Inhibitory NKG2A⁺ and absent activating NKG2C⁺ NK cell responses are associated with the development of EBV⁺ lymphomas

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, which infects over 90% of the adult human population worldwide. After primary infections, EBV is recurrently reactivating in most adult individuals. It is, however, unclear, why these EBV reactivations progress to EBV+ Hodgkin (EBV+HL) or non-Hodgkin lymphomas (EBV+nHL) only in a minority of EBV-infected individuals. The EBV LMP-1 protein encodes for a highly polymorphic peptide, which upregulates the immunomodulatory HLA-E in EBV-infected cells, thereby stimulating the inhibitory NKG2A-, but also the activating NKG2C-receptor on natural killer (NK) cells. Using a genetic-association approach and functional NK cell analyses, we now investigated, whether these HLA-E-restricted immune responses impact the development of EBV+HL and EBV+nHL. Therefore, we recruited a study cohort of 63 EBV+HL and EBV+nHL patients and 192 controls with confirmed EBV reactivations, but without lymphomas. Here, we demonstrate that in EBV+ lymphoma patients exclusively the high-affine LMP-1 GGDPHLPTL peptide variant-encoding EBV-strains reactivate. In EBV+HL and EBV+nHL patients, the high-expressing HLA-E*0103/0103 genetic variant was significantly overrepresented. Combined, the LMP-1 GGDPHLPTL and HLA-E*0103/0103 variants efficiently inhibited NKG2A+ NK cells, thereby facilitating the in vitro spread of EBV-infected tumor cells. In addition, EBV+HL and EBV+nHL patients, showed impaired pro-inflammatory NKG2C+ NK cell responses, which accelerated the in vitro EBV-infected tumor cells spread. In contrast, the blocking of NKG2A by monoclonal antibodies (Monalizumab) resulted in efficient control of EBV-infected tumor cell growth, especially by NKG2A+NKG2C+ NK cells. Thus, the HLA-E/LMP-1/NKG2A pathway and individual NKG2C+ NK cell responses are associated with the progression toward EBV+ lymphomas.</p

Patients' and clinicians' perceptions of the clinical utility of predictive risk models for chemotherapy-related symptom management : qualitative exploration using focus groups and interviews

Background: Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. Objective: We aim to explore patients’ and clinicians’ perspectives of the utility and real-world application of PRMs to improve the management of CRS. Methods: Focus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. Results: Both clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. Conclusions: Findings from this study provide information on clinicians’ and patients’ perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted

Real time remote symptom monitoring during chemotherapy for cancer: European multicentre randomised controlled trial (eSMART)

Objective: To evaluate effects of remote monitoring of adjuvant chemotherapy related side effects via the Advanced Symptom Management System (ASyMS) on symptom burden, quality of life, supportive care needs, anxiety, self-efficacy, and work limitations. Design: Multicentre, repeated measures, parallel group, evaluator masked, stratified randomised controlled trial. Setting: Twelve cancer centres in Austria, Greece, Norway, Republic of Ireland, and UK. Participants: 829 patients with non-metastatic breast cancer, colorectal cancer, Hodgkin’s disease, or non-Hodgkin’s lymphoma receiving first line adjuvant chemotherapy or chemotherapy for the first time in five years. Intervention: Patients were randomised to ASyMS (intervention; n=415) or standard care (control; n=414) over six cycles of chemotherapy. Main outcome measures: The primary outcome was symptom burden (Memorial Symptom Assessment Scale; MSAS). Secondary outcomes were health related quality of life (Functional Assessment of Cancer Therapy—General; FACT-G), Supportive Care Needs Survey Short-Form (SCNS-SF34), State-Trait Anxiety Inventory—Revised (STAI-R), Communication and Attitudinal Self-Efficacy scale for cancer (CASE-Cancer), and work limitations questionnaire (WLQ). Results: For the intervention group, symptom burden remained at pre-chemotherapy treatment levels, whereas controls reported an increase from cycle 1 onwards (least squares absolute mean difference −0.15, 95% confidence interval −0.19 to −0.12; P&lt;0.001; Cohen’s D effect size=0.5). Analysis of MSAS sub-domains indicated significant reductions in favour of ASyMS for global distress index (−0.21, −0.27 to −0.16; P&lt;0.001), psychological symptoms (−0.16, −0.23 to −0.10; P&lt;0.001), and physical symptoms (−0.21, −0.26 to −0.17; P&lt;0.001). FACT-G scores were higher in the intervention group across all cycles (mean difference 4.06, 95% confidence interval 2.65 to 5.46; P&lt;0.001), whereas mean scores for STAI-R trait (−1.15, −1.90 to −0.41; P=0.003) and STAI-R state anxiety (−1.13, −2.06 to −0.20; P=0.02) were lower. CASE-Cancer scores were higher in the intervention group (mean difference 0.81, 0.19 to 1.43; P=0.01), and most SCNS-SF34 domains were lower, including sexuality needs (−1.56, −3.11 to −0.01; P&lt;0.05), patient care and support needs (−1.74, −3.31 to −0.16; P=0.03), and physical and daily living needs (−2.8, −5.0 to −0.6; P=0.01). Other SCNS-SF34 domains and WLQ were not significantly different. Safety of ASyMS was satisfactory. Neutropenic events were higher in the intervention group. Conclusions: Significant reduction in symptom burden supports the use of ASyMS for remote symptom monitoring in cancer care. A “medium” Cohen’s effect size of 0.5 showed a sizable, positive clinical effect of ASyMS on patients’ symptom experiences. Remote monitoring systems will be vital for future services, particularly with blended models of care delivery arising from the covid-19 pandemic

Krankheitsspezifische Bildungsprozesse von PatientInnen mit diagnostizierter onkologischer Erkrankung

Angst und Depressivität gelten als häufige Begleiterscheinungen einer Krebserkrankung (Krebsgesellschaft 2011). Um diesen entgegenzuwirken und in weiterer Folge Gesundheit entsprechend dem bio-psycho-sozialen Ansatz nach Schwartz (1978, 1979, 1982, 1988) herzustellen, wurden mittels der Fragebogenmethode Werte für Angst und Depressivität anhand der HADS-D Skala nach Zigmont und Snait (1983) sowie körperliche und sozioökonomische Daten (Schulbildung und Einkommen) ermittelt. Die Ergebnisse der Studie wurden anhand drei exemplarisch ausgewählter Bildungstheorien analysiert und interpretiert. Dabei wurden die Bildungstheorien nach Humboldt (1960), Hentig (1996) und Klafki (1959; 1996) herangezogen. Durch statistische Auswertungen mittels SPSS konnten vier negative Korrelationen festgestellt werden, welche besagen: Je geringer die Schulbildung bzw. das Familiennettoeinkommen desto höher die Werte für Angst bzw. Depressivität bei KrebspatientInnen. Aus bildungswissenschaftlicher Sicht konnten ein nicht angemessener Umgang mit spezifischen Fragen bzw. Rat, Kritik oder Belehrung (Hentig 1996), eine nicht gegebene Wechselwirkung zwischen Ich und Welt (Humboldt 1960) sowie eine entsprechende Methode zur selbständigen Aneignung eines Gegenstandes (Klafki 1959) als Gründe für Angst bzw. Depressivität bei KrebspatientInnen mit geringer Schulbildung festgestellt werden. Bei KrebspatientInnen mit geringem Einkommen sind die Gründe für Angst bzw. Depressivität auf existenzielle sowie finanzielle Sorgen (Bourdieu 1983) zurückzuführen. Der Angst bzw. Depressivität bei KrebspatientInnen mit geringer Schulbildung kann durch Übungen (Angenendt 2011), welchen ein Schulungsinhalt vorausgeht (Hentig 1996), sowie durch Bewältigungsstrategien (Angenendt 2011), um innewohnende Kräfte zu entfalten (Klafki 1959) entgegenwirkt werden. Um sozioökonomisch bedingter Angst und Depressivität von KrebspatientInnen entgegenzuwirken, können mehrere kurze Gespräche zwischen dem/der ÄrztIn und dem/der PatientIn letztendlich durch Kontinuität zu Hoffnung und einem Gefühl der Sicherheit verhelfen (Fässler-Weibel 2009, Klocker-Kaiser 2013).Anxiety and depression are frequently side effects of cancer (Krebsgesellschaft 2011). In order to counteract this and rebuild health within the meaning of the bio-psycho-social model of Schwartz (1978, 1979, 1982, 1988), a questionnaire was developed which includes the HADS-D scale of Zigmont and Snait (1983), physical and socioeconomic factors (e. g. education and net income). The results were analyzed and interpreted by three exemplarily selected educational theories. These were the following: Wilhelm von Humboldt (1960), Hartmut von Hentig (1996) and Wolfgang Klafki (1959; 1996). Statistical analysis by using SPSS offer four negative correlations: the lower education or family net income was, the higher values for anxiety and depression of cancer patients is. Based on interpretations of education science point of view there are the following results: there is no dealing appropriately with specific questions or advice, criticism or instruction (Hentig 1996), no interaction between self and world (Humboldt 1960) and no appropriate method to autonomous acquisition of an object. The reasons for anxiety and depression of cancer patients with lower net income attributable to existential and financial worries (Bourdieu 1983). Exercises, which include instructions (Hentig 1996), and coping strategies (Angenendt 2011), which unfold inherent powers (Klafki 1959), could counteract anxiety and depression of cancer patients with low education. To oppose socioeconomic-related anxiety and depression of cancer patients several short conversations between the doctor and the patient may be useful by continuity in order to gain hope and a sense of security help (Fässler-Weibel, Gaiger 2009; Klocker-Kaiser 2013)

Latent structure and measurement invariance of the Hospital Anxiety and Depression Scale in cancer outpatients

The aim of the present study was to compare competing psychometric models and analyze measurement invariance of the Hospital Anxiety and Depression Scale (HADS) in cancer outpatients. Method: The sample included 3,260 cancer outpatients. Latent structure of the HADS was analyzed using confirmatory factor analysis (CFA) with robust maximum likelihood estimation (MLR). Measurement invariance was tested for age, time of response, gender, and cancer type by comparing nested multigroup CFA models with parameter restrictions. Results: Except for the one-factor solutions, all models showed acceptable model fit and measurement invariance. The model with the best fit was the originally proposed two-factor model with exclusion of two items. The one-factor solutions showed inacceptable model fit and were not invariant for age and gender. Conclusions: The HADS has a robust two-factor structure in cancer outpatients. We recommend excluding item 7 and 10 when screening for anxiety and depression

Prevalence and biopsychosocial indicators of fatigue in cancer patients

Abstract Introduction Symptoms of cancer‐related fatigue (CRF) can have a significant impact on patients' quality of life and treatment adherence. We aimed to investigate the relationship between CRF and multiple psychosocial and somatic indicators within a large mixed cancer sample. Methods In this cross‐sectional study, N = 1787 outpatients with cancer were assessed for CRF, pain, anxiety, and depression using validated screening instruments. We further obtained clinical parameters (Hb, CRP, creatinine, leukocytes, ASAT, and ALAT), sociodemographic data (age, gender, income, education level, marital status, parenthood, and living area), and lifestyle factors. Multivariate linear regression models were applied to estimate the impact of each indicator on CRF. Results Overall, 90.6% of patients experienced some CRF, with 14.8% experiencing severe CRF. No gender difference was found in the prevalence of CRF. Patients with higher levels of pain, depressive symptoms, and lower Hb levels had significantly higher levels of CRF (ps <0.001). Lower levels of CRF were observed in patients who had children (p = 0.03), had less education (p < 0.001), and were physically active for more than 2 h per week before their oncological diagnosis (p = 0.014). The latter was only a significant indicator in the male subsample. Conclusion The present results demonstrate a high prevalence of CRF and highlight that not only somatic and psychosocial factors, but also lifestyle factors prior to diagnosis appear to be associated with the etiology and persistence of CRF. To effectively treat CRF, a biopsychosocial, personalized approach is recommended

Patients’ and Clinicians’ Perceptions of the Clinical Utility of Predictive Risk Models for Chemotherapy-Related Symptom Management: Qualitative Exploration Using Focus Groups and Interviews

BackgroundInterest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. ObjectiveWe aim to explore patients’ and clinicians’ perspectives of the utility and real-world application of PRMs to improve the management of CRS. MethodsFocus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. ResultsBoth clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. ConclusionsFindings from this study provide information on clinicians’ and patients’ perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted. Trial RegistrationClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT0235608