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Objectives: The extent of health‐related quality of life (HRQOL) impairments in older hematological cancer survivors (HCS) has not been sufficiently studied. We therefore examined HRQOL in older HCS compared to a community sample (CS) and investigated sociodemographic, disease‐ and treatment‐specific, geriatric, and psychosocial factors associated with reduced HRQOL. Materials and Methods: In this cancer‐register‐based cross‐sectional comparative study 200 HCS, aged ≥70 years, and 252 persons of an age‐ and gender‐matched CS completed validated questionnaires including the EORTC QLQ‐C30 and EORTC QLQ‐ELD14. Results: Older HCS reported a reduced HRQOL in the dimensions of global QOL, physical, role, and social functioning (small clinical significance) and higher symptom burden of fatigue, nausea and vomiting, appetite loss, and poorer mobility compared to the CS (fatigue and mobility with medium, the others with small clinical significance). Perceived disease burden of comorbidities, functional disabilities, psychological distress, and depression showed statistical significance for reduced HRQOL in older HCS in multiple linear regression analysis (R2 =.602, p <.001). Discussion: The screening and treatment of functional limitations and individual symptoms and the integration of a geriatric assessment into oncological practice can help to identify supportive care needs, to implement individualized, patient‐centered cancer survivorship care programs and to improve older HCS's HRQOL. [ABSTRACT FROM AUTHOR]

Objectives Osteoarticular infection (OAI) is a feared complication of Staphylococcus aureus bacteraemia (SAB) and is associated with poor outcomes. We aimed to explore the risk of OAI and death following SAB in patients with and without rheumatoid arthritis (RA) and to identify risk factors for OAI in patients with RA. Methods Danish nationwide cohort study of all patients with microbiologically verified first-time SAB between 2006–18. We identified RA, SAB, comorbidities, and RA-related characteristics (e.g. orthopaedic implants and antirheumatic treatment) in national registries including the rheumatology registry DANBIO. We estimated the cumulative incidence of OAI and death and adjusted hazard ratios (HRs, multivariate Cox regression). Results We identified 18 274 patients with SAB (n  = 367 with RA). The 90-day cumulative incidence of OAI was 23.1% (95% CI 18.8; 27.6) for patients with RA and 12.5% (12.1; 13.0) for patients without RA (non-RA) [HR 1.93 (1.54; 2.41)]. For RA patients with orthopaedic implants cumulative incidence was 29.4% (22.9; 36.2) [HR 1.75 (1.08; 2.85)], and for current users of tumor necrosis factor inhibitors (TNFi) it was 41.9% (27.0; 56.1) [HR 2.27 (1.29; 3.98) compared with non-users]. All-cause 90-day mortality following SAB was similar in RA [35.4% (30.6; 40.3)] and non-RA [33.9% (33.2; 34.5), HR 1.04 (0.87; 1.24)]. Conclusion Following SAB, almost one in four patients with RA contracted OAI corresponding to a doubled risk compared with non-RA. In RA, orthopaedic implants and current TNFi use were associated with approximately doubled OAI risk. One in three died within 90 days in both RA and non-RA. These findings encourage vigilance in RA patients with SAB to avoid treatment delay of OAI. [ABSTRACT FROM AUTHOR]

Abstract Background Demoralisation is a clinically significant problem among cancer patients with a prevalence of 13%–18%. It is defined by difficulty in adjusting to a stressor, wherein the person feels trapped in their predicament and experiences helplessness, hopelessness, loss of confidence and loss of meaning in life. Demoralisation has a strong link with the desire for hastened death and suicidal ideation among the medically ill. This study explored whether a group of symptoms could be identified, distinct from depression, but consistent with adjustment difficulties with demoralisation and linked to ideation of death and suicide. Methods Exploratory Graph Analysis, a network psychometrics technique, was conducted on a large German study of 1529 cancer patients. Demoralisation was measured with the Demoralisation Scale II and depressive symptoms with the PHQ‐9. Results A network of symptoms, with four stable communities, was identified: 1. Loss of hope and meaning; 2. Non‐specific emotionality; 3. Entrapment; 4. Depressive symptoms. The first three communities were clearly distinct from the PHQ‐9 depressive symptoms, except for suicidality and fear of failure. Community 1, Loss of hope and meaning, had the strongest association with thoughts of death and suicide. Hopelessness, loss of role in life, tiredness, pointlessness and feeling trapped were the most central symptoms in the network. Conclusions Communities 1 to 3 are consistent with poor coping without anhedonia and other classic depression symptoms, but linked to suicidal ideation. For people facing the existential threat of cancer, this may indicate poor psychological adjustment to the stressors of their illness.

IntroductionHigh-dose interleukin-2 (HD IL-2) and pembrolizumab are each approved as single agents by the U.S. F.D.A. for the treatment of metastatic melanoma. There is limited data using the agents concurrently. The objectives of this study were to characterize the safety profile of IL-2 in combination with pembrolizumab in patients with unresectable or metastatic melanoma.MethodsIn this Phase Ib study, patients received pembrolizumab (200 mg IV every 3 weeks) and escalating doses of IL-2 (6,000 or 60,000 or 600,000 IU/kg IV bolus every 8 hours up to 14 doses per cycle) in cohorts of 3 patients. Prior treatment with a PD-1 blocking antibody was allowed. The primary endpoint was the maximum tolerated dose (MTD) of IL-2 when co-administered with pembrolizumab.ResultsTen participants were enrolled, and 9 participants were evaluable for safety and efficacy. The majority of the evaluable participants (8/9) had been treated with PD-1 blocking antibody prior to enrollment. Patients received a median of 42, 22, and 9 doses of IL-2 in the low, intermediate, and high dose cohorts, respectively. Adverse events were more frequent with increasing doses of IL-2. No dose limiting toxicities were observed. The MTD of IL-2 was not reached. One partial response occurred in 9 patients (11%). The responding patient, who had received treatment with an anti-PD-1 prior to study entry, was treated in the HD IL-2 cohort.DiscussionAlthough the sample size was small, HD IL-2 therapy in combination with pembrolizumab appears feasible and tolerable.Clinical trial registrationClinicalTrials.gov, identifier NCT02748564.

BackgroundAnxiety is a frequent condition in patients and in the general population. The aim of this study was to investigate changes in anxiety over time and to test several psychometric properties of the Generalized Anxiety Disorder Screener (GAD-7) from a longitudinal perspective.MethodsThe GAD-7 was included in an examination with two waves, six years apart. The study sample (n = 5355) was comprised of representatively selected adults from the general population with a mean age of 57.3 (SD = 12.3) years.ResultsDuring the 6-year time interval, anxiety increased significantly from 3.28 ± 3.16 (t1) to 3.66 ± 3.46 (t2). Confirmatory factor analyses proved the longitudinal measurement invariance of the GAD-7. Reliability of the GAD-7 was established both for the cross-sectional and the longitudinal perspective. The test-retest correlation was r = 0.53, and there were no substantial sex or age differences in these coefficients of temporal stability. The mean changes in anxiety were similar for males and females, and there was no linear age trend in the changes measured by the GAD-7. Changes in anxiety over the 6-year period were correlated with changes in satisfaction with life (r = -0.30), bodily complaints (r = 0.31), and the mental component of quality of life (r = -0.48).ConclusionThe GAD-7 is a suitable instrument for measuring changes in anxiety. Age and gender have only minor significance when interpreting change scores.

BackgroundComplementary and Alternative Medicine (CAM) has become increasingly popular among cancer patients. The prevalence of CAM use differs worldwide and depends on different sociodemographic and medical characteristics. Findings on predictors for CAM use and its benefits for quality of Life (QoL) have been inconclusive in recent studies.ObjectiveThe aim of the study was to determine the prevalence and methods of CAM use in breast cancer (BC) and gynecological cancer (GC) patients, to compare CAM users vs. non-CAM users regarding their sociodemographic and medical characteristics, and to investigate the relationship between CAM use and QoL.MethodsIn a sub-analysis from a multicenter, cross-sectional study in Germany, we examined 1,214 female cancer patients (897 with BC and 317 with GC). We obtained data from self-reports via standardized questionnaires and measured QoL with the EORTC QLQ-C30.ResultsIn total, 565 of the 1,214 patients (46.5%) used some form of CAM. Its use was higher in BC than in GC patients (48.6% vs. 40.7%). In both cancer groups, the users evaluated CAM as being helpful (BC: 60.8%, GC: 59.6%) The most frequently used CAM methods were vitamins/minerals/micronutrients, homeopathy, and mistletoe therapy. CAM users are younger, more highly educated, and financially better off than non-CAM users. They are also characterized by having been diagnosed with cancer a longer time ago, being at more advanced stages of the disease, and experiencing higher distress levels. CAM use is significantly associated with a lower global health status/ QoL in GC patients. Predictors for CAM use are: high level of vocational education, middle or high monthly income, time span since diagnosis of more than 12 months, the status of currently ongoing chemotherapy or hormone therapy treatment, and distress.ConclusionOur data support the findings of previous studies and highlight the need to develop a consistent CAM definition with respect to comparability and evaluation of CAM services. More longitudinal studies are desirable to establish viable associations between CAM use and relevant outcomes such as QoL or disease management.

ObjectivePrevious symptom prevalence studies show a diverse spectrum of symptoms and a large diversity in symptom intensities in patients being just diagnosed as having incurable cancer. It is unclear, how physical symptoms and psychosocial burden should be recorded in order to determine the variable need for palliative care and further support. Therefore, we compared two different strategies for detecting physical symptoms and psychosocial burden of patients with newly diagnosed incurable cancer and their effects on the further course of the disease.MethodsSCREBEL is a controlled, randomized, non-blinded, longitudinal study of the research network of the Palliative Medicine Working Group (APM) of the German Cancer Society (DKG). We compared: a less complex repeated brief screening for symptoms and burden in patients using the NCCN Distress Thermometer and IPOS questionnaire versus a multidimensional comprehensive assessment using the FACT-G and their entity-specific questionnaires, the PHQ4 scales, SCNS-34-SF, IPOS and NCCN Distress Thermometer. The primary study endpoint was quality of life (QoL), measured using FACT-G, after six months. Secondary study endpoints were QoL by using evaluation of secondary scores (NCCN DT, IPOS, PHQ4, SCNS-SF-34G) at time 6 months, the number of hospital days, the utilization of palliative care, emergency services, and psychosocial care structures. To assess effects and differences, multiple linear regression models were fitted and survival analyses were conducted.Results504 patients were included in the study. 262 patients were lost to follow-up, including 155 fatalities. There were no significant differences between the low-threshold screening approach and a comprehensive assessment with respect to symptoms and other aspects of QoL. Using the IPOS, we were able to measure an improvement in the quality of life in the low-threshold screening arm by a decrease of 0.67 points (95%-CI: 0.34 to 0.99) every 30 days. (p

BackgroundAntibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy.MethodsPatients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti-PD-L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks. Treatment-related AEs (TRAEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). In post hoc analyses, immune-related AEs (irAEs) were identified via an expanded AE list and medical review, and infusion-related reactions (IRRs) occurring ≤2 days after infusion and symptoms occurring ≤1 day after infusion and resolving ≤2 days after onset were identified based on prespecified Medical Dictionary for Regulatory Activities (MedDRA) terms.ResultsOf the 1738 patients analyzed, grade ≥3 TRAEs occurred in 177 (10.2%); the most common were fatigue (17 patients; 1.0%) and IRR (10 patients; 0.6%). TRAEs led to discontinuation in 107 patients (6.2%) and death in 4 patients (0.2%). Grade ≥3 irAEs occurred in 39 patients (2.2%) and led to discontinuation in 34 patients (2.0%). IRRs or related symptoms occurred in 439 patients (25.3%; grade 3 in 0.5% [9 patients] and grade 4 in 0.2% [3 patients]). An IRR occurred at the time of first infusion in 79.5% of 439 patients who had an IRR, within the first 4 doses in 98.6% of 439 patients who had an IRR, and led to discontinuation in 35 patients (2.0%).ConclusionsAvelumab generally was found to be well tolerated and to have a manageable safety profile. A minority of patients experienced grade ≥3 TRAEs or irAEs, and discontinuation was uncommon. IRRs occurred mainly at the time of first infusion, and repeated events were infrequent. Cancer 2018;124:2010-7. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

ObjectiveIt is well-known that patients with cancer frequently experience sleep problems, and that sleep quality is associated with general quality of life (QoL). The aims of this study were to analyze the relationship between sleep problems and other components of QoL in more detail and to investigate sex and age differences in sleep quality in cancer patients in comparison with the general population.MethodThis study comprised one general population sample (n = 4,476) and eight samples with cancer patients (n between 323 and 4,020). Sleep Quality was measured using the QoL questionnaire EORTC QLQ-C30.ResultsAll of the cancer patient groups reported more sleep problems than the general population. Sleep problems were associated with all facets of QoL both in cancer patients and in the general population. The highest associations were found in cancer patients for fatigue (r = 0.52) and emotional functioning (r = −0.47). The association between sleep quality and general QoL was lower in the cancer samples (r = −0.37) than in the general population (r = −0.46). Female cancer patients reported markedly more sleep problems than male patients did (d = 0.45), while this sex difference was lower in the general population (d = 0.15). In contrast to the general population, younger cancer patients had greater trouble sleeping than older patients did (d = −0.17).ConclusionThe results underline the significance of the role mental factors play in sleep problems. Health care providers should pay special attention to female patients and younger patients concerning this issue.

Abstract Background Immune‐related adverse events (irAEs) are common, clinically significant autoinflammatory toxicities observed with immune checkpoint inhibitors (ICI). Preexisting immune‐mediated inflammatory disease (pre‐IMID) is considered a relative contraindication to ICI due to the risk of inciting flares. Improved understanding of the risks and benefits of treating pre‐IMID patients with ICI is needed. Methods We studied melanoma patients treated with ICI and enrolled in a prospective clinicopathological database. We compiled a list of 23 immune‐mediated inflammatory diseases and evaluated their presence prior to ICI. We tested the associations between pre‐IMID and progression‐free survival (PFS), overall survival (OS), and irAEs. Results In total, 483 melanoma patients were included in the study; 74 had pre‐IMID and 409 did not. In patients receiving ICI as a standard of care (SoC), pre‐IMID was significantly associated with irAEs (p = 0.04) as well as improved PFS (p = 0.024) and OS (p = 0.007). There was no significant association between pre‐IMID and irAEs (p = 0.54), PFS (p = 0.197), or OS (p = 0.746) in patients treated through a clinical trial. Pre‐IMID was significantly associated with improved OS in females (p = 0.012), but not in males (p = 0.35). Conclusions The dichotomy of the impact of pre‐IMID on survival and irAEs in SoC versus clinical trial patients may reflect the inherit selection bias in patients accrued in clinical trials. Future mechanistic work is required to better understand the differences in outcomes between female and male pre‐IMID patients. Our data challenge the notion that clinicians should avoid ICI in pre‐IMID patients, although close monitoring and prospective clinical trials evaluating ICI in this population are warranted.

Objective Successful uptake of biosimilars in rheumatology is limited by lack of real-world evidence regarding effectiveness of biosimilar-to-biosimilar switching. We investigated infliximab biosimilars CT-P13-to-GP1111 switching among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA).Methods Observational cohort study from the DANBIO registry. Patients were classified as originator-naïve or originator-experienced. Retention rates of 1-year GP1111 treatment were explored (Kaplan-Meier). We identified baseline factors (at the time of switch) associated with withdrawal of GP1111 (multivariable Cox-regression analyses with HRs including originator treatment history). Changes in subjective and objective measures of disease activity 4 months before and after the switch were assessed in individual patients.Results Of 1605 patients (685 RA, 314 PsA and 606 AxSpA, median disease duration was 9 years, 37% in Clinical Disease Activity Index/Ankylosing Spondylitis Disease Activity Score remission), 1171 were originator-naïve. Retention rates at 1-year were 83% (95% CI: 81% to 85%) and 92% (95% CI: 90% to 95%) for the originator-naïve and originator-experienced, respectively. GP1111 retention rates were higher in originator-experienced compared to originator-naïve with RA (HR=0.4 (95% CI: 0.2 to 0.7)) and PsA (HR=0.2 (95% CI: 0.1 to 0.8)), but not significantly for AxSpA: HR=0.6 (95% CI: 0.3 to 1.2). Lower disease activity was associated with higher retention. Changes in disease activity preswitch and postswitch were close to zero.Conclusion This real-world observational study of more than 1600 patients with inflammatory arthritis showed high 1-year retention following a nationwide infliximab biosimilar-to-biosimilar switch. Retention was higher in originator-experienced and in patients with low disease activity, suggesting outcomes to be affected by patient-related rather than drug-related factors.

Summary: Background: Reliable estimates of frequency, severity and associated factors of both fatigue and cognitive impairment after COVID-19 are needed. Also, it is not clear whether the two are distinct sequelae of COVID-19 or part of the same syndrome.'' Methods: In this prospective multicentre study, frequency of post-COVID fatigue and cognitive impairment were assessed in n = 969 patients (535 [55%] female) ≥6 months after SARS-CoV-2 infection with the FACIT-Fatigue scale (cut-off ≤30) and Montreal Cognitive Assessment (≤25 mild, ≤17 moderate impairment) between November 15, 2020 and September 29, 2021 at University Medical Center Schleswig-Holstein, Campus Kiel and University Hospital Würzburg in Germany. 969 matched non-COVID controls were drawn from a pre-pandemic, randomised, Germany-wide population survey which also included the FACIT-Fatigue scale. Associated sociodemographic, comorbid, clinical, psychosocial factors and laboratory markers were identified with univariate and multivariable linear regression models. Findings: On average 9 months after infection, 19% of patients had clinically relevant fatigue, compared to 8% of matched non-COVID controls (p

Background OX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949.Methods Phase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7–1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics.Results Eighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) cancers. Patients received a median three (range 1–9) prior therapies, including immunotherapy in 24 patients (27.6%). Maximum tolerated dose was not reached; one patient (1.1%) receiving 350 mg dose reported dose-limiting toxicity of grade 3 colitis. Treatment-related adverse events were reported in 45 patients (51.7%), with fatigue (16 (18.4%)), rash (6 (6.9%)), and diarrhea (6 (6.9%)) being most frequent. One patient (1.1%) with metastatic gallbladder cancer achieved a partial response (duration of 6.3 months), and 23 patients (26.4%) achieved stable disease (lasting >6 months in one patient). OX40 receptor occupancy was maintained over 90% among all patients receiving doses of ≥200 mg, while no treatment-emergent antidrug antibodies were detected across all dose levels. Pharmacodynamic results demonstrated that treatment with INCAGN01949 did not enhance proliferation or activation of T cells in peripheral blood or reduce circulating Tregs, and analyses of tumor biopsies did not demonstrate any consistent increase in effector T-cell infiltration or function, or decrease in infiltrating Tregs.Conclusion No safety concerns were observed with INCAGN01949 monotherapy in patients with metastatic or advanced solid tumors. However, tumor responses and pharmacodynamic effects on T cells in peripheral blood and post-therapy tumor biopsies were limited. Studies evaluating INCAGN01949 in combination with other therapies are needed to further evaluate the potential of OX40 agonism as a therapeutic approach in patients with advanced solid tumors.Trial registration number NCT02923349.

IntroductionCancer-affected patients experience high distress due to various burdens. One way to expand psycho-oncological support is through digital interventions. This protocol describes the development and structure of a web-based psycho-oncological intervention, the Make It Training optimized. This intervention is currently evaluated in the Reduct trial, a multicenter randomized controlled trial.MethodsThe Make It Training optimized was developed in six steps: A patient need and demand assessment, development and acceptability analysis of a prototype, the formation of a patient advisory council, the revision of the training, implementation into a web app, and the development of a motivation and evaluation plan.ResultsThrough a process of establishing cancer-affected patients’ needs, prototype testing, and patient involvement, the Make It Training optimized was developed by a multidisciplinary team and implemented in a web app. It consists of 16 interactive self-guided modules which can be completed within 16 weeks.DiscussionIntervention protocols can increase transparency and increase the likelihood of developing effective web-based interventions. This protocol describes the process and results of developing a patient-oriented intervention. Future research should focus on the further personalization of web-based psycho-oncological interventions and the potential benefits of combining multiple psychotherapeutic approaches.