First known extinct feathertail possums (Acrobatidae, Marsupialia): palaeobiodiversity, phylogenetics, palaeoecology and palaeogeography

Four new fossil feathertail possum species (Marsupialia, Diprotodontia, Phalangerida, Petauroidea, Acrobatidae) are described from late Oligocene to middle Miocene fossil deposits in the Riversleigh World Heritage Area, northwestern Queensland. They are the first pre-Pleistocene fossil representatives of this family to be described. Two species are referred to the modern genus Acrobates and two to the modern genus Distoechurus. These species are distinguished from each other and from the living Distoechurus pennatus and Acrobates pygmaeus on the basis of qualitative and quantitative characters of the first lower molar (m1), which is the only tooth known for all four fossil species. Fortunately, m1 is morphologically the most variable tooth in the cheektooth row of acrobatids, and it exhibits numerous genus- and species-specific features. Phylogenetic analyses based on dental characters strongly support monophyly of Acrobatidae relative to other petauroids, as well as providing relatively strong support for reciprocal monophyly of Acrobates and Distoechurus, including the newly described fossil members of these genera. Recognition of species of Acrobates and Distoechurus in these fossil deposits is broadly congruent with recent estimates for the time of divergence of the two modern genera based on molecular data, and also provides an additional fossil calibration point for future studies of marsupial divergence times. These fossil species provide new insights into the biogeographical and ecological history of this enigmatic family of small possums, specifically that the oldest known species of Acrobates occurred in closed forest environments (in contrast to the living species, A. pygmaeus and Acrobates frontalis, which today inhabit open sclerophyll forests and woodlands) and that Distoechurus appears to have originated in Australia, only subsequently dispersing to New Guinea before becoming extinct in its Australian homeland

Goserelin for Ovarian Protection During Breast-Cancer Adjuvant Chemotherapy

Premature ovarian failure is a devastating long-term toxic effect of chemotherapy for premenopausal women. The survival benefit of adjuvant chemotherapy in young women with operable hormone receptor–negative breast cancer is well known, but concern over becoming infertile may influence the choice of treatment for many women. A number of trials have investigated the combined use of a gonadotropin-releasing hormone (GnRH) agonist and adjuvant chemotherapy in an attempt to protect ovarian function in premenopausal women. Results of such studies were mixed, and there were few data on pregnancy outcomes. The aim of this randomized trial was to determine whether administration of the GnRH agonist goserelin with chemotherapy would reduce the rate of ovarian failure after adjuvant or neoadjuvant treatment of hormone-receptor–negative early-stage breast cancer. A total of 257 premenopausal women with operable hormone receptor–negative breast cancer were randomized to receive standard chemotherapy with goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The rate of ovarian failure at 2 years was the primary study end point. Ovarian failure was defined as the absence of menses for the preceding 6 months and follicle-stimulating hormone levels in the postmenopausal range at 2 years. Conditional logistic regression was used to compare rates. Secondary end points evaluated included pregnancy outcomes and disease-free and overall survival. Of the 257 patients, 218 were eligible and could be evaluated: 113 in the chemotherapy-alone group and 105 in the goserelin group. Complete primary end-point data were available for 135 of the 218 patients who could be evaluated. Among these, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group; the odds ratio was 0.30, with a 95% confidence interval of 0.09 to 0.97; 2-sided P = 0.04. To determine the effect of the missing primary end-point data on the main study findings, sensitivity analyses were performed. The results of these analyses showed that the missing data had no significant effect on the association between treatment and stratification variables (age and planned chemotherapy regimen). Among the 218 patients who could be evaluated, more women became pregnant in the goserelin group than in the chemotherapy-alone group (21% vs 11%, P = 0.03). Kaplan-Meier curves showed that more women in the goserelin group had improved disease-free survival (P = 0.04) and overall survival (P = 0.05). Consistent with the findings of previous randomized trials, these data suggest that administration of a GnRH agonist with chemotherapy protects ovarian function, reducing the risk of early menopause and improving prospects for fertility. Although missing primary-end-point data weaken interpretation of the findings, there is no evidence that the missing data influenced the relative comparison between randomized groups

Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance).

LBA505 Background: Premature ovarian failure (POF) is a common toxicity of CT. Risk depends on type and amount of CT, age, and perhaps ovarian cycling at the time of CT. POEMS is a SWOG-coordinated phase III randomized study to evaluate whether LHRH analog administration with CT for early-stage breast cancer (BC) would reduce POF.Premenopausal patients (PT) age <50 with stage I-IIIA ER/PR-negative BC to be treated with CT were randomized to receive standard cyclophosphamide-containing CT with or without monthly goserelin (GN) 3.6 mg SQ starting 1 week prior to the first CT dose. The primary endpoint is 2-year POF, defined as amenorrhea for the prior 6 months and post-menopausal FSH. Other endpoints include pregnancies and survival. Endpoints were analyzed in multivariable regression adjusting for stratification factors (age and CT regimen).Between 2/04 and 5/11, 257 PT enrolled. Among 218 evaluable PT, 62% had complete primary endpoint data. Dropouts (n=83) were mostly due to deaths (n=14) or lack of FSH data. There was no strong evidence of informative missing data by arm according to stratification factors (p>.05). POF rates were 22% in the standard arm and 8% in the GN arm (OR=0.30, 95% CI: 0.10-0.87, p=.03 [unadjusted analysis]; OR=0.36, 95%CI: 0.11-1.14, p=0.08 [adjusted logistic regression analysis]). In a sensitivity analysis defining 2-year POF more liberally as either amenorrhea or elevated FSH, 45% in the standard arm and 20% in the GN arm had POF (OR=0.29, 95% CI: 0.12-0.70, p=.006). There were 13 pregnancies in the standard arm and 22 in the GN arm (OR=2.22, 95% CI: 1.00-4.92, p=.05). DFS and OS were better in the GN arm (Cox regression, including stage: HR=0.49, 95% CI: 0.24-0.97, p=.04; HR=0.43, 95% CI: 0.18-1.00, p=.05, respectively).LHRH analog administration with CT was associated with less POF and more pregnancies. In an exploratory analysis, GN use in premenopausal ER-negative BC was associated with improved DFS and OS.NCT00068601

Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance).

LBA505 Background: Premature ovarian failure (POF) is a common toxicity of CT. Risk depends on type and amount of CT, age, and perhaps ovarian cycling at the time of CT. POEMS is a SWOG-coordinated phase III randomized study to evaluate whether LHRH analog administration with CT for early-stage breast cancer (BC) would reduce POF.Premenopausal patients (PT) age <50 with stage I-IIIA ER/PR-negative BC to be treated with CT were randomized to receive standard cyclophosphamide-containing CT with or without monthly goserelin (GN) 3.6 mg SQ starting 1 week prior to the first CT dose. The primary endpoint is 2-year POF, defined as amenorrhea for the prior 6 months and post-menopausal FSH. Other endpoints include pregnancies and survival. Endpoints were analyzed in multivariable regression adjusting for stratification factors (age and CT regimen).Between 2/04 and 5/11, 257 PT enrolled. Among 218 evaluable PT, 62% had complete primary endpoint data. Dropouts (n=83) were mostly due to deaths (n=14) or lack of FSH data. There was no strong evidence of informative missing data by arm according to stratification factors (p>.05). POF rates were 22% in the standard arm and 8% in the GN arm (OR=0.30, 95% CI: 0.10-0.87, p=.03 [unadjusted analysis]; OR=0.36, 95%CI: 0.11-1.14, p=0.08 [adjusted logistic regression analysis]). In a sensitivity analysis defining 2-year POF more liberally as either amenorrhea or elevated FSH, 45% in the standard arm and 20% in the GN arm had POF (OR=0.29, 95% CI: 0.12-0.70, p=.006). There were 13 pregnancies in the standard arm and 22 in the GN arm (OR=2.22, 95% CI: 1.00-4.92, p=.05). DFS and OS were better in the GN arm (Cox regression, including stage: HR=0.49, 95% CI: 0.24-0.97, p=.04; HR=0.43, 95% CI: 0.18-1.00, p=.05, respectively).LHRH analog administration with CT was associated with less POF and more pregnancies. In an exploratory analysis, GN use in premenopausal ER-negative BC was associated with improved DFS and OS.NCT00068601

Final Analysis of the Prevention of Early Menopause Study (POEMS)/SWOG Intergroup S0230.

Premature menopause is a serious long-term side effect of chemotherapy. We evaluated long-term pregnancy and disease-related outcomes for patients in S0230/POEMS, a study in premenopausal women with stage I-IIIA estrogen receptor-negative, progesterone receptor-negative breast cancer to be treated with cyclophosphamide-containing chemotherapy. Women were randomly assigned to standard chemotherapy with or without goserelin, a gonadotropin-releasing hormone agonist, and were stratified by age and chemotherapy regimen. All statistical tests were two-sided. Of 257 patients, 218 were eligible and evaluable (105 in the chemotherapy + goserelin arm and 113 in the chemotherapy arm). More patients in the chemotherapy + goserelin arm reported at least one pregnancy vs the chemotherapy arm (5-year cumulative incidence = 23.1%, 95% confidence interval [CI] = 15.3% to 31.9%; and 12.2%, 95% CI = 6.8% to 19.2%, respectively; odds ratio = 2.34; 95% CI = 1.07 to 5.11; P = .03). Randomization to goserelin + chemotherapy was associated with a nonstatistically significant improvement in disease-free survival (hazard ratio [HR] = 0.55; 95% CI = 0.27 to 1.10; P = .09) and overall survival (HR = 0.45; 95% CI = 0.19 to 1.04; P = .06). In this long-term analysis of POEMS/S0230, we found continued evidence that patients randomly assigned to receive goserelin + chemotherapy were not only more likely to avoid premature menopause, but were also more likely to become pregnant without adverse effect on disease-related outcomes

Final Analysis of the Prevention of Early Menopause Study (POEMS)/SWOG Intergroup S0230.

Premature menopause is a serious long-term side effect of chemotherapy. We evaluated long-term pregnancy and disease-related outcomes for patients in S0230/POEMS, a study in premenopausal women with stage I-IIIA estrogen receptor-negative, progesterone receptor-negative breast cancer to be treated with cyclophosphamide-containing chemotherapy. Women were randomly assigned to standard chemotherapy with or without goserelin, a gonadotropin-releasing hormone agonist, and were stratified by age and chemotherapy regimen. All statistical tests were two-sided. Of 257 patients, 218 were eligible and evaluable (105 in the chemotherapy + goserelin arm and 113 in the chemotherapy arm). More patients in the chemotherapy + goserelin arm reported at least one pregnancy vs the chemotherapy arm (5-year cumulative incidence = 23.1%, 95% confidence interval [CI] = 15.3% to 31.9%; and 12.2%, 95% CI = 6.8% to 19.2%, respectively; odds ratio = 2.34; 95% CI = 1.07 to 5.11; P = .03). Randomization to goserelin + chemotherapy was associated with a nonstatistically significant improvement in disease-free survival (hazard ratio [HR] = 0.55; 95% CI = 0.27 to 1.10; P = .09) and overall survival (HR = 0.45; 95% CI = 0.19 to 1.04; P = .06). In this long-term analysis of POEMS/S0230, we found continued evidence that patients randomly assigned to receive goserelin + chemotherapy were not only more likely to avoid premature menopause, but were also more likely to become pregnant without adverse effect on disease-related outcomes

Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy.

BackgroundOvarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes.MethodsWe randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival.ResultsAt baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05).ConclusionsAlthough missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.)

Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy.

BackgroundOvarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes.MethodsWe randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival.ResultsAt baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05).ConclusionsAlthough missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.)

Anthropometrische Messungen in der NAKO Gesundheitsstudie: mehr als nur Größe und Gewicht

High levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research. The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging. BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes. The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases. © 2020, The Author(s)