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The number of long-term survivors of malignant diseases is steadily increasing, which is due to the further development and optimization of multimodal therapy strategies and the mechanisms of new substance classes. These can now be combined with classical treatment methods or used sequentially. At the same time the number of patients who suffer from physical and psychosocial long-term consequences of cancer therapies or have to live with chronic side effects under the long-term therapies increases. Every therapy, whether radiation, chemotherapy, targeted therapy, or operation, has undesirable long-term side effects that contribute to the decrease of one's quality of life. These affect all parts of the body. As a result, patients can be heavily burdened. In oncology and in other disciplines involved in aftercare, these consequences must therefore be increasingly addressed and clarified and treatment strategies further developed. Unfortunately, there is still a considerable need for research in this area; moreover, there is a lack of clinical studies examining the evidence of a wide variety of holistic therapy methods.Die Anzahl der Langzeitüberlebenden von malignen Erkrankungen nimmt stetig zu, was auf die Weiterentwicklung und Optimierung der multimodalen Therapiestrategien sowie auf die Wirkmechanismen neuer Substanzklassen zurückzuführen ist. Diese können nun mit „klassischen“ Behandlungsverfahren kombiniert oder sequenziell eingesetzt werden. Gleichzeitig erhöht sich dadurch aber auch die Anzahl der Patient:innen, die an körperlichen und psychosozialen Langzeitfolgen der Krebstherapien leiden oder mit chronischen Nebenwirkungen unter den Langzeittherapien leben müssen. Jede Therapieform, egal ob Bestrahlung, Chemo‑, Immun-, zielgerichtete und auch die endokrine Therapie oder die Operationen an sich, kann körperliche Langzeitfolgen nach sich ziehen. Diese können jeden Teil des Körpers betreffen und die Patient:innen stark belasten. In der Onkologie und in anderen Disziplinen, die in die Nachsorge von Tumorpatient:innen involviert sind, müssen daher diese Folgen vermehrt thematisiert, darüber aufgeklärt und Behandlungsstrategien weiterentwickelt werden. Leider besteht in diesem Bereich noch erheblicher Forschungsbedarf und es fehlen klinische Studien, die die Evidenz verschiedenster ganzheitlicher Therapieverfahren untersuchen.

Purpose Distress screening has become mandatory and essential in comprehensive cancer care. We evaluated an electronic psycho-oncological adaptive screening (EPAS) which assesses objective indicators of care needs and subjectively perceived care needs and subsequently provides patient feedback with individualized recommendations about psychosocial care services. Methods Patients were assessed within clusters, i.e., different oncological facilities of the competence network of the University Cancer Center Hamburg (UCCH). Patients in the intervention arm underwent the screening, controls received standard care. Patients were assessed at baseline (t0), 3-month (t1), and 6-month (t2) follow-up. Outcomes included information level and use of/access to nine psychosocial services at UCCH, well-being (GAD-7, PHQ-9, SF-8), and treatment satisfaction (SCCC). Conditional linear and logistic regressions were used to identify screening effects at t1 and t2. Results Of 1320 eligible patients across 11 clusters, 660 were included (50%). The average age was 60 years; 46% were female. The intervention was associated with increased information level for all psychosocial services at t1 and t2 (all p p ≤ .02), and better evaluation of access (e.g., more recommendations for services provided by physicians, p p = .02). Conclusions EPAS may improve information about psychosocial services as well as utilization of and access to these services. The effect on information level seems not to be generalizable to other aspects of oncological care. Future studies should incorporate novel technologies and condense the procedure to its core factors. Implications for Cancer Survivors: The screening may help to enhance self-management competencies among cancer survivors. Trial registration The trial was retrospectively registered (2/2021) at ClinicalTrials.gov (number: NCT04749056).

Purpose In clinical cancer care, distress screening is recommended to identify highly burdened patients in objective need for psychosocial support to improve psychological distress and quality of life and to enhance patient empowerment. It is however unclear whether distress screeners are suitable for psychosocial care planning and thus whether they can predict the willingness that is need, intention, and utilization, to seek psychosocial support. Methods In a secondary analysis of a cluster intervention study, we assessed cancer patients with three distress screeners (DT, PHQ-9, GAD-7) at baseline. The willingness to seek psychosocial support services was assessed binary for psychosocial services at 3 and 6 months. Logistic regression models were applied to examine the predictive effect of the screeners on need, intention, and utilization. We corrected all models for multiple testing. Results The 660 patients included in the study were on average 60 years, 54% were male. At the 3- and 6-month follow-up, 353 and 259 patients participated, respectively. The screeners were best in predicting the need for support (OR reaching up to 1.15, 1.20, and 1.22 for the PHQ-9, GAD-7, and DT respectively). The intention was predicted by the PHQ-9 and GAD-7, whereas utilization of psychosocial support services was not predicted by the screeners. Conclusion The three distress screeners might be useful in psychosocial care planning, as they are able to predict the need and to some degree the intention to seek psychosocial support. Future research needs to examine potential barriers and supporting factors that may explain utilization of psychosocial support. Trial registration The study was retrospectively registered (2/2021) at ClinicalTrials.gov (number: NCT04749056).

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. Abstract 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.

Purpose: Patients with cancer and their relatives often experience a deterioration of mental health while dealing with the consequences of the disease. The aim of the present study was to evaluate changes of mental health during and after brief psychosocial support at cancer counselling centers.Methods: In this non-randomized controlled trial n = 885 participants were recruited and n = 449 were eligible for the analysis. The intervention group (IG, n = 264) was recruited at two cancer counselling centers in Germany. The control group (CG, n = 195) were cancer patients or relatives who did not seek support at one of the aforementioned cancer counseling centers. To compare differences between IG and CG across three points in time (before the first counseling session and subsequently after two twelve weeks), a linear mixed model analysis (LLM) was performed. The primary outcome was distress; secondary outcomes were anxiety and depressive symptoms, well-being, cancer specific and generic quality of life (QoL), self-efficacy, and fatigue. Results: The LLM showed significant differences between IG and CG at follow-up for distress (d = 0.36), depressive (d = 0.22) and anxiety symptoms (d = 0.22), well-being (d = 0.26), quality of life (QoL mental, d = 0.26), cancer specific QoL (symptoms, d = 0.13) and QoL (global, d = 0.27). The changes were not significant for QoL (physical), cancer specific QoL (functional) and fatigue. Conclusion: The results suggest that brief psychosocial support is associated with the improvement of mental health of cancer patients and their relatives after three months.The study was approved by the Center of Psychosocial Medicine (LPEK) at the University Clinic Hamburg-Eppendorf on 22nd of August 2018 (No: LPEK-007). The study was registered prior to data collection with the German Registration of Clinical Trials (DRKS, ID: DRKS00015516) in September 2018.

Immuntherapie bei malignen Erkrankungen ist definiert als ein systemtherapeutischer Ansatz, der auf die Fahigkeit des korpereigenen Immunsystems abzielt, die Entstehung von malignen Tumoren zu verhindern, bzw. bestehende Tumoren zu bekampfen. Hierunter fallen heutzutage sehr unterschiedliche Therapieformen, wie Immuncheckpoint-Inhibitoren, BiTEs, CAR-T-Zellen und onkolytische Viren, die unterschiedliche Wirkmechanismen und Angriffspunkte haben und auch eine sehr unterschiedliche Effizienz in der Behandlung von soliden und hamatologischen Malignomen aufweisen. Zweifellos bereichern diese Ansatze das therapeutische Portfolio in der Onkologie, in der palliativen Systemtherapie, aber auch im Zusammenspiel mit operativen und ablativen lokaltherapeutischen Ansatzen.

(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.

Distress screening has become mandatory and essential in comprehensive cancer care. We evaluated an electronic psycho-oncological adaptive screening (EPAS) which assesses objective indicators of care needs and subjectively perceived care needs and subsequently provides patient feedback with individualized recommendations about psychosocial care services.Patients were assessed within clusters, i.e., different oncological facilities of the competence network of the University Cancer Center Hamburg (UCCH). Patients in the intervention arm underwent the screening, controls received standard care. Patients were assessed at baseline (t0), 3-month (t1), and 6-month (t2) follow-up. Outcomes included information level and use of/access to nine psychosocial services at UCCH, well-being (GAD-7, PHQ-9, SF-8), and treatment satisfaction (SCCC). Conditional linear and logistic regressions were used to identify screening effects at t1 and t2.Of 1320 eligible patients across 11 clusters, 660 were included (50%). The average age was 60 years; 46% were female. The intervention was associated with increased information level for all psychosocial services at t1 and t2 (all p .001), increased use in some of these services at t1 and t2, respectively (p ≤ .02), and better evaluation of access (e.g., more recommendations for services provided by physicians, p .01). At t2, the intervention was associated with a lower level of satisfaction with disease-related information (p = .02).EPAS may improve information about psychosocial services as well as utilization of and access to these services. The effect on information level seems not to be generalizable to other aspects of oncological care. Future studies should incorporate novel technologies and condense the procedure to its core factors.The screening may help to enhance self-management competencies among cancer survivors.The trial was retrospectively registered (2/2021) at ClinicalTrials.gov (number: NCT04749056).

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.

Background: Extramedullary plasma cell (PC) disorders may occur as extramedullary disease in multiple myeloma (MM-EMD) or as primary extramedullary plasmocytoma (pEMP)/solitary osseous plasmocytoma (SOP). In this study, we aimed to obtain insights into the molecular mechanisms of extramedullary spread of clonal PC. Methods: Clinical and biological characteristics of 87 patients with MM-EMD (n = 49), pEMP/SOP (n = 20) and classical MM (n = 18) were analyzed by using immunohistochemistry (CXCR4, CD31, CD44 and CD81 staining) and cytoplasmic immunoglobulin staining combined with fluorescence in situ hybridization (cIg-FISH). Results: High expression of CD44, a cell-surface glycoprotein involved in cell-cell interactions, was significantly enriched in MM-EMD (90%) vs. pEMP/SOP (27%) or classical MM (33%) (p &lt, 0.001). In addition, 1q21 amplification by clonal PC occurred at a similar frequency of MM-EMD (33%), pEMP/SOP (57%) and classical MM (44%). Conversely, del(17p13), t(4, 14) and t(14, 16) were completely absent in pEMP/SOP. Besides this, 1q21 amplification was identified in 64% of not paraskeletal samples from MM-EMD or pEMP compared to 9% of SOP or paraskeletal MM-EMD/pEMP and 44% of classical MM samples, respectively (p = 0.02). Conclusion: Expression of molecules involved in homing and cytogenetic aberrations differ between MM with or without EMD and pEMP/SOP.

Cancer and its multimodal therapy approaches can lead to a number of physical disabilities and/or psychosocial impairments. These complicate or even prevent the return to daily living and work. Cancer rehabilitation contributes to restore physical and psychosocial functioning in all disease settings and thus is the beginning of cancer survivorship.

Immunotherapy for malignant diseases is defined as a systematic therapeutic approach that aims to target the individual's immune system to prevent the development of malignancies or to combat existing tumors. Nowadays, this includes various therapeutic approaches, such as immune checkpoint inhibitors, BiTEs (bispecific T‑cell engagers), CAR T‑cells (CAR: chimeric antigen receptors) and oncolytic viruses, which have not only different mechanisms of action and points of attack, but also have very different efficiencies in the treatment of solid and hematological malignancies. These approaches undoubtedly enrich the therapeutic portfolio in oncology-in palliative systematic therapy and also in the interaction with operative and ablative local therapeutic approaches.

Das Uberleben einer Krebserkrankung durch die onkologische Behandlung geht oft mit physischen und psychosozialen Langzeitfolgen einher, die besonderer Berucksichtigung bedurfen. Der Ubersichtsartikel soll die wesentlichen psychosozialen Langzeitfolgen beschreiben und Ansatze zu ihrer Vorbeugung und Behandlung aufzeigen. Sichtung bestehender relevanter wissenschaftlicher und fachlicher Beitrage im psychoonkologischen Kontext und Darstellung psychoonkologischer Erfahrungen. Sowohl sozial als auch psychologisch bestehen potenziell stark belastende Einschrankungen fur Menschen nach einer Krebserkrankung durch Arbeitsplatzkonflikte, finanzielle Einschrankungen, soziale Konflikte, eine Fatiguesymptomatik oder Angste und depressive Symptome. Es bestehen psychoonkologische Angebote fur Krebspatienten und ihre Angehorigen sowie vereinzelt spezifische Angebote fur Langzeituberlebende einer Krebserkrankung. Es bedarf einer interdisziplinaren Aufmerksamkeit fur die psychosozialen Langzeitfolgen einer Krebserkrankung und ihrer Behandlung und noch mehr spezifischer Angebote.

Kolorektale Karzinome gehoren zu der Gruppe von malignen Tumoren mit mittlerer Prognose. Aufgrund der hohen Inzidenz und einem 5-Jahres Uberleben von > 60 % stellen (ehemalige) Patienten mit kolorektalen Karzinomen nach Mannern mit Prostata- und Frauen mit Mammakarzinomen die drittgroste Gruppe von Krebslangzeituberlebenden dar. In der Zeit nach der Erkrankung und deren Therapie konnen die ehemaligen Patienten durch Lebensstilveranderungen viel selbst dazu beitragen, dass Zweitkrebserkrankungen, Komorbiditaten oder Rezidive verringert bzw. verhindert werden, die Lebensqualitat verbessert wird und Langzeitnebenwirkungen effektiv behandelt werden. Das Uberleben der Krankheit sollte als „teachable moment“ fur nachhaltige Lebensstilveranderungen genutzt werden.

Context Distress and anxiety about issues related to death and dying is commonly experienced in patients with advanced disease and a limited life expectancy. Objectives To evaluate the psychometric properties of the German version of the Death and Dying Distress Scale (DADDS-G) in advanced cancer patients. Methods We recruited advanced patients with mixed tumor entities (Union for International Cancer Control [UICC] Stage III/IV) treated in two German University Medical Centers during their outpatient treatment. After testing a preliminary version of the state-of-the-art translated original Death and Dying Distress Scale, we analyzed the psychometric properties of the shortened nine-item adapted DADDS-G using validated instruments measuring distress, anxiety, depression, fear of progression, and quality of life. Results We obtained complete questionnaires from 77 of 93 patients with advanced cancer (response rate: 83%). Participants were mostly married or cohabiting (75%), well-educated, and both sexes were almost equally represented (52% men; mean age 58 years, SD = 12). The total mean DADDS-G score was 13.3 (SD = 8.5). Patients reported to be most distressed by the feeling of being a burden to others. The exploratory factor analysis led to one factor that accounted for more than 59% of the variance. The DADDS-G's internal consistency was excellent with Cronbach alpha = 0.91. The confirmatory factor analysis demonstrated a very good model fit. Death-related anxiety was significantly associated with distress, depression, anxiety, fear of progression, and lower quality of life ( P Conclusion Results provide further evidence that the DADDS-G is a valid and reliable instrument of high clinical relevance for use in patients with advanced cancer.

ZusammenfassungModerne multimodale Therapieverfahren ermöglichen heute vielen Krebspatienten auch in der metastasierten Situation ein Langzeitüberleben, d. h. ein Überleben 5 Jahre nach Diagnosestellung. In dieser Zeit nach der Erkrankung können die Patienten durch Lebensstilveränderungen viel selbst dazu beitragen, dass Zweitkrebserkrankungen oder andere Komorbiditäten, Rezidive oder Langzeitnebenwirkungen verringert bzw. verhindert werden. Leider hat sich aber am Gesundheitsverhalten der ehemaligen Krebspatienten im Sinne von Tertiärprävention (gesundes Essen, Gewichtsreduktion, Nikotinabstinenz, körperliche Aktivität) in den letzten Jahren kaum etwas verändert. Es muss also unsere Aufgabe sein, die Patienten nachhaltig und niederschwellig mit entsprechenden Programmen über die stationären Rehabilitationsmaßnahmen hinaus zu unterstützen und sie zu einem entsprechenden Gesundheitsverhalten immer wieder aufs Neue zu motivieren.

We investigated the relationship between fear of cancer recurrence (FCR), anxiety, supportive care needs, and utilization of health-care services in a mixed sample of 335 cancer patients. We used validated questionnaires including the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the General Anxiety Disorder Scale (GAD-7) and the Supportive Care Needs Survey (SCNS-SF34). Health-care services utilization was measured by a self-constructed questionnaire recording the use of 22 health and supportive care offers. In our sample, 3.9 % of patients were classified as having high anxiety and 5.1 % had high FCR. Patients reported the highest unmet supportive care needs in the domain health system and information followed by psychological needs. Integrated care and complementary support services were the most frequently used (32 %) followed by medical (31 %), psychological (23 %), spiritual and religious (8 %) and other support services (9 %). Whereas anxiety was related to both unmet psychological and physical/daily living needs (p

a MediClin Reha-Zentrum Reichshof, Reichshof-Eckenhagen, Deutschland; b Reha-Klinik Am Kurpark, Rehazentren-Baden-Wurttemberg, Bad Kissingen, Deutschland; c Psycho-Onkologie Medizinische Klinik III, Klinikum der Universitat Munchen-Groshadern, Munchen, Deutschland; d Klinik Sonnenblick, Marburg, Deutschland; e Klinik fur Tumorbiologie, Freiburg i.Br., Deutschland; f Extraordinarius im Ruhestand, Kinderund Jugendklinik, Universitatsklinikum Erlangen, Comprehensive Cancer Center Erlangen – EMN, Nurnberg, Deutschland; g Kompetenz-Centrum Onkologie, Medizinischer Dienst Nordrhein, Dusseldorf, Deutschland

Personalized medicine is a keyword in modern oncology summarizing biomarker-driven targeted therapies. Those novel agents enhance our therapeutic portfolio and offer new options for our patients. But the term is often misleading and implicates a tailored therapy to the individual person, but it rather means a treatment stratified on genetic characteristics of the tumor. Molecular therapies raise expectations of curability or long-term treatments making former life-threatening diseases to more chronic ones but this is true only for some patients. So we have to carefully communicate with our patients about the options and limitations of those modern therapies not to trigger disappointments.

Personalized medicine is a keyword in modern oncology summarizing biomarker-driven targeted therapies. Those novel agents enhance our therapeutic portfolio and offer new options for our patients. But the term is often misleading and implicates a tailored therapy to the individual person, but it rather means a treatment stratified on genetic characteristics of the tumor. Molecular therapies raise expectations of curability or long-term treatments making former life-threatening diseases to more chronic ones but this is true only for some patients. So we have to carefully communicate with our patients about the options and limitations of those modern therapies not to trigger disappointments.

Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer–testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM. Frequency and characteristics of antibody responses against cancer–testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients. We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-285–90. We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.

Burkitt lymphoma cell lines (BL-CL) are used extensively as in vitro models in genetic studies; however, cytogenetic information is not always available or updated. We provide a comprehensive cytogenetic resource of 44 BL-CL, assessed by G-banding, multicolor-FISH, and FISH with 1q, 3p, 7q, and 13q region-specific probes, including the first cytogenetic characterization of 22 BL-CL and the revision of further 22 commonly used BL-CL. Based on these data, we determined a consensus karyotype, evaluated in detail the secondary chromosomal changes (SCC), and the karyotypic stability of these cell lines. An individual karyotype was identified in all investigated BL-CL, confirming their unique origin. Most of the BL-CL remained cytogenetically relative stable after years of intensive cultivation. The most frequent structural SCC were dup(1q), del(13q) and the most frequent numerical SCC were +7, +13. Common breakpoints were located on 1q12, 7q11, and 13q31. The most common gains were in 1q and 7q and the most common losses were in 11q and 13q. Interestingly, the frequency of 1q gains and 13q losses was significantly higher in the EBV-negative than in the EBV-positive BL-CL. Furthermore, by reviewing karyotypes of 221 primary BL listed in the Mitelman database, we observed similarities between BL-CL and primary BL regarding the frequency of numerical and structural SCC and breakpoint distribution. In BL-CL and in primary BL two SCC, dup(1q), and +12, always occurred mutually exclusive of each other. These findings validate BL-CL as appropriate model for in vitro studies on the significance of SCC in the pathogenesis of BL.

IntroductionIn recent years, medical treatment for cancer has improved, thereby increasing the life expectancy of patients with cancer. Hence, the focus in healthcare shifted towards analysing treatments that offer to decrease distress and improve the quality of life of patients with cancer. The psychological burden of patients with cancer originates from all kinds of psychosocial challenges related to diagnosis and treatment. Cancer counselling centres (CCounCs) try to address these concerns. However, the current literature lacks research on the effectiveness of CCounCs. This study aims to assess the effectiveness of CCounCs with regard to distress and other relevant psychosocial variables (quality of life, anxietyand so on).Methods and analysisThis prospective observational study with a non-randomised control group has three measurement points: before the first counselling session (baseline, t0) and at 2 weeks and 3 months after baseline (t1, t2). Patients and their relatives who seek counselling between December 2018 and November 2020 and have sufficient German language skills will be included. The control group will be recruited at clinics and oncological outpatient centres in Hamburg. Propensity scoring will be applied to adjust for differences between the control and intervention groups at baseline. Sociodemographic data, medical data and counselling concerns are measured at baseline. Distress (distress thermometer), quality of life (Short Form-8 Health Survey, European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire-Core 30), anxiety (Generalized AnxietyDisorder-7), depression (Patient HealthQuestionnaire-9) and further psychosocial variables are assessed at all time points. With a total of 787 participants, differences between the intervention and control groups of a small effect size (f=0.10) can be detected with a power of 80%.Ethics and disseminationThe study was registered prior to data collection with the German Registration of Clinical Trials in September 2018. Ethical approval was received by the local psychological ethical committee of the Center for Psychosocial Medicine at the University Medical Centre Hamburg-Eppendorf in August 2018. The results will be published in peer-reviewed journals.Trial registration numberDRKS00015516; Pre-results.

Summary High-dose chemotherapy followed by autologous haematopoetic stem cell transplantation (ASCT) is a standard frontline therapy for multiple myeloma (MM). Unfortunately, there are no randomized clinical studies examining the role of a second ASCT in patients who relapse after the initial autotransplant. Analysing all available retrospective studies, it seems that salvage ASCT can safely be performed in most patients with an overall treatment-related mortality rate

A better understanding of the role of psychosocial resources and factors associated with participating in patient support groups appears to be important for the development and implementation of cancer survivorship care plans. We therefore investigated the frequency of participation in and satisfaction with patient support groups after completion of a rehabilitation programme and aimed to examine differences in demographic, medical and psychosocial characteristics between group participants and non-participants. We further aimed to identify predictors of participation in patient support groups. A total of 1281 eligible patients (75.5% participation rate) were recruited on average 11 months post diagnosis and assessed at the beginning (t1 ), at the end (t2 ) and 12 months after rehabilitation (t3 ). Study participants completed self-report measures assessing support-group participation and satisfaction, psychosocial distress (anxiety, fear of cancer recurrence, depression), social support, coping, quality of life, pain and treatment-related characteristics. Sixty-seven patients (7.6%) participated in a patient self-help group. Being unemployed, undergoing an increased number of overall treatments, and a higher active emotion-oriented coping style significantly predicted self-help group participation; the predictive power of the multivariate logistic regression model was rather weak (Nagelkerke's R(2) = 0.07). Our data provide evidence that self-help group participation in cancer patients may be largely related to other factors than medical or psychosocial distress.

Within a prospective protocol, the incidence and impact of achievement of molecular remission (mCR) and high-risk cytogenetics was investigated in 73 patients with multiple myeloma (MM) after autologous (auto)–allogeneic (allo) tandem stem cell transplantation (SCT). After induction chemotherapy, patients received melphalan 200 mg/m2 before undergoing auto-SCT, followed 3 months later by melphalan 140 mg/m2 and fludarabine 180 mg/m2 before allo-SCT. Sixteen patients had high-risk cytogenetic features, defined by positive FISH for del(17p13) and/or t(4;14). Overall, 66% of the patients achieved CR or near-CR, and 41% achieved mCR, which was sustained negative (at least 4 consecutive samples negative) in 15 patients (21%), with no significant difference in incidence between the patients with high-risk cytogenetics and others (P = .70). After a median follow-up of 6 years, overall 5-year progression-free survival was 29%, with no significant difference between del 17p13/t(4;14)-harboring patients and others (24% versus 30%; P = .70). The 5-year progression-free survival differed substantially according to the achieved remission: 17% for partial remission, 41% for CR, 57% for mCR, and 85% for sustained mCR. These results suggest that auto–allo tandem SCT may overcome the negative prognostic effect of del(17p13) and/or t(4;14) and that achievement of molecular remission resulted in long-term freedom from disease.

Extramedullary disease in patients with multiple myeloma is a rare event, occurring mostly in advanced disease or relapse. Outcome is poor and prognostic factors predicting the development of extramedullary disease have not been defined. We investigated cytogenetic alterations of myeloma cells in different extramedullary manifestations by adapting the fluorescence in situ hybridization (FISH) technique in combination with cytoplasmic immunoglobulin staining to study the cytogenetics of plasma cell tumours on paraffin embedded material. Thirty six patients were investigated: 19 with extramedullary disease, 11 with skeletal extramedullary disease and six with solitary extramedullary plasmacytoma. The first two groups showed the following results: del(17p13) 32% vs. 27%, del(13q14) 35% vs. 27%, MYC-overrepresentation 28% vs. 18% and t(4;14) 37% vs. 18%. We detected an overall higher incidence of del(17p13) in both groups compared to data from bone marrow samples of multiple myeloma reported to date (range 7-16%). The solitary extramedullary plasmacytomas presented overall less cytogenetic aberrations than the other groups. Most important, three patients with extramedullary disease and one with skeletal extramedullary disease presented different FISH findings in the extramedullary tumour compared to their bone marrow plasma cells. del(17p13), occurring additional in three of four cases, seems a strong marker for extramedullary progression of myeloma.

Although allogeneic hematopoietic stem cell transplantation (HSCT) features severe physical and psychological strain, no previous study has prospectively investigated fatigue beyond 3 years after transplantation. We investigated the temporal course of fatigue over 5 years, compared patients with the general population (GP) and tested for treatment- and complication-related risk factors. Patients were assessed before conditioning (T0, N=239) and at 100-day (T1, N=150), 1-year (T2, N=102) and 5-year (T3, N=45) follow-up. We measured fatigue with the Multidimensional Fatigue Inventory-20. Patients were compared with the GP at T0 and at T3. Global fatigue increased from T0 to T1 (t=3.85, P

Onkologische Patienten nehmen psychosoziale Beratungsangebote unterschiedlich stark in Anspruch. In einer Studie mit DKG-zertifizierten Zentren wurde nach Entitats- bzw. Zentren-spezifischen Merkmalen gesucht, die die unterschiedliche Akzeptanz erklaren konnten.

Multiple myeloma is the second most commonly diagnosed hematologic malignancy. It is characterized by the accumulation of monoclonal plasma cells. It typically manifests in the sixth decade of life or later, whereas the incidence in patients who are younger than 40 years old is extremely rare. Here, we report the case of a 34-year-old prima gravida, diagnosed with a κ light-chain myeloma (Durie&Salmon stage IIIA, International Staging System I) in the 23rd week of pregnancy. Our multimodal therapeutic approach during pregnancy, the delivery of a healthy male, and initiation of intensive anti-myeloma treatment thereafter (induction with bortezomib, cyclophosphamide, and dexamethasone, followed by tandem autologous peripheral blood stem cell transplantation) are described. Furthermore, we provide a comprehensive review of all 18 cases published between 1965 and 2010 in which a multiple myeloma was diagnosed and treated following different regimes and approaches before, during, or shortly after pregnancy. All delivered newborns were healthy, whereas the mothers' outcomes varied strongly. In our specific case, complete remission was achieved after tandem autologous peripheral blood stem cell transplantation. Emerging from these literature data and our case, we conclude that while awaiting delivery, the application of prednisolone as a nontoxic, but active anti-myeloma therapy can be recommended. Intensified postpartum anti-myeloma therapy should be induced as soon as possible to efficiently reduce myeloma burden and avoid organ damage in these young females.

Cancer-testis (CT) antigens are promising targets for antigen-specific therapy of multiple myeloma (MM). Osteolytic lesions represent the most common clinical manifestation of myeloma and it is possible that osseous myeloma lesions differ from bone-infiltrating tumor cells with regard to the extent of CT antigen expression based on the epigenetic regulation of these genes. We, therefore, performed the first analysis of CT antigen expression in osteolytic lesions of myeloma patients to further define the diagnostic, prognostic, and therapeutic value of these proteins. Lytic bone samples were obtained from MM patients during surgical interventions and a tissue microarray was constructed. 105 bone samples and 24 bone marrow biopsies were stained immunohistochemically with antibodies against CT antigens MAGE-C1/CT7 and MAGE-C2/CT10 and Ki-67. MAGE-C1/CT7 and MAGE-C2/CT10 were frequently expressed in osteolytic lesions (46% and 54%) and bone marrow (75% and 54%). Expression of MAGE-C1/CT7 was significantly more frequent in patients with advanced stage of disease (p=0.023) and with a chromosomal deletion 17p13 (p53) (p=0.047). Samples with more than 75% MAGE-C1/CT7 expressing myeloma cells showed a higher proliferative rate (indicated by the expression of Ki67) than those with less than 25% MAGE-C1/CT7 expressing cells (p=0.011). Moreover, a content of ≥50% MAGE-C1/CT7 expressing myeloma cells in a sample was associated with reduced overall survival (p=0.013). Our results, therefore, suggest that expression of MAGE-C1/CT7 and MAGE-C2/CT10 in osteolytic lesions of myeloma patients can be used for diagnostic, prognostic, as well as immunotherapeutic purposes.

We investigated efficacy and toxicity of lenalidomide in 24 heavily pretreated myeloma patients with a median age of 59 years (range: 37-70) and relapse after allo-SCT. Lenalidomide was given at a dose of 15 mg (n=4), or 25 mg (n=20), orally once daily on day 1 to day 1 every 28 days, with (n=20) or without (n=4) DHAP. The median number of lenalidomide cycles was five (range: 2-17). Major side effects were leukopenia (grade 4: 4%, grade 3: 21% and grade 2: 17%) and thrombocytopenia (grade 3: 17% and grade 2: 29%); infectious complications were observed in 50%. Non-hematological toxicity consisted of muscle cramps (n=9), fatigue (n=5) and constipation (n=2). Mild grade I-II GVHD was seen in three patients. Response was achieved in 66%: CR in 8%, VGPR in 8%, PR in 50% and SD in 13%. The median time to progression was 9.7 months (95% confidence interval (CI): 7.5-11.9), and median OS was 19.9 months (95% CI: 17.3-22.5). Immunomonitoring after lenalidomide showed significant increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells, as well as regulatory T cells (CD4(+), CD25(+), CD127(lo)), supporting an immunomodulating anti-myeloma effect of lenalidomide.

Immunotherapies using cancer-testis (CT) antigens as targets represent a potentially useful treatment in patients with multiple myeloma (MM) who commonly show recurrent disease following chemotherapy. We analyzed the expression of 11 CT antigens in bone marrow samples from patients with MM (n = 55) and healthy donors (n = 32) using reverse transcriptase–polymerase chain reaction (RT-PCR). CT antigens were frequently expressed in MM with 56% (MAGEC2), 55% (MAGEA3), 35% (SSX1), 20% (SSX4, SSX5), 16% (SSX2), 15% (BAGE), 7% (NY-ESO-1), and 6% (ADAM2, LIPI) expressing the given antigen. Importantly, CT antigens were not expressed in healthy bone marrow. Analyzing patients with MM (n = 66) for antibody responses against MAGEA3, SSX2, and NY-ESO-1, we found strong antibody responses against CT antigens preferentially in patients who had received allogeneic stem cell transplantation (alloSCT). Antibody responses against NY-ESO-1 correlated with NY-ESO-1–specific CD4+ and CD8+ T-cell responses against peptide NY-ESO-151-62 and CD4+ responses against NY-ESO-1121-140 in 1 of these patients. These allogeneic immune responses were not detectable in pretransplantation samples and in the patients' stem cell donors, indicating that CT antigens might indeed represent natural targets for graft-versus-myeloma effects. Immune responses induced by alloSCT could be boosted by active CT antigen–specific immunotherapy, which might help to achieve long-lasting remissions in patients with MM.

Chromosomal aberrations are the most important prognostic factors in haematological malignancies. Detection of certain genetic changes leads to risk adapted strategies in leukaemia therapy. In multiple myeloma the importance of genetic alterations and their prognostic impact is of growing interest. Several therapeutic approaches seem to be uneffective for patients harbouring certain chromosomal abnormalities. Although the yield of metaphases due to a low proliferation rate is considerably lower in plasma cell dyscrasias, a number of chromosomal changes with prognostic implications have been identified in the past years, particularly due to the introduction of new techniques. This article gives a short survey of the most important genetic alterations and their prognostic influence on the outcome of patients with plasma cell malignancies known to date. Copyright © 2005 John Wiley & Sons, Ltd.

We investigated in a retrospective multicenter study the impact of chromosome arm 13q deletion (13q-) as detected by fluorescence in situ hybridization (FISH) on outcome after dose-reduced allografting in patients with multiple myeloma. In 68 of 140 patients, data on chromosome 13q status were available. Most patients included had advanced myeloma. At 2 years, patients with 13q deletion (n = 31) had a shorter event-free (18% vs 42%; P =.05) and overall survival (18% vs 67%; P =.03) than patients without 13q- (n = 37). Patients with 13q- experienced a higher relapse rate (77% vs 44%; P

pared with nondrinkers, HR = 0.93 [95% CI, 0.85 to 1.02], 0.85 [95% CI, 0.75 to 0.95], 0.88 [95% CI, 0.75 to 1.02], and 0.89 [95% CI, 0.77 to 1.04] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Alcohol consumption after diagnosis was not associated with disease-specific survival (compared with nondrinkers, HR = 0.88 [95% CI, 0.61 to 1.27], 0.80 [95% CI, 0.49 to 1.32], 1.01 [95% CI, 0.55 to 1.87], and 0.83 [95% CI, 0.45 to 1.54] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Results did not vary by beverage type. Women consuming moderate levels of alcohol, either before or after diagnosis, experienced better cardiovascular and overall survival than nondrinkers. Conclusion: Overall alcohol consumption before diagnosis was not associated with disease-specific survival, but we found a suggestion favoring moderate consumption. There was no evidence for an association with postdiagnosis alcohol intake and breast cancer survival. This study, however, does provide support for a benefit of limited alcohol intake for cardiovascular and overall survival in women with breast cancer.