Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Complications of Percutaneous Bone Tumor Cryoablation A 10-year Experience

International audienceBackground Percutaneous cryoablation has been shown to be effective in the management of painful bone tumors. However, knowledge of the complication rate and risk factors for complication is currently lacking. Purpose To report the complication rate and associated risk factors for bone tumor cryoablation. Materials and Methods This retrospective study reviewed complications in 239 consecutive patients (131 men and 108 women; median age, 64 years; age range, 6-86 years) who underwent cryoablation of 320 primary or metastatic bone tumors between January 2008 and November 2017. Common Terminology Criteria for Adverse Events was used to categorize complications as major (grade 3-4) or minor (grade 1-2). Multivariable analysis was performed for variables with P values less than .20, including age, tumor location, adjacent critical structures, number of cryoprobes, and Eastern Cooperative Oncology Group performance status (ECOG-PS). Results Among the 320 tumors, the total complication rate was 9.1% (29 of 320; 95% confidence interval [CI] 6%, 12.2%). The major complication rate was 2.5% (eight of 320; 95% CI 0.8%, 4.2%), with secondary fracture the most frequent complication (1.2% [four of 320]; mean delay, 71 days); cryoablation site infection, tumor seeding, bleeding, and severe hypotension were each observed in 0.3% (one of 320) of procedures. Minor complications included postprocedural pain (2.2% [seven of 320]), peripheral neuropathy (0.9% [three of 320]), and temporary paresthesia (0.9% [three of 320]). For all complications, associated risk factors included ECOG-PS greater than 2 (odds ratio [OR], 3.1 [95% CI 3, 7.6]; P = .01), long-bone cryoablation (OR, 17.8 [95% CI 2.3, 136.3]; P = .01), and use of more than three cryoprobes (OR, 2.5 [95% CI 1.0, 6.0]; P = .04); for major complications, associated risk factors included age greater than 70 years (OR, 7.1 [95% CI 1.6, 31.7]; P = .01) and use of more than three cryoprobes (OR, 23.6 [95% CI 2.8, 199.0]; P = .01). Conclusion Bone tumor cryoablation is safe, with a 2.5% rate of major complications, most commonly secondary fracture (1.2%). Major complications are associated with age greater than 70 years and use of more than three cryoprobes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Jennings in this issue

Percutaneous image-guided ablation of bone metastases local tumor control in oligometastatic patients

International audienceIntroduction - Percutaneous image-guided cryo- (CA) and radiofrequency- (RFA) ablations have been widely used in the treatment of painful bone metastases (BM). However, paucity of data is available for the performance of these treatments when used with a curative intent. The aim of this study is to investigate the local progression free-survival (LPFS) after radical percutaneous image-guided ablation of BM in oligometastatic patients, and to identify predictive factors associated with local tumor progression. Materials and methods - This is a retrospective review of all patients who underwent percutaneous image-guided CA or RFA of BM with a radical intent between 2007 and 2018. Results - Forty-six patients with a total of forty-nine BM underwent percutaneous image-guided CA (N = 37; 75,5%) or RFA (N = 12; 24,5%). Primary malignancies included thyroid (N = 11, 22.5%), breast (N = 21; 42.9%), lung (N = 8; 16.3%) and other (N = 9; 18,3%) cancers. Additional consolidation was performed after ablation in 20.4% cases (N = 10). Mean follow-up was 34.1 ± 22 months. Local progression at the treated site was observed in 28.5% cases (N = 14); 1- and 2-year LPFS was 76.8% and 71.7%, respectively. Size of BM (>2 cm) predicted local tumor progression (p = .002). Conclusions - Percutaneous image-guided locoregional therapies used in the radical treatment of BM in oligometastatic patients demonstrate significant rates of LPFS providing the size of BM ≤2 cm

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3): analysis of individual data from 258 cancer registries in 61 countries

Background: Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods: We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings: 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation: This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group