Efficient inference about the tail weight in multivariate Student tt distributions

We propose a new testing procedure about the tail weight parameter of multivariate Student $t$ distributions by having recourse to the Le Cam methodology. Our test is asymptotically as efficient as the classical likelihood ratio test, but outperforms the latter by its flexibility and simplicity: indeed, our approach allows to estimate the location and scatter nuisance parameters by any root-$n$ consistent estimators, hereby avoiding numerically complex maximum likelihood estimation. The finite-sample properties of our test are analyzed in a Monte Carlo simulation study, and we apply our method on a financial data set. We conclude the paper by indicating how to use this framework for efficient point estimation.Comment: 23 page

Evaluation of multiple transcriptomic gene risk signatures in male breast cancer

Marcadors pronòstics; Biomarcadors tumoralsMarcadores pronósticos; Biomarcadores tumoralesPrognostic markers; Tumour biomarkersMale breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.This work has been funded by the Breast Cancer Research Foundation (BCRF) with additional funding provided by the Government of Ontario to the Ontario Institute of Cancer Research (OICR). This work was funded by the Breast Cancer Research Foundation (BCRF), the Susan G. Komen for the Cure Foundation and the Ontario Institute of Cancer Research (OICR). Funding for OICR is provided by the Government of Ontario

Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer:12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease

The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 (NCT00021450) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiotherapy (EBRT) at 70-78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines. Of 819 patients randomly assigned between EBRT or EBRT plus AS started on day 1 of EBRT, 481 entered with intermediate risk (International Union Against Cancer TNM 1997 cT1b-c or T2a with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≤ 7 and PSA ≤ 20 ng/mL, N0M0) and had EBRT planned at 74 (342 patients, 71.1%) or 78 Gy (139 patients, 28.9%). We report the trial primary end point EFS, DFS, distant metastasis-free survival (DMFS), and overall survival (OS) by intention-to-treat stratified by EBRT dose at two-sided α = 5%. At a median follow-up of 12.2 years, 92 of 245 patients and 132 of 236 had EFS events in the EBRT plus AS and EBRT arm, respectively, mostly PSA relapse (48.7%) or death (45.1%). EBRT plus AS improved EFS and DFS (hazard ratio [HR] = 0.53; CI, 0.41 to 0.70; P < .001 and HR = 0.67; CI, 0.49 to 0.90; P = .008). At 10 years, DMFS was 79.3% (CI, 73.4 to 84.0) with EBRT plus AS and 72.7% (CI, 66.2 to 78.2) with EBRT (HR = 0.74; CI, 0.53 to 1.02; P = .065). With 140 deaths (EBRT plus AS: 64; EBRT: 76), 10-year OS was 80.0% (CI, 74.1 to 84.7) with EBRT plus AS and 74.3% (CI, 67.8 to 79.7) with EBRT, but not statistically significantly different (HR = 0.74; CI, 0.53 to 1.04; P = .082). Six months of concomitant and adjuvant AS statistically significantly improves EFS and DFS in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy. The effects on OS and DMFS did not reach statistical significance

The value at the mode in multivariate t distributions: a curiosity or not?

info:eu-repo/semantics/nonPublishe

Simple Le Cam Optimal Inference for the Tail Weight of Multivariate Student t Distributions: Testing Procedures and Estimation

info:eu-repo/semantics/nonPublishe

Belgian medication exposure during pregnancy ( BeMeP ), a new nationwide linked database: Linkage methods and prevalence of medication use

Abstract Purpose This study aimed to describe the implementation of a new retrospective Belgian national cohort of pregnant women, the Belgian Medication Exposure during Pregnancy (BeMeP). Methods We linked the national dispensing data to birth and death certificates and hospital stay data for a 7‐year period between 2010 and 2016 for the first time in Belgium. We presented the characteristics of pregnancy events associated with the mothers enrolled in the linkage study. Next, we constructed a cohort of pregnancies and compared some characteristics computed using the BeMeP database with the national statistics. Finally, we described the use of medications during pregnancy based on the first level of the Anatomical Therapeutic Chemical (ATC) classification. Results We included 630 457 pregnant women with 900 159 pregnancy‐related events (843 780 livebirths, 1937 stillbirths, 6402 ectopic events, and 47 905 abortions) linked to medication exposure information. Overall, 96.3% of live births and 83.5% of stillbirths (national statistics as reference) were captured from the BeMeP. During pregnancy, excluding the week of birth, 78.9% of live birth pregnancies and 79.6% of stillbirth pregnancies were exposed to at least one medication. The most frequently dispensed medications were anti‐infectives (ATC code J = 50.2%) for live births and for stillbirths (44.0%). Conclusion We linked information on pregnancies, all reimbursed medications dispensed by community pharmacists, all medications dispensed during hospitalization, sociodemographic status, and infant health to create the BeMeP database. The database represents a valuable potential resource for studying exposure‐outcome associations for medication use during pregnancy.info:eu-repo/semantics/publishe

Impact of acute kidney injury on anticancer treatment dosage and long-term outcomes: a pooled analysis of European Organisation for Research and Treatment of Cancer trials.

BACKGROUND: The impact of kidney dysfunction on long-term outcomes of patients with advanced cancer remains unclear. METHODS: Patients with advanced cancer included in trials conducted by the European Organisation for Research and Treatment of Cancer were eligible for this retrospective analysis. Acute kidney injury (AKI) was identified using serum creatinine levels and using adverse events reported by investigators. The impact of baseline estimated glomerular filtration rates (eGFRs) on progression-free survival (PFS) and overall survival (OS) was investigated. Pooled estimates of the impact of AKI on dose intensity, treatment duration, PFS and OS were obtained following a meta-analytic process. RESULTS: Nine trials were included in this study, totalling 2872 metastatic patients with various tumour types and various systemic treatment types. Baseline eGFR had homogeneously no impact on PFS or OS. Most Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (RIFLE) events occurred early during the course of the treatment. AKI was not associated with an increased rate of treatment discontinuation, while it decreased the study treatment dose intensity. Occurrence of a first RIFLE event significantly and homogeneously reduced PFS (pooled hazard ratio = 1.18, 95% confidence interval 1.07-1.30; P = 0.0012), while its impact on OS was more heterogeneous across trials. CONCLUSION: AKI is associated with reduced treatment dose intensity and reduced PFS. Therefore, close monitoring of the kidney function during the first months of treatment should be included in clinical trial protocols and probably also in daily practice to enable early AKI diagnosis and management. Collaboration between oncologists and nephrologists is needed to reduce the risk of undertreatment of patients experiencing AKI.status: Published onlin

Representativeness of trial participants : linking the EORTC boost-no boost trial to the Netherlands cancer registry

Background and Objectives: To evaluate the representativeness of Dutch patients participating in the European Organization for Research and Treatment of Cancer EORTC boost-no-boost trial to the target breast cancer patient population. Methods: All female breast cancer patients diagnosed between 1989 and 1996, aged ≤70 years, treated with breast-conserving surgery and radiation therapy, were selected from the Netherlands Cancer Registry (NCR) and linked to the EORTC trial database. Baseline characteristics were compared between trial and non-trial participants, for the Dutch population and according to seven participating institutions. Kaplan-Meier curves and multivariable Cox regression were used to explore potential heterogeneity in overall survival between low, medium and high-volume institutes. Results: Overall, 20,880 patients were identified from the NCR: 2,445 of 2,602 (94%) trial participants could be linked, and 18,435 were treated outside the trial. Trial participants had similar age, morphology, topography, laterality and socioeconomic status as nontrial participants, but more often stage I (62.7% vs. 56.4%) tumours and less often adjuvant treatment (22.9% vs. 26.5%). Crude 20-year survival ranged from 52.5% to 57.4%, without significant differences in multivariable analyses. Conclusion: This case study showed that participants in the boost-no-boost trial well represented the Dutch target population. Data linkage comes with challenges, but can close the gap between research and clinical practice