Adherence to interdisciplinary tumor board recommendations as an expression of quality-assured patient care: results of a bicentric German analysis.

PURPOSE: Interdisciplinary tumor boards (ITBs) represent a central part of standard cancer care defining a guidelines-guided treatment plan adapted to the patient's capabilities, comorbidities and wishes in a multi-professional team. The implementation rate of ITB recommendations can be monitored by structured adherence analyses. But (inter)national definitions how to measure the level of implementation are missing. Here, we present results of 4 years of ITB adherence analyses in a bicentric German Comprehensive Cancer Center (CCC). METHODS: Between 2018 and 2021, for at least 1 month, the implementation rate of recommendations of 8 different ITBs of 2 CCC sites was evaluated manually according to harmonized criteria between both sites regarding the degree of implementation of ITB's recommendations. RESULTS: In total, 1104 cases were analyzed (65% male, 35% female). Mean distance from patient's home to the CCC was 57 km (range 0.8-560.6 km). For 949 cases (86%) with known follow-up, the adherence rate was 91.9% (95% CI 0.9; 0.935). In 8.1%, ITB decisions were not implemented due to medical reasons (45.4%), patient's wish (35.1%) and unknown reasons (19.5%). Logistic regression revealed neither age (OR = 0.998, p = 0.90), nor gender (OR = 0.98, p = 0.92) or the distance from patient's home to the CCC (OR = 1.001, p = 0.54) were significantly associated with ITB adherence. CONCLUSION: ITB adherences analyses can serve as a quality management tool to monitor the implementation rate of ITB recommendations and to stay in contact with practitioners, other hospitals and state cancer registries to share data and resources in accordance with data protection requirements for continuously improvement of quality management and patient care.

Decision Conflicts in Clinical Care during COVID-19: A Patient Perspective.

(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.

Trust in Healthcare during COVID-19 in Europe: vulnerable groups trust the least.

Aim: We examined predictors of trust in the healthcare system during the COVID-19 pandemic in 27 European countries. Subjects and methods: We used population-based data drawn from the Living, working and COVID-19 survey (N = 21,884, 52% female, ages 18 to 92 years) covering 27 European countries dated June and July 2020. Multilevel linear regression, linear regression, and regression-tree analyses were conducted. Results: We found that most participants tended to trust the healthcare system, although a substantial part could still be classified as distrusting (approx. 21%). Multiple variables, including being middle-aged or of older age, being female, lower levels of education, unemployment, worse general health status, having income difficulties, having unmet needs for healthcare, no healthcare contact during the COVID-19 pandemic, higher mental distress, and loneliness, were significantly associated with lower levels of trust. Among these variables mental distress, income difficulties, and unmet needs for healthcare emerged as especially important and, across European regions and countries, consistent predictors for lower trust in the healthcare system during the COVID-19 pandemic. Conclusions: Medically vulnerable subgroups, such as individuals with unmet healthcare needs, higher levels of mental distress, and older age, as well as people living in socially and economically vulnerable situations, such as higher levels of loneliness and financial difficulties, were the least trusting of the healthcare system during the COVID-19 pandemic. As these vulnerable subgroups are also at highest risk for contracting COVID-19 and experiencing negative COVID-19-related outcomes, more targeted prevention and intervention efforts should be implemented in these groups. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-022-01705-3.

Patterns of Changes in Oncological Care due to COVID-19: Results of a Survey of Oncological Nurses and Physicians from the Region of Hanover, Germany.

BACKGROUND: Healthcare staff is confronted with intensive decisional conflicts during the pandemic. Due to the specific burden of this moral distress in oncology, the investigation aimed at quantification of these conflicts and identification of risk factors that determine the extent and severity of these conflicts. We examined the heterogeneity of changes in oncology care due to COVID-19. METHODS: We conducted a survey of oncological physicians and nurses in the region of Hanover, Germany in the second half of 2020. Overall, N = 200 respondents, 54% nurses, were included in the sample. Indicators of changes in oncology care were used to determine profiles of changes. To characterize these profiles, a diverse set of variables, including decision conflicts, uncertainty, age, gender, work experience, changes in communication with patients, psychological distress, work stress, process organization, and personnel resources, was obtained. Latent class analysis was conducted to determine these latent profiles. RESULTS: We found that three distinct profiles best described the overall changes in oncology care due to COVID-19 in our sample, with each profile being associated with specific characteristics: (1) "Few Changes in Oncology Care" profile with 33% of participants belonging to this profile, (2) "Medium Changes in Oncology Care" profile with 43% of participants, and (3) "Severe Changes in Oncology Care" profile (24%). Participants from these profiles significantly differed regarding their age, work experience, occupational group, the prevalence of decision conflicts, decision uncertainty, quality of communication with patients, and quality of process organization. CONCLUSIONS: Distinct profiles of change in oncology care due to COVID-19 can be identified. Most participants reported small to medium changes, while some participants also reported severe changes. Profiles also differed regarding their associated characteristics. As such, specific consequences for better pandemic preparedness can be derived based on the current study. Future studies should investigate the patterns of changes in routine care due to COVID-19.

[Trans-Sectoral Patient Care in Pediatric Oncology: Quality Assurance by Novel Reimbursement Models for Outpatient Services]. / Sektorenübergreifende Versorgung in der Pädiatrischen Onkologie: Qualitätssicherung durch neue Vergütungsmodelle für nicht-vollstationäre Leistungen.

BACKGROUND: The medical care of pediatric cancer patients in the German health care system relies on special structures. All children and adolescents with a diagnosis of cancer receive uniform treatment within clinical studies or registers and exclusively at centers which can ensure interdisciplinary care by a multiprofessional team. Reimbursement of outpatient services is highly heterogeneous among the centers, and the expenses are often not adequately compensated. METHOD: A nation-wide survey was performed among all centers of the German Society of Pediatric Hematology and Oncology, with a standardized questionnaire inquiring which reimbursement models are used to finance outpatient treatment and whether full coverage of the expenses is achieved. RESULTS: Of 58 Pediatric Oncology Centers in Germany 18 (33%) participated in the survey, including 8 (44%) University Hospitals. The use of available reimbursement tools was highly heterogeneous. Reimbursement for outpatient service was based on a mean of 3,33±1,49 individual components. Of the 18 responding centers, 17 indicated that the revenues do not fully cover the expenses. DISCUSSION AND CONCLUSION: Pediatric oncology centers in Germany can not achieve full coverage of expenses in the outpatient setting. Nationally uniform cost-covering remuneration strategies are needed. This article proposes three individual models for an adequate nationwide financial framework for the outpatient care of pediatric cancer patients.

Correction: Complex Epigenetic Regulation of Chemotherapy Resistance and Biology in Esophageal Squamous Cell Carcinoma via MicroRNAs. Int. J. Mol. Sci. 2018, 19, 499.

We would like to submit a correction to the published paper [...].

The Interaction between Laminin-332 and α3ß1 Integrin Determines Differentiation and Maintenance of CAFs, and Supports Invasion of Pancreatic Duct Adenocarcinoma Cells.

Ranking among the most lethal tumour entities, pancreatic duct adenocarcinoma cells invade neighbouring tissue resulting in high incidence of metastasis. They are supported by tumour stroma fibroblasts which have undergone differentiation into cancer-associated fibroblasts (CAFs). Stiffness of cell substratum, cytokines, such as transforming growth factor-ß (TGF-ß), and stromal matrix proteins, such as laminin-332, are factors which promote CAF differentiation. In a spheroid culture system, differentiation of CAFs was analysed for laminin-332 production, laminin-binding integrin repertoire, adhesion and migration behaviour, and, in heterospheroids, for their interplay with the pancreatic duct adenocarcinoma AsPC-I cells. Our data reveal that CAFs produce laminin-332 thus contributing to its ectopic deposition within the tumour stroma. Moreover, CAF differentiation correlates with an increased expression of α3ß1 integrin, the principal laminin-332-receptor. Beyond its role as novel CAF marker protein, integrin α3ß1 crucially determines differentiation and maintenance of the CAF phenotype, as knock-out of the integrin α3 subunit reversed the CAF differentiated state. AsPC-I cells co-cultured in heterospheroids with integrin α3-deficient CAFs invaded less than from heterospheroids with wild-type CAFs. This study highlights the role of integrin α3ß1 integrin-laminin-332 interaction of CAFs which promotes and sustains differentiation of CAFs and promotes carcinoma invasion.

microRNAs: Key regulators of chemotherapy response and metastatic potential via complex control of target pathways in esophageal adenocarcinoma.

INTRODUCTION: Incidence of esophageal adenocarcinoma (EAC) increased significantly over the last decades. Lack of response to chemotherapy is a major problem in the treatment of this disease. This study aims to assess the biological relevance of characteristic microRNA profiles of chemotherapy resistant EAC cells with regards to response to chemotherapy and biological behavior. METHODS: We selected 3 microRNAs from characteristic microRNA profiles of resistant EAC (miR-27b-3p, miR-200b-3p, and miR-148a-3p). Expression of microRNAs was modified in 6 EAC cell lines. Effects on chemotherapy, adhesion, migration, apoptosis and cell cycle were assessed using standard assays. Target analyses were performed using Western Blot and Luciferase techniques. RESULTS: MiR-27b-3p significantly sensitized cells to 5FU and Cisplatin in 83% respectively in 33% of cell lines, miR-148a-3p in 67% respectively 33% of cases. MiR-200b-3p increased sensitivity only towards 5FU in 50% of cases. Co-transfections with miR-27b-3p/miR-148a-3p showed an additive effect on response to chemotherapy in 50% of cases. Upregulation of miR-148a-3p reduced protein expression levels of DNMT-1, MSK-1, Bcl-2 and Bim, and miR-27b upregulation led to downregulation of Sp1 and PPARy proteins implicating a potential negative post-transcriptional control via the respective microRNAs. Finally, we were able to confirm Bcl-2 for the first time as direct target of miR-148a-3p in EAC. CONCLUSION: This study demonstrates that specific microRNA profiles of chemotherapy resistant EAC in fact determine their response to chemotherapy and biological behavior. Our data further show that microRNA-mediated regulation of chemotherapy resistance is complex, and several microRNAs seem to "co-operate" at various steps within a broad number of pathways what fits very well to our recently proposed understanding of microRNA-mediated regulation as function of cellular functional complexes. These data highlight the promising potential of microRNAs to predict or monitor treatment response to chemotherapy in EAC, and to potentially modulate tumor biology in a therapeutic approach.

Complex Epigenetic Regulation of Chemotherapy Resistance and Biohlogy in Esophageal Squamous Cell Carcinoma via MicroRNAs.

BACKGROUND: Resistance towards chemotherapy is a major obstacle in the treatment of esophageal squamous cell carcinoma (ESCC). We investigated the role of specific microRNAs in chemotherapy resistance and tumor biology. METHODS: We selected three microRNAs from characteristic microRNA signatures of resistant ESCC (hsa-miR-125a-5p, hsa-miR-130a-3p, hsa-miR-1226-3p), and hsa-miR-148a-3p. Effects on chemotherapy, adhesion, migration, apoptosis and cell cycle were assessed in six ESCC cell lines. Target analyses were performed using Western blotting and luciferase techniques. RESULTS: MiR-130a-3p sensitized cells towards cisplatin in 100% of cell lines, miR-148a-3p in 83%, miR-125a-5p in 67%, miR-1226-3p in 50% (p ≤ 0.04). MiR-130a-3p sensitized 83% of cell lines towards 5-FU, miR-148a-3p/miR-125a-5p/miR-1226-3p only 33% (p ≤ 0.015). Several resistance-relevant pathways seem to be targeted on various levels. Bcl-2 was confirmed as a direct target of miR-130a-3p and miR-148a-3p, and p53 as a target of miR-125a-5p. All microRNAs decreased migration and adhesion, except miR-130a-3p, and increased apoptosis. Simultaneous manipulation of two microRNAs exhibited additive sensitizing effects towards cisplatin in 50% (miR-125a-5p/miR-148a-3p), and 75% (miR-148a-3p/miR-130a-3p) of cell lines (p ≤ 0.016) [corrected] CONCLUSION: Our data present strong evidence that specific microRNA signatures are responsible for drug resistance and aggressiveness of ESCC. Final functional readout of these complex processes appears to be more important than single microRNA-target interactions.

From a Content Delivery Portal to a Knowledge Management System for Standardized Cancer Documentation.

Heterogeneous tumor documentation and its challenges of interpretation of medical terms lead to problems in analyses of data from clinical and epidemiological cancer registries. The objective of this project was to design, implement and improve a national content delivery portal for oncological terms. Data elements of existing handbooks and documentation sources were analyzed, combined and summarized by medical experts of different comprehensive cancer centers. Informatics experts created a generic data model based on an existing metadata repository. In order to establish a national knowledge management system for standardized cancer documentation, a prototypical tumor wiki was designed and implemented. Requirements engineering techniques were applied to optimize this platform. It is targeted to user groups such as documentation officers, physicians and patients. The linkage to other information sources like PubMed and MeSH was realized.