Comparison of outcome endpoints in intermediate- and high-risk prostate cancer after combined-modality radiotherapy.

PURPOSE: To compare a standard radio-oncological and a surgical biochemical failure definition after combined-modality radiation therapy (CRT) in men with intermediate- and high-risk prostate cancer. METHODS: 425 men were treated with external beam radiotherapy (59.4 Gy, 33 fractions) and 125J seed-brachytherapy (S-BT, 100 Gy). Biochemical recurrence (BR) was defined either as radio-oncologic (rBR), using a +2 ng/mL prostate-specific antigen (PSA) increase above a nadir value, or as surgical (sBR), using a 2-year posttreatment PSA of ≥0.2 ng/mL. Biochemical recurrence-free, metastasis-free, cancer-specific, and overall survival were calculated at 5 and 10 years using the Kaplan-Meier method. Standard validation tests were used to compare both thresholds. RESULTS: After a median of 7 years, overall recurrence rates were 10.4% and 31.5% for rBR and sBR definitions, respectively. Both failure definitions proved sensitive for the prediction of metastases and cancer-specific death, whereas the rBR definition was significantly more specific. The accuracies of a correct prediction of metastases and death of prostate cancer were 73.1% vs. 96.2% and 72.2% vs. 92.9% for sBR vs. rBR, respectively. The inferior validity results of the sBR definition were attributable to a PSA-bounce phenomenon occurring in 56% of patients with sBR. Still, using the less suitable sBR definition, the results of CRT compared favorably to BRFS rates of surgical interventions. CONCLUSION: After CRT, the radio-oncological (aka Phoenix) failure definition is more reliable than a fixed surgical endpoint. Exclusively in high-risk patients, sBR offers a direct comparison across surgical and nonsurgical treatment options at 5 and 10 years.

Enhanced cortisol secretion in acute transient global amnesia.

INTRODUCTION: Stress-related transient inhibition of memory formation in the hippocampus has been hypothesized as one of the underlying pathomechanisms of transient global amnesia (TGA). TGA episodes, during which patients cannot encode and recall new information (anterograde amnesia affecting episodic long-term memory), are frequently preceded by a psychologically or physically stressful event. METHODS: We measured salivary cortisol during acute TGA in 14 patients, as well as cortisol day-profiles and the effect of experimental exposure to stress (using the socially evaluated cold pressor test) on cortisol levels during the subacute phase. We assessed psychiatric comorbidity as well as depression, trait anxiety and chronic stress. These findings were compared with data of 20 healthy controls. FINDINGS: Nine patients reported a precipitating stressor and all 14 developed typical hippocampal lesions on follow-up MRI. During TGA, salivary cortisol levels were more than 3-fold higher compared to time-matched day levels. While there was no difference in mean cortisol levels of the diurnal rhythm, we found a significant interaction between groups during experimental stress exposure (p = 0.049) with the TGA group revealing a higher cortisol increase. The TGA group reported higher levels of depressive symptomatology (CES-D) and higher scores of chronic stress (TICS) compared with the control group and there was a significant correlation between cortisol increase during TGA and the results of self-rating according to the CES-D (r = 0.615; p = 0.004), as well as to the STAI (r = 0.702; p = 0.001). CONCLUSION: Our findings of enhanced secretion of cortisol in acute TGA patients correlating with symptoms of depression and anxiety and a persisting hyperreactivity to experimental stress in the subacute phase support the hypothesis that stress might be significant for the pathogenesis of TGA.