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Patients with lung cancer under treatment have been associated with a high risk of COVID‐19 infection and potentially worse outcome, but real‐world data on patient‐reported outcomes (PROs) are rare. We assess patients' characteristics and PROs before and during the COVID‐19 pandemic in an advanced non‐small cell lung cancer (NSCLC) cohort in Germany. Patients with locally advanced or metastatic NSCLC from the prospective, multicentre, observational CRISP Registry (NCT02622581) were categorised as pre‐pandemic (March 2019 to Feb 2020, n = 1621) and pandemic (March 2020 to Feb 2021, n = 1317). From baseline to month 15, patients' health‐related quality of life (HRQoL) was assessed by FACT‐L, anxiety and depression by PHQ‐4. Association of pandemic status with time to deterioration (TTD) in QoL scales adjusted for potential covariates was estimated using Cox modelling. PROs were documented for 1166 patients (72%) in the pre‐pandemic, 979 (74%) in the pandemic group. Almost 60% of patients were male, median age was 66 years, comorbidities occurred in 85%. Regarding HRQoL, mean‐change‐from‐baseline plots hardly differed between both samples. Approximately 15%–21% of patients reported anxiety, about 19%–27% signs of depression. For the pandemic group, TTD was slightly, but statistically significantly, worse for the physical well‐being‐FACT‐G subscale (HR 1.15 [95%CI 1.02–1.30]) and the anxiety‐GAD‐2 subscale (HR 1.14 [95%CI 1.01–1.29]). These prospectively collected real‐world data provide valuable insights into PROs before and during the COVID‐19 pandemic in advanced NSCLC. For the patients, the pandemic seemed to be less of a burden than the disease itself, as there was a considerable proportion of patients with anxiety and depression in both groups. [ABSTRACT FROM AUTHOR]

Background: This study aimed to describe treatment patterns and overall survival (OS) in patients with advanced non–small cell lung cancer (aNSCLC) in three countries between 2011 and 2020. Methods: Three databases (US, Canada, Germany) were used to identify incident aNSCLC patients. OS was assessed from the date of incident aNSCLC diagnosis and, for patients who received at least a first line of therapy (1LOT), from the date of 1LOT initiation. In multivariable analyses, we analyzed the influence of index year and type of prescribed treatment on OS. Findings: We included 51,318 patients with an incident aNSCLC diagnosis. The percentage of patients treated with a 1LOT differed substantially between countries, whereas the number of patients receiving immunotherapies/targeted treatments increased over time in all three countries. Median OS from the date of incident diagnosis was 9.9 months in the United States vs. 4.1 months in Canada. When measured from the start of 1LOT, patients had a median OS of 10.7 months in the United States, 10.9 months in Canada, and 10.9 months in Germany. OS from the start of 1LOT improved in all three countries from 2011 to 2020 by approximately 3 to 4 months. Conclusions: Observed continuous improvement in OS among patients receiving at least a 1LOT from 2011 to 2020 was likely driven by improved care and changes in the treatment landscape. The difference in the proportion of patients receiving a 1LOT in the observed countries requires further investigation. Observed continuous improvement in overall survival among patients receiving at least a first line of therapy from 2011 to 2020 was likely driven by improved care and changes in treatment landscape. The difference in the proportion of patients receiving a first line of therapy in the observed countries requires further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a need to better understand the effectiveness of new treatments, such as the recently approved nivolumab, in patients with locally advanced or metastatic non-small cell lung cancer in clinical practice. This study aims to report the characteristics and outcomes of 2784 patients with locally advanced or metastatic non-small cell lung cancer receiving nivolumab in second-line or later in France (ESME-AMLC) and Germany (CRISP) between 2015 and 2020. Two-year survival rates were 26.7% in patients with tumors with squamous histology and 32.8% in patients with non-squamous/others histologies in ESME-AMLC, and 20.9% and 18.9%, respectively, in CRISP. Poorer performance score and shorter duration from the previous line of therapy initiation were significantly associated with shorter treatment duration with nivolumab and overall survival. These real-world data provide insight into the characteristics of patients receiving nivolumab in France and Germany and confirm the efficacy of nivolumab previously observed in clinical trials. This study reports characteristics and outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) receiving nivolumab in second-line or later (2L+) in France and Germany between 2015 and 2020. Patients with aNSCLC (stage IIIB–C/IV) receiving nivolumab in 2L+ were included from the retrospective Epidemiological Strategy and Medical Economics of Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015–2019) and Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients (CRISP, Germany; 2016–2020). Overall, 2262 ESME-AMLC and 522 CRISP patients were included. Median treatment duration (95% confidence intervals) was 2.8 months (2.5–3.2) in squamous and 2.5 months (2.3–2.8) in non-squamous/others patients in ESME-AMLC, and 2.3 months (1.4–3.1) and 2.3 months (2.0–2.8), respectively in CRISP. One-year and two-year overall survival (OS) were 47.2% and 26.7% in squamous and 50.8% and 32.8% in non-squamous/others patients in ESME-AMLC, and 43.1% and 20.9%, and 37.7% and 18.9%, respectively in CRISP. Poorer performance score and shorter time from start of previous line of therapy initiation were significantly associated with shorter treatment duration and OS. This study confirms, in real-world clinical databases, the efficacy of nivolumab previously observed in clinical trials. [ABSTRACT FROM AUTHOR]

• Treatments and outcomes in locally advanced/metastatic non-small cell lung cancer. • Real-world patients in France and Germany (2015–2018) without ALK/EGFR mutations. • In first-line-treated patients, >50 % received an immune checkpoint inhibitor (ICI) • Future analyses will allow evaluation of the impact of wider ICI use in first-line. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: The early COVID-19-pandemic was characterized by changes in decision making, decision-relevant value systems and the related perception of decisional uncertainties and conflicts resulting in decisional burden and stress. The vulnerability of clinical care professionals to these decisional dilemmas has not been characterized yet. Methods: A cross-sectional questionnaire study (540 patients, 322 physicians and 369 nurses in 11 institutions throughout Germany) was carried out. The inclusion criterion was active involvement in clinical treatment or decision making in oncology or psychiatry during the first year of COVID-19. The questionnaires covered five decision dimensions (conflicts and uncertainty, resources, risk perception, perception of consequences for clinical processes, and the perception of consequences for patients). Data analysis was performed using ANOVA, Pearson rank correlations, and the Chi²-test, and for inferential analysis, nominal logistic regression and tree classification were conducted. Results: Professionals reported changes in clinical management (27.5%) and a higher workload (29.2%), resulting in decisional uncertainty (19.2%) and decisional conflicts (22.7%), with significant differences between professional groups (p < 0.005), including anxiety, depression, loneliness and stress in professional subgroups (p < 0.001). Nominal regression analysis targeting "Decisional Uncertainty" provided a highly significant prediction model (LQ p < 0.001) containing eight variables, and the analysis for "Decisional Conflicts" included six items. The classification rates were 64.4% and 92.7%, respectively. Tree analysis confirmed three levels of determinants. Conclusions: Decisional uncertainty and conflicts during the COVID-19 pandemic were independent of the actual pandemic load. Vulnerable professional groups for the perception of a high number of decisional dilemmas were characterized by individual perception and the psychological framework. Coping and management strategies should target vulnerability, enable the handling of the individual perception of decisional dilemmas and ensure information availability and specific support for younger professionals. [ABSTRACT FROM AUTHOR]

Simple Summary: Pandemics induce many changes in clinical management. The consequences and extent of these changes are perceived in an individual manner and differ between various stakeholder groups. Using a cross-sectional questionnaire in 11 German institutions we evaluated the different perceptions of related risks and decision-making processes. All the investigated groups share concerns about the impact of the COVID-19 pandemic on healthcare management and clinical processes, but to very different extent. Their perception is dissociated in projection towards other stakeholders. Specific awareness should avoid this dissociation that potentially results in impaired shared decision-making. Background: Pandemics are related to changes in clinical management. Factors that are associated with individual perceptions of related risks and decision-making processes focused on prevention and vaccination, but perceptions of other healthcare consequences are less investigated. Different perceptions of patients, nurses, and physicians on consequences regarding clinical management, decisional criteria, and burden were compared. Study Design: Cross-sectional OnCoVID questionnaire studies. Methods: Data that involved 1231 patients, physicians, and nurses from 11 German institutions that were actively involved in clinical treatment or decision-making in oncology or psychiatry were collected. Multivariate statistical approaches were used to analyze the stakeholder comparisons. Results: A total of 29.2% of professionals reported extensive changes in workload. Professionals in psychiatry returned severe impact of pandemic on all major aspects of their clinical care, but less changes were reported in oncology (p < 0.001). Both patient groups reported much lower recognition of treatment modifications and consequences for their own care. Decisional and pandemic burden was intensively attributed from professionals towards patients, but less in the opposite direction. Conclusions: All of the groups share concerns about the impact of the COVID-19 pandemic on healthcare management and clinical processes, but to very different extent. The perception of changes is dissociated in projection towards other stakeholders. Specific awareness should avoid the dissociated impact perception between patients and professionals potentially resulting in impaired shared decision-making. [ABSTRACT FROM AUTHOR]

(1) Background: Uncertainty is typical for a pandemic or similar healthcare crisis. This affects patients with resulting decisional conflicts and disturbed shared decision making during their treatment occurring to a very different extent. Sociodemographic factors and the individual perception of pandemic-related problems likely determine this decisional dilemma for patients and can characterize vulnerable groups with special susceptibility for decisional problems and related consequences. (2) Methods: Cross-sectional data from the OnCoVID questionnaire study were used involving 540 patients from 11 participating institutions covering all major regions in Germany. Participants were actively involved in clinical treatment in oncology or psychiatry during the COVID-19 pandemic. Questionnaires covered five decision dimensions (conflicts and uncertainty, resources, risk perception, perception of consequences for clinical processes, perception of consequences for patients) and very basic demographic data (age, gender, stage of treatment and educational background). Decision uncertainties and distress were operationalized using equidistant five-point scales. Data analysis was performed using descriptive and various multivariate approaches. (3) Results: A total of 11.5% of all patients described intensive uncertainty in their clinical decisions that was significantly correlated with anxiety, depression, loneliness and stress. Younger and female patients and those of higher educational status and treatment stage had the highest values for these stressors (p < 0.001). Only 15.3% of the patients (14.9% oncology, 16.2% psychiatry; p = 0.021) considered the additional risk of COVID-19 infections as very important for their disease-related decisions. Regression analysis identified determinants for patients at risk of a decisional dilemma, including information availability, educational level, age group and requirement of treatment decision making. (4) Conclusions: In patients, the COVID-19 pandemic induced specific decisional uncertainty and distress accompanied by intensified stress and psychological disturbances. Determinants of specific vulnerability were related to female sex, younger age, education level, disease stages and perception of pandemic-related treatment modifications, whereas availability of sufficient pandemic-related information prevented these problems. The most important decisional criteria for patients under these conditions were expected side effects/complications and treatment responses. [ABSTRACT FROM AUTHOR]

Background: This phase IV routine care study evaluated ovarian responses when using a biosimilar follitropin alfa r-hFSH (Bemfola®) for controlled ovarian stimulation (COS) in women undergoing assisted reproductive technology (ART) treatment who were pituitary-suppressed with a gonadotrophin-releasing hormone (GnRH) antagonist. Methods: This multicenter, prospective, non-comparative, non-interventional study (Germany/Austria) was conducted with 885 women (Mean age of 34.0±4.4 years) for whom COS with Bemfola® and GnRH-antagonist for pituitary suppression were applied as part of in vitro fertilization (IVF) treatment with/without intracytoplasmic sperm injection (ICSI) observing routine clinical-practice protocols. Primary endpoint was the number of retrieved cumulus-oocyte-complexes (COCs). Results: Among 986 ART cycles, COS was given for 9.9±1.8 days (First-day r-hFSH dose of 220.7±68.9 IU; mean total dose of 2184.3±837.5 IU). It was revealed that 99.1% of cycles resulted in follicular puncture, with mean of 10.7±6.6 oocytes retrieved. Successful fertilization took place after IVF/ICSI in 93.8% of follicular punctures. Freeze-all was performed in 14.2% of cycles. Fresh embryo transfer was performed in 76.9% of cycles with follicular puncture; mean day of transfer was 3.5±1.3 and average number of transferred embryos was 1.76±0.50. Clinical pregnancy rate was 30.2% of embryo-transfer cycles and 23.4% of started cycles. Sixty-nine reports of ovarian hyperstimulation syndrome (7.0% of started cycles) were documented. Conclusion: COS with Bemfola® in GnRH-antagonist IVF/ICSI protocols in a routine care setting led to an appropriate ovarian response allowing oocyte retrieval in 99.1% of initiated cases. [ABSTRACT FROM AUTHOR]

• The CRISP registry collects representative, nationwide data on NSCLC in Germany. • CRISP mirrors the treatment and disease trajectory of patients with advanced NSCLC. • Biomarker testing rates increased over time, yet are still improvable. • 17.7 % of the patients presented with a druggable alteration. • Median PFS was longer for patients with a druggable EGFR or ALK alteration. An increasing number of treatment-determining biomarkers has been identified in non-small cell lung cancer (NSCLC) and molecular testing is recommended to enable optimal individualized treatment. However, data on implementation of these recommendations in the "real-world" setting are scarce. This study presents comprehensive details on the frequency, methodology and results of biomarker testing of advanced NSCLC in Germany. This analysis included 3,717 patients with advanced NSCLC (2,921 non-squamous; 796 squamous), recruited into the CRISP registry at start of systemic therapy by 150 German sites between December 2015 and June 2019. Evaluated were the molecular biomarkers EGFR , ALK , ROS1 , BRAF , KRAS , MET , TP53 , RET , HER2 , as well as expression of PD-L1. In total, 90.5 % of the patients were tested for biomarkers. Testing rates were 92.2 % (non-squamous), 70.7 % (squamous) and increased from 83.2 % in 2015/16 to 94.2% in 2019. Overall testing rates for EGFR , ALK , ROS1 , and BRAF were 72.5 %, 74.5 %, 66.1 %, and 53.0 %, respectively (non-squamous). Testing rates for PD-L1 expression were 64.5 % (non-squamous), and 58.5 % (squamous). The most common testing methods were immunohistochemistry (68.5 % non-squamous, 58.3 % squamous), and next-generation sequencing (38.7 % non-squamous, 14.4 % squamous). Reasons for not testing were insufficient tumor material or lack of guideline recommendations (squamous). No alteration was found in 37.8 % (non-squamous), and 57.9 % (squamous), respectively. Most common alterations in non-squamous tumors (all patients/all patients tested for the respective biomarker): KRAS (17.3 %/39.2 %), TP53 (14.1 %/51.4 %), and EGFR (11.0 %/15.1 %); in squamous tumors: TP53 (7.0 %/69.1 %), MET (1.5 %/11.1 %), and EGFR (1.1 %/4.4 %). Median PFS (non-squamous) was 8.7 months (95 % CI 7.4–10.4) with druggable EGFR mutation, and 8.0 months (95 % CI 3.9–9.2) with druggable ALK alterations. Testing rates in Germany are high nationwide and acceptable in international comparison, but still leave out a significant portion of patients, who could potentially benefit. Thus, specific measures are needed to increase implementation. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to describe the real-world treatment and overall survival (OS) of German patients with a diagnosis of advanced non-small cell lung cancer (aNSCLC), and to explore factors associated with the real-world mortality risk.Methods: This was a retrospective German claims data analysis of incident aNSCLC patients. Data were available from 01/01/2011 until 31/12/2016. Identification of eligible patients took place between 01/01/2012-31/12/2015, to allow for at least 1-year pre-index and follow-up periods. Inpatient and outpatient mutation test procedures after aNSCLC diagnosis were observed. Further, prescribed treatments and OS since first (incident) aNSCLC diagnosis and start of respective treatment lines were described both for all patients and presumed EGFR/ALK/ROS-1-positive patients. Factors associated with OS were analyzed in multivariable Cox regression analysis.Results: Overall, 1741 aNSCLC patients were observed (mean age: 66·97 years, female: 29·87%). The mutation test rate within this population was 26·31% (n = 458), 26·6% of these patients (n = 122) received a targeted treatment and were assumed to have a positive EGFR/ALK/ROS-1 test result. Most often prescribed treatments were pemetrexed monotherapy as 1 L (21·23% for all and 11·11% for mutation-positive patients) and erlotinib monotherapy as 2 L (25·83%/38·54%). Median OS since incident diagnosis was 351 days in all and 571 days in mutation-positive patients. In a multivariable Cox regression analysis, higher age, a stage IV disease, a higher number of chronic drugs in the pre-index period and no systemic therapy increased the risk of early death since first aNSCLC diagnosis. On the other hand, female gender and treatment with therapies other than chemotherapy were associated with a lower risk of early death.Conclusions: Despite the introduction of new treatments, the real-world survival prognosis for aNSCLC patients remains poor if measured based on an unselected real-world population of patients. Still, the majority of German aNSCLC patients do not receive a mutation test. [ABSTRACT FROM AUTHOR]

Background: Anti-PD1 monoclonal antibody nivolumab is an approved therapy option for the treatment of advanced squamous cell non-small cell lung cancer (SQ-NSCLC) patients. Data outside clinical trials about therapy efficacy and safety in later therapy line treatments have rarely been described until now. Methods: We performed a retrospective data analysis of patients who were enrolled into the nivolumab Compassionate Use Program (CUP) in Germany. Sufficient clinical data of 40 patients were available for efficacy and safety analysis. Results: Overall, 47.5% of all treated patients were not affected by any adverse events (AEs); 17.5% of patients suffered from severe AEs. The 1-year survival rate was 61.3%. Estimated median progression-free survival (PFS) was 5.3 months. Patients who received nivolumab as third or later therapy line treatment (77.5%) achieved similar median PFS and 12-month overall survival rate of 52%. Conclusion: Our findings of immunotherapy treatment outside clinical trials support the results of studies in the past and confirm the efficacy and favorable toxicity profile of nivolumab treatment in advanced SQ-NSCLC patients. In addition, we can present some rarely described information about nivolumab treatment of heavily pretreated patients, which provides some evidence that immunotherapy could also be useful in later therapy lines. [ABSTRACT FROM AUTHOR]

Study Question: What is the performance of previously established regression models in predicting low and high ovarian response to 150 μg corifollitropin alfa/GnRH-antagonist ovarian stimulation in an independent dataset?Summary Answer: The outcome of ovarian stimulation with 150 μg corifollitropin alfa in a fixed, multiple dose GnRH-antagonist protocol can be validly predicted using logistic regression models with AMH being of paramount importance.What Is Known Already: Predictors of ovarian response have been identified in FSH/GnRH agonist protocols as well as ovarian stimulation with corifollitropin alfa/GnRH-antagonist. Multivariable response models have been established already, however, external validation of model performance has so far been lacking.Study Design, Size, Duration: Data from a prospective, multi-centre (n = 5), multi-national, investigator-initiated, observational cohort study were analysed. Infertile women (n = 211), body weight >60 kg, were undergoing ovarian stimulation with 150 μg corifollitropin alfa in a GnRH-antagonist multiple dose protocol for transvaginal oocyte retrieval for IVF. Demographic, sonographic and endocrine parameters were prospectively assessed on cycle Day 2 or 3 of spontaneous menstruation before ovarian stimulation. Main outcomes were low (<6 oocytes) and high (>18 oocytes) ovarian response.Participants/materials, Setting, Methods: Firstly, previously established prediction models for low ovarian response (LOR) and high ovarian response (HOR) were tested using the original parameters. Secondly, re-estimated parameters generated from the present data were tested on the established models. Thirdly, for the development of new predictive models of both LOR and HOR, several logistic regression models were estimated. Resulting prediction models were compared by means of the area under the receiver operating characteristic curve (AUC) and bias-corrected Akaike's Information Criterion (AICc) to identify the most reasonable model for each scenario.Main Results and the Role Of Chance: The previously established prediction models for low and high response performed remarkably well on this dataset (low response AUC 0.8879 (95% CI: 0.8185-0.9573) and high response AUC 0.8909 (95% CI: 0.8251-0.9568)). A newly developed simplified model for LOR with log-transformed AMH values and only age as another covariate showed an AUC of 0.8920 (95% CI: 0.8237-0.9603) with the lowest AICc of all models compared. For predicting HOR, we suggest a simplified model using AMH, FSH and AFC (AUC of 0.8976, 95% CI: 0.8206-0.9746).Limitations, Reasons For Caution: All analyses were done on data from women with a body weight >60 kg. The newly developed simplified models may suffer from overfitting and need to be tested in further independent data sets.Wider Implications Of the Findings: Patient selection for ovarian stimulation with corifollitropin alfa should utilize established response prediction models. The clinical impact of this needs to be evaluated in future studies.Study Funding/competing Interest(s): The study was funded by university funds. M.O.S., T.L. and I.R.K. have nothing to declare. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott, Marckryl Pharma, VitroLife, NMC Healthcare, ReprodWissen, ZIVA and BioSilu.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to determine levels of anxiety during the course of IVF treatment and gender differences in treatment anxiety.Methods: This was a prospective cohort study set in a university affiliated, tertiary care IVF program. 119 women and 82 men entering the clinic to undergo IVF treatment filled out questionnaires containing the Spielberger state-trait-anxiety-inventory (STAI) as well as further items on specific stress triggers.Results: Women and men undergoing IVF have higher levels of anxiety than the average population in Germany. Overall, female patients show significantly higher values (mean ± SD) for state and trait anxiety (47.4 ± 11.0 and 40.1 ± 9.85) than their male partners (41.4 ± 9.66 and 35.3 ± 8.57, p < 0.01). Over the course of several IVF cycles, average STAI scores increased for both genders. When asked about specific stress factors on a 4-point scale from 'not at all' to 'very much so', women report as their main anxiety the failure to achieve a successful pregnancy, scoring significantly higher on questions like 'obtaining a negative pregnancy test' (3.24 ± 0.82, p < 0.01) and 'disclosure of infertility' (3.02 ± 1.10, p < 0.001). Their male partners are more concerned about the health risks the women have to take such as 'side effects of ovarian stimulation' (2.55 ± 0.77, p = 0.002) and 'bleeding or infection after the oocyte aspiration' (2.58 ± 0.84, p = 0.007). Both genders indicated to be very little worried about multiple pregnancies after IVF.Conclusions: Women show a higher level of anxiety during IVF treatment and hold different concerns. Neither of the sexes appears to be familiar with the risks associated with multiple pregnancies, a matter that should better be addressed. [ABSTRACT FROM AUTHOR]

Background. Afatinib, an irreversible ErbB family blocker, is approved for treatment of patients with previously untreated non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. Efficacy of afatinib in EGFR tyrosine kinase inhibitor-naï ve (TKI-naïve) patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 point mutations) has been reported; however, efficacy in TKI-pretreated patients with uncommon EGFR mutations is unknown. Materials and Methods. In the afatinib compassionate use program (CUP), patients with advanced or metastatic, histologically confirmed NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment were enrolled. Demographic data, mutation type, response rates, time to treatment failure (TTF), and safety in patients harboring uncommon EGFR mutations were reported. Results. In 60 patients (63% female, median age 63 years [range: 30-84 years]), a total of 66 uncommon EGFR mutations including 30 T790M mutations were reported (18.4% and 11%, respectively, of known EGFR mutations within the CUP). Most patients (67%) received afatinib as third- or fourth-line treatment. Median TTF was 3.8 months (range: 0.2 to >24.6 months; p = .244) in patients with uncommon mutations compared with 5.1 months (range: 0.1 to >21.1 months) in patients with common mutations (n = 165). Pronounced activity was observed with E709X mutations (TTF >12 months). No new safety signals were detected. Conclusion. Afatinib is clinically active and well tolerated in many TKI-pretreated NSCLC patients harboring uncommon EGFR mutations. Compared with results reported in TKI-naTve patients, activity was also indicated in patients with T790M and exon 20 insertion mutations. [ABSTRACT FROM AUTHOR]

The place of GnRH antagonists in ovarian stimulation is controversial. Meta-analyses on studies comparing GnRH agonist and GnRH antagonist treatment regimens have suggested a comparatively lower efficacy of GnRH antagonists, which is likely to have influenced clinicians’ attitudes. This report describes GnRH antagonist utilization for ovarian stimulation in Germany from 2000–2003. Data from the national IVF registry were analysed. The majority of ovarian stimulation cycles are still performed in long GnRH agonist protocols, although a significant increase in GnRH antagonist usage has been noted (P < 0.0001). Two observations support the notion that GnRH antagonists are often utilized as a treatment option in cycles with an unfavourable a priori prognosis: (i) the proportion of GnRH antagonist cycles increases with cycle rank (P < 0.0001, χ2 for linear trend); and (ii) GnRH antagonist cycles are more often conducted in older patients as compared to GnRH agonist cycles (P < 0.0001). This has important implications for interpreting clinical performance of GnRH antagonists outside a research context. [ABSTRACT FROM AUTHOR]

The article focuses on the use of the polar body analysis (PBA) in the diagnosis of monogenic diseases (MD) in Germany. For carriers of MD in Germany who want preconceptional diagnosis, PBA is the only way to contemplate pregnancy without any risk. Every PBA needs in vitro fertilization and intracellular sperm injection (ICSI) is also carried out. After ovarian stimulation and harvesting of oocytes, the zona pellucida is opened by laser and the polar bodies removed using a micropipette.

• NSCLC patients with oligometastastic disease benefit from locally ablative and systemic therapy. • Neoadjuvant immunotherapy results in high pCR and MPR rates. • Neoadjuvant immunotherapy is a promising therapeutic concept for oligometastastic disease. Immune checkpoint inhibitors (ICI) have significantly improved outcome of patients with advanced NSCLC and recently also showed benefit in early-stage disease. Patients with oligometastatic disease (OMD) harbor limited metastases, resectable primary tumors and derive benefit from treatment with multimodal locally ablative and systemic therapy approaches. Nothing is known about feasibility and efficacy of neoadjuvant ICI in this setting. We here provide data from a multicenter retrospective study comprising 13 patients with NSCLC and OMD (≤3 distant metastases) from 5 university medical centers in Germany who have been treated with neoadjuvant ICI alone (n = 4) or in combination with chemotherapy (CT) (n = 9) prior to resection of the primary tumor. We analyzed complete (pCR) and major pathological remission (MPR) rates. These data show that neoadjuvant immunotherapy applied mostly in combination with CT results in high rates of pCR and MPR (54 and 69%, respectively). Up to now, 85% of patients are free of progression with a median follow-up of 9 months (3–28 months). Single cell RNASeq analysis of tumor tissue from one patient treated with CT-ICI indicates a strong predominance of adaptive immune cell populations over a small minority of epithelial (tumor) cells. Neoadjuvant ICI with or without CT is a promising therapeutic concept in patients with OMD. [ABSTRACT FROM AUTHOR]

BRAF mutations have been subtyped in three functional classes with different oncogenic modes of action. The clinical impact of BRAF mutational subtypes in non–small-cell lung cancer (NSCLC) remains to be defined. So far, ambiguous results were reported from analyses of heterogeneous patient cohorts. We studied patients with metastatic or recurrent NSCLC who were sequentially enrolled in precision oncology programs at two large German lung cancer centres from 2009 to 2019. The study period allowed evaluating the specific impact of BRAF V600E-targeting. In a cohort of 72 patients, BRAF mutation subtyping revealed p.V600E mutations in 31 cases (43%), whereas 41 cases (57%) harboured 18 different BRAF mutational subtypes of functional classes II/III. Functionally relevant comutations were observed in 6.4% of class I, and 24.4% of class II/III BRAF mutations. Most patients were treated with chemotherapy. Targeted therapy was administered in 11 patients with a response rate of 72.7%. PD-1/PD-L1-immunotherapy was given in 14 patients with a response rate of 28.6%. Overall survival of patients with BRAF -mutated NSCLC was inferior (HR 1.38, p = 0.048) as compared to patients with BRAF wild-type cancers. Median time-to-treatment-failure with BRAF-targeting agents was shorter as compared to approved targeted therapy of other oncogenic drivers (HR 1.97, p = 0.05). Survival outcomes were not impacted by BRAF mutation subtype functional class. Patients with BRAF -mutated NSCLC have an inferior prognosis, which is not determined by BRAF mutation functional class. In contrast to NSCLC with other tractable driver mutations, BRAF -mutated NSCLC exhibit high susceptibility to immune checkpoint inhibitors. • PD-1/PD-L1 immunotherapy is effective in BRAF -mutant NSCLC. • Patients with BRAF -mutated NSCLC have inferior overall survival. • BRAF mutation functional class does not associate with clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract Research question What is the association between assisted reproductive technologies and human sex ratio as a proportion of male offspring at birth. Design A total of 59,628 singleton deliveries resulting from IVF, intracytoplasmic sperm injection (ICSI) and intrauterine insemination (IUI) or ovulation induction from 101 IVF clinics in Germany, that had been documented in a national German IVF registry, were analysed. Sex ratio after assisted reproductive technology was also compared with the sex ratio reported in the birth records of the German Federal Statistical Office. Results The sex ratio was 50.0% (95% CI 49.5% to 50.5%) for ICSI, 52.2% (95% CI 51.5% to 52.9%) for IVF, 52.2% (95% CI 50.9% to 53.5%) for IUI or ovulation induction and 51.3% in the national birth records, respectively. Significant differences existed across the three treatment groups (P = 6.86 × 10−7) as well as in pairwise comparisons between ICSI versus IVF (P = 6.88 × 10−7) and ICSI versus IUI or ovulation induction (P = 0.003). No difference existed between the groups IUI or ovulation induction versus IVF. Same results were also present after stratification by maternal age: IVF versus ICSI (P = 6.433 × 10−7), ICSI versus IUI or ovulation induction (P = 0.003), and IVF versus IUI or ovulation induction (non-significant). Compared with the national birth records, ICSI is associated with a lower sex ratio compared with the reference group (P < 0.001), whereas IVF is associated with a higher sex ratio (P = 0.015). Conclusions The use of ICSI is associated with an equal proportion of sexes at birth, which is not the case for IVF, IUI or ovulation induction, or natural conception. This phenomenon is not influenced by maternal age. [ABSTRACT FROM AUTHOR]