Platinum Plus Research Articles

Atezolizumab and Platinum Plus Pemetrexed With or Without Bevacizumab for Metastatic Nonsquamous Non–Small Cell Lung Cancer

The combination of an antibody to programmed cell death-1 (PD-1) or to its ligand (PD-L1) with chemotherapy is the standard first-line treatment for metastatic non-small cell lung cancer (NSCLC). Bevacizumab is expected to enhance the efficacy not only of chemotherapy but also of PD-1/PD-L1 antibodies through blockade of vascular endothelial growth factor-mediated immunosuppression, but further data are needed to support this. To evaluate the efficacy and safety of bevacizumab administered with platinum combination therapy and atezolizumab in patients with advanced nonsquamous NSCLC. An open-label phase 3 randomized clinical trial was conducted at 37 hospitals in Japan. Patients with advanced nonsquamous NSCLC without genetic driver alterations or those with genetic driver alterations who had received treatment with at least 1 approved tyrosine kinase inhibitor were enrolled between January 20, 2019, and August 12, 2020. Patients were randomly assigned to receive either atezolizumab plus carboplatin with pemetrexed (APP) or atezolizumab, carboplatin plus pemetrexed, and bevacizumab (APPB). After 4 cycles of induction therapy, maintenance therapy with atezolizumab plus pemetrexed or with atezolizumab, pemetrexed, and bevacizumab was administered until evidence of disease progression, development of unacceptable toxic effects, or the elapse of 2 years from the initiation of protocol treatment. The primary end point was progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the intention-to-treat (ITT) population. A total of 412 patients were enrolled (273 men [66%]; median age, 67.0 [range, 24-89] years) and randomly assigned, with 205 in the APPB group and 206 in the APP group of the ITT population after exclusion of 1 patient for good clinical practice violation. The median BICR-assessed PFS was 9.6 months with APPB vs 7.7 months with APP (stratified hazard ratio [HR], 0.86; 95% CI, 0.70-1.07; 1-sided stratified log-rank test; P = .92). According to prespecified subgroup analysis of BICR-assessed PFS, an improved PFS with APPB vs APP was apparent specifically in driver oncogene-positive patients (median, 9.7 vs 5.8 months; stratified HR, 0.67; 95% CI, 0.46-0.98). Toxic effects related to bevacizumab were increased in the APPB group. The findings of this trial did not show superiority of APPB over APP for patients with nonsquamous NSCLC; however, this regimen showed a similar tolerability and improved survival relative to APP in patients with driver oncogenes. Japan Registry of Clinical Trials Identifier: jRCT2080224500.

Evaluation of the Chronic Reproductive Toxicity of a Fluorine-Free Firefighting Foam and a Short-Chain Fluorinated Foam to Northern Bobwhite Quail (Colinus virginianus).

The development of fluorine-free firefighting foams has been proposed as a way to reduce the adverse environmental consequences of foams containing per- and poly-fluoroalkyl substances. While there are likely fewer environmental and ecological concerns with these new fluorine-free foams in terms of persistence and bioaccumulation, it is prudent to evaluate the ecotoxicity of these fluorine-free foam products given the absence of data. Oral chronic drinking water exposure studies on adult pairs of northern bobwhite quail (Colinus virginianus) were conducted with a short-chain fluorinated and a fluorine-free foam: Buckeye Platinum Plus C6 and National Foam Avio Green KHC, respectively, at three exposure concentrations (0.01%, 0.1%, and 0.25%). Adults were monitored for survival, growth, and reproductive output; and chicks were monitored for survival and growth. Growth parameters in adult quail were not affected by exposure to the Buckeye or Avio foam. However, liver lipid content was higher in adult males exposed to the Buckeye foam or the Avio foam at the highest exposure concentrations. Chicks were heavier and had higher growth rates after adult exposure to Avio at the highest exposure level (0.25%) and to Buckeye at the two lowest exposure levels but not at the highest exposure level. The two adverse reproductive effects observed from avian exposure to Buckeye were an increased percentage of cracked eggs and earlier arrested embryonic development. Similarly, chronic exposure to Avio also induced earlier arrested embryonic development. These results show that the fluorine-free foams tested did cause toxicity to bobwhite quail, but whether they pose a risk at contaminated sites requires further laboratory and field study and additional exposure data. Environ Toxicol Chem 2024;43:211-221. © 2023 SETAC.

Cost Effectiveness and Budget Impact of Nivolumab Plus Ipilimumab Versus Platinum Plus Pemetrexed (with and Without Bevacizumab) in Patients with Unresectable Malignant Pleural Mesothelioma in Switzerland.

Malignant pleural mesotheliomas (MPMs) are aggressive and often unresectable. In the past, chemotherapy was the standard for palliative treatment. However, immunotherapy with nivolumab+ipilimumab has recently received marketing approval. This study evaluated the cost effectiveness of nivolumab+ipilimumab versus pemetrexed+platinum (with/without bevacizumab) for Swiss patients with unresectable MPM, overall and by histological subtype. We developed a three-state Markov cohort model with a cycle length of 1month, a 30-year time horizon, and a discount rate of 3% per year for costs and benefits. The model included the updated survival and treatment-dependent utility results from the Checkmate-743 and MAPS registration trials. A Swiss statutory health insurance perspective was considered with unit costs for 2022 from publicly available and real-world sources. We assumed a willingness-to-pay (WTP) threshold of CHF100,000/QALY. Model robustness was explored in sensitivity and scenario analyses. Compared with chemotherapy, nivolumab+ipilimumab incurred additional costs of CHF109,115 and 0.57 additional quality-adjusted life-years (QALYs), yielding an incremental cost-effectiveness ratio (ICER) of CHF192,585/QALY (i.e. USD201,829/QALY) gained. Relative to their 2022 list price, nivolumab+ipilimumab may be cost effective if priced at 48% across all histologies. Assuming cisplatin-based instead of carboplatin-based chemotherapy reduced the ICER to CHF158,911/QALY (i.e. USD166,539/QALY). For the non-epithelioid subtype, nivolumab+ipilimumab was cost effective compared with chemotherapy (ICER of CHF97,894/QALY, i.e. USD102,593/QALY). Chemotherapy+bevacizumab was often a dominated strategy or would require a bevacizumab cost reduction to 28%. Our model projected nivolumab+ipilimumab to be cost effective for the non-epithelioid subtype but not for all histologies. Substantial discounts for nivolumab+ipilimumab would be necessary to achieve cost effectiveness for all histologies.

Comparison of spatio-temporal gait parameters between the GAITRite® platinum plus classic and the GAITRite® CIRFACE among older adults: a retrospective observational study

BackgroundThe GAITRite® system is one of the gold standards for gait electronic analysis, especially for older adults. Previous GAITRite® systems were composed of an electronic roll-up walkway. Recently, a new GAITRite® electronic walkway, named CIRFACE, was commercialized. It is composed of a changeable association of stiff plates, unlike previous models. Are the gait parameters measured similar between these two walkways among older adults and according to the cognitive status, the history of falls, and the use of walking aids?MethodsIn this retrospective observational study, 95 older ambulatory participants (mean, 82.6 ± 5.8 years) were included. Ten spatio-temporal gait parameters were measured simultaneously with the two GAITRite® systems in older adults while walking at comfortable self-selected pace. The GAITRite® Platinum Plus Classic (26’) was superimposed on the GAITRite® CIRFACE (VI). Comparisons between the parameters of the two walkways were performed using Bravais-Pearson correlation, between-method differences (corresponding to bias), percentage errors and Intraclass Correlation Coefficients (ICC2,1). Subgroup analyses were performed according to the cognitive status, the history of falls in the last 12 months and the use of walking aids.ResultsThe whole walk parameters recorded by the two walkways were extremely correlated with a Bravais-Pearson correlation coefficient ranging from 0.968 to 0.999, P < .001, indicating a very high correlation. According to the ICC2,1 calculated for absolute agreement, all gait parameters had excellent reliability (ranging from 0.938 to 0.999). Mean bias for 9 parameters out of 10 were ranged from − 0.27 to 0.54, with clinically acceptable percentage errors (1.2–10.1%). Step length showed a substantially higher bias (1.4 ± 1.2 cm), nevertheless the percentage errors remained clinically acceptable (5%).ConclusionWhen walking at comfortable self-selected pace, the standard spatio-temporal walk parameters provided by both the GAITRite® PPC and the GAITRite® CIRFACE seem similar and very highly correlated in older adults with various cognitive or motor status. The data of studies using these systems can be compared and mixed with a very low risk of bias in a meta-analytic process. Also, the geriatric care units can choose the most ergonomic system according to their infrastructure without affecting their gait data.Trial registrationNCT04557592 (21/09/2020).

Platinum Plus Tegafur-Uracil versus Platinum Alone during Concurrent Chemoradiotherapy in Patients with Nonmetastatic Nasopharyngeal Carcinoma: A Propensity-Score-Matching Analysis.

Simple SummaryThe current guidelines suggest that concurrent chemoradiotherapy (CCRT) with a cisplatin-based regimen is the standard treatment for patients with nonmetastatic NPC. However, little is known regarding the addition of tegafur–uracil (UFUR) to CCRT in patients with NPC. Our study showed that the median RFS was not reached (NR) in the CCRT-UP group, and it was 12.5 months in the CCRT-P group (p < 0.001). The median OS was NR in the CCRT-UP group, and it was 15.9 months in the CCRT-P group (p < 0.001). Grade 3–4 AEs were insignificant between the CCRT-UP and CCRT-P arms. In summary, CCRT-UP had better RFS and OS in nonmetastatic NPC patients with similar toxic profiles.Concurrent chemoradiotherapy (CCRT) with a cisplatin-based regimen is the standard treatment for patients with nasopharyngeal carcinoma (NPC). Our study was a propensity-score-matching analysis and it aimed to investigate the oncologic outcomes of platinum plus tegafur–uracil versus platinum alone during CCRT in patient with nonmetastatic NPC. Patients with pathologic confirmed NPC in 2018–2022 were reviewed. Patients treated with platinum plus tegafur–uracil (CCRT-UP) or platinum alone (CCRT-P) during CCRT were recruited into this study. A propensity-score-matching analysis was conducted to diminish the selection bias. The recurrence-free survival (RFS) and overall survival (OS) were presented with Kaplan–Meier curves. The treatment-related adverse effects (AEs) were recorded according to the National Cancer Institute’s Common Terminology Criteria V3.0. A total of 44 patients with CCRT-UP and 44 patients with CCRT-P were identified after propensity score matching. The median RFS was not reached (NR) in the CCRT-UP group, and it was 12.5 months in the CCRT-P group (p < 0.001). The median OS was NR in the CCRT-UP group, and it was 15.9 months in the CCRT-P group (p < 0.001). The overall response rate and disease-control rate were insignificant between the CCRT-UP and CCRT-P groups. A subgroup analysis showed that the median OS was significantly longer in the CCRT-UP group than in the CCRT-P group, regardless of the clinical stage. A multivariate analysis exhibited that CCRT-UP was independently correlated with survival. The grade 3–4 AEs were insignificant between the CCRT-UP and CCRT-P arms. CCRT-UP had better RFS and OS in nonmetastatic NPC patients with similar toxic profiles. Further larger-scaled prospective randomized control trials are warranted to validate our conclusions.

Pemetrexed and Platinum Plus Pembrolizumab in Patients With Metastatic Nonsquamous NSCLC by Tumor Burden at Baseline: A Post Hoc Efficacy Analysis of KEYNOTE-189

IntroductionThe aim of this study was to evaluate the efficacy of pemetrexed and platinum plus pembrolizumab by baseline tumor burden. MethodsA total of 616 patients in the intention-to-treat population of the KEYNOTE-189 study were included in this analysis. Baseline tumor burden subgroups were identified on the basis of extent of distant metastasis (M1a versus M1b), median number (≤3 versus >3) of organ systems with lesions, or symptom severity score of patient-reported lung cancer-associated symptoms (≤median versus >median). Overall survival (OS), progression-free survival (PFS), and PFS-2 were evaluated by Kaplan-Meier and univariate Cox methods. Objective response rate was analyzed using logistic regression models, and duration of response was analyzed descriptively. Efficacy outcomes were also analyzed according to the programmed death-ligand 1 expression levels. ResultsOS and PFS were significantly improved with pemetrexed and platinum plus pembrolizumab in all baseline tumor burden subgroups (M1a stage: OS hazard ratio [HR] = 0.54, p = 0.0037; PFS HR = 0.48, p = 0.0001; M1b stage: OS HR = 0.58, p ≤ 0.0001; PFS HR = 0.51, p ≤ 0.0001; number of organ systems with lesion ≤ 3: OS HR = 0.49, p ≤ 0.0001 PFS HR = 0.41, p ≤ 0.0001; >3: OS HR = 0.67, p = 0.0068; PFS HR = 0.59, p = 0.0001; symptom severity score ≤ median: HR = 0.51, p ≤ 0.0001; PFS HR 0.49, p ≤ 0.0001; > median: OS HR = 0.60, p = 0.0003; PFS HR = 0.48, p ≤ 0.0001). PFS2 and objective response rate were also improved with pemetrexed and platinum plus pembrolizumab in all baseline tumor burden subgroups. Efficacy outcomes were generally consistent regardless of programmed death-ligand 1 expression levels. ConclusionsPemetrexed and platinum plus pembrolizumab were found to have relevant efficacy regardless of the extent of baseline tumor burden and the variables used to define it. These results further support pemetrexed and platinum plus pembrolizumab as the standard of care in the first-line treatment of metastatic nonsquamous NSCLC.

Acute Oral Toxicity of Nonfluorinated Fire-Fighting Foams to Northern Bobwhite Quail (Colinus virginianus).

Long-chain per- and poly-fluoroalkyl substances (PFAS) have been the active ingredients in firefighting foams for more than 50 years. Due to their extreme persistence, regulatory agencies are concerned about their potential adverse environmental and health impacts. Recently, nonfluorinated chemical constituents have been proposed for use in fire-fighting foams in an effort to reduce the potential negative impacts of PFAS on terrestrial and aquatic flora and fauna. However, it is important to also determine the potential ecotoxicity of these nonfluorinated foam products, because we have little toxicological information for many of them. In preparation for a chronic study, we conducted an acute (24-h) oral toxicity test in northern bobwhite quail (Colinus virginianus) using six different fluorine-free foams; five were commercial foams (BioEx ECOPOL A, Fomtec Enviro USP, National Foam Avio Green KHC, National Foam NFD 20-391, and Solberg Re-Healing Foam), and one was an experimental foam (NRL 502W). A short-chain PFAS-based foam (Buckeye Platinum Plus C6) was also evaluated for comparative purposes. Groups of five birds were initially pseudogavaged with a volume of each product corresponding to a "limit" (the highest exposure concentration expected to occur environmentally). Only one bird (1 of 35) died during the limit test, indicating that all seven products have an acute median lethal dose in adult quail at or above the limit (~1500 mg/kg body wt). Environ Toxicol Chem 2022;41:2003-2007. © 2022 SETAC.

Acute Toxicity of Eight Aqueous Film-Forming Foams to 14 Aquatic Species.

Researchers have developed numerous per- and polyfluoroalkyl substances (PFAS)-free aqueous film-forming foam (AFFF) formulations to replace PFAS-containing AFFF used for fire suppression. As part of the Department of Defense's Strategic Environmental Research and Development Program (SERDP), we examined the direct lethal effects of seven PFAS-free AFFF and a PFAS-containing AFFF on 14 aquatic species using a series of lethal concentration (LC50) tests. We assessed the LC10, LC50, and LC90 values using log-logistic and logit analyses. Across all aquatic species tested, we discovered that exposure to at least one PFAS-free AFFF was more or as toxic as exposure to the PFAS-containing AFFF. For most cases, National Foam Avio F3 Green KHC 3% and Buckeye Platinum Plus C6MILSPEC 3% were the most and least toxic formulations, respectively. Moreover, we found consistency among results from multiple experiments using the same minnow species (Pimephales promelas) and among closely related taxa (e.g., daphnids, amphibians). Lastly, the LC50 values for AFFF formulations trended lower for tested marine species as compared to those of freshwater species. These results dramatically increase the current knowledge on the potentially toxic effects of AFFF but also highlight the need for additional research and the development of new PFAS-free AFFF that are more "ecologically friendly" than those containing persistent PFAS.

Treatment and Survival Outcomes Associated With Platinum Plus Low-Dose, Long-term Fluorouracil for Metastatic Nasopharyngeal Carcinoma

The treatment of metastatic nasopharyngeal carcinoma (mNPC) is a major challenge because of drug resistance and the toxic effects of chemotherapy. To evaluate the survival and toxicity outcomes and safety associated with the use of a modified low-dose fluorouracil protocol compared with standard regimens recommended in current guidelines for treatment of mNPC. This retrospective cohort study was based on data retrieved from electronic medical records from Sun Yat-sen University Cancer Center in China for 1397 patients with mNPC diagnosed from January 1, 2006, to December 31, 2017. Data analyses were conducted from October 1, 2020, to May 1, 2021. Patients received chemotherapy, including platinum plus low-dose, long-term fluorouracil (PFLL); cisplatin plus standard dose, short-term fluorouracil (PFSS); cisplatin plus gemcitabine (GP); cisplatin plus taxane (TP); and cisplatin plus taxane plus fluorouracil (TPF). The main outcomes included overall survival (OS); subsequent-line, treatment-free survival (sTFS), defined as the period from metastasis to the date requiring subsequent-line treatment or death; and the survival to toxicity ratio (STR), defined as person-year rate of OS divided by person-year rate of severe hematologic toxic effects. Cox regression models were used to compare the outcomes of patients receiving PFLL vs other regimens, adjusting for baseline characteristics. Of 1397 patients with mNPC included in this study (1152 men; median age, 46 years [range, 18-70 years]) 134 received PFLL, 203 received GP, 330 received PFSS, 366 received TP, and 364 received TPF. A total of 764 patients died (75 in treatment group PFLL; 107 in group GP; 204 in group PFSS; 207 in group TP; and 171 in group TPF), and 979 patients had subsequent-line treatment or died, whichever occurred first (PFLL, 77; GP, 144; PFSS, 262; TP, 269; and TPF, 227). The median follow-up was 46.9 months (IQR, 25.4-82.4 months), and the 5-year OS rate among patients who received PFLL was 25.4% (95% CI, 16.7%-38.8%), which was not significantly different from that among patients who did not receive PFLL (30.2%; 95% CI, 27.1%-33.5%; P = .13) or who received GP (25.1%; 95% CI, 18.1%-35.0%; P = .81), PFSS (23.6%; 95% CI, 18.5%-30.0%; P = .80), or TP (28.1%; 95% CI, 22.8%-34.7%; P = .99) but was lower than that for patients who received TPF (40.4%; 95% CI, 34.7%-47.1%; P = .001). The 5-year sTFS among patients who received PFLL (24.1%; 95% CI, 15.4%-37.6%) was significantly higher than that among patients who did not receive PFLL (18.5%; 95% CI, 16.1%-21.3%; P = .005) or who received GP (14.3%; 95% CI, 9.1%-22.5%; P = .001) but similar to that for patients who received TPF (28.0%; 95% CI, 23.0%-34.0%; P = .74). The STR of PFLL was 0.81, substantially better than that of GP (0.41) and TPF (0.65). The results of this cohort study suggest that, compared with the use of standard treatment regimens, administration of PFLL was associated with similar OS but prolonged sTFS. PFLL also had better STR than other regimens, which could indicate less severe toxic effects. Thus, PFLL may be an option for first-line treatment of mNPC.

A Phase II Study of Osimertinib Combined With Platinum Plus Pemetrexed in Patients With EGFR-Mutated Advanced Non–Small-cell Lung Cancer: The OPAL Study (NEJ032C/LOGIK1801)

BackgroundOsimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is now a standard treatment of previously untreated EGFR-mutated advanced non–small-cell lung cancer (NSCLC). However, disease progression occurs within 19 months of treatment. In the NEJ009 study, gefitinib plus carboplatin plus pemetrexed demonstrated significantly better progression-free and overall survival compared with gefitinib monotherapy. Furthermore, the Lung Oncology Group in Kyushu and North East Japan Study Group, major clinical trial groups in Japan, conducted a randomized phase II study to evaluate the efficacy and safety of second-line osimertinib plus carboplatin plus pemetrexed versus osimertinib monotherapy for patients with disease progression during first-line EGFR tyrosine kinase inhibitor therapy and the EGFR T790M resistance mutation (TAKUMI trial; trial registration no., jRCTs071180062). In the first treatment course for the initial 24 patients, no safety issues were reported in the combination arm. Thus, we have planned this phase II study to evaluate the safety and preliminary efficacy of osimertinib plus cisplatin/carboplatin plus pemetrexed therapy for patients with previously untreated EGFR-mutated NSCLC. Patients and MethodsA total of 66 patients will be enrolled, because this sample size will be adequate for assessing treatment safety and efficacy. The co-primary endpoints include safety and the objective response rate, and the secondary endpoints include the complete response rate, disease control rate, and progression-free survival. ConclusionsThis is the first study to explore the efficacy and safety of osimertinib combined with platinum-based chemotherapy in previously untreated NSCLC patients with EGFR-sensitizing mutations. Our findings could provide valuable information for phase III studies such as FLAURA2 and for developing treatment strategies for EGFR-mutated NSCLC.

P2.12-12 Plasma Vitamin D Level is an Independent Prognosis Factor in SCLC Patients Treated with Platinum Plus Etoposide as First-Line Chemotherapy

Small cell lung cancer accounts for approximately 13.6% of all lung cancer cases, which is a very aggressive form of lung cancer and associated with a very poor prognosis.Investigations into the prognostic factors of SCLC may help in the development of new biotherapeutic regimens.VD deficiency has been well documented to be unfavorable for the prognosis of patients with several types of cancer.However,there is no study focus on the relationship between the plasma VD level and the prognosis of SCLC patients. The primary objective of this study was to examine the prognostic role of the plasma 25-hydroxyvitamin D (25(OH)D) level in SCLC patients treated with platinum plus etoposide as first-line chemotherapy. A total of 178 SCLC patients were consecutively and prospectively hospitalized to receive platinum plus etoposide as first-line chemotherapy. The baseline 25(OH)D level was measured at the time of diagnosis. Main outcome measures included overall survival (OS) and progression-free survival (PFS). The median OS values of patients with 25(OH)D < 10ng/mL and ≥10ng/mL were 12.5 months (95% confidence interval[CI], 9.4–18.0 months) and 21.3 months (95%CI,12.8–29.1months),respectively; the median PFS values were 6.6 months(95%CI,5.1–7.6months) and 12.7months (95%CI,9.1–17.7months), respectively. Both univariate and multivariate analyses showed that having a plasma 25(OH)D level < 10 ng/mL was associated with a significantly shorter OS(P = 0.000; P =0.000) and PFS(P = 0.000; P =0.000).The median OS values of patients with 25(OH)D < 20ng/mL and ≥20ng/mL were 14.7 months (95% confidence interval[CI], 10.7–22.1 months) and 29.1 months (95%CI, 26.9–38.9 months), respectively; the median PFS values were 8.2months(95%CI, 6.5–10.7 months) and 22.4 months (95%CI, 21.2–24.2 months), respectively. Both univariate and multivariate analyses showed that having a plasma 25(OH)D level <20 ng/mL was associated with a significantly shorter OS (P = 0.000), while the baseline plasma 25(OH)D level was not significantly associated with PFS. Plasma vitamin D level is an independent prognosis factor in small cell lung cancer patients treated with platinum plus etoposide as first-line chemotherapy.

Platinum Plus Gemcitabine as the Most Effective Regimen in the First Line of Chemotherapy in Advanced Squamous Cell Lung Cancer

Platinum Plus Gemcitabine as the Most Effective Regimen in the First Line of Chemotherapy in Advanced Squamous Cell Lung Cancer

Platinum Plus Gemcitabine as the Most Effective Regimen in the First Line of Chemotherapy in Advanced Squamous Cell Lung Cancer

Platinum Plus Gemcitabine as the Most Effective Regimen in the First Line of Chemotherapy in Advanced Squamous Cell Lung Cancer

Twelve-month results of a prospective, multicentre trial to assess the everolimus-eluting coronary stent system (PROMUS Element): the PLATINUM PLUS all-comers randomised trial.

The aim of the study was to compare the safety and efficacy of the platinum-chromium-based everolimus-eluting stent (EES) with a cobalt-chromium EES. We performed a prospective, multicentre, single-blind non-inferiority all-comers study randomising patients with stable or unstable coronary artery disease (2:1) to treatment with the platinum-chromium EES (n=1,952) or the control cobalt-chromium EES (n=1,028) in Europe (PLATINUM PLUS trial). The primary endpoint was target vessel failure (TVF) at 12 months, a composite of target vessel-related cardiac death, myocardial infarction (MI), and ischaemia-driven target vessel revascularisation (TVR). Among 2,980 patients, 33% presented with acute coronary syndromes, and 48% with multivessel disease. At 12 months, the intention-to-treat analysis determined that the platinum-chromium EES was non-inferior to the cobalt-chromium EES for the primary endpoint (86 [4.6%] patients vs. 32 [3.2%], absolute difference 1.4%, 95% confidence interval [CI]: -0.1-2.9; upper limit of the one-sided 95% CI: 2.57%; non-inferiority p=0.012; superiority analysis: hazard ratio [HR] 1.44, 95% CI: 0.96-2.16, p=0.08). In the per protocol analysis, however, the primary endpoint was significantly more common in the platinum-chromium EES (HR 1.64, 95% CI: 1.05-2.55, p=0.03). There were no significant differences in the rates of cardiac death (1.1% vs. 1.0%, p=0.78), MI (1.6% vs. 0.8%, p=0.09), or ischaemia-driven TLR (2.0% vs. 1.6%, p=0.49). The rates of ARC definite or probable stent thrombosis were comparable between platforms (0.8% vs. 0.5%, p=0.44). At one year, the platinum-chromium EES satisfied the pre-specified criteria for non-inferiority relative to the control cobalt-chromium EES in this all-comers trial.

Twelve-month results of a prospective, multicentre trial to assess the everolimus-eluting coronary stent system (PROMUS Element): the PLATINUM PLUS all-comers randomised trial.

The aim of the study was to compare the safety and efficacy of the platinum-chromium-based everolimus-eluting stent (EES) with a cobalt-chromium EES. We performed a prospective, multicentre, single-blind non-inferiority all-comers study randomising patients with stable or unstable coronary artery disease (2:1) to treatment with the platinum-chromium EES (n=1,952) or the control cobalt-chromium EES (n=1,028) in Europe (PLATINUM PLUS trial). The primary endpoint was target vessel failure (TVF) at 12 months, a composite of target vessel-related cardiac death, myocardial infarction (MI), and ischaemia-driven target vessel revascularisation (TVR). Among 2,980 patients, 33% presented with acute coronary syndromes, and 48% with multivessel disease. At 12 months, the intention-to-treat analysis determined that the platinum-chromium EES was non-inferior to the cobalt-chromium EES for the primary endpoint (86 [4.6%] patients vs. 32 [3.2%], absolute difference 1.4%, 95% confidence interval [CI]: -0.1-2.9; upper limit of the one-sided 95% CI: 2.57%; non-inferiority p=0.012; superiority analysis: hazard ratio [HR] 1.44, 95% CI: 0.96-2.16, p=0.08). In the per protocol analysis, however, the primary endpoint was significantly more common in the platinum-chromium EES (HR 1.64, 95% CI: 1.05-2.55, p=0.03). There were no significant differences in the rates of cardiac death (1.1% vs. 1.0%, p=0.78), MI (1.6% vs. 0.8%, p=0.09), or ischaemia-driven TLR (2.0% vs. 1.6%, p=0.49). The rates of ARC definite or probable stent thrombosis were comparable between platforms (0.8% vs. 0.5%, p=0.44). At one year, the platinum-chromium EES satisfied the pre-specified criteria for non-inferiority relative to the control cobalt-chromium EES in this all-comers trial.

PCN52 - Comparative Effectiveness of Platinum Plus Paclitaxel Versus Platinum Plus Cyclophosphamide Among Patients with Early-Stage Ovarian Cancer in Taiwan

PCN52 - Comparative Effectiveness of Platinum Plus Paclitaxel Versus Platinum Plus Cyclophosphamide Among Patients with Early-Stage Ovarian Cancer in Taiwan

Monte Carlo derivation of filtered tungsten anode X-ray spectra for dose computation in digital mammography.

ObjectiveDerive filtered tungsten X-ray spectra used in digital mammography systems by means of Monte Carlo simulations.Materials and MethodsFiltered spectra for rhodium filter were obtained for tube potentials between 26 and 32 kV. The half-value layer (HVL) of simulated filtered spectra were compared with those obtained experimentally with a solid state detector Unfors model 8202031-H Xi R/F & MAM Detector Platinum and 8201023-C Xi Base unit Platinum Plus w mAs in a Hologic Selenia Dimensions system using a direct radiography mode.ResultsCalculated HVL values showed good agreement as compared with those obtained experimentally. The greatest relative difference between the Monte Carlo calculated HVL values and experimental HVL values was 4%.ConclusionThe results show that the filtered tungsten anode X-ray spectra and the EGSnrc Monte Carlo code can be used for mean glandular dose determination in mammography.

TCT-15 Results of the Primary Endpoint of the PLATINUM PLUS Trial: A Prospective, Randomized, Multi-center Trial to Assess the Everolimus-Eluting Coronary Stent System (PROMUS Element) for Coronary Revascularization in a Population of Unrestricted Patients

A drug-eluting stent consists of 3 components of equal importance: a metallic platform, a polymer and a drug, all influencing acute and long term results both in safety and efficacy. The PLATINUM PLUS trial was designed to compare the PROMUS Element(tm) stent (Boston Scientific; Natick, MA, US) to

VS2. Video Presentation Thoracic Endovascular Aortic Repair with Left Subclavian Artery Laser Fenestration

A significant need exists for a versatile and accessible method to revascularize aortic branches during thoracic endovascular aortic repair (TEVAR). We present a video of an emergent zone II TEVAR with revascularization of the left subclavian artery (LSCA) with retrograde laser fenestration. We present a 58 year old African American female with a symptomatic thoracic aortic aneurysm secondary to a chronic type B thoracic aortic dissection. Emergent TEVAR was carried out using Captiva (Medtronic, Minneapolis, MN) endografts. The proximal endograft was positioned immediately distal to the bovine arch orifice of the innominate and left carotid arteries. Through retrograde left open brachial artery access, we placed an 8.5 French St. Jude lamp septal, 45 degree sheath (St. Jude Medical, Saint Paul, MN), which provides a gentle preformed angle at the tip. An 0.018” Platinum Plus wire (Boston Scientific, Natick, MA) through a 2.5mm laser catheter (Spectranetics, Colorado Springs, CO) were then placed at the ostium of the LSCA perpendicular to the endograft. After deployment of the endograft, laser energy of 45 millijoules/mm2 at 25 pulses/second was applied in conjunction with gentle laser-endograft contact pressure for 3-5 seconds to create a fenestration. The 0.018” wire was then advanced through the laser catheter into the endograft lumen and exchanged for a stiff 0.035” wire. After endograft predilation using a 6mm balloon, an ICAST covered 9x38mm balloon expandable stent (Atrium, Hudson, NH) was deployed approximately ¼ into the lumen and ¾ into the branch vessel. The endograft portion of the covered stent was then flared. Finally, completion aortograms were performed to demonstrate TEVAR and left SCA fenestration patency with no endoleaks. Computed tomography angiography (CTA) was performed prior to discharge and at 1-3 month intervals post procedure to assess for TEVAR and left SCA fenestration patency, endoleak, and aneurysm/dissection exclusion.

Effects of a Feed Supplement Containing Fatty Acids and Chromium on Insulin Sensitivity in Old Mares: A Preliminary Study

s / Journal of Equine Veterinary Science 31 (2011) 230-356 252 Effects of a Feed Supplement Containing Fatty Acids and Chromium on Insulin Sensitivity in Old Mares: A Preliminary Study S. Otabachian , T. Hembrooke , E.M. Carnevale , and T.M. Hess 1 1 Colorado State University, Fort Collins, CO, USA, 2 Platinum Performance Inc. , Buellton, CA, USA Introduction: Older horses are prone to developing decreased insulin sensitivity (SI) due to an increase in fat accumulation and a decrease in physical activity [1]. Studies show a relationship between obesity and inflammation with reduced SI in horses [2,3]. An increased inflammatory status in older horses is thought to be a possible cause of pituitary pars intermedia dysfunction (PPID) which predisposes horses to laminitis and insulin resistance [4]. Polyunsaturated fatty acids (PUFA) such as n-3 a-linolenic acid (ALA) are absorbed and incorporated into cell membranes. In rat and human studies PUFAs change fatty acid composition of phospholipids surrounding insulin receptors found in muscle [5,6] and reduce inflammation when incorporated into white blood cells [7]. Chromium has been found to be beneficial in diabetic experimental animals and also in conditions resulting from insulin sensitivity and defects in glucose transportation [8]. The objectives of this study were: to investigate the effects of a fatty acid supplement containing a-linoleic acid and chromium yeast in old mares (ages 16-27 years) on insulin sensitivity and inflammatory markers. Materials and Methods: Mares (n 1⁄4 14; mean 21 .6 years) were supplemented for 9 months with 190 g per day of Equine Platinum Plus Metabolic Support (EPPMS): a fatty-acid formula from Platinum Performance containing ALA with an addition of Chromium Yeast and other minerals and vitamins. Mares were fed an average 1.5 kg of a commercial concentrate (Nutrena Safe Choice ) and 7.2 kg of mixed alfalfa and grass hay divided in 2 feedings. Mares served as their own controls and were fed the same diet throughout treatment. Mares stayed at the Colorado State University Equine Reproductive Laboratory (ERL) in a nonpregnant reproductive status. In July of 2009, after 30 days of acclimation to diet and environment at the ERL, fasting blood was collected (ten hours post-feed), mares were weighed, and treatment began. At the end of the summer the horses were returned and continued treatment at the direction of the owners. Mares were maintained in a similar daily routine experienced at the ERL meaning two feedings per day, a stall with a run, and no work. In February 2010 mares returned to the ERL and in May, fasting blood samples were collected. Blood was transferred into collection tubes, centrifuged and serum maintained at -20Â C for later analysis. PAXgene Blood RNA Tubes (Â 2010 PreAnalytix GmbH) were refrigerated at 4 C for two hours post collection and then maintained in 20 C until time of RNA isolation to assess gene expression. Plasma glucose was analyzed by an enzymatic assay; insulin and cortisol analyzed by radioimmunoassay; and endogenous ACTH was analyzed using Siemens Immulite 1000 Chemiluminescence technology. Basal proxies were calculated [9] and horses were classified into two groups: metabolic (RISQUI .29). Treatments were evaluated by ANOVA, with horses nested with metabolic as a random variable and treatment and metabolic as main factors. Significant results were analyzed by the least square means analysis. Results and Discussion: Mares treated with EPPMS had lower (P < .01) plasma glucose (91.2 2.10 mg/dL) insulin (9.6 1.0 I1⁄4U/mL) concentrations, as well as lower (P < .04) beta pancreatic response (MIRG 1⁄4 4.9 .37), compared to before treatment (98.0 1.9 mg/dL glucose; 13.8 .9 I1⁄4U/mL insulin; MIRG 1⁄4 5.9 .33). Insulin sensitivity as measured by RISQUI as well as weights were higher (P < .03) after treatment (RISQUI 1⁄4 .40 .04; 498.7 10.6 kg) compared to pretreatment (.27 .03; 472.7 10.2 kg). Cortisol levels trended lower (P < .09) in treated mares (109.5 10.7 nmol/L) compared to non-treated mares (130.3 9.8 nmol/L). Inflammatory cytokines were not significantly affected by treatment. Vitamins, minerals and amino acids were present in the supplement, but effects on insulin sensitivity are inconclusive. Conclusion: Although mares treated with EPPMS showed improved insulin sensitivity in the first sample post treatment, a control group of similar breed, age, and body conditionwould be necessary to confirm results. Although body weight was evaluated, fat composition was not accessed in the initial sampling so changes are unknown.