significant alteration was detected in CNAWM. Regional cerebral blood volume was significantly reduced in both enhancing tissue (28% decrease, P < 0.005) and in CNAWM (20% decrease, P < 0.001). Bolus first-moment mean transit time significantly increased (2.0 s prolongation, P < 0.05) in CNAWM, whereas there was no significant change (1.4 s prolongation, P > 0.05) within enhancing tissue. CONCLUSION: Glucocorticoid-analogue therapy not only affects the permeability of the blood-lesion barrier and lesion blood volume but also affects blood flow within normal-appearing contralateral parenchyma. There is a need for controls in steroid therapy in magnetic resonance imaging studies, which involve assessments of cerebrovascular function.

Power systems often depend upon reservoir operations to generate hydropower, as well as to support thermal (nuclear and fossil) power generation. Thermal power plants frequently utilize reservoirs/rivers to provide condenser cooling water, dissipate thermal waste discharges, and/or supply safety intake water for emergency cooling systems at nuclear plants. Support of power production, however, must usually be balanced against other reservoir multiple uses such as flood control, navigation, recreation, water supplies, and environmental management.

e20019 Background: The anti-CTLA4 antibody, ipi, improves survival in metastatic melanoma. Combined radiotherapy (RT) and ipi may increase immune response to improve outcomes but also increase toxicity. This study reports the outcomes, including incidence of radionecrosis (RN), in patients (pt) with MBM treated with ipi and brain radiosurgery (SRS) and whole brain treatment (WBRT). Methods: Pt with MBM treated with WBRT or SRS and ipi at the Princess Margaret from 2008-2014 were reviewed to evaluate clinical characteristics, time between RT and ipi treatment, toxicity, response and survival. Results: We identified 54 pts treated with ipi and RT (SRS and/or WBRT), 34 who were evaluable (20 were excluded due to lack of follow up imaging), (see table). Median follow up was 7.4 months (m); OS 6.4m, PFS 2.7m. No RN was seen with WBRT alone, but RN occurred in 11/27 (41%) pt who received SRS: 7 received RT within 4m of ipi (SRS = 4, SRS+WBRT = 3) and 4 received RT outside of this window (SRS = 2, SRS+WBRT= 2). Larger tumor volume and V12Gy was associated with a higher rate of RN. Symptomatic RN was treated with steroids in 6 pt. Only 1 of 6 pt needed surgical excision, which showed necrosis, inflammatory T cells, macrophages, and treated melanoma. Intracranial MBM progression during ipi occurred in 7 pt: 6 discontinued ipi after 1-3 cycles and 1 continued to complete all 4 cycles ipi. Eventual MBM response was seen in the pt who completed ipi and 1 pt who received 3 cycles. Conclusions: When brain RT is combined with ipi, RN occurred in 41% of pts treated with SRS (± WBRT) and ipi but 0% after WBRT and ipi. Symptomatic RN generally responded to steroids. In 1 case requiring surgery, pathology demonstrated an increased immunological effect. MBM progression during ipi did not prohibit later cranial response. Characteristic Number Age Median (range) 53 (24-82) Sex Male 22 Female 12 Ipilimumab infusions Median (range) 4 (1-4) Radiotherapy treatment SRS 12 SRS + WBRT 15 WBRT 7 Median SRS dose (range) 21(15-24) Median no. fractions 2(1-4) LDH Median (range) 242 (155-1148)