Apalutamide for non-metastatic castration-resistant prostate cancer (nmCRPC): real world data of a multicenter study.

PURPOSE: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Nevertheless real-world data are limited. The aim of this multicenter study was to generate real-world data from nmCRPC patients treated with ADT plus apalutamide. METHODS: In this observational cohort based investigator initiated trial data of nmCRPC patients receiving apalutamide plus ADT were collected focusing on patient demographic data, prostate-specific antigen (PSA) declines, safety profile including dose modification/discontinuation as well as subsequent therapy and metastasis-free survival (MFS). RESULTS: Data from a total of 31 nmCRPC patients were documented. Compared to the Phase III study Spartan real-world patients are older, showed a higher ECOG-PS and more aggressive tumors. In the cohort PSA decreased about 98.1%, 74% of patients showed a PSA decrease over 90% and 54.8% reached a PSA-level < 0.2ng/ml. Apalutamide was well tolerated in real world patients: adverse events occurred in 67.7% but were in the majority mild (≥ grade 3: 6.5%). Dose reduction was necessary in 38.7% and 32.2% discontinued apalutamide treatment. MFS was 43 months and majority of patients were subsequently treated with abiraterone. CONCLUSION: In real world more comorbid nmCRPC patients with a higher ECOG-PS and more aggressive tumors are treated with apalutamide plus ADT. Nevertheless efficacy results as well as side effects are similar in real-world compared to Spartan trial showing also a rapid, durable and deep PSA response with a median MFS of 43 months.

Influence of preparation design and ceramic thicknesses on fracture resistance and failure modes of premolar partial coverage restorations.

STATEMENT OF PROBLEM: Preparation designs and ceramic thicknesses are key factors for the long-term success of minimally invasive premolar partial coverage restorations. However, only limited information is presently available on this topic. PURPOSE: The purpose of this in vitro study was to evaluate the fracture resistance and failure modes of ceramic premolar partial coverage restorations with different preparation designs and ceramic thicknesses. MATERIAL AND METHODS: Caries-free human premolars (n=144) were divided into 9 groups. Palatal onlay preparation comprised reduction of the palatal cusp by 2 mm (Palatal Onlay Standard), 1 mm (Palatal-Onlay-Thin), or 0.5 mm (Palatal Onlay Ultrathin). Complete-coverage onlay preparation additionally included the buccal cusp (Occlusal Onlay Standard; Occlusal Onlay Thin; Occlusal Onlay Ultrathin). Labial surface preparations with chamfer reductions of 0.8 mm (Complete-Veneer-Standard), 0.6 mm (Complete-Veneer-Thin), and 0.4 mm (Complete Veneer Ultrathin) were implemented for complete veneer restorations. Restorations were fabricated from a pressable lithium disilicate ceramic (IPS-e.max-Press) and cemented adhesively (Syntac-Classic/Variolink-II). All specimens were subjected to cyclic mechanical loading (F=49 N, 1.2 million cycles) and simultaneous thermocycling (5°C to 55°C) in a mouth-motion simulator. After fatigue, restorations were exposed to single-load-to-failure. Two-way ANOVA was used to identify statistical differences. Pair-wise differences were calculated and P-values were adjusted by the Tukey-Kramer method (α=.05). RESULTS: All specimens survived fatigue. Mean (SD) load to failure values (N) were as follows: 837 (320/Palatal-Onlay-Standard), 1055 (369/Palatal-Onlay-Thin), 1192 (342/Palatal-Onlay-Ultrathin), 963 (405/Occlusal-Onlay-Standard), 1108 (340/Occlusal-Onlay-Thin), 997 (331/Occlusal-Onlay-Ultrathin), 1361 (333/Complete-Veneer-Standard), 1087 (251/Complete-Veneer-Thin), 883 (311/Complete-Veneer-Ultrathin). Palatal-onlay restorations revealed a significantly higher fracture resistance with ultrathin thicknesses than with standard thicknesses (P=.015). Onlay restorations were not affected by thickness variations. Fracture loads of standard complete veneers were significantly higher than thin (P=.03) and ultrathin (P<.001) restorations. CONCLUSIONS: In this in vitro study, the reduction of preparation depth to 1.00 and 0.5 mm did not impair fracture resistance of pressable lithium-disilicate ceramic onlay restorations but resulted in lower failure loads in complete veneer restorations on premolars.

Monolithic and bi-layer CAD/CAM lithium-disilicate versus metal-ceramic fixed dental prostheses: comparison of fracture loads and failure modes after fatigue.

OBJECTIVES: The authors analyzed the effect of fatigue on the survival rate and fracture load of monolithic and bi-layer CAD/CAM lithium-disilicate posterior three-unit fixed dental prostheses (FDPs) in comparison to the metal-ceramic gold standard. MATERIALS AND METHODS: The authors divided 96 human premolars and molars into three equal groups. Lithium-disilicate ceramic (IPS-e.max-CAD) was milled with the CEREC-3-system in full-anatomic FDP dimensions (monolithic: M-LiCAD) or as framework (Bi-layer: BL-LiCAD) with subsequent hand-layer veneering. Metal-ceramic FDPs (MC) served as control. Single-load-to-failure tests were performed before and after mouth-motion fatigue. RESULTS: No fracture failures occurred during fatigue. Median fracture loads in [N], before and after fatigue were, respectively, as follows: M-LiCAD, 1,298/1,900; BL-LiCAD, 817/699; MC, 1,966/1,818. M-LiCAD and MC FPDs revealed comparable fracture loads and were both significantly higher than BL-LiCAD. M-LiCAD and BL-LiCAD both failed from core/veneer bulk fracture within the connector area. MC failures were limited to ceramic veneer fractures exposing the metal core. Fatigue had no significant effect on any group. CONCLUSIONS: Posterior monolithic CAD/CAM fabricated lithium-disilicate FPDs were shown to be fracture resistant with failure load results comparable to the metal-ceramic gold standard. Clinical investigations are needed to confirm these promising laboratory results. CLINICAL RELEVANCE: Monolithic CAD/CAM fabricated lithium-disilicate FDPs appeared to be a reliable treatment alternative for the posterior load-bearing area, whereas FDPs in bi-layer configuration were susceptible to low load fracture failure.

All-ceramic systems: laboratory and clinical performance.

Several all-ceramic systems have been developed in dentistry to meet the increased expectations of patients and dentists for highly aesthetic, biocompatible, and long-lasting restorations. However, early bulk fractures or chippings have led the research community to investigate the mechanical performance of the all-ceramic systems. This overview explores the current knowledge of monolithic and bilayer dental all-ceramic systems, addressing composition and processing mechanisms, laboratory and clinical performance, and possible future trends for all-ceramic materials.