Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.</p> <p>Methods/Design</p> <p>This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (¹²⁵I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with ¹²⁵I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during ¹²⁵I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.</p> <p>The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.</p> <p>Discussion</p> <p>To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.</p> <p>Trial registration</p> <p>UMIN000003992</p

Low temperature fabrication of (Y,Gd,Sm)-doped ceria electrolyte

A general procedure based on the oxalate coprecipitation route was developed to produce very sinterable ceria (CeO2) powder doped with Gd2O3, Sm2O3 or Y2O3. The method is simple, reliable and very reproducible. Without any milling step, powder of 20 mol% GdO1.5, SmO1.5 or YO1.5-CeO2 could be fired translucent dense (97% relative to theoretical) at 1300 °C (4 h) already, as pressed compacts. This compares to typical values of 95% relative density obtained after firing at 1500–1600 °C in the standard literature. Cast tapes from the intensively milled powders were fired equally dense at 1400 °C (2 h), among the best results yet reported for tape cast doped ceria. Owing to their high density, excellent ionic conductivity values were observed for the doped ceria electrolytes, on the order of 5–7 S m−1 at 750 °C in air

Fabrication and sintering of fine yttria-doped ceria powder

Yttria-doped ceria powder was prepared from oxalate precursors. The oxalate coprecipitation bath parameters were closely monitored and found to influence the sintering behavior of the subsequently obtained oxide powders strongly. The use of concentrated (Ce,Y) metal nitrate solutions and dilute neutralized oxalic acid for coprecipitation were identified as the most-important parameters. Following calcination at 700°C, compacts of such powders were sintered to high density (98%) at 1400°C (4 h). Ball milling of the powder further reduced the sintering temperature. Dry milling, for tape-casting applications of the powder in particular, was more effective than wet milling. Tape-cast membranes were fired at 1400°C (2 h), with resulting densities of 98%