Survey of treatment and care practices in small-cell lung cancer among German radiation oncologists.

BACKGROUND: The management of small-cell lung cancer shows differences, particularly with regard to the use of radio- (RT), chemo-, and immunotherapy. We performed a survey among German radiation oncologists to assess the management of small-cell lung cancer (SCLC). METHODS: A 34-question online survey was created and sent out by e­mail to radiation oncologists throughout Germany. The survey period extended from August 2020 to January 2021. The questions addressed indications for RT, planning techniques, dosing/fractionation, target volume definition for consolidative thoracic irradiation, and the use of prophylactic cranial irradiation (PCI). At the same time, we surveyed the use of atezolizumab. The survey addressed the treatment practice for limited-stage SCLC (LS-SCLC) and extensive-stage SCLC (ES-SCLC). RESULTS: We received 74 responses. In LS-SCLC, treatment is planned predominantly based on diagnostic information from computed tomography (CT) of the thorax/abdomen/pelvis (88%), PET-CT (86%), and pulmonary function testing (88%). In LS-SCLC, 99% of respondents perform radiation concurrently with chemotherapy, preferably starting with cycle one or two (71%) of chemotherapy. The most common dose and fractionation schedule was 60-66 Gy in 30-33 fractions (once daily: 62% of all respondents). In ES-SCLC, 30 Gy in 10 fractions (once daily: 33% of all respondents) was the most commonly used regimen in consolidative thoracic irradiation. Only 25% use chemosensitization with RT. The inclusion criteria for PCI were similar for limited and extensive disease, with Karnofsky index (78% and 75%) being the most important decision factor. Respondents use a schedule of 30 Gy in 15 fractions most frequently in both stages (68% limited stage [LS], 60% extensive stage [ES]). Immunotherapy was used regularly or occasionally in LS-SCLC by 45% of respondents, with reduced lung function (37%), cardiac comorbidities (30%), and hepatic insufficiency (30%) being the most commonly mentioned exclusion criteria for this form of therapy. In ES-SCLC, atezolizumab use was reported in 78% of all questionnaires. Half of the respondents (49%) administer it simultaneously with cranial irradiation. CONCLUSION: Our survey showed variability in the management of SCLC. Results from future studies might help to clarify open questions regarding the optimal treatment paradigms. In addition, new treatment modalities, such as immunotherapy, might change practices in the near future.

Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations : An overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO).

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.

Prognostic impact of gross tumor volume during radical radiochemotherapy of locally advanced non-small cell lung cancer-results from the NCT03055715 multicenter cohort study of the Young DEGRO Trial Group.

BACKGROUND: In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT. METHODS: A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models. RESULTS: GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5-877) and GTV2 of 106.2 ml (95% CI: 0.5-589.5), resulting in an estimated reduction of 48.2 ml (p < 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12-6.75, p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9-2, p > 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0-69, 0.32-1.49, p > 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01-13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64-0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2. CONCLUSION: Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.

Serum dietary fatty acids and coronary heart disease risk - A nested case-control-study within the CARLA cohort.

BACKGROUND AND AIMS: Diet is known to play a decisive role in the development of coronary heart disease (CHD). One factor believed to decrease lifetime risk of CHD is the consumption of omega-3 fatty acids. Yet, conclusive evidence regarding the potential cardioprotective effects of fatty acids is far from being reached. The present study aimed to provide further evidence on the association of serum fatty acid profiles with CHD risk. METHODS AND RESULTS: The CARdio-vascular Disease, Living and Ageing in Halle study (CARLA study) is an observational cohort study comprising an older adult's general population with a high level of cardiovascular risk factors. In a matched case-control design the serum fatty acid concentrations of 73 subjects with an incident fatal or nonfatal CHD event were compared to 146 controls matched for sex and age. Our data show that the participants of the CARLA study are underserved in unsaturated fatty acids with respect to current dietary recommendations. In addition, the ratio of omega-6 to omega-3 fatty acids was determined to be 8:1 which underlines the consumption of a Western-style diet enriched in omega-6 fatty acids. There were no significant differences in fatty acid patterns between cases and controls. Thus, no clear association of particular serum fatty acid levels with cardiovascular risk was found. CONCLUSION: Our results support the conclusion that in populations with a homogenous low level of omega-3 polyunsaturated fatty acids consumption, serum fatty acid levels are not associated with CHD risk.

Instability of personal human metabotype is linked to all-cause mortality.

Disruption of metabolic homeostasis is an important factor in many diseases. Various metabolites have been linked to higher risk of morbidity and all-cause mortality using metabolomics in large population-based cohorts. In these studies, baseline metabolite levels were compared across subjects to identify associations with health outcomes, implying the existence of 'healthy' concentration ranges that are equally applicable to all individuals. Here, we focused on intra-individual changes in metabolite levels over time and their link to mortality, potentially allowing more personalized risk assessment. We analysed targeted metabolomics data for 134 blood metabolites from 1409 participants in the population-based CARLA cohort at baseline and after four years. Metabotypes of the majority of participants (59%) were extremely stable over time indicated by high correlation between the subjects' metabolite profiles at the two time points. Metabotype instability and, in particular, decrease of valine were associated with higher risk of all-cause mortality in 7.9 years of follow-up (hazard ratio (HR) = 1.5(95%CI = 1.0-2.3) and 0.2(95%CI = 0.1-0.3)) after multifactorial adjustment. Excluding deaths that occurred in the first year after metabolite profiling showed similar results (HR = 1.8(95%CI = 1.1-2.8)). Lower metabotype stability was also associated with incident cardiovascular disease (OR = 1.2(95%CI = 1.0-1.3)). Therefore, changes in the personal metabotype might be a valuable indicator of pre-clinical disease.

Educational status and differences in left ventricular mass and ejection fraction - The role of BMI and parameters related to the metabolic syndrome: A longitudinal analysis from the population-based CARLA cohort.

BACKGROUND AND AIMS: Higher ventricular mass has been reported in non-white US-Americans with low educational status and in socially isolated people. To assess the impact of education on cardiac mass and function in the general population and to identify mediators. METHODS AND RESULTS: Data from a German population-based sample were used (CARLA cohort, n = 1779 at baseline, n = 1436 at the four-year follow-up). Ventricular mass indexed on height (LVMI) and ejection fraction, using Teichholz's formula (EFTZ), were measured. Education was assessed using the ISCED classification. Mediator analyses were performed using the R-macro 'mediation' to compute the average direct effect and the average causal mediated effect after confounder adjustment. Sensitivity analyses for unobserved confounders were performed. Considered mediators were BMI, waist-to-hip ratio, HbA1c, and systolic and diastolic blood pressures. We found differences in LVMI and EFTZ, both at baseline and follow-up, between educational levels in women (lowest vs highest educational level: 15.6 g, 95% CI: -25.7, -5.6), but not in men. Similarly, women (lowest vs highest educational level at baseline: 3.3%, 95% CI: 0.8-5.7), but not men, of higher educational levels had a higher EFTZ of comparable magnitude at baseline and follow-up. Of the considered mediators, BMI explained 55.9% at baseline and 54.1% at follow-up of the educational effect, while other potential mediators had no significant effect. Relations remained constant between baseline and follow-up. CONCLUSIONS: Women with low educational levels tend to have a higher ventricular mass and lower EF, which can be explained by a higher BMI in this group.

Educational level and chronic inflammation in the elderly--the role of obesity: results from the population-based CARLA study.

This study aimed to assess the mediating role of anthropometric parameters in the relation of education and inflammation in the elderly. Cross-sectional data from the population-based CARdio-vascular Disease, Living and Ageing in Halle study were used after excluding subjects with a plasma level of high-sensitive C-reactive protein (hsCRP) above 10 mg L(-1) (916 men/760 women remaining). Education was categorized in accordance with International Standard Classification of Education. As inflammation parameters, the soluble tumour necrosis factor type 1 (sTNF-R1), hsCRP and interleukin 6 (IL-6) were taken into account. Anthropometric parameters were the body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHeR). We used covariate adjusted mixed models to assess associations. Effect measures were the natural indirect effect (NIE), controlled direct effect and total effect (TE). Education was associated with sTNF-R1, hsCRP and IL-6 in men, and sTNF-R1 and hsCRP in women. Anthropometric parameters correlated with all inflammation parameters after covariate adjustment. BMI and WHeR were strong mediators of educational differences in sTNF-R1 (percentage of NIE of TE: 28% in men; 33% in women) and hsCRP (percentage of NIE of TE: 35% in men; 52% in women), while WHR was the weakest mediator. General obesity mediates roughly one-third of the association of education with chronic inflammation in the elderly.

Inflammation and echocardiographic parameters of ventricular hypertrophy in a cohort with preserved cardiac function.

OBJECTIVE: To investigate the association between inflammation and selective echocardiographic parameters (EP) characteristic for ventricular hypertrophy in cross-sectional and longitudinal population-based analyses. METHODS: Baseline (711 men, 659 women: 45-83 years) and 4-year follow-up data (622 men, 540 women) of the prospective, population-based CARdio-vascular disease, Living and Ageing in Halle (CARLA)study after exclusion of participants with cardiacvascular diseases were analysed. Inflammation parameters: soluble tumour necrosis factor receptor 1 (sTNF-R1), high-sensitivity C reactive protein (hsCRP) and interleukin 6 (IL-6). EPs: left ventricular mass (LVM), left atrial systolic dimension (LADS), interventricular septum diameter (IVSD), posterior wall dimension (PWD), left ventricular diastolic diameter (LVDD), ejection fraction according to Teichholz (EF). For the longitudinal analyses baseline to follow-up differences were considered. Effect sizes were determined by using multiple linear regression and mixed models. Missing values were replaced by means of multiple imputations. RESULTS: Men had higher sTNF-R1 levels; means of hsCRP and IL-6 were similar in men and women. In multiple regression models, sTNF-R1 was associated with LADS (1.4 mm/1000 pg/mL sTNF-R1, 95% CI 0.6 to 2.1) in men. Respecting confounder hsCRP was associated with LVM (5.2 g/10 mg/L hsCRP, 95% CI 1.6 to 8.8), IVSD (0.2 mm/10 mg/L hsCRP, 95% CI 0 to 0.3) and PWD (0.2 mm/10 mg/L hsCRP, 95% CI 0.1 to 0.3) in women, while there were no relevant effects in analysis of IL-6 in both sexes. The baseline to follow-up change in EPs was not relevantly associated with sTNF-R1, hsCRP or IL-6. CONCLUSIONS: STNF-R1, hsCRP and IL-6 were inadequate predictors for structural changes of the heart at follow-up, while weak cross-sectional associations are restricted to certain EPs and depend on sex.

Mortality on match days of the German national soccer team: a time series analysis from 1995 to 2009.

BACKGROUND: There is inconsistent evidence on population mortality, especially cardiovascular disease mortality, on match days of national soccer teams during particular international tournaments. This study examines the number of deaths in Germany on match days of the national soccer team during a long-term period including several tournaments. METHODS: We analysed all registered daily deaths in Germany from 1995 to 2009 (11 225 966 cases) using time series analysis methods. Following the Box/Jenkins approach, we applied a seasonal autoregressive integrated moving average model. To assess the effect of match days, we performed an intervention analysis by including a transfer function model representing match days of the national team in the statistical analyses. We conducted separate analyses for all matches and for matches during international tournaments (European and World Championships) only. Time series and results were stratified in terms of sex, age (<50 years, 50-70 years, >70 years) and cause of death (cardiovascular deaths, injuries, others). We performed a further independent analysis focusing only on the effect of match results (victory, loss, draw) and kind of tournament (international championships, qualifications, friendly matches). RESULTS: Most of the results did not indicate a distinct effect of matches of the national team on general mortality. Moreover, all null value deviations were small when compared with the average number of daily deaths (n=2270). CONCLUSIONS: There is no relevant increase or decrease in mortality on match days of the German national soccer team.