Impact of multiple firings on fracture load of veneered zirconia restorations.

OBJECTIVES This investigation evaluated the impact of multiple firings during the veneering process of anterior all-ceramic restorations on the fracture load (FL) of zirconia crowns veneered with different ceramics (ZRT, ZRO, HFZ, STR). METHODS All-ceramic crowns with anatomically reduced zirconia frameworks were prepared using four different veneering ceramics (N = 192/n = 48 per veneering ceramic). The crowns were fired 2 and 10 times. Half of them were thermocycled (5000 cycles, 5 °C/55 °C, 20s). FL using Voss shear test was measured. Data was analyzed using ANOVA with partial eta squared and post-hoc Scheffé-test as well as t-test and Weibull analysis. RESULTS Regarding FL, greatest differences were among the number of firings (p<0.001, ηp2 = 0.369). FL was not influenced by the interaction of both number of firings and aging level (p = 0.231) and the interaction of number of firings and veneering ceramic (p = 0.222). Differences were found comparing FL values of ZRT and STR (p<0.001) and of HFZ and STR (p<0.001). No differences occurred among the veneering ceramics after 2 (p = 0.430) and after 10 firings (p = 0.057) in respect to initial FL. For all initially tested veneering ceramics, FL showed higher values after 10 firings (p≤0.001-0.014). When aged, ZRO, HFZ, and STR also provided higher FL values after 10 firings (p≤0.001). For ZRT, FL values differed between initial and aged testing after 2 firings (p = 0.001) with aged specimens providing higher FL values. After 10 firings, none of the veneering ceramics showed differences regarding FL values between initial and aged testing. Weibull modulus was higher for ZRT specimens after 10 firings when tested initially (m = 10.1) and for aged ZRT specimens after 2 firings (m = 11.1). Failures occurred either with chipping of the veneer or total fracture. SIGNIFICANCE Veneered zirconia restorations tested presented higher FL after 10 firings compared to 2 firings. Aging via thermocycling showed a positive effect on the FL

Impact of multiple firings on thermal properties and bond strength of veneered zirconia restorations.

OBJECTIVES This investigation evaluated the impact of multiple firings during the veneering process of all-ceramic restorations on the thermal properties and bond strength between veneering ceramics and zirconia. METHODS For the measurements of the coefficient of thermal expansion (CTE) prismatic specimens of four different veneering ceramics (ZRT/ZRO/HFZ/STR; N = 40/n = 10 per veneering ceramic) and rod-shaped zirconia specimens (N = 2) were produced. 2 specimens of each veneering ceramic were fired 2, 4, 6, 8, and 10 times simulating dentine-firing. Measurements were performed in a dilatometer and glass transition temperature (Tg) was determined graphically. To analyze bond strength (BS), crack initiation test specimens were prepared using the same veneering ceramics and zirconia (N = 600/n = 150 per veneering ceramic). 30 specimens of each veneering ceramic were fired 2, 4, 6, 8, and 10 times. Half of them were thermocycled (5000 cycles, 5 °C/55 °C, 20s). The crack initiation test was conducted in a universal testing machine. Data was analyzed using ANOVA with partial eta squared statistics and post-hoc Scheffé test as well as Pearson correlation test. RESULTS CTE was mostly affected by the choice of veneering ceramic (p < 0.001/ηp2 = 0.983). For the leucite-free ceramic, the CTE values were in same value range (p = 0.171) along the number of firings. Tg was not influenced by the number of firings. The highest effect on BS showed veneering ceramics (p < 0.001/ηp2 = 0.055) followed by the number of firings (p = 0.011/ηp2 = 0.023). The global difference in BS was lower for 10 firings compared to 2 firings (p = 0.048). Highest BS were measured for the leucite-free veneering ceramic (ZRT). Artificial aging by thermocycling showed no impact on BS (p = 0.755). Correlations were found for HFZ between the BS and the CTE (r = -0.651/p = 0.021). A correlation between CTE and Tg was observed (r = 0.303/p = 0.029). SIGNIFICANCE Thermal stability seemed to be more predictable for leucite-free veneering ceramics with superior BS. All BS results exceeded the minimum clinical requirements

The Efficacy of Lapatinib in Metastatic Breast Cancer with HER2 Non-Amplified Primary Tumors and EGFR Positive Circulating Tumor Cells: A Proof-Of-Concept Study

<div><p>Background</p><p>Analysis of circulating tumor cells (CTCs) provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which may in turn lead to clinical benefits.</p><p>Patients and Methods</p><p>Patients with metastatic breast cancer and HER2 non-amplified primary tumors with EGFR-positive CTCs were recruited and lapatinib 1500 mg daily was administered, in a standard two step phase 2 trial.</p><p>Results</p><p>There were no responses leading to termination at the first analysis with 16 patients recruited out of 43 screened. In 6 out of 14 (43%) individuals eligible for the efficacy analysis, a decrease in CTCs was observed with most of these having a greater decrease in their EGFR-positive CTC pool.</p><p>Conclusions</p><p>This is one of the first studies of CTC-directed therapeutics and suggests that lapatinib monotherapy is not having any demonstrable clinical effects by reducing the EGFR-positive pool of CTCs in HER2 non-amplified primary tumors. Our attempt to expand the pool of patients eligible for a targeted therapy was unsuccessful; the role of clonal populations in cancer biology and therapeutic strategies to control them will require extensive evaluation in years to come.</p><p>Trial Registration</p><p>Clinical trials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00820924" target="_blank">NCT00820924</a></p></div

Eight out of fourteen evaluable advanced breast cancer patients demonstrated a consistent or increased quantity of CTCs in 7.5 ml blood following the first cycle of Lapatinib treatment.

<p>Graphs show CTC measurements and EGFR positivity at screening or baseline and at follow-up after Lapatinib treatment in each patient (A – H). Seven patients also showed an increase in EGFR positive CTCs after Lapatinib treatment (B, C, D, E, F, G and H). Serial CTCs were taken with ethical approval (07/Q0401/20) and additional consent.</p

CONSORT 2010 flow diagram for patients enrolled in this study.

<p>CONSORT 2010 flow diagram for patients enrolled in this study.</p

Primary tumor characteristics, prior treatments and CTC screening measurements of patients with advanced breast cancer.

<p>Sixteen patients were recruited to the trial of a daily dose of lapatinib monotherapy. All patients had one or more EGFR positive CTCs. Twelve patients were assessed for HER2 positivity in their CTCs, and of the eleven assessable, ten (91%) had a proportion that were HER2 positive.</p>a<p>Eastern Cooperative Oncology Group Status. 0 - Fully active, able to carry on all pre-disease performance without restriction, 1-Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 2 - Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.</p>b<p>IDC – Invasive ductal carcinoma, ILC – Invasive lobular carcinoma, PAP - Papillary.</p>c<p>CTCs present in 7.5 ml blood at screening or baseline as assessed by the CellSearch system.</p><p>NK = not known, the assessment of EGFR on the primary tumor being made according to our published methods <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062543#pone.0062543-Stebbing2" target="_blank">[25]</a>.</p

Six out of fourteen evaluable advanced breast cancer patients demonstrated a decrease in the quantity of CTCs in 7.5 ml blood following the first cycle of Lapatinib treatment.

<p>Graphs show CTC measurements and EGFR positivity at screening or baseline and at follow-up after Lapatinib treatment in each patient (A–F). Four patients also showed a decrease in EGFR positive CTCs after lapatinib treatment (A, B, C and F). Serial CTCs were taken with ethical approval (07/Q0401/20) and additional consent.</p

Randomized, Phase III Trial of Sequential Epirubicin and Docetaxel Versus Epirubicin Alone in Postmenopausal Patients With Node-Positive Breast Cancer

Purpose The Docetaxel Epirubicin Adjuvant (DEVA) trial evaluated the efficacy and toxicity of incorporating docetaxel after epirubicin to create a sequential anthracycline-taxane regimen in early breast cancer. Patients and Methods After complete tumor excision, postmenopausal women with node-positive early breast cancer were randomly assigned to either epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks for six cycles (EPI x 6) or three cycles of epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks followed by three cycles of docetaxel 100 mg/m(2) on day 1 every 3 weeks (EPI-DOC). A subset of patients also participated in a quality of life (QOL) study. The primary end point was disease-free survival (DFS). Results From 1997 to 2005, 803 patients entered DEVA (EPI x 6, n = 397; EPI-DOC, n = 406). At a median follow-up of 64.7 months (interquartile range, 45.2 to 84.4 months), 198 DFS events had been reported (EPI x 6, n = 114; EPI-DOC, n = 84). The 5-year DFS rates were 72.7% (95% CI, 68.0% to 77.3%) for epirubicin alone and 79.5% (95% CI, 75.2% to 83.8%) for epirubicin followed by docetaxel; evidence of improvement in DFS was observed with EPI-DOC (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.91; P = .008). One hundred twenty-seven patients have died (EPI x 6, n = 75; EPI-DOC, n = 52); a reduction in deaths was observed with EPI-DOC (HR, 0.66; 95% CI, 0.46 to 0.94; P = .02). The 5-year overall survival rates were 81.8% (95% CI, 77.7% to 85.9%) for epirubicin and 88.9% (95% CI, 85.5% to 92.2%) for epirubicin followed by docetaxel. Assessment of toxicity and QOL showed that EPI-DOC was associated with greater toxicity but with no difference in QOL between arms during follow-up. Conclusion These results suggest, within a relatively small trial, that substitution of docetaxel for epirubicin for the last three cycles of chemotherapy results in improved outcome in postmenopausal women with node-positive, early breast cancer compared with six cycles of epirubicin monotherapy. J Clin Oncol 29:3247-3254. (C) 2011 by American Society of Clinical Oncolog

Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study

Purpose: Intergroup Exemestane Study (IES), an investigator-led study in 4,724 postmenopausal patients with early-stage breast cancer has demonstrated clinically important benefits from switching adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane. Now, with longer follow-up, a large number of non–breast cancer–related events have been reported. Exploratory analyses describe breast cancer–free survival (BCFS) and explore incidence and patterns of the different competing events. Patients and Methods: Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years of adjuvant endocrine therapy. At this planned analysis, the median follow-up was 91 months. Principal analysis focuses on 4,052 patients with estrogen receptor (ER) –positive and 547 with ER-unknown tumors. Results: In all, 930 BCFS events have been reported (exemestane, 423; tamoxifen, 507), giving an unadjusted hazard ratio (HR) of 0.81 (95% CI, 0.71 to 0.92; P = .001) in favor of exemestane in the ER-positive/ER unknown group. Analysis partitioned at 2.5 years after random assignment showed that the on-treatment benefit of switching to exemestane (HR, 0.60; 95% CI, 0.48 to 0.75; P < .001) was not lost post-treatment, but that there was no additional gain once treatment had ceased (HR, 0.94; 95% CI, 0.80 to 1.10; P = .60). Improvement in overall survival was demonstrated, with 352 deaths in the exemestane group versus 405 deaths in the tamoxifen group (HR, 0.86; 95% CI, 0.75 to 0.99; P = .04). Of these, 222 were reported as intercurrent deaths (exemestane, 107; tamoxifen, 115). Conclusion: The protective effect of switching to exemestane compared with continuing on tamoxifen on risk of relapse or death was maintained for at least 5 years post-treatment and was associated with a continuing beneficial impact on overall survival