Donna P Ankerst

Technische Universität München, München, Bavaria, Germany

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Publications (84)618.9 Total impact

  • Ian M Thompson, Robin J Leach, Donna P Ankerst
    JAMA The Journal of the American Medical Association 08/2014; · 29.98 Impact Factor
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    ABSTRACT: Purpose. To evaluate progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) as potential surrogate endpoints (SEP) for overall survival (OS) in second-line treatment for metastatic colorectal cancer (mCRC). Methods. A systematic literature search of randomised trials of second-line chemotherapy for mCRC reported from January 2000 to July 2013 was performed. Correlation coefficients weighted by number of patients in the treatment arms between median PFS, ORR and DCR with median OS were estimated. Results. Twenty-three trials reflecting 10 800 patients met the inclusion criteria. Median PFS and OS across all trials were 4.5 months and 11.5 months and median ORR and DCR were 11.4% and 65%, respectively. PFS showed moderate correlation with OS [RPFS = 0.73; 95% confidence interval (CI) 0.61-0.82]. In contrast, ORR only weakly correlated with OS (RORR = 0.58; 95% CI 0.38-0.72, n = 22). Despite a small number of studies (n = 10) reporting on DCR, moderate correlation with OS was observed (RDCR = 0.74; 95% CI 0.56-0.86). Conclusion. Based on the available trial-level data, PFS may serve as an appropriate SEP in second-line chemotherapy for mCRC. A small number of studies revealed moderate correlation of DCR with OS that justifies further investigation.
    Acta oncologica (Stockholm, Sweden) 07/2014; · 2.27 Impact Factor
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    ABSTRACT: To modify the Prostate Cancer Prevention Trial risk calculator (PCPTRC) to predict low- vs high-grade (Gleason grade ≥7) prostate cancer and incorporate percent free-prostate-specific antigen (PSA).
    Urology 06/2014; 83(6):1362-8. · 2.42 Impact Factor
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    ABSTRACT: It is well known that increased spring temperatures cause earlier onset dates of leaf unfolding and flowering. However, a temperature increase in winter may be associated with delayed development when species' chilling requirements are not fulfilled. Furthermore, photosensitivity is supposed to interfere with temperature triggers. To date, neither the relative importance nor possible interactions of these three factors have been elucidated. In this study, we present a multispecies climate chamber experiment to test the effects of chilling and photoperiod on the spring phenology of 36 woody species. Several hypotheses regarding their variation with species traits (successional strategy, floristic status, climate of their native range) were tested. Long photoperiods advanced budburst for one-third of the studied species, but magnitudes of these effects were generally minor. In contrast to prior hypotheses, photosensitive responses were not restricted to climax or oceanic species. Increased chilling length advanced budburst for almost all species; its effect greatly exceeding that of photoperiod. Moreover, we suggest that photosensitivity and chilling effects have to be rigorously disentangled, as the response to photoperiod was restricted to individuals that had not been fully chilled. The results indicate that temperature requirements and successional strategy are linked, with climax species having higher chilling and forcing requirements than pioneer species. Temperature requirements of invasive species closely matched those of native species, suggesting that high phenological concordance is a prerequisite for successful establishment. Lack of chilling not only led to a considerable delay in budburst but also caused substantial changes in the chronological order of species' budburst. The results reveal that increased winter temperatures might impact forest ecosystems more than formerly assumed. Species with lower chilling requirements, such as pioneer or invasive species, might profit from warming winters, if late spring frost events would in parallel occur earlier.
    Global Change Biology 01/2014; 20(1):170-82. · 8.22 Impact Factor
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    ABSTRACT: Adiponectin has been reported to have a prohibitory effect on prostate cancer. The goal of this study was to evaluate the diagnostic value of adiponectin multimers for prostate cancer. Total adiponectin, high- and low molecular weight (HMW, LMW), ratios of these measures, and body mass index (BMI) were compared in a prospective prostate cancer screened cohort. Multivariable logistic regression was used to assess the association between adiponectin measures, their interaction with BMI, and risk of prostate cancer and Gleason score upgrading from biopsy to prostatectomy. 228 prostate cancer cases and 239 controls were analyzed: 72 (31.6%) of the cancer cases were high-grade (Gleason grade >7). Only percent HMW had a statistically significant relationship with prostate cancer [p = 0.04]. Among normal and overweight men, the risk of prostate cancer increased as percent HMW increased (OR = 1.24 for a doubling of percent HMW, 95% confidence interval [0.41,3.75] and 1.81[1.02,3.20], respectively), whereas among obese men, the risk of prostate cancer decreased (OR = 0.62, [0.32,1.18]). Among 97 patients who underwent radical prostatectomy, there was no association between Gleason score upgrading and any of the adiponectin multimers. This study was unable to confirm the utility of total adiponectin as a biomarker for prostate cancer risk. For the adiponectin multimers, only HWM showed increases with prostate cancer but not in all weight classes. While adiponectin may play a role in the pathogenesis of prostate cancer, our results do not support adiponectin multimers as biomarkers of detection.
    Cancer Epidemiology Biomarkers &amp Prevention 12/2013; · 4.56 Impact Factor
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    ABSTRACT: To examine the effect of prostate volume, number of biopsy cores, and American Urological Association symptom score (AUASS) for prostate cancer risk assessment among men receiving finasteride in the Prostate Cancer Prevention Trial. Data from 4509 men on the finasteride arm of the Prostate Cancer Prevention Trial who were on treatment at the time of their AUASS and prostate-specific antigen (PSA) measurement before biopsy were included in multivariable logistic regression analyses. Six hundred eighty-two (15.1%) participants had prostate cancer; 257 (37.7%) of these had high-grade disease. For prostate cancer risk, the model included PSA (odds ratio corresponding to a 2-fold increase in PSA: 2.70; P <.0001), digital rectal examination (2.53; P <.0001), age (1.03; P = .001), and prostate volume (odds ratio 0.54 for a 2-fold increase in volume; P <.0001). For high-grade disease, PSA (3.39; P <.0001), digital rectal examination (2.75; P <.0001), age (1.05; P = .001), and volume (0.55; P <.0001) were statistically significant. AUASS was not statistically significant in any of the models that included prostate volume, but was in models in which volume was not included. The number of biopsy cores did not significantly improve risk assessment in any of the models considered. Although in the general population, obtaining a cancer diagnosis is improved by assessing prostate volume and increasing the number of biopsy cores, neither steps are required in men receiving finasteride. Obtaining fewer biopsy cores in men receiving finasteride preserves biopsy sensitivity and will likely reduce cost and morbidity.
    Urology 09/2013; · 2.42 Impact Factor
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    ABSTRACT: Purpose We assessed the independent predictive value of prostate volume, number of biopsy cores and AUASS (American Urological Association symptom score) compared to risk factors included in the PCPTRC (Prostate Cancer Prevention Trial risk calculator for prostate cancer) and PCPTHG (Prostate Cancer Prevention Trial risk calculator for high grade cancer [Gleason grade 7 or greater]). Materials and Methods Of 5,519 PCPT (Prostate Cancer Prevention Trial) participants used to construct the PCPTRC 4,958 with AUASS and prostate specific antigen 10 ng/ml or less were included on logistic regression analysis. Risk algorithms were evaluated in 571 EDRN (Early Detection Research Network) participants using the ROC AUC. Results A total of 1,094 participants (22.1%) had prostate cancer, of whom 232 (21.2%) had high grade disease. For prostate cancer prediction higher prostate specific antigen, abnormal digital rectal examination, family history of prostate cancer and number of cores were associated with increased risk, while volume was associated with decreased risk. Excluding prostate volume and number of cores, a history of negative biopsy and increased AUASS were also associated with lower risk. For high grade cancer higher prostate specific antigen, abnormal digital rectal examination, black race and number of cores were associated with increased risk and volume, while AUASS was associated with decreased risk. The AUC of the PCPTRC adjusted for volume and number of cores was 72.7% (using EDRN data), 68.2% when adjusted for AUASS alone and 67.6% PCPTRC. For high grade disease the AUCs were 74.8%, 74.0% and 73.5% (PCPTHG), respectively. Conclusions Adjusted PCPT risk calculators for volume, number of cores and AUASS improve cancer detection.
    The Journal of urology 07/2013; 190(1):70–76. · 4.02 Impact Factor
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    ABSTRACT: BACKGROUND: The Prostate Cancer Prevention Trial (PCPT) Risk Calculator is a widely used prediction tool for aiding decisions about biopsy for prostate cancer. This study hypothesized that recently reported differences between predictions from the model and findings from other cohorts were due to how prostate-specific antigen (PSA) was entered into the statistical model, and to the inclusion of protocol end-of-study biopsies for which there was no clinical indication. METHODS: Data was obtained from the 5088 PCPT participants and was used to construct the PCPT Risk Calculator. The relationship between PSA and the risk of a positive biopsy was modeled by using locally-weighted regression (lowess), an empirical estimate of actual risks observed which does not depend on a statistical model. Risks were estimated with and without the 3514 end-of-study biopsies. RESULTS: For PSA levels above biopsy thresholds (∼4 ng/mL), the PCPT Risk Calculator greatly overestimated actual empirical risks (eg, 44% versus 26% at 5 ng/mL). The change in risk with increasing PSA was less among for-cause biopsies compared with the end-of-study biopsies (P = .001). Risk of high-grade disease was overestimated at PSA level of ≥ 6 ng/mL. CONCLUSIONS: The PCPT Risk Calculator overestimates risks for PSAs close to and above typical biopsy thresholds. Separating for-cause biopsies from end-of-study biopsies and using empirical rather than model-based risks reduces overall risk estimates and replicates prior findings that, in men who have been screened with PSA, there is no rapid increase in prostate cancer risk with higher PSA. Revision of the PCPT Risk Calculator should be considered. Cancer 2013. © 2013 American Cancer Society.
    Cancer 05/2013; · 5.20 Impact Factor
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    ABSTRACT: Phenology ranks among the best ecosystem processes for fingerprinting climate change since temperature explains a high percentage of the interannual or spatial variation in phenological onset dates. However, roles of other environmental variables, such as foliar nutrient concentrations, are far from adequately understood. This observational study examined the effects of air temperature and 11 nutrients on spring phenology of Betula pendula Roth (birch) along an urban-rural gradient in Munich, Germany, during the years 2010/2011. Moreover, the influence of temperature, nutrients, and air pollutants (NO2 and O3) on the amounts of pollen and catkin biomass in 2010 was evaluated. In addition to the influence of higher temperatures advancing phenological onset dates, higher foliar concentrations of potassium, boron, zinc, and calcium were statistically significantly linked to earlier onset dates. Since flushing of leaves is a turgor-driven process and all the influential nutrients are involved in cell extension, membrane function, and stability, there might be a reasonable physiological interpretation of the observed association. The amounts of pollen were negatively correlated with temperature, atmospheric NO2, and foliar iron concentration, suggesting that these variables restrict pollen production. The results of this study suggested an influence of nutritional status on both phenology and pollen production. The interaction of urbanization and climate change should be considered in the assessment of the impact of global warming on ecosystems and human health.
    Journal of Experimental Botany 04/2013; 64(7):2081-92. · 5.24 Impact Factor
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    ABSTRACT: Summary Patients who were previously treated for prostate cancer with radiation therapy are monitored at regular intervals using a laboratory test called Prostate Specific Antigen (PSA). If the value of the PSA test starts to rise, this is an indication that the prostate cancer is more likely to recur, and the patient may wish to initiate new treatments. Such patients could be helped in making medical decisions by an accurate estimate of the probability of recurrence of the cancer in the next few years. In this article, we describe the methodology for giving the probability of recurrence for a new patient, as implemented on a web-based calculator. The methods use a joint longitudinal survival model. The model is developed on a training dataset of 2386 patients and tested on a dataset of 846 patients. Bayesian estimation methods are used with one Markov chain Monte Carlo (MCMC) algorithm developed for estimation of the parameters from the training dataset and a second quick MCMC developed for prediction of the risk of recurrence that uses the longitudinal PSA measures from a new patient.
    Biometrics 02/2013; · 1.41 Impact Factor
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    ABSTRACT: PURPOSE: The large international variation in the incidence of prostate cancer (PC) is well known but the underlying reasons are not understood. We want to compare PC incidence and survival among immigrants to Sweden in order to explain the international differences. METHODS: Cancer data were obtained from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for PC in first-degree immigrants by country of birth. The immigrants were classified into four groups by SIR and area of origin. Survival in PC was assessed by hazard ratio (HR) in the four groups. In some analyses, clinical stage of PC was assessed by the tumor, node, and metastasis classification. RESULTS: The SIR was 0.47 (95 % confidence interval 0.43-0.51) for immigrants with the lowest risk, constituting men from Turkey, Middle East, Asia, and Chile. The HR was 0.60 (0.45-0.81) for these men and it was 0.49 if they had stayed 20+ years in Sweden. The SIR in screening detected PC, T1c, was 0.55. Among these men, screening detected PC constituted 34.5 % of all PC, compared to 29.0 % among Swedes (p = 0.10). CONCLUSIONS: The results showed that the non-European immigrants, of mainly Middle East, Asian, and Chilean origin, with the lowest risk of PC, also had the most favorable survival in PC. As the available clinical features of PC at diagnosis or the distribution of known risk factors could not explain the differences, a likely biological mechanism through a favorable androgenic hormonal host environment is suggested as an explanation of the observed effects.
    World Journal of Urology 01/2013; · 2.89 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate progression-free survival (PFS) as potential surrogate endpoint (SEP) for overall survival (OS) in metastatic colorectal cancer (mCRC) with focus on applicability to trials containing targeted therapy with anti-VEGF- or anti-EGFR directed monoclonal antibodies. Methods: A systematic literature search of randomized trials of first-line chemotherapy for mCRC reported from January 2000 to January 2012 was performed. Adjusted weighted linear regression was used to calculate correlations within PFS and OS (endpoints; REP) and between treatment effects on PFS and on OS (treatment effects; RTE). RESULTS: Fifty trials reflecting 22,736 patients met the inclusion criteria. Correlation between treatment effects on PFS and OS and between the endpoints PFS and OS were high across all studies (RTE = 0.87, REP = 0.86). This was also observed in chemotherapy-only trials (RTE = 0.93, REP = 0.81), but less so for trials containing monoclonal antibodies (RTE = 0.47; REP = 0.52). Limiting the analysis to bevacizumab-based studies (eleven trials, 3,310 patients) yielded again high correlations between treatment effects on PFS and on OS (RTE = 0.84), while correlation within PFS and OS was low (REP = 0.45). In seven trials (1,335 patients) investigating cetuximab or panitumumab-based studies, contrasting correlations with very wide confidence intervals were observed (RTE = 0.28; REP = 0.96). CONCLUSIONS: PFS demonstrated consistently high correlation with OS of an order that would justify its use as an SEP in chemotherapy regimens. For validation of surrogacy in anti-VEGF and anti-EGFR-directed therapies, further research and a larger set of trials is needed.
    Clinical Cancer Research 11/2012; · 7.84 Impact Factor
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    Donna P Ankerst, Ian M Thompson
    European Urology 07/2012; 62(1):180. · 10.48 Impact Factor
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    ABSTRACT: MATERIALS AND METHODS: Risks of prostate cancer (CaP) and high-grade CaP were evaluated using the Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) in an age-stratified random sample of 1,021 Caucasian and African-American men with no previous diagnosis of CaP, aged 55-74 years, residing in King County, WA, USA. RESULTS: Median PCPTRC risks of CaP (high-grade CaP) were 15.6% (1.2%), 18.7% (2.0%), 18.5% (2.2%), and 26.4% (5.1%) for 55-59, 60-64, 65-69, and 70-74-year-old men, respectively; 25.2% of men aged 55-59 had a 25% or greater PCPTRC risk of CaP; this increased to 53.1% in men aged 70-74; 9.4% of men aged 55-59 had a 6% or greater PCPTRC risk of high-grade CaP, increasing to 44.1% in men aged 70-74. CONCLUSIONS: PCPTRC risk of CaP in a community of US males is high and confounded with overdetected cancers. In contrast, average community PCPTRC risk of high-grade disease is low and increases gradually by age and may better serve for counseling purposes.
    Urologic Oncology 05/2012; · 3.65 Impact Factor
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    ABSTRACT: OBJECTIVES: To assess the applicability of the Prostate Cancer Prevention Trial High Grade (Gleason grade ≥ 7) Risk Calculator (PCPTHG) in ten international cohorts, representing a range of populations. METHODS: A total of 25,512 biopsies from 10 cohorts (6 European, 1 UK and 3 US) were included; 4 implemented 6-core biopsies, and the remaining had 10 or higher schemes; 8 were screening cohorts, and 2 were clinical. PCPTHG risks were calculated using prostate-specific antigen, digital rectal examination, age, African origin and history of prior biopsy and evaluated in terms of calibration plots, areas underneath the receiver operating characteristic curve (AUC) and net benefit curves. RESULTS: The median AUC of the PCPTHG for high-grade disease detection in the 10- and higher-core cohorts was 73.5 % (range, 63.9-76.7 %) compared with a median of 78.1 % (range, 72.0-87.6 %) among the four 6-core cohorts. Only the 10-core Cleveland Clinic cohort showed clear evidence of under-prediction by the PCPTHG, and this was restricted to risk ranges less than 15 %. The PCPTHG demonstrated higher clinical net benefit in higher-core compared with 6-core biopsy cohorts, and among the former, there were no notable differences observed between clinical and screening cohorts, nor between European and US cohorts. CONCLUSIONS: The PCPTHG requires minimal patient information and can be applied across a range of populations. PCPTHG risk thresholds ranging from 5 to 20 %, depending on patient risk averseness, are recommended for clinical prostate biopsy decision-making.
    World Journal of Urology 04/2012; · 2.89 Impact Factor
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    Ian M Thompson, Donna P Ankerst
    World Journal of Urology 01/2012; 30(2):129-30. · 2.89 Impact Factor
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    ABSTRACT: Increasing risk of pollinosis (hay fever) is one of the most anticipated consequences of climate change on human health. Wind-pollinated plants are representative of allergenic species because they include species with the highest capability of causing allergy-related diseases in humans. Therefore, changes in wind-pollinated species may reflect impacts of climate change on allergenic plants. In particular, flowering is one of the developmental stages most affected by climate change. This report specifically addresses changes in flowering dates that have occurred during the three decades 1971—2000 as a function of pollination mode and woodiness. The assessment is made using a phenological data set comprising trends of flowering dates of 29 species in 983 locations in Europe. Linear mixed models assessing the statistical significance of trends while adjusting for spatial correlation are used. The main results indicate for the first time that the onset of flowering of wind-pollinated plants advanced more than for insect-pollinated plants, while full flowering phases tended to advance less. These novel findings are contrary to the results of Fitter and Fitter (2002) for Oxfordshire, who reported larger advances of insect-pollinated plants. Onset of flowering and full flowering of insect-pollinated species are more likely to advance for seasons early in the year; instead, wind-pollinated plants showed no dependence of trends on the season (first flowering) or a decreased advance of phases that are early in the year (full flowering). The effect of woodiness could not be unambiguously defined, but seems to be of minor importance. The presented findings suggest a lengthening of the flowering period in general, which might lead to an increasing time of exposure to airborne pollen of allergic subjects, with consequent likely increment in severity and incidence of allergic symptoms.
    Ecography 01/2012; 35(11):1017-1023. · 5.12 Impact Factor
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    ABSTRACT: The diagnosis and detection of prostate cancer has undergone profound changes over the past three decades, due primarily to the development and widespread clinical use of prostate-specific antigen (PSA) testing. These changes have led to substantial differences in the prostate cancer phenotype. It is important to understand these changes to develop appropriate treatment options for contemporarily diagnosed prostate cancer. We explored a group of four temporal changes in prostate cancer detection that occurred after the advent of PSA testing. Through changes in the use of PSA testing, performance of prostate biopsy, application of PSA testing in different age groups, and pathologic tumor grading, a significant increase in detection of potentially inconsequential prostate cancers has occurred. The prostate cancer of 2011 is generally a smaller, lower-grade tumor and more often observed in younger men. These changes in detection will allow for increased use of active surveillance for prostate cancer.
    JNCI Monographs 01/2012; 2012(45):162-8.
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    ABSTRACT: This study reports on alterations in the magnitude and frequency of extremes in reproductive phenology using long‐term records (1951–2008) for plant species widely distributed across Germany. For each of fourteen indicator phases studied, time series of annual onset dates at up to 119 stations, providing 50–58 years of observation, were standardized by their station mean and standard deviation. Four alternative statistical models were applied and compared to derive probabilities of extreme early or late onset times for the phases: (1) Gaussian models were used to describe decadal probabilities of standardized anomalies, defined by data either falling below the 5th or exceeding the 95th percentile. (2) Semi‐parametric quantile regression was employed for flexible and robust modelling of trends in different quantiles of onset dates. (3) Generalized extreme value distributions (GEV) were fitted to annual detrended minima and maxima of standardized anomalies, and (4) Generalized Pareto distributions (GPD) were fitted to extremes defined as peaks over threshold. Probabilities of extreme early phenological events inferred from Gaussian models, increased on average from 3 to 12%, whereas probabilities of extreme late phenological events decreased from 6 to 2% over the study period. Based on quantile regressions, summer and autumn phases revealed a more pronounced advancing pattern than spring phases. Estimated return levels by GEV were similar for the GPD methods, indicating that extreme early phenological events of magnitudes 2.5, 2.8, and 3.6 on the detrended standardized anomaly scale would occur every 20 years for spring, summer and autumn phases, respectively. This corresponds to absolute onset advances of up to 2 months depending on the season and species. This study demonstrates how extreme phenological events can be accurately modelled even in cases of inherently small numbers of observations, and underlines the need for additional evaluation related to their impacts on ecosystem functioning.
    Global Change Biology 01/2012; 18(7). · 8.22 Impact Factor
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    ABSTRACT: To evaluate the discrimination, calibration, and net benefit performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) across five European randomized study of screening for prostate cancer (ERSPC), 1 United Kingdom, 1 Austrian, and 3 US biopsy cohorts. PCPTRC risks were calculated for 25,733 biopsies using prostate-specific antigen (PSA), digital rectal examination, family history, history of prior biopsy, and imputation for missing covariates. Predictions were evaluated using the areas underneath the receiver operating characteristic curves (AUC), discrimination slopes, chi-square tests of goodness of fit, and net benefit decision curves. AUCs of the PCPTRC ranged from a low of 56% in the ERSPC Goeteborg Rounds 2-6 cohort to a high of 72% in the ERSPC Goeteborg Round 1 cohort and were statistically significantly higher than that of PSA in 6 out of the 10 cohorts. The PCPTRC was well calibrated in the SABOR, Tyrol, and Durham cohorts. There was limited to no net benefit to using the PCPTRC for biopsy referral compared to biopsying all or no men in all five ERSPC cohorts and benefit within a limited range of risk thresholds in all other cohorts. External validation of the PCPTRC across ten cohorts revealed varying degree of success highly dependent on the cohort, most likely due to different criteria for and work-up before biopsy. Future validation studies of new calculators for prostate cancer should acknowledge the potential impact of the specific cohort studied when reporting successful versus failed validation.
    World Journal of Urology 12/2011; 30(2):181-7. · 2.89 Impact Factor

Publication Stats

2k Citations
618.90 Total Impact Points

Institutions

  • 2012–2014
    • Technische Universität München
      • • Chair of Ecoclimatology
      • • Department of Ecology and Ecosystem Management
      • • Department of Mathematical Statistics
      München, Bavaria, Germany
  • 2006–2014
    • University of Texas Health Science Center at San Antonio
      • Department of Urology
      San Antonio, Texas, United States
    • Dokuz Eylul University
      • Department of Psychiatry
      İzmir, Izmir, Turkey
  • 2011–2012
    • Ludwig-Maximilian-University of Munich
      München, Bavaria, Germany
  • 2009
    • American Cancer Society
      Atlanta, Georgia, United States
  • 2008
    • Vanderbilt University
      • Department of Biostatistics
      Nashville, MI, United States
  • 2005–2007
    • Fred Hutchinson Cancer Research Center
      • Division of Public Health Sciences
      Seattle, Washington, United States
    • Texas Tech University Health Sciences Center
      • Department of Urology
      Lubbock, TX, United States