Caring for dependent children impacts practical and emotional problems and need for support, but not perceived distress among cancer patients.

OBJECTIVE: More than one in 10 cancer patients care for dependent children. It is unclear whether this status makes a difference in terms of the distress and associated problems they experience, or whether it is linked to differences in the need for or utilization of psychosocial support. METHODS: Secondary analysis of a cross-sectional German study in National Comprehensive Cancer Centers using self-report standardized questionnaires administered to inpatients. Patients living with dependent children (n = 161) were matched by age and sex with a subsample of 161 cancer patients not living with dependent children. The resulting sample was tested for between-group differences in Distress Thermometer (DT) scores and the corresponding DT Problem List. Additionally, between-group differences in measures of the need for and utilization of psychosocial support were examined. RESULTS: More than 50% of all patients suffered from clinically relevant distress. Patients living with dependent children reported significantly more practical (p < 0.001, η2 p = 0.04), family (p < 0.001, η2 p = 0.03), and emotional problems (p < 0.001, η2 p = 0.01). Although reporting a greater need for psychological support, parents with cancer were not found to more frequently utilize any type of psychosocial support. CONCLUSIONS: The specific problems and needs of parents with cancer who care for dependent children are currently not sufficiently addressed in the clinical care pathways. All families should be helped to establish open and honest communication as well as understand the available support systems and what they can provide. Tailored interventions should be implemented for highly distressed families.

What Kind of Patients Receive Inpatient and Day-Hospital Treatment in Departments of Psychosomatic Medicine and Psychotherapy in Germany?

INTRODUCTION: Germany is one of the few countries with a medical specialty of psychosomatic medicine and psychotherapy and many treatment resources of this kind. OBJECTIVE: This observational study describes the psychosomatic treatment programs as well as a large sample of day-hospital and inpatients in great detail using structured diagnostic interviews. METHODS: Mental disorders were diagnosed according to ICD-10 and DSM-IV by means of Mini-DIPS and SCID-II. In addition to the case records, a modified version of the CSSRI was employed to collect demographic data and service use. The PHQ-D was used to assess depression, anxiety, and somatization. RESULTS: 2,094 patients from 19 departments participated in the study after giving informed consent. The sample consisted of a high proportion of "complex patients" with high comorbidity of mental and somatic diseases, severe psychopathology, and considerable social and occupational dysfunction including more than 50 days of sick leave per year in half of the sample. The most frequent diagnoses were depression, somatoform and anxiety disorders, eating disorders, personality disorders, and somato-psychic conditions. CONCLUSIONS: Inpatient and day-hospital treatment in German university departments of psychosomatic medicine and psychotherapy is an intensive multimodal treatment for complex patients with high comorbidity and social as well as occupational dysfunction.

German physicians' perceptions and views on complementary medicine in pediatric oncology: a qualitative study.

Complementary and alternative medicine (CAM) use in children with cancer has a high prevalence. If (parents of) patients bring up the topic of CAM, pediatric oncologists (POs) face considerable challenges regarding knowledge and professional behavior. In this study, we explore German POs' understanding of CAM and related attitudes as well as challenges and strategies related to CAM discussions by means of semi-structured interviews analyzed according to principles of qualitative thematic analysis with parents of children with cancer. We could conduct 14 interviews prior to theoretical saturation. The interviews had a duration of 15-82 min (M = 30.8, SD = 18.2). Professional experience in pediatric oncology was between 0.5 and 26 years (M = 13.8, SD = 7.6). Main themes identified were a heterogeneous understanding and evaluation of CAM, partly influenced by personal experiences and individual views on plausibility; the perception that CAM discussions are a possible tool for supporting parents and their children and acknowledgement of limitations regarding implementation of CAM discussions; and uncertainty and different views regarding professional duties and tasks when being confronted with CAM as a PO. Our interdisciplinary interpretation of findings with experts from (pediatric) oncology, psychology, and ethics suggests that there is need for development of a consensus on the minimal professional standards regarding addressing CAM in pediatric oncology.

Return to work after cancer: Improved mental health in working cancer survivors.

OBJECTIVE: Aim of the study was to compare working and non-working patients over a period of 12 months regarding socio-demographic, cancer-specific and mental health parameters. METHODS: This study was conducted as part of a Germany-wide longitudinal survey among 1398 patients in 13 national Comprehensive Cancer Centers. The sample used for analysis consisted of n = 430 cancer patients younger than 65 years (age M = 52.4 years, SD = 8.1; 67.0% females). Socio-demographic, cancer-specific and mental health parameters (Depression: Patient Health Questionnaire, Anxiety: Generalized Anxiety Disorder Scale, Distress: Distress Thermometer) were assessed at baseline during hospitalization and at 12 months follow-up. RESULTS: 73.7% of all patients (n = 317) have returned to work after one year. While working and non-working patients did not differ in socio-demographic parameters, there were significant differences in the presence of metastases, tumor and treatment status. Mixed analysis of variances revealed significant interactions between working status and time for depression (p = 0.009), anxiety (p = 0.003) and distress (p = 0.007). Non-working patients reported higher levels of depression, anxiety and distress than working patients over time. A logistic regression showed significant associations between lower depression (p = 0.019), lower distress (p = 0.033) and the absence of a tumor (p = 0.015) with working status. CONCLUSIONS: The majority of cancer survivors returned to work. Non-working patients had higher levels of depression, anxiety and distress than working patients. After controlling for cancer-specific factors, mental health parameters were still independently associated with working status. Return to work can thus be associated with an improved mental health in cancer survivors. In order to establish causality, further research is necessary.

[Use of complementary and alternative medicine in chronic pain : A survey among patients in a pain clinic]. / Anwendung von Komplementärmedizin bei chronischen Schmerzen : Eine Fragebogenerhebung unter Patienten einer Schmerztagesklinik.

BACKGROUND: Chronic pain patients represent the population with the highest use of complementary and alternative medicine (CAM). Current data on the usage, prescription and reasons for using CAM in Germany remain unclear and have not yet been published. OBJECTIVES: The aim of this study was to evaluate details regarding interest and use as well as reasons for using CAM in chronic pain patients. METHODS: In all, 60 of 64 consecutive patients referred to the multimodal pain therapy program in a specialized day hospital participated in the study. In addition to the German Pain Questionnaire, patients answered a self-developed questionnaire on CAM use. CAM was defined according to the guidelines of the NCCIH (National Center for Complementary and Integrative Health). RESULTS: The study showed that 96.7% of patients were interested in CAM and all 60 participants had used CAM to influence pain (3-26 different CAM modalities, median: 12). The most frequently used were massage (95%), acupuncture (73%), nutriceuticals and vitamin preparations (72% each). The success of the therapies was predominantly evaluated as short-lasting. CAM was often prescribed by a specialist (61.7%) or family doctor (60%). For most patients, the greatest motivation for using CAM was the desire to become active themselves (76.7%). Greater impairment due to pain was associated with increased use of biological CAM methods, while higher pain intensity was associated with decreased use of biological and alternative CAM methods. CONCLUSIONS: The high use of CAM in chronic pain patients highlights the need for physicians to have adequate medical knowledge about each CAM modality and to communicate competently with the patients about them.

Psychiatric and Psychosomatic Consultation-Liaison Services in General Hospitals: A Systematic Review and Meta-Analysis of Effects on Symptoms of Depression and Anxiety.

BACKGROUND: Psychiatric and psychosomatic consultation-liaison services (CL) are important providers of diagnosis and treatment for hospital patients with mental comorbidities and psychological burdens. OBJECTIVE: To perform a systematic review and meta-analysis investigating the effects of CL on depression and anxiety. METHODS: Following PRISMA guidelines, a systematic literature search was conducted until 2017. Included were published randomized controlled trials using CL interventions with adults in general hospitals, treatment as usual as control groups, and depression and/or anxiety as outcomes. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Level of integration was assessed using the Standard Framework for Levels of Integrated Healthcare. Meta-analyses were performed using random effects models and meta-regression for moderator effects. RESULTS: We included 38 studies (9,994 patients). Risk of bias was high in 17, unclear in 15, and low in 6 studies. Studies were grouped by type of intervention: brief interventions tailored to the patients (8), interventions based on specific treatment manuals (19), and integrated, collaborative care (11). Studies showed small to medium effects on depression and anxiety. Meta-analyses for depression yielded a small effect (d = -0.19, 95% CI: -0.30 to -0.09) in manual studies and a small effect (d = -0.33, 95% CI: -0.53 to -0.13) in integrated, collaborative care studies, the latter using mostly active control groups with the possibility of traditional consultation. CONCLUSIONS: CL can provide a helpful first treatment for symptoms of depression and anxiety. Given that especially depressive symptoms in medically ill patients are long-lasting, the results underline the benefit of integrative approaches that respect the complexity of the illness.

Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia.

Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P = .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age ≤65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8+ T cells. Long-term OS was correlated with interferon-γ+ and tumor necrosis factor-α+ WT1-specific responses in delayed-type hypersensitivity-infiltrating CD8+ T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD8+ T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224.

Impact of social support on psychosocial symptoms and quality of life in cancer patients: results of a multilevel model approach from a longitudinal multicenter study.

Background: This prospective multicenter study aimed to investigate the courses of positive support (PS) and detrimental interaction (DI), two different aspects of social support, and the relation between social support and psychosocial distress and/or health-related quality of life (HRQOL) in a large sample of patients with different cancers. Methods: For this observational study, we enrolled adult patients with cancer from 13 comprehensive cancer centers (CCCs) in Germany. We included a total of 1087 patients in our analysis. We assessed the outcomes via standardized self-report questionnaires at three measurement points: at admission for acute care (T1), 6 (T2) and 12 months (T3) thereafter. Our outcome variables included PS and DI, depression and anxiety symptoms, distress, mental quality of life (MQoL) and physical QoL (PQoL). Data were analyzed using three-level hierarchical linear modeling (HLM) and group-based trajectory modeling. Results: During the first year after the cancer diagnosis, both PS and DI decreased in our sample. Baseline depression symptom severity was a significant predictor of PS and DI. Further analyses revealed significant associations between PS, DI and the course of depression and anxiety symptoms, and MQoL. PS buffered the negative effects of DI with regards to these variables. Low DI was associated with better PQoL, whereas PS was not. In general, the impact of social support on psychosocial outcomes was weak to moderate. Conclusions: Our findings provide evidence for the influence of PS and DI on psychosocial symptoms and HRQOL, and emphasize the importance of psycho-oncological interventions that strengthen PS and prevent or reduce DI for patients with cancer and their relatives.

Psychosocial distress and utilization of professional psychological care in cancer patients: An observational study in National Comprehensive Cancer Centers (CCCs) in Germany.

OBJECTIVE: The study aimed to assess cancer patients' use of psychological care and its correlates in a large sample of cancer patients in Comprehensive Cancer Centers (CCCs) in Germany. METHODS: In a multicenter study in Germany, cancer patients with various diagnoses were evaluated for self-reported use of psychological support. We measured psychological distress, depression and anxiety, quality of life, and social support with standardized questionnaires and analyzed its association with the utilization of psychological care using multivariable logistic regression. This paper focuses on a cross-sectional analysis of the data assessed during inpatient care. RESULTS: Three thousand fifty-four (50%) of hospitalized patients were asked for participation, and n = 1632 (53.6%) participated. We were able to analyze n = 1,398 (45.9%) patients. Three hundred ninety-seven (28.4%) of the sample utilized psychological support. Users of psychological care were significantly younger than nonusers (odds ratio [OR]: 0.967, P < 0.001) and were more often female (OR: 1.878, P < 0.001), whereas educational level was not associated with the use of psychological care. In the multivariable analysis, effects on the use of psychological care were observed for Hospital Anxiety and Depression Scale (HADS) anxiety (OR: 1.106, P = 0.001) and both subscales of the 12-item Short Form Health Survey (SF-12) quality of life measure (mental, OR: 0.97, P = 0.002; physical, OR: 0.97, P = 0.002). CONCLUSION: Psychological distress and anxiety are higher, and quality of life is lower in users of psychological care in comparison with nonusers during inpatient cancer treatment. Although psychooncological services should be provided to all patients who need them, special efforts should be made to reach populations that report low utilization.

Attitudes and preferences concerning interprofessional education of first-year students and experienced medical and nursing staff.

In order to enhance patient outcome and patient safety in healthcare, interprofessional education (IPE) has over the years become a specific area of interest focusing on teaching concepts, research methods, and implementation strategies. To achieve commitment and positive attitudes as part of the institutional readiness towards IPE, the adoption of change management aspects can support its early implementation. This short report presents results of a baseline survey on attitudes and preferences for IPE among first-year students in medicine and nursing, as well as among chief physicians, nurse directors, and administrative directors at the associated university hospital. For the survey, the UWE-IP (University of the West of England Interprofessional Questionnaire) was used along with ten customised questions. Overall, a high degree of approval for IPE was observed in all participants. Furthermore, participants showed positive attitudes in three of the four UWE-IP subscales. However, neutral to negative attitudes were documented in subscale interprofessional interaction.

[Psychosomatic medicine in old age]. / Psychosomatik im Alter.

Approximately 25% of people over 65 years old suffer from psychiatric disorders but in cases of simultaneously occurring somatic diseases the prevalence is increased. Sickness, loss of important reference persons and life crises in older age often reactivate traumatic experiences from earlier life stages. It can be difficult to differentiate between psychological disorders and the psychological symptoms accompanying somatic illness. The biographic medical history and estimation of cognitive skills within a geriatric basis assessment should be standard in geriatric diagnostics. Psychological disorders are often overlooked or inadequately treated in older people. In the case of psychopharmacological treatment, effects on somatic sickness as well as drug-drug interactions have to be kept in mind. Psychotherapeutic approaches focusing on resources and social support particularly in group therapy seem to be very helpful.

[Attachment Representation and Emotion Regulation in Patients with Burnout Syndrome]. / Repräsentationen früher Bindungsbeziehungen und Emotionsregulation bei Patienten mit Burnout-Syndrom.

OBJECTIVE: Burnout describes a syndrome of exhaustion resulting from insufficient coping with work-related distress. We investigated if patients that are being clinically treated for burnout show insecure and unresolved attachment representation more often compared with healthy controls. METHODS: 50 out of 60 consecutive burnout patients participated in the study. Mental representation of attachment was measured by using the Adult Attachment Interview. Additionally, we administered the Self Report Questionnaire to Assess Emotional Experience and Emotion Regulation and several burnout specific questionnaires. A population sample was used as control group. RESULTS: Burnout patients were classified as insecurely attached significantly more often than controls. Unresolved attachment status concerning loss or trauma was found significantly more often within the burnout sample. Patients with insecure attachment representation reported a lower subjective significance of work. Patients with avoidant insecure attachment showed more depersonalisation. Patients with unresolved loss/trauma reported less social support. They showed more passive-negative emotion experience and emotion regulation characterized by externalization. CONCLUSION: The results of the study suggest that an insecure or unresolved attachment representation might constitute an intrapersonal risk factor for the development of burnout syndrome.

[Evaluation of the German Version of the "INTERMED-Self-Assessment"-Questionnaire (IM-SA) to Assess Case Complexity]. / Evaluation der deutschsprachigen Version des "INTERMED-Self-Assessment"- Fragebogens (IM-SA) zur Erfassung von Patienten mit komplexem Versorgungsbedarf.

INTRODUCTION: The INTERMED- interview (IM-CAG=INTERMED complexity assessment grid) is a well validated instrument for the identification of complex patients in need of integrated health care (score ≥21). The IM-SA (INTERMED self-assessment)-questionnaire, derived from the INTERMED- interview, was developed in cooperation with the international INTERMED group in order to facilitate its use in various clinical settings and to foster the patients' perspective on health-care needs. METHODS: The German version of the IM-SA was evaluated in a clinical sample (n=136) of psychosomatic outpatients and compared to the IM-CAG. Construct validity was examined by analyzing the correlations of the IM-SA with quality-of-life (SF-36) and anxiety/depression (HADS). Sensitivity and specificity for the identification of complex patients were examined by using ROC (Receiver Operating Characteristic) analysis. RESULTS: The correlations between the total score and the subscales of the IM-SA, compared to the INTERMED, were high (total score r=0.79 (95%-KI: [0.70; 0.85]). Cronbach's α was 0.77, and construct validity was high (SF-36 mental component score: r=-0.57; HADS Depression: r=0.59). The IM-SA total score was significantly lower compared to IM-CAG, mainly because of low IM-SA scores in the somatic domain. According to ROC analysis, the IM-SA-cut-off for identifying complex patients has to be lowered (score ≥17). DISCUSSION: The IM-SA can be used as an instrument to identify complex patients in need of integrated bio-psycho-social care. CONCLUSION: The IM-SA is a reliable instrument to be used in various clinical settings to identify complex patients and to provide integrated, bio-psycho-social care.

Engineering monocyte-derived dendritic cells to secrete interferon-α enhances their ability to promote adaptive and innate anti-tumor immune effector functions.

Dendritic cell (DC) vaccination has demonstrated potential in clinical trials as a new effective cancer treatment, but objective and durable clinical responses are confined to a minority of patients. Interferon (IFN)-α, a type-I IFN, can bolster anti-tumor immunity by restoring or increasing the function of DCs, T cells and natural killer (NK) cells. Moreover, type-I IFN signaling on DCs was found to be essential in mice for tumor rejection by the innate and adaptive immune system. Targeted delivery of IFN-α by DCs to immune cells could boost the generation of anti-tumor immunity, while avoiding the side effects frequently associated with systemic administration. Naturally circulating plasmacytoid DCs, major producers of type-I IFN, were already shown capable of inducing tumor antigen-specific T cell responses in cancer patients without severe toxicity, but their limited number complicates their use in cancer vaccination. In the present work, we hypothesized that engineering easily generated human monocyte-derived mature DCs to secrete IFN-α using mRNA electroporation enhances their ability to promote adaptive and innate anti-tumor immunity. Our results show that IFN-α mRNA electroporation of DCs significantly increases the stimulation of tumor antigen-specific cytotoxic T cell as well as anti-tumor NK cell effector functions in vitro through high levels of IFN-α secretion. Altogether, our findings mark IFN-α mRNA-electroporated DCs as potent inducers of both adaptive and innate anti-tumor immunity and pave the way for clinical trial evaluation in cancer patients.

Except for C-C chemokine receptor 7 expression, monocyte-derived dendritic cells from patients with multiple sclerosis are functionally comparable to those of healthy controls.

BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy has shown potential to counteract autoimmunity in multiple sclerosis (MS). METHODS: We compared the phenotype and T-cell stimulatory capacity of in vitro generated monocyte-derived DC from MS patients with those from healthy controls. RESULTS: Except for an increase in the number of C-C chemokine receptor 7-expressing DC from MS patients, no major differences were found between groups in the expression of maturation-associated membrane markers or in the in vitro capacity to stimulate autologous T cells. CONCLUSIONS: Our observations may pave the way for the development of patient-tailored DC-based vaccination strategies to treat MS.

Determinants of workload-related clinician stress levels in general hospital consultation liaison psychiatry services during the COVID-19 pandemic in England and Ireland. Short report.

OBJECTIVE: To explore workload-related stress levels experienced by consultation liaison psychiatry (CLP) staff in England and Ireland, and factors relevant to such a burden, during the COVID-19 pandemic. METHODS: Data were obtained for England and Ireland from a European survey among CLP services in general hospitals spread via CLP networks (11th June - 3rd October 2021). The heads of respective CLP services in general hospitals responded on behalf of each service, on 100 CLP hospital staff in total. DEPENDENT VARIABLE: workload-related stress levels in CLP services due to COVID-19 (0-10 point scale). INDEPENDENT VARIABLES: hospital size, CLP service size, degree of hospital involvement in COVID-19-related care, and the number of support options available to hospital staff. Spearman's rho correlation analyses were performed. RESULTS: There was a significant association between the hospital's involvement in COVID-19-related care and workload-related stress levels as reported by CLP staff: r(22) = 0.41, p = 0.045, R2 = 0.17. There were no significant associations between workload-related stress levels and other variables including staff support (p = 0.74). CONCLUSION: Our findings suggest that perceived workload-related stress levels of CLP staff during the COVID-19 pandemic can be an indicator of COVID-19 involvement of the hospitals. Staff support seemed not to alleviate work stress in the context of the pandemic. Healthcare policies should improve working conditions for CLP hospital staff that play an essential role from a population health perspective. Rigorous measures may be needed to ensure mental healthcare provision remains tenable and sustainable in the long term.

12-Month Trajectories of Health-Related Quality of Life Following Hospitalization in German Cancer Centers-A Secondary Data Analysis.

Patient-reported outcomes (PROs) offer a diverse array of potential applications within medical research and clinical practice. In comparative research, they can serve as tools for delineating the trajectories of health-related quality of life (HRQoL) across various cancer types. We undertook a secondary data analysis of a cohort of 1498 hospitalized cancer patients from 13 German cancer centers. We assessed the Physical and Mental Component Scores (PCS and MCS) of the 12-Item Short-Form Health Survey at baseline (t0), 6 (t1), and 12 months (t2), using multivariable generalized linear regression models. At baseline, the mean PCS and MCS values for all cancer patients were 37.1 and 44.3 points, respectively. We observed a significant improvement in PCS at t2 and in MCS at t1. The most substantial and significant improvements were noted among patients with gynecological cancers. We found a number of significant differences between cancer types at baseline, t1, and t2, with skin cancer patients performing best across all time points and lung cancer patients performing the worst. MCS trajectories showed less pronounced changes and differences between cancer types. Comparative analyses of HRQoL scores across different cancer types may serve as a valuable tool for enhancing health literacy, both among the general public and among cancer patients themselves.

Adjuvant Wilms' tumour 1-specific dendritic cell immunotherapy complementing conventional therapy for paediatric patients with high-grade glioma and diffuse intrinsic pontine glioma: protocol of a monocentric phase I/II clinical trial in Belgium.

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms' tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety of WT1 mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG. METHODS AND ANALYSIS: 10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m2 daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8-10×106 cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150-200 mg/m2 on days 1-5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life. ETHICS AND DISSEMINATION: The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences. TRIAL REGISTRATION NUMBER: NCT04911621.

Preoperative serum C- reactive protein: a prognostic marker in patients with upper urinary tract urothelial carcinoma.

BACKGROUND: To analyse the prognostic significance of preoperative C-reactive protein (CRP) serum level in patients with upper urinary tract urothelial carcinoma (UUT-UC). METHODS: We evaluated 158 UUT-UC patients who had undergone surgery in the University Hospital of Hannover (MHH). 143 (89.4%) suffered from cancer in the renal pelvis, 13 (8.1%) patients presented with tumour located in the ureter. A preoperative CRP value was available for 115 patients. The mean (median) follow-up for these patients was 28.3 (15.1) months. RESULTS: The median (mean) CRP value of all evaluable patients was 10.0 (40.7) mg/l. The CRP-level, stratified into two subgroups (CRP ≤5 vs. >5 mg/l), correlated significantly with muscle invasive tumour stage (36.4 vs. 78.9%; p<0.001), the risk of presenting nodal disease (4.5 vs. 26.8%; p=0.002) and distant metastasis (2.3 vs. 16.9%; p<0.016). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 54.2 and 26.4% for patients with preoperative CRP levels ≤ and >5 mg/l, respectively (p<0.006). Next to age and the presence of metastasis, multivariate analysis also identified CRP as a continuous variable as an independent prognosticator for CSS. CONCLUSIONS: A high preoperative serum CRP level is associated with locally advanced and metastatic disease in patients with UUT-UC. Its routine use could allow better risk stratification and risk-adjusted follow-up of UUT-UC patients.

Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination.

Active immunization using tumor antigen-loaded dendritic cells holds promise for the adjuvant treatment of cancer to eradicate or control residual disease, but so far, most dendritic cell trials have been performed in end-stage cancer patients with high tumor loads. Here, in a phase I/II trial, we investigated the effect of autologous dendritic cell vaccination in 10 patients with acute myeloid leukemia (AML). The Wilms' tumor 1 protein (WT1), a nearly universal tumor antigen, was chosen as an immunotherapeutic target because of its established role in leukemogenesis and superior immunogenic characteristics. Two patients in partial remission after chemotherapy were brought into complete remission after intradermal administration of full-length WT1 mRNA-electroporated dendritic cells. In these two patients and three other patients who were in complete remission, the AML-associated tumor marker returned to normal after dendritic cell vaccination, compatible with the induction of molecular remission. Clinical responses were correlated with vaccine-associated increases in WT1-specific CD8+ T cell frequencies, as detected by peptide/HLA-A*0201 tetramer staining, and elevated levels of activated natural killer cells postvaccination. Furthermore, vaccinated patients showed increased levels of WT1-specific IFN-gamma-producing CD8+ T cells and features of general immune activation. These data support the further development of vaccination with WT1 mRNA-loaded dendritic cells as a postremission treatment to prevent full relapse in AML patients.