Randomized comparison between KTd and KRd induction therapy followed by maintenance therapy with K or observation in transplant-ineligible patients with newly diagnosed multiple myeloma.

Randomized comparison between KTd and KRd induction followed by second randomization to carfilzomib in transplant-ineligable patients with newly diagnosed multiple myeloma.

Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry.

BACKGROUND: About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC). PATIENTS AND METHODS: The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included. RESULTS: As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74-1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68-1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients. CONCLUSION: Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.

A prospective, multicenter pilot study to investigate the feasibility and safety of a 1-year controlled exercise training after adjuvant chemotherapy in colorectal cancer patients.

INTRODUCTION: Despite advances in adjuvant chemotherapy, 20-30% of patients in stages II-III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients. PATIENTS AND METHODS: The training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week. RESULTS: Overall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels. CONCLUSION: Exercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.

Clinical decision-making and health-related quality of life during first-line and maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC): findings from a real-world setting.

BACKGROUND: Maintenance therapy (MT) with pemetrexed has been shown to improve overall and progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC), without impairing patients' health-related quality of life (HRQOL) substantially. Comprehensive data on HRQOL under real-life conditions are necessary to enable informed decision-making. This study aims to (1) assess HRQOL during first-line chemotherapy and subsequent MT and (2) record patients' and physicians' reasons leading to clinical decisions on MT. METHODS: Patients treated for NSCLC at three Austrian medical centres were included. HRQOL was assessed at every chemotherapy cycle using the EORTC QLQ-C30/+LC13 questionnaire. Semi-structured interviews were conducted before MT initiation and at the time of discontinuation to evaluate patients' and physicians' reasons for treatment decisions. Longitudinal QOL analysis was based on linear mixed models. RESULTS: Sixty-one (73%) out of 84 patients were considered for MT. Thirty-six patients (43%) received MT and 29 (35%) discontinued therapy. Decisions on MT initiation (in 20 cases by the physician vs 4 by the patient) and discontinuation (19 vs 10) were mainly voiced by the physician. Treatment toxicity of first-line chemotherapy was the main reason for rejection of MT in patients with stable disease and was more often indicated by patients than clinicians. HRQOL data were collected from 83 patients at 422 assessment time points and indicated significantly lower symptom severity during MT compared with first-line therapy for nausea and vomiting (p = 0.006), sleep disturbances (p < 0.001), appetite loss (p = 0.043), constipation (p = 0.017) and chest pain (p = 0.022), and a deterioration in emotional functioning (p = 0.023) and cognitive functioning (p = 0.044) during MT. CONCLUSIONS: Our results indicate that HRQOL and symptom burden improve between first-line treatment to MT in some respects, although some late toxicity persists. Discrepancies between patients' and physicians' perception of reasons for rejecting MT were evident. Thus, the integration of patient-reported outcomes, such as HRQOL, is required to enable shared decision-making and personalised healthcare based on mutual understanding of treatment objectives.

Thresholds for clinical importance for four key domains of the EORTC QLQ-C30: physical functioning, emotional functioning, fatigue and pain.

BACKGROUND: The EORTC QLQ-C30 is one of the most widely used quality of life questionnaires in cancer research. Availability of thresholds for clinical importance for the individual questionnaire domains could help to increase its interpretability. The aim of our study was to identify thresholds for clinical importance for four EORTC QLQ-C30 scales: Physical Functioning (PF), Emotional Functioning (EF), Pain (PA) and Fatigue (FA). METHODS: We recruited adult cancer patients from Austria, the Netherlands, Poland and the UK. No restrictions were placed on diagnosis or type or stage of treatment. Patients completed the QLQ-C30 and three anchor items reflecting potential attributes of clinically important levels of PF, EF, PA and FA. We merged the anchor items assessing perceived burden, limitations in daily activities and need for help into a dichotomous external criterion to estimate thresholds for clinical importance using Receiver Operator Characteristic (ROC) analysis. RESULTS: In our sample of 548 cancer patients (mean age 60.6 years; 54 % female), the QLQ-C30 scales showed high diagnostic accuracy in identifying patients reporting burden, limitations and/or need for help related to PF, EF, PA and FA. All areas under the curve were above 0.86. CONCLUSIONS: We were able to estimate thresholds for clinical importance for four QLQ-C30 scales. When used in daily clinical practice, these thresholds can help to identify patients with clinically important problems requiring further exploration and possibly intervention by health care professionals.

Assessing quality of life on the day of chemotherapy administration underestimates patients' true symptom burden.

BACKGROUND: In chemotherapy trials quality of life (QOL) is assessed mostly at the days of chemotherapy administration (i.e. event-driven) during treatment and follows fixed time intervals in the aftercare phase (i.e. time-driven). Specific QOL impairments and treatment side-effects are known to be time dependent following different trajectories. Therefore, acute problems are likely to be missed if assessments are done infrequently or at inappropriate time points. Since the planning of supportive care interventions during chemotherapy depends on knowledge about symptom trajectories, such information may be of substantial importance to a clinician. METHODS: Cancer patients receiving chemotherapy at Kufstein County Hospital were assessed using an electronic version of the EORTC QLQ-C30 at the day of chemotherapy administration at the hospital. One and two weeks later assessments were repeated via the internet while patients were at home. Assessments at home and the hospital were conducted using the web-based software CHES. Data were analysed by means of linear mixed models. RESULTS: A sample of 54 chemotherapy outpatients participated in electronic QOL assessments at the hospital and at home. For 9 out of the 15 QOL domains of the EORTC QLQ-C30 patients reported increased burden one week after chemotherapy administration compared to the day of chemotherapy administration. Most pronounced differences were found for Fatigue, Constipation, and Appetite Loss. CONCLUSIONS: Our results indicate that patients experience most severe QOL impairments in the week following chemotherapy administration. This is a period that is usually not covered by QOL assessments in chemotherapy trials which may result in underestimation of true treatment burden. Our findings suggest to conduct QOL assessments not only event- or time-driven, but to rely on specific hypotheses on symptom and functioning trajectories.

Incidence of Medication-Related Osteonecrosis of the Jaw in Patients With Breast Cancer During a 20-Year Follow-Up: A Population-Based Multicenter Retrospective Study.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of antiresorptive therapy, which is standard practice for patients with breast cancer and bone metastases. However, the population-based incidence of MRONJ is not well established. We therefore performed a retrospective multicenter study to assess the incidence for a whole Austrian federal state (Tyrol). MATERIALS AND METHODS: This retrospective multicenter study was conducted between 2000 and 2020 at all nine breast centers across Tyrol, Austria. Using the cancer registry, the total Tyrolean population was screened for all patients with breast cancer. All patients with breast cancer and bone metastases receiving antiresorptive therapy were finally included in the study. RESULTS: From 8,860 patients initially screened, 639 individuals were eligible and included in our study. Patients received antiresorptive therapy once per month without de-escalation of therapy. MRONJ was diagnosed in 56 (8.8%, 95% CI, 6.6 to 11.0) patients. The incidence of MRONJ was 11.6% (95% CI, 8.0 to 15.3) in individuals treated with denosumab only, 2.8% (95% CI, 0.7 to 4.8) in those treated with bisphosphonates only, and 16.3% (95% CI, 8.8 to 23.9) in the group receiving bisphosphonates followed by denosumab. Individuals developed MRONJ significantly earlier when treated with denosumab. Time to MRONJ after treatment initiation was 4.6 years for individuals treated with denosumab only, 5.1 years for individuals treated with bisphosphonates only, and 8.4 years for individuals treated with both consecutively. CONCLUSION: MRONJ incidence in breast cancer patients with bone metastases was found to be considerably higher, especially for patients receiving denosumab, when compared with available data in the literature. Additionally, patients treated with denosumab developed MRONJ significantly earlier.

Quality of life across chemotherapy lines in patients with cancers of the pancreas and biliary tract.

BACKGROUND: In patients with cancers of the pancreatic and biliary tract quality of life (QOL) improvement is the main treatment goal, since survival can be prolonged only marginally. Up to date, knowledge on QOL impairments throughout the entire treatment process, often including several chemotherapy lines, is scarce. Our study aimed at investigating QOL trajectories from adjuvant treatment to palliative 3rd-line therapy METHODS: Patients were included in routine electronic patient-reported outcome monitoring at Kufstein County Hospital at the time of diagnosis and assessed with the EORTC QLQ-C30 during each chemotherapy cycle. RESULTS: Eighty out of 147 patients with pancreatic cancer or cancer of the bile ducts treated at the Kufstein County Hospital, fulfilled inclusion criteria and could be included in the study (mean age 67.4 years; 53.8% women). Physical, Emotional and Cognitive Functioning, and Global QOL deteriorated across chemotherapy lines, whereas Fatigue, Pain, Dyspnoea, Sleeping Disturbances, Diarrhoea, and Taste Alterations increased. With regard to Physical Functioning, Global QOL, Fatigue, Dyspnoea, Diarrhoea and Taste Alterations, the patients receiving adjuvant or 1st-line palliative chemotherapy did not differ significantly. Most patients in 2nd- or 3rd-line chemotherapy showed significantly higher impairments and symptom burden. However, patients under 1st and 2nd-line treatment showed stable QOL trajectories, whereas 3rd-line patients perceived substantial deteriorations. CONCLUSIONS: The results suggest early palliative treatment initiation to stabilise QOL on a level as high as possible. The continuous QOL improvement during adjuvant treatment, probably reflecting post-operative recovery, may indicate that deleterious effects of adjuvant chemotherapy on QOL are highly unlikely.

Taste alterations in breast and gynaecological cancer patients receiving chemotherapy: prevalence, course of severity, and quality of life correlates.

BACKGROUND: Taste alterations (TAs) are frequently reported by chemotherapy patients. However, research on this topic is very scarce. The etiologies of TAs are not fully known and prevalences may vary across tumour types and chemotherapy regimens. The aim of the present study was to longitudinally investigate TAs in patients with breast cancer or gynaecological cancers receiving chemotherapy, and to provide expected values for TAs for these patient populations. PATIENTS AND METHODS: One hundred and nine cancer patients (32.1% gynaecological cancer, 67.9% breast cancer) receiving chemotherapy at the Department for Internal Medicine of Kufstein County Hospital were consecutively included in the study. At each visit the Quality of Life Questionnaire-Core30 and a screening scale for TAs, consisting of two validated questions taken from the European Organisation for Research and Treatment of Cancer item bank was administered. Statistical analysis was performed using mixed-effect models. RESULTS: The prevalence of TAs in breast cancer and gynaecological cancer patients receiving chemotherapy was high (76.1%). There were differences in the extent of TAs as well as in their time course across treatment groups. The lowest TAs were found in breast cancer and gynaecological cancer patients treated with gemcitabine. The highest TAs were found in breast cancer patients treated with epirubicin/docetaxel/capecitabine. The steepest increase of TAs was found in patients treated with epirubicin/docetaxel. Moreover, significant associations between TAs and appetite loss as well as fatigue were found. CONCLUSION: The results show that TAs are an issue in breast and gynaecological cancer patients receiving different chemotherapy regimens. There is a need for a more systematic investigation of TAs in chemotherapy patients in general as well as the need to address this issue in clinical practice.

The Computer-based Health Evaluation Software (CHES): a software for electronic patient-reported outcome monitoring.

BACKGROUND: Patient-reported Outcomes (PROs) capturing e.g., quality of life, fatigue, depression, medication side-effects or disease symptoms, have become important outcome parameters in medical research and daily clinical practice. Electronic PRO data capture (ePRO) with software packages to administer questionnaires, storing data, and presenting results has facilitated PRO assessment in hospital settings. Compared to conventional paper-pencil versions of PRO instruments, ePRO is more economical with regard to staff resources and time, and allows immediate presentation of results to the medical staff.The objective of our project was to develop software (CHES - Computer-based Health Evaluation System) for ePRO in hospital settings and at home with a special focus on the presentation of individual patient's results. METHODS: Following the Extreme Programming development approach architecture was not fixed up-front, but was done in close, continuous collaboration with software end users (medical staff, researchers and patients) to meet their specific demands. Developed features include sophisticated, longitudinal charts linking patients' PRO data to clinical characteristics and to PRO scores from reference populations, a web-interface for questionnaire administration, and a tool for convenient creating and editing of questionnaires. RESULTS: By 2012 CHES has been implemented at various institutions in Austria, Germany, Switzerland, and the UK and about 5000 patients participated in ePRO (with around 15000 assessments in total). Data entry is done by the patients themselves via tablet PCs with a study nurse or an intern approaching patients and supervising questionnaire completion. DISCUSSION: During the last decade several software packages for ePRO have emerged for different purposes. Whereas commercial products are available primarily for ePRO in clinical trials, academic projects have focused on data collection and presentation in daily clinical practice and on extending cancer registries with PRO data. CHES includes several features facilitating the use of PRO data for individualized medical decision making. With its web-interface it allows ePRO also when patients are home. Thus, it provides complete monitoring of patients'physical and psychosocial symptom burden.

Prior Vaccination Exceeds Prior Infection in Eliciting Innate and Humoral Immune Responses in Omicron Infected Outpatients.

Antibody response following Omicron infection is reported to be less robust than that to other variants. Here we investigated how prior vaccination and/or prior infection modulates that response. Disease severity, antibody responses and immune transcriptomes were characterized in four groups of Omicron-infected outpatients (n=83): unvaccinated/no prior infection, vaccinated/no prior infection, unvaccinated/prior infection and vaccinated/prior infection. The percentage of patients with asymptomatic or mild disease was highest in the vaccinated/no prior infection group (87%) and lowest in the unvaccinated/no prior infection group (47%). Significant anti-Omicron spike antibody levels and neutralizing activity were detected in the vaccinated group immediately after infection but were not present in the unvaccinated/no prior infection group. Within two weeks, antibody levels against Omicron, increased. Omicron neutralizing activity in the vaccinated group exceeded that of the prior infection group. No increase in neutralizing activity in the unvaccinated/no prior infection group was seen. The unvaccinated/prior infection group showed an intermediate response. We then investigated the early transcriptomic response following Omicron infection in these outpatient populations and compared it to that found in unvaccinated hospitalized patients with Alpha infection. Omicron infected patients showed a gradient of transcriptional response dependent upon whether or not they were previously vaccinated or infected. Vaccinated patients showed a significantly blunted interferon response as compared to both unvaccinated Omicron infected outpatients and unvaccinated Alpha infected hospitalized patients typified by the response of specific gene classes such as OAS and IFIT that control anti-viral responses and IFI27, a predictor of disease outcome.

Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module.

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display enhanced binding to the ACE2 receptor and reduced neutralizing activity by vaccine-elicited antibodies, prompt specific genomic immune responses. To test this, we generated and investigated the transcriptomes in BCs from hospitalized patients infected with either the Alpha variant (n = 36) or with the Alpha variant that had acquired the E484K escape mutation (Alpha+E484K) (n = 13). We identified a gene module preferentially activated in patients infected with the Alpha+E484K variant and in patients infected with the Beta (n = 9) and Gamma (n = 3) variants that also carry by the E484K escape mutation. The E484K signature was enriched for genes preferentially expressed in monocytes and linked to severe viral infection. However, both cohorts had undergone similar treatments and no differences in disease severity were reported suggesting that this signature reflects a variant response and does not necessarily associate with disease outcome. Additionally, longitudinal transcriptome analyses revealed a more persistent retention of immune signatures in Alpha+E484K patients throughout the entire course of COVID-19 disease and convalescence. While the OAS1 Neanderthal mutation has been linked to a milder COVID-19 pathology, we did not identify significant immune transcriptomes differences in the 25 patients homozygous for this mutation. Our study offers insights into distinct molecular immune responses elicited by SARS-CoV-2 variants carrying the E484K escape mutation throughout the COVID-19 disease.

BNT162b2 vaccination enhances interferon-JAK-STAT-regulated antiviral programs in COVID-19 patients infected with the SARS-CoV-2 Beta variant.

Background: SARS-CoV-2 infection activates interferon-controlled signaling pathways and elicits a wide spectrum of immune responses and clinical manifestations in human patients. Methods: Here, we investigate the impact of prior vaccination on the innate immune response of hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant through RNA sequencing of peripheral blood immune cells. Four patients had received the first dose of BNT162b2 about 11 days prior to the onset of COVID-19 symptoms and five patients were unvaccinated. Patients had received dexamethasone treatment. Immune transcriptomes were obtained at days 7-13, 20-32 and 42-60 after first symptomology. Results: RNA-seq reveals an enhanced JAK-STAT-mediated immune transcriptome response at day 10 in vaccinated patients as compared to unvaccinated ones. This increase subsides by day 35. Expression of the gene encoding the antiviral protein oligoadenylate synthetase (OAS) 1, which is inversely correlated with disease severity, and other key antiviral proteins increases in the vaccinated group. We also investigate the immune transcriptome in naïve individuals receiving their first dose of BNT162b2 and identify a gene signature shared with the vaccinated COVID-19 patients. Conclusions: Our study demonstrates that RNA-seq can be used to monitor molecular immune responses elicited by the BNT162b2 vaccine, both in naïve individuals and in COVID-19 patients, and it provides a biomarker-based approach to systems vaccinology.

Immune transcriptomes from hospitalized patients infected with the SARS-CoV-2 variants B.1.1.7 and B.1.1.7 carrying the E484K escape mutation.

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. B.1.1.7 (VOC-202012/01) has become the predominant variant in many countries and a new lineage (VOC-202102/02) harboring the E484K escape mutation in the B.1.1.7 background emerged in February 2021 1 . This variant is of concern due to reduced neutralizing activity by vaccine-elicited antibodies 2,3 . However, it is not known whether this single amino acid change leads to an altered immune response. Here, we investigate differences in the immune transcriptome in hospitalized patients infected with either B.1.1.7 (n=28) or B.1.1.7+E484K (n=12). RNA-seq conducted on PBMCs isolated within five days after the onset of COVID symptoms demonstrated elevated activation of specific immune pathways, including JAK-STAT signaling, in B.1.1.7+E484K patients as compared to B.1.1.7. Longitudinal transcriptome studies demonstrated a delayed dampening of interferon-activated pathways in B.1.1.7+E484K patients. Prior vaccination with BNT162b vaccine (n=8 one dose; n=1 two doses) reduced the transcriptome inflammatory response to B.1.1.7+E484K infection relative to unvaccinated patients. Lastly, the immune transcriptome of patients infected with additional variants (B.1.258, B.1.1.163 and B.1.7.7) displayed a reduced activation compared to patients infected with B.1.1.7. Acquisition of the E484K substitution in the B.1.1.7 background elicits an altered immune response, which could impact disease progression.

Impact of BNT162b first vaccination on the immune transcriptome of elderly patients infected with the B.1.351 SARS-CoV-2 variant.

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. The B.1.351 variant carrying the escape mutation E484K in the receptor binding domain is of particular concern due to reduced immunological protection following vaccination. Protection can manifest as early as 10 days following immunization with full protection two weeks following the second dose, but the course is not well-characterized for variants. Here, we investigated the immune transcriptome of six elderly individuals (average age 82 yr.) from an old people's home, who contracted B.1.351, with four having received the first dose of BNT162b eight to 11 days prior to the onset of COVID-19 symptoms. The patients were hospitalized and received dexamethasone treatment. Immune transcriptomes were established from PBMCs approximately 10 and 35 days after the onset of COVID-19 symptomology. RNA-seq revealed a more intensive immune response in vaccinated patients as compared to unvaccinated ones. Specifically, transcription factors linked to the JAK/STAT pathway, interferon stimulated genes, and genes associated with innate antiviral immunity and COVID-19-SARS-CoV-2 infection were highly enriched in vaccinated patients. This rendered the transcriptomes of the older vaccinated group significantly different than older unvaccinated individuals infected at the same institution and more similar to the immune response of younger unvaccinated individuals (age range 48-62) following B.1.351 infection. All individuals in this study whether vaccinated or not were hospitalized due to B.1.351 infection and one vaccinated patient died illustrating that although an enhanced immune response was documented infection it was insufficient to protect from disease. This highlights the need for maintaining physical distancing and prevention measures throughout the time course of vaccination in older adults.

Potent SARS-CoV-2-Specific T Cell Immunity and Low Anaphylatoxin Levels Correlate With Mild Disease Progression in COVID-19 Patients.

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.

Taste alterations in cancer patients receiving chemotherapy: a neglected side effect?

BACKGROUND: Taste alterations (TAs) are a frequent but under-recognized treatment side effect in cancer patients undergoing chemotherapy (CT). CT regimens with different toxicity profiles may vary in their impact on TAs, but research on this topic is lacking. This study assesses the prevalence of TAs and their relation to sociodemographic and clinical variables, especially CT regimens. Furthermore, the association between TAs and quality of life (QOL) is investigated. PATIENTS AND METHODS: TAs and QOL data were collected longitudinally in 197 cancer patients (lung cancer, 54.3%; pancreatic cancer, 19.3%; colorectal cancer, 26.4%; age, 65.2 +/-10.4 years; male, 57.4%) who were receiving CT at the Department of Internal Medicine at Kufstein County Hospital, giving rise to a total of 1,024 assessment times. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and two additional questions taken from the EORTC item bank concerning TAs. Statistical analyses were performed using mixed-effect models. RESULTS: The study showed that the prevalence of TAs in chemotherapy patients is alarmingly high (69.9%). There were clear differences in TA scores among treatment groups: patients receiving irinotecan reported significantly more TAs than patients in other treatment groups; patients receiving a combination of gemcitabine and a platinum agent reported the lowest TAs. Additionally, significant associations between TAs and several QOL dimensions were found, especially with appetite loss and fatigue. CONCLUSION: The high prevalence of TAs and their impact on QOL in CT patients underscore the urgent need for increased attention to this side effect, both in research and in clinical practice.

Are gender-associated differences in quality of life in colorectal cancer patients disease-specific?

PURPOSE: The purpose of this study was to investigate gender-associated differences in quality of life in colorectal cancer patients and compare such differences to the general population. METHODS: Colorectal cancer patients attending three oncological centres in Austria were consecutively recruited and assessed with the EORTC QLQ-C30. For the purpose of comparison, a gender- and age-matched healthy control group was drawn from a representative sample of the Austrian general population. RESULTS: About 206 patients (47.1% women; mean age 64.8 years) with colorectal cancer were included and compared with 206 persons from the general population. A two-way analysis of variance showed significant main effects (gender and colorectal cancer vs. healthy) for most EORTC QLQ-C30 scales, but a significant interaction effect was only found for diarrhea. This means that gender-associated differences specific for colorectal cancer patients were only found for diarrhea. CONCLUSION: The vast majority of studies on gender-associated differences in quality of life compare male and female oncological patients and neglect the issue of the disease-specificity of such differences. Our study revealed that women and men suffering from colorectal cancer scored differently across many aspects of quality of life, but with the exception of diarrhea, these differences were also found in the general population, i.e. they indicated no gender-specific reaction to disease.

Rituximab maintenance overcomes the negative prognostic factor of obesity in CLL: Subgroup analysis of the international randomized AGMT CLL-8a mabtenance trial.

No data are available regarding obesity and outcome in Chronic Lymphocytic Leukemia (CLL). We analyzed 263 patients from the AGMT CLL-8a Mabtenance trial for the impact of obesity. The trial included patients after rituximab-containing induction treatment in first or second line that had achieved at least a PR. A randomization to rituximab maintenance treatment (375 mg/m2 q3 months for 2 years) vs observation was performed. In this cohort 22% of the patients (58/263) were classified as obese. The baseline response to induction treatment was inferior in obese patients with a lower CR rate (43.1% vs 60.5% in obese vs non-obese, P = 0.018) and with a lower rate of patients achieving MRD negativity after chemoimmunotherapy induction treatment (19.6% vs 35.8%, P = 0.02). The PFS outcome of obese patients was significantly worse in the observation group of the trial (24 vs 39 months median PFS, P = 0.03). However, in the rituximab maintenance group the outcome for obese vs non-obese was not different (P = 0.4). In summary, obesity was overall associated with a worse outcome of chemoimmunotherapy induction. However, rituximab maintenance treatment seems to be able to overcome this negative effect.