In this paper we analyze the Multi-Level Cell (MLC) capability in Phase-Change Memory 4kb arrays based on Ge-rich GeSbTe alloys featuring high temperature data retention. Two Ge-rich alloys with a different amount of Ge are investigated and their MLC performances are compared with standard $\mathbf{Ge}_2 \mathbf{Sb}_2 \mathbf{Te}_5$ . Both Ge-rich materials feature a comparable data retention performance at 250°C in 1bit/cell mode, making them suitable for embedded automotive applications. Single pulse and Program-and-Verify MLC approaches are investigated to achieve 2 bits/cell. We compare the final distributions of the cell resistance levels and their evolution (drift) in time and in temperature. Finally, we show how the engineering of both materials stoichiometry and MLC programming strategy enable four distinguishable resistance levels even after one-hour bake at 150°C. These results prove MLC capability in Ge-rich GeSbTe PCM arrays.
Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes are improved by concomitant androgen-deprivation therapy (ADT) with radiation therapy, but not by concomitant ADT with surgery. Luteinizing hormone-releasing hormone agonist (LHRHa; leuprolide acetate) does not reduce serum androgens as effectively as abiraterone acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testosterone (< 1 ng/dL) and improves survival in metastatic PCa. The possibility that greater androgen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the reassessment of neoadjuvant ADT with more robust androgen suppression.A neoadjuvant randomized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa (N = 58). For the first 12 weeks, patients were randomly assigned to LHRHa versus LHRHa plus AA. After a research prostate biopsy, all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy.The levels of intraprostatic androgens from 12-week prostate biopsies, including the primary end point (dihydrotestosterone/testosterone), were significantly lower (dehydroepiandrosterone, Δ(4)-androstene-3,17-dione, dihydrotestosterone, all P < .001; testosterone, P < .05) with LHRHa plus AA compared with LHRHa alone. Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease, with residual T3- or lymph node-positive disease in the majority.LHRHa plus AA treatment suppresses tissue androgens more effectively than LHRHa alone. Intensive intratumoral androgen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden.
Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival.After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group.The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer. (Funded by Janssen Research and Development; LATITUDE ClinicalTrials.gov number, NCT01715285 .).
