P-move: a randomized control trial of exercise in patients with advanced pancreatic or biliary tract cancer (aPBC) receiving beyond first-line chemotherapy.

PURPOSE: Patients with advanced pancreatic and biliary tract cancer (aPBC) frequently suffer from high symptom burden. Exercise can reduce treatment side effects and improve patient-related outcomes (PROMs). However, evidence from prospective studies regarding feasibility and efficacy in advanced settings are sparse. The primary aim of this prospective, randomized-controlled study was to evaluate the feasibility and effects of exercise (ET) in patients with aPBC. METHODS: Patients with aPBC beyond first-line therapy were randomized according to the minimization procedure with stratification by gender, age, and loss of body weight in the past six months. The intervention group (IG) completed 3 training units/week for 8 weeks (1x supervised strength sessions, 2x individualized home-based sessions). Control group (CG) received recommendations on physical activity during cancer. RESULTS: 41 patients (stage IV pancreatic or biliary tract cancer) were included no adverse events related to exercise occurred during the trial. Physical function increased significantly in IG in 5 out of 7 physical domains. Comparison of IG and CG at 8 weeks (t2) showed significant differences in favour of IG in leg press (p=0.001), bench press (p=0.011), sit-to-stand (p=0.001) and crunch (0.006). Constipation revealed a significant difference in favour of IG at t2 (p=0.033). Quality of life stabilized/increased in IG during the study period compared to a decrease in CG. Throughout/Over the 8 weeks, fatigue notably reduced in the IG (p=0.028). CONCLUSION: Exercise is safe and feasible in patients with aPBC undergoing further line therapy. Significant improvements in physical functioning and increased quality of life were achieved. German Clinical Trials Register ID: DRKS00021179; Registration date 15.05.2020.

Falling off the screening grid-Predictors for postponed utilization of psycho-oncological support in cancer patients and its implications for distress assessment and management.

OBJECTIVE: Distress assessment of cancer patients is considered state-of-the-art. In addition to distress scores, individual care needs are an important factor for the initiation of psycho-oncological interventions. In a mono-centric, observational study, we aimed for characterization of patients indicating a subjective need but declining to utilize support services immediately to facilitate implementation of adapted screenings. METHODS: This study analyzed retrospective data from routine distress screening and associated data from hospital records. Descriptive, variance and regression analyses were used to assess characteristics of postponed support utilization in patients with mixed cancer diagnoses in different treatment settings. RESULTS: Of the total sample (N = 1863), 13% indicated a subjective need but postponed support utilization. This subgroup presented as being as burdened by symptoms of depression (p < 0.001), anxiety (p < 0.001) and distress (p < 0.001) as subjectively distressed patients with intent to directly utilize support. Time periods since diagnosis were shorter (p = 0.007) and patients were more often inpatients (p = 0.045). CONCLUSIONS: Despite high heterogeneity among the subgroups, this study identified distress-related factors and time since diagnosis as possible predictors for postponed utilization of psycho-oncological interventions. Results suggest the necessity for time-individualized support which may improve utilization by distressed patients.

Cancer Patients' Age-Related Benefits from Mobile Neurofeedback-Therapy in Quality of Life and Self-efficacy: A Clinical Waitlist Control Study.

Electroencephalographic neurofeedback (EEG NF) can improve quality of life (QoL) and reduce distress by modifying the amplitude of selected brain frequencies. This study aims to investigate the effects of NF therapy on QoL and self-efficacy in cancer patients and to explore age-related reactions. In a waitlist control paradigm, psychometric data (EORTC QLQ-C30, General Self-Efficacy Scale) of 20 patients were collected at three different time points, each five weeks apart. An outpatient 10-session NF intervention (mobile) was conducted between the second and third measurement point. QoL and self-efficacy changed significantly over time (QoL: F(2,36) = 5.294, p < .05, η2 = .227; Self-efficacy: F(2,26) = 8.178, p < .05, η2 = .386). While QoL increased in younger patients, older patients initially showed a decrease in QoL, which then increased during intervention. Younger patients did not differ from older patients in QoL in both waitlist control (T0-T1) and intervention phase (T1-T2). QoL in older patients significantly differed between waitlist control and intervention phase (Z = - 2.023, p < .05, d = 1.085). Self-efficacy increased in both age categories. Younger and older patients did not differ in self-efficacy in waitlist control, but in intervention phase (F(1,16) = 7.014, p < .05, η2 = .319). The current findings suggest that NF therapy is a promising treatment modality for improving QoL in cancer patients. Our study reveals NF being a tool to influence self-efficacy, which should receive more appreciation in clinical care. However, the effect of NF in different age groups as well as the influence on further cancer-related symptoms should be investigated in future research.

[PARPACT: Paramedic Palliative Care Test : Validation of a questionnaire to assess palliative care knowledge and self-efficacy expectations of paramedics]. / PARPACT ­ Paramedic Palliative Care Test : Validierung eines Tests für palliatives Wissen und Selbstwirksamkeitserwartung bei Mitarbeiter*innen im Rettungswesen.

BACKGROUND: Given the large number of palliative patients cared for by the emergency services, education and training in palliative care topics are playing an increasingly important role. To support decision-making in an emergency setting a palliative or emergency card has been introduced in many cities. OBJECTIVES: To assess the success of educational interventions and the effect of the palliative or emergency card, a questionnaire was developed and validated to determine palliative knowledge and palliative self-efficacy expectations in the emergency services. MATERIALS AND METHODS: A Delphi process was applied for development and content validation. Factor analysis was used for construct validation. Criterion validity was assessed with the help of 22 nurses specially trained in palliative care. Reliability was determined using Cronbach's alpha as a measure of internal consistency. RESULTS: In all, 291 of 750 paramedics participated in the voluntary survey. After completion of the Delphi process, there was consensus that the important topics of pain, dyspnea, sedation, end-of-life care, euthanasia, and legal aspects were covered in the questionnaire. Factor analysis was in favor of a six-factor solution. Criterion validation revealed a significant difference in palliative knowledge between palliative care nurses (MRang 289.73) and paramedics (MRang 146.97, U = 281.000, r = 0.40, p < 0.001). Cronbach's alpha was 0.70 for the knowledge questions and 0.82 for the palliative care self-efficacy expectancy subscale. CONCLUSIONS: The Paramedic Palliative Care Test (PARPACT) is a validated measurement tool for testing educational interventions in paramedicine.

Targeted deep sequencing revealed variants in cell-free DNA of hormone receptor-positive metastatic breast cancer patients.

Cell-free DNA (cfDNA) is described to mirror intratumoral heterogeneity and gives insight about clonal evolution for improved therapeutic decisions. We sequenced cfDNA of a hormone receptor-positive, HER2-negative metastatic breast cancer (MBC) cohort with a high coverage to examine the prevalence and relevance of any detected variant. cfDNA of 44 MBC patients was isolated, followed by library construction using a customized targeted DNA panel with integrated unique molecular indices analyzing AKT1, AR, BRCA1, BRCA2, EGFR, ERCC4, ERBB2, ERBB3, ESR1, FGFR1, KRAS, MUC16, PIK3CA, PIK3R1, PTEN, PTGFR, and TGFB1. CfDNA was sequenced on the NextSeq® 550 platform (Illumina) and variants were analyzed with Ingenuity Variant Analysis (QIAGEN). We evaluated cfDNA variants in 40 of the 44 hormone receptor-positive and HER2-negative patients with a high mean coverage of 22,000×, resulting in MUC16, BRCA2, ERBB3, and AR variant calling in > 90% of the patients. 47% of all AR variants were pathogenic and at least one pathogenic or likely pathogenic variant was detected in each patient. A specific BRCA1 variant and > 3.5 pathogenic variants significantly associated with a reduced survival after diagnosis of metastasis. Longitudinal monitoring revealed an increase of pathogenic and likely pathogenic PIK3CA and ESR1 variant allele frequency under everolimus and exemestane, 8 months before proof of therapy failure by visual staging in one exemplary case. The identification of new variants with high prevalence, prognostic value, and dynamics under treatment by deep sequencing of cfDNA might empower sensitive monitoring and personalized therapeutic decisions.

RNA Profiles of Circulating Tumor Cells and Extracellular Vesicles for Therapy Stratification of Metastatic Breast Cancer Patients.

BACKGROUND: Liquid biopsies are discussed to provide surrogate markers for therapy stratification and monitoring. We compared messenger RNA (mRNA) profiles of circulating tumor cells (CTCs) and extracellular vesicles (EVs) in patients with metastatic breast cancer (MBC) to estimate their utility in therapy management. METHODS: Blood was collected from 35 hormone receptor-positive/HER2-negative patients with MBC at the time of disease progression and at 2 consecutive staging time points. CTCs were isolated from 5 mL of blood by positive immunomagnetic selection, and EVs from 4 mL of plasma by a membrane affinity-based procedure. mRNA was reverse transcribed, preamplified, and analyzed for 18 genes by multimarker quantitative polymerase chain reaction (qPCR) assays. RNA profiles were normalized to healthy donor controls (n = 20), and results were correlated with therapy outcome. RESULTS: There were great differences in mRNA profiles of EVs and CTCs, with only 5% (21/403) of positive signals identical in both fractions. Transcripts involved in the PI3K signaling pathway were frequently overexpressed in CTCs, and AURKA, PARP1, and SRC signals appeared more often in EVs. Of all patients, 40% and 34% showed ERBB2 and ERBB3 signals, respectively, in CTCs, which was significantly associated with disease progression (P = 0.007). Whereas MTOR signals in CTCs significantly correlated with response (P = 0.046), signals in EVs indicated therapy failure (P = 0.011). The presence of AURKA signals in EVs seemed to be a marker for the indication of unsuccessful treatment of bone metastasis. CONCLUSIONS: These results emphasize the potential of CTCs and EVs for therapy monitoring and the need for critical evaluation of the implementation of any liquid biopsy in clinical practice.

Predictors of outpatients' request for palliative care service at a medical oncology clinic of a German comprehensive cancer center.

PURPOSE: Early integration of palliative care (PC) is recommended. The determination of predictors for patients' request for PC may guide implementation in clinical practice. Toward this end, we analyzed the symptom burden and distress of cancer patients in outpatient care and examined their need and request for PC. METHODS: Between October 2013 and March 2016, 705 patients receiving outpatient cancer treatment took part in the survey. We used the new MInimal DOcumentation System to detect symptom clusters. Additionally, patients' request for palliative and psychosocial support was assessed. Groups of patients with PC request were compared to patients without PC request regarding their symptom clusters. Logistic regression analysis was applied to discover significant predictors for the requested inclusion of PC. RESULTS: A total of 159 patients (25.5%) requested additional support by PC. Moderate and severe tiredness (40.3%), weakness (37.9%), pain (25.0%), loss of appetite (22.3%), and dyspnea (19.1%) were the most frequent symptoms. The group of patients requesting PC differed significantly in terms of pain, nausea, dyspnea, constipation, weakness, loss of appetite, tiredness, depression, and anxiety from patients without request for PC (p < .01). The perceived need for PC was identified by the significant predictors "depression," "anxiety," and "weakness" with an explained variance of 22%. CONCLUSION: Combining a standardized screening questionnaire and the assessment of patients' request for PC allows systematic monitoring for patients' need for PC in a large Medical Oncology clinic. Depression, anxiety, and weakness are predictors of requesting PC service by patients receiving outpatient cancer treatment.

Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to Therapy in Metastatic Breast Cancer.

BACKGROUND: Circulating tumor cells (CTCs) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTCs of MBC patients on the basis of the expression of 46 genes. METHODS: From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest EMT-2/StemCellSelectTM (QIAGEN). Patients were grouped into (a) responder (R) and non-responder (NR) at TP1 and (b) overall responder (OR) and overall non-responder (ONR) at TP2. A 46-gene PCR assay was used for preamplification and high-throughput gene expression profiling. Data were analyzed by use of GenEx (MultiD) and SAS. RESULTS: The CTC positivity was defined by the four-gene signature (EPCAM, KRT19, MUC1, ERBB2 positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC- patients (KRT19, FLT1, EGFR, EPCAM, GZMM, PGR, CD24, KIT, PLAU, ALDH1A1, CTSD, MKI67, TWIST1, and ERBB2). KRT19 was highly expressed in CTC+ patients and ADAM17 in the NR at TP1. A significant differential expression of 4 genes (KRT19, EPCAM, CDH1, and SCGB2A2) was observed between OR and ONR when stratifying the samples into CTC+ or CTC-. CONCLUSIONS: ADAM17 could be a key marker in distinguishing R from NR, and KRT19 was powerful in identifying CTCs.

Comparison of the HER2, estrogen and progesterone receptor expression profile of primary tumor, metastases and circulating tumor cells in metastatic breast cancer patients.

BACKGROUND: The expression of HER2, estrogen (ER) and progesterone (PR) receptor can change during the course of the disease in breast cancer (BC). Therefore, reassessment of these markers at the time of disease progression might help to optimize treatment decisions. In this context, characterization of circulating tumor cells (CTCs) could be of relevance since metastatic tissue may be difficult to obtain for repeated analysis. Here we compared HER2/ER/PR expression profiles of primary tumors, metastases and CTCs. METHODS: Ninety-six patients with metastatic BC from seven University BC Centers in Germany were enrolled in this study. Blood was obtained at the time of first diagnosis of metastatic disease or disease progression and analyzed for CTCs using the AdnaTest BreastCancer (QIAGEN Hannover GmbH, Germany) for the expression of EpCAM, MUC-1, HER2, ER and PR. HER2 expression on CTCs was additionally assessed by immunocytochemistry using the CellSearch® assay. RESULTS: The detection rate for CTCs using the AdnaTest was 43 % (36/84 patients) with the expression rates of 50 % for HER2 (18/36 patients), 19 % for ER (7/36 patients) and 8 % for PR (3/36 patients), respectively. Primary tumors and CTCs displayed a concordant HER2, ER and PR status in 59 % (p = 0.262), 39 % (p = 0.51) and 44 % (p = 0.62) of cases, respectively. For metastases and CTCs, the concordance values were 67 % for HER2 (p = 0.04), 43 % for ER (p = 0.16) and 46 % for PR (p = 0.6). Using the CellSearch® assay, the CTC-positivity rate was 53 % (42/79 patients) with HER2 expressed in 29 % (12/42) of the patients. No significant concordance (58 % and 53 %) was found when HER2 on CTCs was compared with HER2 on primary tumors (p = 0.24) and metastases (p = 0.34). Interestingly, primary tumors and metastases were highly concordant for HER2 (84 %, p = 1.13E-08), ER (90 %, p = 3.26E-10) and PR (83 %, p = 2.09E-09) and ER-and PR-positive metastases were significantly found to be of visceral origin (p = 0.03, p = 0.02). CONCLUSION: Here we demonstrate that the molecular detection of HER2 overexpression in CTC is predictive of the HER2 status on metastases. Detailed analysis of ER and PR expression rates in tissue samples and CTCs may provide useful information for making treatment decisions.

Symptom burden and relief in palliative care units of German Comprehensive Cancer Center and other hospitals.

PURPOSE: The National Hospice and Palliative Registry contains patient data from German hospice and palliative care facilities about symptoms. The aim of the study at hand is to differentiate symptom burden of patients in palliative care units between Comprehensive Cancer Center (CCC) and other hospitals regarding symptom burden and relief of patients in palliative care units. METHODS: The registry analysis provided data of patients in palliative care units (2014-2018). We analyzed characteristic and symptom-related data on 18 symptoms, with considerable symptom-burdened patients (moderate or severe). We followed a cancer (yes/no) and facility-specific descriptive analysis (f, %, µ, Mdn, SD, V, r) using SPSS. RESULTS: We evaluated 10,447 patient records (CCC: 4234 pts/non CCC 6,213 pts), 82% with a cancer diagnosis. For cancer patients, the mean age in CCC-affiliated palliative care units was 68 (SD 19-99) years, in others 73 (SD 23-104) years (p < 0.05; V = 0.2). The proportion of patients with significant symptom burden is lower in CCC-affiliated than in other palliative care units. The difference between facilities shows a significant weak effect in pain, vomiting and constipation, depressiveness, anxiety, and tension. The proportion of cases which symptom burden could be alleviated is higher in CCC-affiliated palliative care units with significant weak/medium effect in pain, nausea, vomiting, shortness of breath, constipation, wound care problems, depressiveness, anxiety, tension, confusion, and problems in organizing care. CONCLUSION: We found differences in symptom burden and symptom relief between CCC-affiliated and other palliative care units. CCCs should continue to feel responsible for sharing knowledge about symptom relief, such as through standard operating procedures and education.

Comparison of Palliative Knowledge and Self-Efficacy Expectation of German Paramedics Between a Rural and an Urban Structured Emergency Medical Service Area.

OBJECTIVE(S): Differences in the German emergency medical service (EMS) can be seen in the countryside in contrast to the city with regard to travel distances to hospitals and in the access routes of EMS-physicians. In order to investigate the success of establishment of palliative crisis cards associated with training and the rural and urban EMS structures, two urban and two rural EMS areas were compared using the Paramedic Palliative Care Test (PARPACT). Methods: The PARPACT includes test items on palliative knowledge (PK, maximum score: 15 points) and palliative self-efficacy expectations (PSE, maximum score: 18 points), as well as items on palliative attitudes in dealing with palliative care patients. We used a 4-point Likert-type scale. For data analysis, nonparametric tests (χ-test and Mann-Whitney U test) were used in addition to descriptive analysis (frequencies, means, medians, standard deviations, and ranges). Results: In total, 291 out of 750 ambulance or EMS personnel participated in the voluntary survey. Rural ambulance or EMS personnel answered the PK-questions correctly more often on average (mean: 11.19, SD: 1.85) than urban ambulance or EMS personnel (mean: 9.18, SD: 2.39; Mann-Whitney U test: U=5040.000, P=.001). In addition, ambulance or EMS personnel with the highest level of training (3-year-trained paramedics) performed better in PK (mean: 10.38, SD: 2.31) than less intensively training ambulance or EMS personnel (mean: 9.58, SD: 2.43; Mann-Whitney U-test: U=8446.500, P=.004). In terms of PSE, rural ambulance or EMS personnel also achieved higher mean PSE-scores (mean: 12.55, SD: 2.60) than urban ambulance or EMS personnel (mean: 9.77, SD: 3.41; Mann-Whitney U-test: U=5148.500, P=.001). Conclusions: Better training in the EMS is associated with improved PK compared to less qualified nonphysician EMS staff. The establishment of palliative crisis cards and the structures in the city alone do not lead to improved knowledge and PSE.

Drivers and barriers of patients' acceptance of video consultation in cancer care.

Background: Due to digitization in the medical sector, many healthcare interactions are switched to online services. This study assessed the acceptance of video consultations (VCs) in cancer care, and determined drivers and barriers of acceptance. Methods: A cross-sectional online-based survey study was conducted in Germany from February 2022 to February 2023. Recruitment took place at oncology outpatient clinics, general practitioners, oncology practices and via cancer-related social media channels. Inclusion criteria were a cancer diagnosis, cancer treatment and internet access. Sociodemographic, medical data, eHealth-related data were acquired via an online assessment. The Unified Theory of Acceptance and Use of Technology (UTAUT) model was used to determine the acceptance of VC and its predictors. Results: Of N = 350 cancer patients, 56.0% (n = 196) reported high acceptance of VC, 28.0% (n = 98) stated moderate acceptance and 16.0% (n = 56) indicated low acceptance. Factors influencing acceptance were younger age (ß = -.28, p < .001), female gender (ß = .35, p = .005), stage of disease (ß = .11, p = .032), high digital confidence (ß = .14, p = .010), low internet anxiety (ß = -.21, p = .001), high digital overload (ß = -.12, p = .022), high eHealth literacy (ß = .14, p = .028), personal trust (ß = -.25, p < .001), internet use (ß = .17, p = .002), and the UTAUT predictors: performance expectancy (ß = .24, p < .001), effort expectancy (ß = .26, p < .001), and social influence (ß = .34, p < .001). Conclusions: Patients' acceptance of VC in cancer care is high. Drivers and barriers to acceptance identified should be considered for personalized applications. Considering the growing demand for cancer care establishing digital healthcare solutions is justified.

Preemptive tumor profiling for biomarker-stratified early clinical drug development in metastatic breast cancer patients.

Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast cancer patients. The utility of agents modulating hormone receptors, synthesis of steroid hormones, or HER2-targeting agents has been greatly enhanced by the detection of predictive biomarkers in diagnostic tumor samples. Based on deeper understanding of breast cancer biology multiple drug candidates have been developed to modulate additional molecular targets which may associate with specific biomarker profiles. Accordingly, exploratory biomarkers are increasingly incorporated in early clinical trials, thus demanding a new process of patient selection. Here, we describe the implementation of preemptive, multiplexed biomarker profiling linked to standard diagnostic algorithms for metastatic breast cancer patients treated at the West German Cancer Center. Profiling for experimental biomarkers was prospectively offered to patients with metastatic breast cancer who met generic clinical trial inclusion criteria. Formalin-fixed, paraffin-embedded tumor samples were retrieved and studied for potentially "actionable" biomarkers related to active clinical trials by immunohistochemistry, amplicon sequencing, and in situ hybridization. The clinical course of those "profiled" patients was closely monitored to offer trial participation whenever applicable. Here, we report results from the first 131 patients enrolled in this program. PIK3CA mutations (23 %) and amplifications (2 %), loss of PTEN expression (13 %), and FGFR1 amplifications (8 %) were detected next to established biomarkers such as estrogen (67 %) and progesterone receptor expression (52 %), and HER2 overexpression or amplification (23 %). So far 16 "profiled" patients (12 %) have been enrolled in biomarker-stratified early clinical trials. Preemptive profiling of investigational biomarkers can be integrated into the diagnostic algorithm of a large Comprehensive Cancer Center. Extensive administrative efforts are required to successfully enroll "profiled" patients with metastatic breast cancer in early clinical trials stratified by exploratory biomarkers.

Neurofeedback Treatment Affects Affective Symptoms, But Not Perceived Cognitive Impairment in Cancer Patients: Results of an Explorative Randomized Controlled Trial.

BACKGROUND: EEG biofeedback (NF) is an established therapy to enable individuals to influence their own cognitive-emotional state by addressing changes in brainwaves. Psycho-oncological approaches of NF in cancer patients are rare and effects are hardly studied. OBJECTIVE: The aim of this explorative, randomized controlled trial was to test the effectiveness of an alpha and theta NF training protocol, compared to mindfulness based therapy as an established psycho-oncological treatment. METHODS: Of initially 62 screened patients, 56 were included (inclusion criteria were cancer independent of tumor stage, age >18 years, German speaking; exclusion criteria suicidal ideation, brain tumor). Randomization and stratification (tumor stage) was conducted by a computer system. Participants got 10 sessions over 5 weeks, in (a) an NF intervention (n = 21; 13 female, 8 male; MAge = 52.95(10 519); range = 31 to 73 years)) or (b) a mindfulness group therapy as control condition (CG; n = 21; ie, 15 female, 6 male; MAge = 50.33(8708); range = 32 to 67 years)). Outcome parameters included self-reported cognitive impairment (PCI) as primary outcome, and secondary outcomes of emotional distress (DT, PHQ-8, GAD-7), fatigue (MFI-20), rumination (RSQ), quality of life (QoL, EORTC-30 QoL), self-efficacy (GSE), and changes in EEG alpha, and theta-beta band performance in the NF condition. RESULTS: No changes in cognitive impairment were found (P = .079), neither in NF nor CG. High affective distress was evident, with 70.7% showing elevated distress and 34.1% showing severe depressive symptoms. Affective symptoms of distress (P ≤ .01), depression (P ≤ .05) and generalized anxiety (P ≤ .05) decreased significantly over time. No differences between NF and CG were found. There was a significant increase of the alpha band (P ≤ .05; N = 15) over the NF sessions. Self-efficacy predicted QoL increase in NF with P ≤ .001 and an explained variance of 48.2%. CONCLUSION: This is the first study to investigate NF technique with regard to basic mechanisms of effectiveness in a sample of cancer patients, compared to an established psycho-oncological intervention in this field. Though there were no changes in cognitive impairment, present data show that NF improves affective symptoms comparably to mindfulness-based therapy and even more pronounced in QoL and self-efficacy.Trial registration: ID: DRKS00015773.

Ratios of monocytes and neutrophils to lymphocytes in the blood predict benefit of CDK4/6 inhibitor treatment in metastatic breast cancer.

Biomarkers to identify metastatic breast cancer (mBC) patients resistant to CDK4/6 inhibition (CDK4/6i) are currently missing. We evaluated the usefulness of the monocyte-to-lymphocyte ratio (MLR), the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as predictive markers for de novo resistance to CDK4/6i. Various blood cell counts and MLR, NLR, PLR were recorded before treatment initiation (baseline) and four weeks later from 97 mBC patients receiving endocrine therapy (ET) alone or in combination with CDK4/6i. Binary blood cell count/ratios (mean = cut-off) were related to outcome using Cox regression. High MLR (p = 0.001) and high NLR (p = 0.01) at baseline significantly correlated with a shorter progression-free survival (PFS) in the CDK4/6i cohort, independent of any other clinical parameter as determined by multivariate Cox regression. Both, high MLR (p = 0.008) and high NLR (p = 0.043) as well as a decrease in PLR after four weeks of CDK4/6i first line treatment (p = 0.01) indicated a shorter overall survival. Moreover, decreasing PLR (p = 0.043) and increasing mean corpuscular volume (MCV; p = 0.011) within the first cycle of CDK4/6i correlated with a shorter PFS and decreasing MLR (p = 0.039) within the first cycle of first-line CDK4/6i was also correlated with shorter PFS. In summary, easily assessable blood cell parameter were shown to have predictive, monitoring and prognostic value and thus, could, in future, be used for individualized CDK4/6i therapy management. Most importantly, the imbalance of NLR and MLR at baseline might serve as predictive marker for de novo resistance to CDK4/6i in mBC patients.

Electronic Patient-Reported Outcome Measures (ePROMs) Improve the Assessment of Underrated Physical and Psychological Symptom Burden among Oncological Inpatients.

For advanced cancer inpatients, the established standard for gathering information about symptom burden involves a daily assessment by nursing staff using validated assessments. In contrast, a systematic assessment of patient-reported outcome measures (PROMs) is required, but it is not yet systematically implemented. We hypothesized that current practice results in underrating the severity of patients' symptom burden. To explore this hypothesis, we have established systematic electronic PROMs (ePROMs) using validated instruments at a major German Comprehensive Cancer Center. In this retrospective, non-interventional study, lasting from September 2021 to February 2022, we analyzed collected data from 230 inpatients. Symptom burden obtained by nursing staff was compared to the data acquired by ePROMs. Differences were detected by performing descriptive analyses, Chi-Square tests, Fisher's exact, Phi-correlation, Wilcoxon tests, and Cohen's r. Our analyses pointed out that pain and anxiety especially were significantly underrated by nursing staff. Nursing staff ranked these symptoms as non-existent, whereas patients stated at least mild symptom burden (pain: meanNRS/epaAC = 0 (no); meanePROM = 1 (mild); p < 0.05; r = 0.46; anxiety: meanepaAC = 0 (no); meanePROM = 1 (mild); p < 0.05; r = 0.48). In conclusion, supplementing routine symptom assessment used daily by nursing staff with the systematic, e-health-enabled acquisition of PROMs may improve the quality of supportive and palliative care.

Systematic symptom screening in patients with advanced cancer treated in certified oncology centers: results of the prospective multicenter German KeSBa project.

PURPOSE: Guidelines recommend a structured symptom screening (SC) for especially advanced cancer patients (CPs). The aim of this multicenter German prospective quality assurance project KeSBa (Kennzahl Symptom- und Belastungserfassung) was to gain knowledge on SC procedures in Oncology Centers (OCs) for advanced cancer patients and a first impression on the consequences of SC. METHODS: The KeSBa project consisted of three phases: pilot, 3 months screening and feedback phase. Participating OCs decided to use either the Minimal Documentation System (MIDOS) or the Integrated Palliative care Outcome Scale (IPOS) and defined the cutoff values for positive screening results. RESULTS: Out of 172 certified German OCs, 40 (23%) participated in the KeSBa pilot phase, 29 (16.8%) in the 3 months screening phase using MIDOS (n = 18, 58.6%) or IPOS (n = 11, 41.3%) and in the feedback round. 25/29 performed paper-based screening (86.2%). 2.963 CPs were screened. Results were documented for 1255 (42.2%, SC +) positive and 874 (29.5%, SC-) negative screenings depending on the center´s schedules: 452 SC + CPs (28.4%) and 42 SC- CPs (2.6%) had contact to specialized palliative care or other supportive specialist teams afterwards, 458 SC + CPs (28.8%) and 605 SC- CPs (38.1%) remained in standard oncology care. In the feedback round missing resources (personal and IT) and improved communication were mentioned most often. CONCLUSION: Routine SC is feasible in advanced CPs treated in OCs but associated with considerable workload. In 42.2% of CPs SC was classified as positive, indicating the need of further diagnostics or professional judgment. SC requires staff and IT resources.

Web-based mindfulness and skills-based distress reduction for patients with cancer: study protocol of the multicentre, randomised, controlled confirmatory intervention trial Reduct.

INTRODUCTION: Many patients with cancer experience severe psychological distress, but as a result of various barriers, few of them receive psycho-oncological support. E-mental health interventions try to overcome some of these barriers and the limitation of healthcare offers, enabling patients with cancer to better cope with psychological distress. In the proposed trial, we aim to assess the efficacy and cost-effectiveness of the manualised e-mental health intervention Make It Training- Mindfulness-Based and Skills-Based Distress Reduction in Oncology. Make It Training is a self-guided and web-based psycho-oncological intervention, which includes elements of cognitive behavioural therapy, mindfulness-based stress reduction and acceptance and commitment therapy. The training supports the patients over a period of 4 months. We expect the Make It Training to be superior to treatment as usual optimised (TAU-O) in terms of reducing distress after completing the intervention (T1, primary endpoint). METHODS AND ANALYSIS: The study comprises a multicentre, prospective, randomised controlled confirmatory interventional trial with two parallel arms. The proposed trial incorporates four distinct measurement time points: the baseline assessment before randomisation, a post-treatment assessment and 3 and 6 month follow-up assessments. We will include patients who have received a cancer diagnosis in the past 12 months, are in a curative treatment setting, are 18-65 years old, have given informed consent and experience high perceived psychological distress (Hospital Anxiety and Depression Scale ≥13) for at least 1 week. Patients will be randomised into two groups (Make It vs TAU-O). The aim is to allocate 600 patients with cancer and include 556 into the intention to treat analysis. The primary endpoint, distress, will be analysed using a baseline-adjusted ANCOVA for distress measurement once the intervention (T1) has been completed, with study arm as a binary factor, baseline as continuous measurement and study centre as an additional categorical covariate. ETHICS AND DISSEMINATION: The Ethics Committee of the Medical Faculty Essen has approved the study (21-10076-BO). Results will be published in peer-reviewed journals, conference presentations, the project website, and among self-help organisations. TRIAL REGISTRATION NUMBER: German Clinical Trial Register (DRKS); DRKS-ID: DRKS00025213.

Comparison of estrogen and progesterone receptor status of circulating tumor cells and the primary tumor in metastatic breast cancer patients.

OBJECTIVES: The expression of predictive markers including the estrogen (ER) and progesterone receptor (PR) expression can change during the course of the disease. Therefore, reassessment of these markers at the time of disease progression might help to optimize treatment decisions. Metastatic tissue may be difficult to obtain for repeated analysis. In this context, characterization of circulating tumor cells (CTCs) could be of relevance. It was the purpose of the present study (1) to reevaluate the ER/PR expression by CTCs and (2) to compare the hormone receptor status expression profile of CTCs with the primary tumor. METHODS: We evaluated 193 blood samples from metastatic breast cancer patients at the time of first diagnosis of metastatic disease or disease progression. All samples underwent immunomagnetic enrichment using the AdnaTest BreastCancerSelect (AdnaGen AG, Germany) within 4h after blood withdrawal followed by RNA isolation and subsequent gene expression analysis by reverse transcription and Multiplex-PCR in separated tumor cells using the AdnaTest BreastCancerDetect. CTCs were analyzed for the three breast cancer-associated markers: EpCAM, Muc-1, Her-2 and actin as an internal PCR control. Expression of the ER and PR was assessed in an additional RT-PCR. The analysis of PCR products was performed by capillary electrophoresis on the Agilent Bioanalyzer 2100. RESULTS: The overall detection rate for CTCs was 45% (87/193 patients) with the expression rates of 71% for EpCAM (62/87 patients), 73% for MUC1 (64/87 patients), 48% for HER2 (42/87 patients), 19% for ER (17/87 patients) and 10% for PR (9/87 patients), respectively. Comparisons with the primary tumor were only performed in CTC+ patients (n=87). In 48/62 (77%) patients with ER+ tumors, CTCs were ER- and 46/53 (87%) patients with PR+ tumors did not express PR on CTCs. Primary tumors and CTCs displayed a concordant ER and PR status in only 41% (p=0.260) and 45% (p=0.274) of cases, respectively. CONCLUSION: Most of the CTCs were ER/PR-negative despite the presence of an ER/PR- positive primary tumor. The predictive value of hormone receptor status expression profile of CTCs for palliative endocrine therapy has to be prospectively evaluated. STATEMENT: We recently demonstrated in more than 400 primary breast cancer patients that the expression profile between CTCs and the primary tumor with regard to ER/PR/HER2 positivity differs. The concordance rate between ER, PR and HER2 status of CTCs and the primary tumor was 29%, 25% and 53%, respectively (Fehm T et al., Breast Cancer Res Aug 10 2009, 11(4) pR59). Based on these results we studied blood samples of 193 metastatic breast cancer patients participating in the German DETECT study (1) to reevaluate the ER/PR expression by CTCs and (2) to compare the hormone receptor status expression profile of CTCs with the primary. As already shown for primary breast cancer, most of the CTCs were ER/PR-negative despite the presence of an ER/PR- positive primary tumor. In the metastatic setting the phenotype of CTC reflects the phenotype of metastatic disease. Therefore palliative treatment selected based on the expression profile may not be effective since the phenotype has changed during disease progression. To our knowledge, this study is one of the biggest to compare hormonal receptor expression on CTC and the primary tumor. We hope that our manuscript is suitable for publication in Gynecologic Oncology.

Symptoms During Outpatient Cancer Treatment and Options for Their Management

BACKGROUND: Cancer patients account for a large segment of the German healthcare system, with a 5-year prevalence of around 1.7 million persons. Advances in oncological treatment, now frequently performed on an outpatient basis, are granting many of these individuals a longer life span. At the same time, cancer patients often suffer disease-related symptoms and adverse effects from their tumor treatment, which may strongly impair their quality of life despite the improved techniques for management of side effects. METHODS: This review is based on a selective literature search of the PubMed and Cochrane Library databases carried out in December 2019 and January 2020. Special attention was paid to guidelines, expert opinions, and recommendations from professional societies. RESULTS: Alongside decreased well-being, cancer patients often suffer from fatigue (70-100%), loss of appetite (6-53%), pain (30-80 %), and dyspnea (10-70%). The prevalence and severity of the symptoms varies depending on the tumor entity and the patient's sex. A meta-analysis showed that besides causal treatment, physical activity achieves moderately strong effects in tumor-associated fatigue syndrome (Cohen's d = 0.30 [0.25; 0.36]). The WHO recommends early use of opioids in tumor-associated pain. A meta-analysis of randomized trials described symptom relief by means of opioids also in dyspnea (standardized mean difference: -0.32 [-0.53; -0.10]). Increasingly, guidelines are recommending regular palliative medical symptom screening. CONCLUSION: Regular documentation of symptoms in outpatients offers the opportunity for targeted management of symptoms during treatment with the involvement of various disciplines such as palliative medicine, exercise therapy, and psychotherapy.