Fairness and transparency throughout a digital humanities workflow: Challenges and recommendations

How can we achieve sufficient levels of transparency and fairness for (humanities) research based on historical newspapers? Which concrete measures should be taken by data providers such as libraries, research projects and individual researchers? We approach these questions from the vantage point that digitised newspapers are complex sources with a high degree of heterogeneity caused by a long chain of processing steps, ranging, e.g., from digitisation policies, copyright restrictions to the evolving performance of tools for their enrichment such as OCR or article segmentation. Overall, we emphasise the need for careful documentation of data processing, research practices and the acknowledgement of support from institutions and collaborators

Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: A phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy

<p>Abstract</p> <p>Background</p> <p>In recent years, preoperative volume reduction of locally advanced breast cancers, resulting in higher rates of breast-conserving surgery (BCS), has become increasingly important also in postmenopausal women. Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors (AIs), including letrozole, for such neoadjuvant endocrine treatment. This usually lasts 3–4 months and has been extended to up to 12 months, but optimal treatment duration has not been fully established.</p> <p>Methods</p> <p>This study was designed as a multicenter, open-label, single-arm, exploratory phase IIb/III clinical trial of letrozole 2.5 mg, one tablet daily, for 4–8 months. The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration. Tumor regression (by clinical examination, mammography, and ultrasound), shift towards BCS eligibility, and safety assessments were the main outcome measures. Standard parametric and nonparametric descriptive statistics were performed.</p> <p>Results</p> <p>Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women (median (range): 67.0 (56–85) years) with unilateral, initially BCS-ineligible primary breast cancer (clinical stage ≥ T2, N0, M0). Letrozole treatment duration in the modified intent-to-treat (ITT; required 4 months' letrozole treatment) analysis population (29 patients) was 4 months in 14 patients and > 4 months in 15 patients. The respective per-protocol (PP) subgroup sizes were 14 and 11. The majority of partial or complete responses were observed at 4 months, though some beneficial responses occurred during prolonged letrozole treatment. Compared with baseline, median tumor size in the ITT population was reduced by 62.5% at Month 4 and by 70.0% at final study visit (Individual End). Similarly, in the PP population, respective reductions were 64.0% and 67.0%. Whereas initially all patients were mastectomy candidates, letrozole treatment enabled BCS (lumpectomy) in 22 ITT (75.9%) and 18 PP (72.0%) patients.</p> <p>Conclusion</p> <p>Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment. While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients, there is no clear optimum for treatment duration. Letrozole has a favorable overall safety and tolerability profile.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier NCT00535418.</p

Impact of immune checkpoint inhibitors on the management of locally advanced or metastatic non-small cell lung cancer in real-life practice in patients initiating treatment between 2015 and 2018 in France and Germany

International audienceObjectives: To describe the impact of immune checkpoint inhibitors (ICIs) on treatment patterns and survival outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) in France and Germany. Materials and Methods: Patients with aNSCLC without known ALK or EGFR mutations receiving first-line (1L) therapy were included from (i) the retrospective Epidemiological-Strategy and Medical Economics Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015–2018) and (ii) the prospective Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients platform (CRISP, Germany; 2016–2018). Analyses were stratified according to histology. Survival outcomes were estimated using Kaplan–Meier methodology and stratified by year of 1L therapy. Data sources were analysed separately. Results: In ESME-AMLC and CRISP, 8,046 and 2,359 patients were included in the study, respectively. In both countries, approximately 20 % of all patients received pembrolizumab monotherapy as 1L treatment in 2018. In ESME-AMLC, the proportion receiving an ICI over the course of treatment (any line) increased from 42.2 % (2015) to 56.1 % (2018) in patients with squamous histology, and 28.9 % to 51.9 % with non-squamous/other; in CRISP, it increased from 50.6 % (2016) to 65.2 % (2018) with squamous histology, and 40.8 % to 62.7 % with non-squamous/other. Two-year overall survival from 1L initiation was 36.8 % and 25.6 % in the squamous cohorts and 36.5 % and 30.8 % in the non-squamous/other cohorts in ESME-AMLC and CRISP, respectively. No significant change in overall survival was observed over time; however, the follow-up time available was limited in the later years of the analysis. Conclusion: The results of this joint research from two large clinical databases in France and Germany demonstrate the growing use of ICIs in the management of aNSCLC. Future analyses will allow for the evaluation of the impact of ICIs on long-term survival of patients with aNSCLC