30 results on '"Holdenrieder, Stefan"'
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2. German Society for Clinical Chemistry and Laboratory Medicine – areas of expertise: Division reports from the German Congress of Laboratory Medicine 2022 in Mannheim, 13–14 October 2022
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Nauck Matthias, Holdenrieder Stefan, Klein Hanns-Georg, Findeisen Peter, Winter Christof, Ceglarek Uta, Petersmann Astrid, Klouche Mariam, Lichtinghagen Ralf, Biemann Ronald, Adler Jakob, Streichert Thomas, von Meyer Alexander, Wieland Eberhard, Hofmann Walter, Aufenanger Johannes, Orth Matthias, Shipkova Maria, Bidlingmaier Martin, Birschmann Ingvild, Blüthner Martin, Conrad Karsten, Luppa Peter B., Kiehntopf Michael, Bietenbeck Andreas, Baum Hannsjörg, and Renz Harald
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german congress for laboratory medicine 2022 ,german society for clinical chemistry and laboratory medicine (dgkl) ,areas of expertise ,division reports ,Medical technology ,R855-855.5 - Abstract
The programme of the German Congress for Laboratory Medicine 2022 was essentially designed by the divisions of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL). Almost all chairpersons of the divisions organised a 90-min symposium on current topics, i.e. conceptualised the symposia and invited speakers. For this article all chairpersons summarised the lectures that were given within the symposia. The DGKL’s work is structured into 5 areas of expertise: Molecular Diagnostics, Learning & Teaching, Quality & Management, Laboratory & Diagnostics and Biobanks & Informatics. The areas of expertise are in turn subdivided into divisions. About the history of the establishment of this new structure within the DGKL you can find information in the editorial of this issue.
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- 2024
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3. Moving Forward on Tumor Pathology Research Reporting: A Guide for Pathologists From the World Health Organization Classification of Tumors Living Evidence Gap Map by Tumour Type Group
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Colling, Richard, Indave, Iciar, Del Aguilla, Javier, Cierco Jimenez, Ramon, Campbell, Fiona, Chechlinska, Magdalena, Kowalewska, Magdalena, Holdenrieder, Stefan, Trulson, Inga, Worf, Karolina, Pollán, Marina, Plans-Beriso, Elena, Pérez-Gómez, Beatriz, Craciun, Oana, García-Ovejero, Ester, Michalek, Irmina Maria, Maslova, Kateryna, Rymkiewicz, Grzegorz, Didkowska, Joanna, Tan, Puay Hoon, Diyana Bte MD Nasir, Nur, Myles, Nickolas, Giesen, Christine, Goldman-Lévy, Gabrielle, Lokuhetty, Dilani, and Cree, Ian A.
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- 2024
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4. Quantification of ventricular stress in univentricular hearts during early childhood using age-independent zlog-NT-proBNP
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Palm, Jonas, Ono, Masamichi, Niedermaier, Carolin, Hörer, Jürgen, Hoffmann, Georg, Holdenrieder, Stefan, Klawonn, Frank, and Ewert, Peter
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- 2024
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5. Systemic inflammatory response syndrome in patients undergoing transcatheter aortic valve implantation
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Syryca, Finn, Pellegrini, Costanza, Rheude, Tobias, Zobel, Florian, Kornhuber, Katharina, Xhepa, Erion, Mayr, N. Patrick, Alvarez-Covarrubias, Hector A., Holdenrieder, Stefan, Schunkert, Heribert, Thilo, Christian, Kastrati, Adnan, and Joner, Michael
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- 2024
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6. A New Hierarchy of Research Evidence for Tumor Pathology: A Delphi Study to Define Levels of Evidence in Tumor Pathology
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Colling, Richard, Indave, Iciar, del Aguila, Javier, Jimenez, Ramon Cierco, Campbell, Fiona, Chechlińska, Magdalena, Kowalewska, Magdalena, Holdenrieder, Stefan, Trulson, Inga, Worf, Karolina, Pollán, Marina, Plans-Beriso, Elena, Pérez-Gómez, Beatriz, Craciun, Oana, García-Ovejero, Ester, Michałek, Irmina Maria, Maslova, Kateryna, Rymkiewicz, Grzegorz, Didkowska, Joanna, Tan, Puay Hoon, Md Nasir, Nur Diyana, Myles, Nickolas, Goldman-Lévy, Gabrielle, Lokuhetty, Dilani, and Cree, Ian A.
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- 2024
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7. External quality assessment-based tumor marker harmonization simulation; insights in achievable harmonization for CA 15-3 and CEA.
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Van Rossum, Huub H., Holdenrieder, Stefan, Yun, Yeo-Min, Patel, Dina, Thelen, Marc, Song, Junghan, Unsworth, Nick, Partridge, Katherine, Moore, Melanie, Cui, Wei, Ramanathan, Lakshmi, Meng, Qing H., Ballieux, Bart E.P.B., Sturgeon, Catharine, and Vesper, Hubert
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TUMOR markers , *COLORECTAL cancer , *BREAST cancer , *CLINICAL medicine , *CANCER treatment - Abstract
CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an
in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples.CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020–2021) and KEQAS (2020–2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%).Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from −29.28 to 9.86 %, into −0.09–0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from −23.78 to 2.00 % pre-harmonization to −3.13–1.42 % post-harmonization.The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs. [ABSTRACT FROM AUTHOR]- Published
- 2024
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8. A Novel Tool for the Rapid and Transparent Verification of Reference Intervals in Clinical Laboratories.
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Hoffmann, Georg, Klawitter, Sandra, Trulson, Inga, Adler, Jakob, Holdenrieder, Stefan, and Klawonn, Frank
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COLOR codes ,RAPID tooling ,INTEGRATED software ,PATHOLOGICAL laboratories ,EXTRAPOLATION - Abstract
Background/Objectives: We present a software package called reflimR (Version 1.0.6), which enables rapid and transparent verification of reference intervals from routine laboratory measurements. Our method makes it easy to compare the results with specified target values and facilitates the interpretation of deviations using traffic light colors. Methods: The algorithm includes three procedural steps: (a) definition of an appropriate distribution model, based on Bowley's quartile skewness, (b) iterative truncation, based on a modified boxplot method to obtain the central 95% of presumably inconspicuous results, and (c) extrapolation of reference limits from a truncated normal quantile–quantile plot. Results: All algorithms have been combined into one consolidated library, which can be called in the R environment with a single command reflim (x). Using an example dataset included in the package, we demonstrate that our method can be applied to mixed data containing a substantial proportion of pathological values. It leads to similar results as the direct guideline approach as well as the more sophisticated indirect refineR software package. As compared to the latter, reflimR works much faster and needs smaller datasets for robust estimates. For the interpretation of the results, we present an intuitive color scheme based on tolerance ranges (permissible uncertainty of laboratory results). We show that a relatively high number of published reference limits require careful reevaluation. Conclusions: The reflimR package closes the gap between direct guideline methods and the more sophisticated indirect refineR method. We recommend reflimR for the rapid routine verification of large amounts of reference limits and refineR for a careful analysis of unclear or doubtful results from this check. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Longitudinal evaluation of external quality assessment results for CA 15-3, CA 19-9, and CA 125.
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Kremser, Marcel, Weiss, Nathalie, Kaufmann-Stoeck, Anne, Vierbaum, Laura, Schmitz, Arthur, Schellenberg, Ingo, and Holdenrieder, Stefan
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- 2024
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10. Personalisierte Medizin.
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Renz, Bernhard W., Holdenrieder, Stefan, and Angele, Martin K.
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CIRCULATING tumor DNA , *COLORECTAL cancer , *BLOOD testing , *BIOPSY , *THERAPEUTICS - Abstract
The article discusses the use of circulating tumor DNA (ctDNA) in blood tests to improve the personalized treatment of colorectal cancer by providing more accurate prognosis and monitoring therapy response, especially in early-stage disease detection and post-operative care. It highlights the role of ctDNA in liquid biopsies and its potential for revolutionizing cancer management by predicting treatment outcomes and identifying minimal residual disease.
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- 2024
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11. Investigating the Current Harmonization Status of Tumor Markers Using Global External Quality Assessment Programs: A Feasibility Study.
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Rossum, Huub H van, Holdenrieder, Stefan, Ballieux, Bart E P B, Badrick, Tony C, Yun, Yeo-Min, Zhang, Chuanbao, Patel, Dina, Thelen, Marc, Song, Junghan, Wojtalewicz, Nathalie, Unsworth, Nick, Vesper, Hubert W, Cui, Wei, Ramanathan, Lakshmi V, Sturgeon, Catharine, and Meng, Qing H
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- 2024
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12. Plasma Soluble Glycoprotein VI, Platelet Function, Bleeding, and Ischemic Events in Patients Undergoing Elective Percutaneous Coronary Intervention.
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Lahu, Shqipdona, Adler, Kristin, Mayer, Katharina, Hein-Rothweiler, Ralph, Bernlochner, Isabell, Ndrepepa, Gjin, Schüpke, Stefanie, Holdenrieder, Stefan, Bongiovanni, Dario, Laugwitz, Karl-Ludwig, Schunkert, Heribert, Gawaz, Meinrad, Massberg, Steffen, Kastrati, Adnan, and Münch, Götz
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- 2024
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13. PATHFINDER-CHD: prospective registry on adults with congenital heart disease, abnormal ventricular function, and/or heart failure as a foundation for establishing rehabilitative, prehabilitative, preventive, and health-promoting measures: rationale, aims, design and methods
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Freilinger, Sebastian, Kaemmerer, Harald, Pittrow, Robert D., Achenbach, Stefan, Baldus, Stefan, Dewald, Oliver, Ewert, Peter, Freiberger, Annika, Gorenflo, Matthias, Harig, Frank, Hohmann, Christopher, Holdenrieder, Stefan, Hörer, Jürgen, Huntgeburth, Michael, Hübler, Michael, Kohls, Niko, Klawonn, Frank, Kozlik-Feldmann, Rainer, Kaulitz, Renate, and Loßnitzer, Dirk
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HEART failure ,CONGENITAL heart disease ,HEART assist devices ,CARDIAC pacemakers ,MEDICALLY underserved persons ,ADULTS ,THERAPEUTICS ,TRANSPLANTATION of organs, tissues, etc. - Abstract
Background: Adults with congenital heart defects (ACHD) globally constitute a notably medically underserved patient population. Despite therapeutic advancements, these individuals often confront substantial physical and psychosocial residua or sequelae, requiring specialized, integrative cardiological care throughout their lifespan. Heart failure (HF) is a critical challenge in this population, markedly impacting morbidity and mortality. Aims: The primary aim of this study is to establish a comprehensive, prospective registry to enhance understanding and management of HF in ACHD. Named PATHFINDER-CHD, this registry aims to establish foundational data for treatment strategies as well as the development of rehabilitative, prehabilitative, preventive, and health-promoting interventions, ultimately aiming to mitigate the elevated morbidity and mortality rates associated with congenital heart defects (CHD). Methods: This multicenter survey will be conducted across various German university facilities with expertise in ACHD. Data collection will encompass real-world treatment scenarios and clinical trajectories in ACHD with manifest HF or at risk for its development, including those undergoing medical or interventional cardiac therapies, cardiac surgery, inclusive of pacemaker or ICD implantation, resynchronization therapy, assist devices, and those on solid organ transplantation. Design: The study adopts an observational, exploratory design, prospectively gathering data from participating centers, with a focus on patient management and outcomes. The study is non-confirmatory, aiming to accumulate a broad spectrum of data to inform future hypotheses and studies. Processes: Regular follow-ups will be conducted, systematically collecting data during routine clinical visits or hospital admissions, encompassing alterations in therapy or CHD-related complications, with visit schedules tailored to individual clinical needs. Assessments: Baseline assessments and regular follow-ups will entail comprehensive assessments of medical history, ongoing treatments, and outcomes, with a focus on HF symptoms, cardiac function, and overall health status. Discussion of the design: The design of the PATHFINDER-CHD Registry is tailored to capture a wide range of data, prioritizing real-world HF management in ACHD. Its prospective nature facilitates longitudinal data acquisition, pivotal for comprehending for disease progression and treatment impacts. Conclusion: The PATHFINDER-CHD Registry is poised to offer valuable insights into HF management in ACHD, bridging current knowledge gaps, enhancing patient care, and shaping future research endeavors in this domain. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Targeted Sequencing of Human Satellite 2 Repeat Sequences in Plasma cfDNA Reveals Potential Breast Cancer Biomarkers.
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Gezer, Ugur, Oberhofer, Angela, Worf, Karolina, Stoetzer, Oliver, Holdenrieder, Stefan, and Bronkhorst, Abel
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TUMOR markers ,CELL-free DNA ,BREAST cancer ,NUCLEOTIDE sequence ,CANCER patients ,FACIOSCAPULOHUMERAL muscular dystrophy - Abstract
Liquid biopsies are revolutionizing the detection and management of malignant diseases. While repetitive DNA sequences, such as LINE-1 and ALU are established in cell-free DNA (cfDNA) research, their clinical applications remain limited. In this study, we explore human satellite 2 (HSATII), a prevalent repeat DNA sequence in plasma that exhibits increased levels in cancer patients, thereby positioning it as a potential pan-cancer biomarker. We employed targeted sequencing and copy number variation (CNV) analysis using two primer pairs to assess the differential abundance of HSATII sequences in the plasma of breast cancer patients compared to healthy individuals. PCR amplicons of HSATII from 10 patients and 10 control subjects were sequenced, generating 151 bp paired-end reads. By constructing a pooled reference dataset, HSATII copy ratios were estimated in the patients. Our analysis revealed several significant CNVs in HSATII, with certain sequences displaying notable gains and losses across all breast cancer patients, suggesting their potential as biomarkers. However, we observed pronounced fragmentation of cfDNA in cancer, leading to the loss of longer PCR amplicons (>180 bp). While not all observed losses can be attributed to fragmentation artifacts, this phenomenon does introduce complexity in interpreting CNV data. Notably, this research marks the first instance of targeted HSATII sequencing in a liquid biopsy context. Our findings lay the groundwork for developing sequencing-based assays to detect differentially represented HSATII sequences, potentially advancing the field of minimally-invasive cancer screening. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Influence of a 7‐day Transalpine Trail Run on cardiac biomarkers and myocardial function.
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Esefeld, Katrin, Geisberger, Marisa, Dinges, Sophia Marie‐Theres, Hambrecht, Johanna, Stegmüller, Felix, Rasper, Michael, Nadjiri, Jonathan, Roeschenthaler, Franz, Holdenrieder, Stefan, Scharhag, Jürgen, and Halle, Martin
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TROPONIN ,PEARSON correlation (Statistics) ,LONG-distance running ,DATA analysis ,RUNNING ,SCIENTIFIC observation ,PILOT projects ,BLOOD collection ,DYNAMICS ,PEPTIDE hormones ,MAGNETIC resonance imaging ,DESCRIPTIVE statistics ,MYOCARDIAL injury ,LONGITUDINAL method ,ATHLETES ,HEART beat ,MYOCARDIUM ,PHYSICAL fitness ,STATISTICS ,SYSTOLIC blood pressure ,HEALTH outcome assessment ,DATA analysis software ,CONFIDENCE intervals ,BIOMARKERS ,TIME ,ECHOCARDIOGRAPHY - Abstract
Intense physical exercise is known to increase cardiac biomarkers; however, it is unclear, whether this phenomenon is physiological, or if it indicates myocardial tissue injury. The aim of our study was to investigate the effects of seven consecutive days of excessive endurance exercise on continuous assessment of cardiac biomarkers, function, and tissue injury. During a 7‐day trail‐running competition (Transalpine Run, distance 267.4 km, altitude ascent/descent 15556/14450 m), daily blood samples were obtained for cardiac biomarkers (hs‐TnT, NT‐proBNP, and suppression of tumorigenicity‐2 protein (ST2)) at baseline, after each stage and 24–48 h post‐race. In addition, echocardiography was performed every second day, cardiac magnetic resonance imaging (CMR) before (n = 7) and after (n = 16) the race. Twelve (eight males) out of 17 healthy athletes finished all seven stages (average total finish time: 43 ± 8 h). Only NT‐proBNP increased significantly (3.6‐fold, p = 0.009) during the first stage and continued to increase during the race. Hs‐TnT revealed an incremental trend during the first day (2.7‐fold increase, p = 0.098) and remained within the pathological range throughout the race. ST2 levels did not change during the race. All cardiac biomarkers completely returned to physiological levels post‐race. NT‐proBNP kinetics correlated significantly with mild transient reductions in right ventricular function (assessed by TAPSE, tricuspid annular plane systolic function; r = −0.716; p = 0.014). No significant echocardiographic changes in LV dimensions, LV function, or relevant alterations in CMR were observed post‐race. In summary, this study shows that prolonged, repetitive, high‐volume exercise induced a transient, significant increase in NT‐proBNP associated with right ventricular dysfunction without corresponding left ventricular functional or structural impairment. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Bioactive adrenomedullin (bio-ADM) is associated with endothelial dysfunction in infants and children with complex congenital heart disease undergoing open-heart surgery on cardiopulmonary bypass.
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Schaefer, Maike, Stein, Andreas, Ruf, Bettina, Balling, Gunter, Palm, Jonas, Simmelbauer, Andreas, Cleuziou, Julie, Sander, Michaela, Auer, Josef, Borgmann, Kristina, Struck, Joachim, Hartmann, Oliver, Schulte, Janin, Hörer, Jürgen, Tassani-Prell, Peter, Ewert, Peter, Holdenrieder, Stefan, and Wolf, Cordula M.
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CONGENITAL heart disease ,CARDIOPULMONARY bypass ,ENDOTHELIUM diseases ,CARDIAC surgery ,ADRENOMEDULLIN ,CHILD patients - Abstract
Children with congenital heart disease (CHD) undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at risk for systemic inflammation leading to endothelial dysfunction associated with increased morbidity. Bioactive adrenomedullin (bio-ADM) is a peptide regulating vascular tone and endothelial permeability. The aim of this study was to evaluate the dynamics of plasma bio-ADM in this patient cohort and its role in capillary leak. Plasma samples from 73 pediatric CHD patients were collected for bio-ADM measurement at five different timepoints (TP) in the pre-, intra-, and post-operative period. The primary endpoint was a net increase in bio-ADM levels after surgery on CPB. Secondary endpoints included association of bio-ADM levels with clinical signs for endothelial dysfunction. Bio-ADM levels increased after surgery on CPB from pre-operative median of 12 pg/mL (IQR [interquartile range] 12.0–14.8 pg/mL) to a maximum post-operative median of 48.8 pg/mL (IQR 34.5–69.6 pg/mL, p<0.001). Bio-ADM concentrations correlated positively with post-operative volume balance, (r=0.341; p=0.005), increased demand for vasoactive medication (duration: r=0.415; p<0.001; quantity: TP3: r=0.415, p<0.001; TP4: r=0.414, p<0.001), and hydrocortisone treatment for vasoplegia (bio-ADM median [IQR]:129.1 [55.4–139.2] pg/mL vs. 37.9 [25.2–64.6] pg/mL; p=0.034). Patients who required pleural effusion drainage revealed higher bio-ADM levels compared to those who did not (median [IQR]: 66.4 [55.4–90.9] pg/mL vs. 40.2 [28.2–57.0] pg/mL; p<0.001). Bio-ADM is elevated in children after cardiac surgery and higher levels correlate with clinical signs of capillary leakage. The peptide should be considered as biomarker for endothelial dysfunction and as potential therapeutic target in this indication. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Clinical and laboratory considerations: determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19.
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Holdenrieder, Stefan, Dos Santos Ferreira, Carlos Eduardo, Izopet, Jacques, Theel, Elitza S., and Wieser, Andreas
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- 2024
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18. Prognostic value of tumor markers ProGRP, NSE and CYFRA 21-1 in patients with small cell lung cancer and chemotherapy-induced remission.
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Muley, Thomas, Herth, Felix J., Heussel, Claus Peter, Kriegsmann, Mark, Thomas, Michael, Meister, Michael, Schneider, Marc A., Wehnl, Birgit, Mang, Anika, and Holdenrieder, Stefan
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SMALL cell lung cancer ,PROGNOSIS ,TUMOR markers ,CANCER remission ,OVERALL survival - Abstract
BACKGROUND: Despite successful response to first line therapy, patients with small-cell lung cancer (SCLC) often suffer from early relapses and disease progression. OBJECTIVE: To investigate the relevance of serum tumor markers for estimation of prognosis at several time points during the course of disease. METHODS: In a prospective, single-center study, serial assessments of progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1) and carcino-embryogenic antigen (CEA) were performed during and after chemotherapy in 232 SCLC patients, and correlated with therapy response and overall survival (OS). RESULTS: ProGRP, NSE and CYFRA 21-1 levels decreased quickly after the first chemotherapy cycle and correlated well with the radiological response. Either as single markers or in combination they provided valuable prognostic information regarding OS at all timepoints investigated: prior to first-line therapy, after two treatment cycles in patients with successful response to first-line therapy, and prior to the start of second-line therapy. Furthermore, they were useful for continuous monitoring during and after therapy and often indicated progressive disease several months ahead of radiological changes. CONCLUSIONS: The results indicate the great potential of ProGRP, NSE and CYFRA 21-1 for estimating prognosis and monitoring of SCLC patients throughout the course of the disease. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Lack of clinical utility of serum macrophage migration inhibitory factor (MIF) for monitoring therapy response and estimating prognosis in advanced lung cancer.
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Rupp, Alexander, Bahlmann, Sophie, Trimpop, Nicolai, von Pawel, Joachim, and Holdenrieder, Stefan
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MACROPHAGE migration inhibitory factor ,LUNG cancer ,TREATMENT effectiveness ,NON-small-cell lung carcinoma ,ENZYME-linked immunosorbent assay - Abstract
BACKGROUND: Lung cancer is a major burden to global health and is still among the most frequent and most lethal malignant diseases. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in a variety of processes including tumorigenesis, formation of a tumor microenvironment and metastasis. It is therefore a potential prognostic biomarker in malignant diseases. OBJECTIVE: In this study, we investigated the applicability of MIF in serum samples as a biomarker in lung cancer. METHODS: In a retrospective approach, we analyzed the sera of 79 patients with non-small-cell lung cancer (NSCLC) and 14 patients with small-cell lung cancer (SCLC) before the start of chemotherapy, as well as before the second and third chemotherapy cycle, respectively. Serum MIF levels were measured using a sandwich immunoassay with a sulfo-tag-labelled detection antibody, while pro-gastrin releasing peptide (proGRP) levels were determined with an enzyme-linked immunosorbent assay. RESULTS: No difference in serum MIF levels between responders and non-responders to chemotherapy was observed at all time points, while proGRP levels were significantly lower in responders before the second chemotherapy cycle (p = 0.012). No differences in biomarker levels depending on the histopathological classification of NSCLC patients was found. Moreover, in ROC curve analyses MIF was not able to distinguish between responders and non-responders to therapy. proGRP could differentiate between responders and non-responders before the second chemotherapy cycle (p = 0.015) with sensitivities of 43% at 90% and 95% specificity, respectively. Likewise, proGRP yielded significantly longer survival times of patients with low proGRP concentrations before the second chemotherapy cycle (p = 0.015) in Kaplan-Meier analyses, yet MIF showed no significant differences in survival times at all time points. Comparison with the biomarkers CEA and CYFRA 21-1 in the same cohort showed that these established biomarkers clearly performed superior to MIF and proGRP. CONCLUSIONS: From the present results, there is no indication that serum MIF may serve as a biomarker in prognosis and monitoring of response to therapy in lung cancer. Limitations of this study include its retrospective design, the inclusion of a larger NSCLC and a smaller SCLC subgroup, the classical chemotherapeutic treatment, the use of a non-diagnostic immunoassay (RUO-test) for MIF measurement and the lack of a validation cohort. Strengths of the study are its highly standardized procedures concerning sample collection, preanalytic treatment, measurements and quality control of the laboratory assays. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Lung cancer tumor marker analysis: A clinical laboratory perspective.
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van Rossum, Huub H. and Holdenrieder, Stefan
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TUMOR markers ,LUNG cancer ,PATHOLOGICAL laboratories ,LUNG tumors ,BIOMARKERS - Abstract
Clinical laboratories are responsible for performing lung cancer tumor marker testing as part of routine clinical care. It is their responsibility to guarantee that the reported tumor marker results are reliable and meet the necessary quality standards for proper clinical use. During the different laboratory phases, pre-analytical, analytical and post-analytical, specific steps and processes can introduce errors and generate incorrect clinical interpretation. This editorial briefly outlines critical laboratory issues related to lung cancer tumor markers, specific for each of these three laboratory phases. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Lung cancer biomarkers: Raising the clinical value of the classical and the new ones.
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Holdenrieder, Stefan, van Rossum, Huub H., and van den Heuvel, Michel
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TUMOR markers ,LUNG cancer ,CIRCULATING tumor DNA ,BIOMARKERS ,COMPANION diagnostics - Abstract
Blood-based diagnostics for lung cancer support the diagnosis, estimation of prognosis, prediction, and monitoring of therapy response in lung cancer patients. The clinical utility of serum tumor markers has considerably increased due to developments in serum protein tumor markers analytics and clinical biomarker studies, the exploration of preanalytical and influencing conditions, the interpretation of biomarker combinations and individual biomarker kinetics, as well as the implementation of biostatistical models. In addition, circulating tumor DNA (ctDNA) and other liquid biopsy markers are playing an increasingly prominent role in the molecular tumor characterization and the monitoring of tumor evolution over time. Thus, modern lung cancer biomarkers may considerably contribute to an individualized companion diagnostics and provide a sensitive guidance for patients throughout the course of their disease. In this special edition on Tumor Markers in Lung Cancer, experts summarize recent developments in clinical laboratory diagnostics of lung cancer and give an outlook on future challenges and opportunities. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Improvement of differential diagnosis of lung cancer by use of multiple protein tumor marker combinations.
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Trulson, Inga, Klawonn, Frank, von Pawel, Joachim, and Holdenrieder, Stefan
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SMALL cell lung cancer ,LUNG cancer ,TUMOR markers ,NON-small-cell lung carcinoma ,TUMOR proteins - Abstract
BACKGROUND: Differential diagnosis of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in hospitalized patients is crucial for appropriate treatment choice. OBJECTIVE: To investigate the relevance of serum tumor markers (STMs) and their combinations for the differentiation of NSCLC and SCLC subtypes. METHODS: Between 2000 and 2003, 10 established STMs were assessed retrospectively in 311 patients with NSCLC, 128 with SCLC prior systemic first-line therapy and 51 controls with benign lung diseases (BLD), by automatized electrochemiluminescence immunoassay technology. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic efficacy of both individual and multiple STMs with corresponding sensitivities at 90% specificity. Standards for Reporting of Diagnostic Accuracy (STARD guidelines) were followed. RESULTS: CYFRA 21-1 (cytokeratin-19 fragment), CEA (carcinoembryonic antigen) and NSE (neuron specific enolase) were significantly higher in all lung cancers vs BLD, reaching AUCs of 0.81 (95% CI 0.76–0.87), 0.78 (0.73–0.84), and 0.88 (0.84–0.93), respectively. By the three marker combination, the discrimination between benign and all malignant cases was improved resulting in an AUC of 0.93 (95% CI 0.90–0.96). In NSCLC vs. BLD, CYFRA 21-1, CEA and NSE were best discriminative STMs, with AUCs of 0.86 (95% CI 0.81–0.91), 0.80 (0.74–0.85), and 0.85 (0.79–0.91). The three marker combination also improved the AUC: 0.92; 95% CI 0.89–0.96). In SCLC vs. BLD, ProGRP (pro-gastrin-releasing peptide) and NSE were best discriminative STMs, with AUCs of 0.89 (95% CI 0.84–0.94) and 0.96 (0.93–0.98), respectively, and slightly improved AUC of 0.97 (95% CI 0.95–0.99) when in combination. Finally, discrimination between SCLC and NSCLC was possible by ProGRP (AUC 0.86; 95% CI 0.81–0.91), NSE (AUC 0.83; 0.78–0.88) and CYFRA 21-1 (AUC 0.69; 0.64–0.75) and by the combination of the 3 STMs (AUC 0.93; 0.91–0.96), with a sensitivity of 88% at 90% specificity. CONCLUSIONS: The results confirm the power of STM combinations for the differential diagnosis of lung cancer from benign lesions and between histological lung cancer subtypes. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Missing prognostic value of soluble PD-1, PD-L1 and PD-L2 in lung cancer patients undergoing chemotherapy – A CEPAC-TDM biomarker substudy.
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Geiger, Kimberly, Joerger, Markus, Roessler, Max, Hettwer, Karina, Ritter, Christoph, Simon, Kirsten, Uhlig, Steffen, and Holdenrieder, Stefan
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PROGNOSIS ,PROGRAMMED cell death 1 receptors ,PROGRAMMED death-ligand 1 ,LUNG cancer ,APOPTOSIS ,MOVEMENT disorders - Abstract
BACKGROUND: Programmed cell death receptors and ligands in cancer tissue samples are established companion diagnostics for immune checkpoint inhibitor (ICI) therapies. OBJECTIVE: To investigate the relevance of soluble PD-1, PD-L1 and PD-L2 for estimating therapy response and prognosis in non-small cell lung cancer patients (NSCLC) undergoing platin-based combination chemotherapies. METHODS: In a biomarker substudy of a prospective, multicentric clinical trial (CEPAC-TDM) on advanced NSCLC patients, soluble PD-1, PD-L1 and PD-L2 were assessed in serial serum samples by highly sensitive enzyme-linked immunosorbent assays and correlated with radiological response after two cycles of chemotherapy and with overall survival (OS). RESULTS: Among 243 NSCLC patients, 185 achieved response (partial remission and stable disease) and 58 non-response (progression). The distribution of PD-1, PD-L1 and PD-L2 at baseline (C1), prior to staging (C3) and the relative changes (C3/C1) greatly overlapped between the patient groups with response and non-response, thus hindering the discrimination between the two groups. None of the PD markers had prognostic value regarding OS. CONCLUSIONS: Neither soluble PD-1, PD-L1 nor PD-L2 did provide clinical utility for predicting response to chemotherapy and prognosis. Studies on the relevance of PD markers in ICI therapies are warranted. [ABSTRACT FROM AUTHOR]
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- 2024
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24. A pocket companion to cell-free DNA (cfDNA) preanalytics.
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Bronkhorst, Abel J. and Holdenrieder, Stefan
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CELL-free DNA ,MACHINE learning ,INDIVIDUALIZED medicine ,CIRCULATING tumor DNA - Abstract
The cumulative pool of cell-free DNA (cfDNA) molecules within bodily fluids represents a highly dense and multidimensional information repository. This "biological mirror" provides real-time insights into the composition, function, and dynamics of the diverse genomes within the body, enabling significant advancements in personalized molecular medicine. However, effective use of this information necessitates meticulous classification of distinct cfDNA subtypes with exceptional precision. While cfDNA molecules originating from different sources exhibit numerous genetic, epigenetic, and physico-chemical variations, they also share common features that complicate analyses. Considerable progress has been achieved in mapping the landscape of cfDNA features, their clinical correlations, and optimizing extraction procedures, analytical approaches, bioinformatics pipelines, and machine learning algorithms. Nevertheless, preanalytical workflows, despite their profound impact on cfDNA measurements, have not progressed at a corresponding pace. In this perspective article, we emphasize the pivotal role of robust preanalytical procedures in the development and clinical integration of cfDNA assays, highlighting persistent obstacles and emerging challenges. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Relevance of tumor markers for prognosis and predicting therapy response in non-small cell lung cancer patients: A CEPAC-TDM biomarker substudy.
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Geiger, Kimberly, Joerger, Markus, Roessler, Max, Hettwer, Karina, Ritter, Christoph, Simon, Kirsten, Uhlig, Steffen, and Holdenrieder, Stefan
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NON-small-cell lung carcinoma ,TUMOR markers ,CANCER patients ,TREATMENT effectiveness ,BIOMARKERS - Abstract
BACKGROUND: Protein tumor markers are released in high amounts into the blood in advanced non-small cell lung cancer (NSCLC). OBJECTIVE: To investigate the relevance of serum tumor markers (STM) for prognosis, prediction and monitoring of therapy response in NSCLC patients receiving chemotherapy. METHODS: In a biomarker substudy of a prospective, multicentric clinical trial (CEPAC-TDM) on 261 advanced NSCLC patients, CYFRA 21-1, CEA, SCC, NSE, ProGRP, CA125, CA15-3 and HE4 were assessed in serial serum samples and correlated with radiological response after two cycles of chemotherapy and overall (OS) and progression-free survival (PFS). RESULTS: While pretherapeutic STM levels at staging did not discriminate between progressive and non-progressive patients, CYFRA 21-1, CA125, NSE and SCC at time of staging did, and yielded AUCs of 0.75, 0.70, 0.69 and 0.67 in ROC curves, respectively. High pretherapeutic CA15-3 and CA125 as well as high CYFRA 21-1, SCC, CA125 and CA15-3 levels at staging were prognostic for shorter PFS and OS –also when clinical variables were added to the models. CONCLUSIONS: STM at the time of first radiological staging and pretherapeutic CA15-3, CA125 are predictive for first-line treatment response and highly prognostic in patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Prognostic value of blood-based protein biomarkers in non-small cell lung cancer: A critical review and 2008–2022 update.
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Trulson, Inga and Holdenrieder, Stefan
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NON-small-cell lung carcinoma ,PROGNOSIS ,SQUAMOUS cell carcinoma ,TUMOR markers ,BIOMARKERS - Abstract
BACKGROUND: Therapeutic possibilities for non-small cell lung cancer (NSCLC) have considerably increased during recent decades. OBJECTIVE: To summarize the prognostic relevance of serum tumor markers (STM) for early and late-stage NSCLC patients treated with classical chemotherapies, novel targeted and immune therapies. METHODS: A PubMed database search was conducted for prognostic studies on carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase, squamous-cell carcinoma antigen, progastrin-releasing-peptide, CA125, CA 19-9 and CA 15-3 STMs in NSCLC patients published from 2008 until June 2022. RESULTS: Out of 1069 studies, 141 were identified as meeting the inclusion criteria. A considerable heterogeneity regarding design, patient number, analytical and statistical methods was observed. High pretherapeutic CYFRA 21-1 levels and insufficient decreases indicated unfavorable prognosis in many studies on NSCLC patients treated with chemo-, targeted and immunotherapies or their combinations in early and advanced stages. Similar results were seen for CEA in chemotherapy, however, high pretherapeutic levels were sometimes favorable in targeted therapies. CA125 is a promising prognostic marker in patients treated with immunotherapies. Combinations of STMs further increased the prognostic value over single markers. CONCLUSION: Protein STMs, especially CYFRA 21-1, have prognostic potential in early and advanced stage NSCLC. For future STM investigations, better adherence to comparable study designs, analytical methods, outcome measures and statistical evaluation standards is recommended. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Serum tumor markers for response prediction and monitoring of advanced lung cancer: A review focusing on immunotherapy and targeted therapies.
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van den Heuvel, Michel, Holdenrieder, Stefan, Schuurbiers, Milou, Cigoianu, Daniel, Trulson, Inga, van Rossum, Huub, and Lang, David
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BIOMARKERS ,TUMOR markers ,LUNG cancer ,CANCER patients ,SMALL cell lung cancer - Abstract
BACKGROUND: The value of serum tumor markers (STMs) in the current therapeutic landscape of lung cancer is unclear. OBJECTIVE: This scoping review gathered evidence of the predictive, prognostic, and monitoring value of STMs for patients with advanced lung cancer receiving immunotherapy (IT) or targeted therapy (TT). METHODS: Literature searches were conducted (cut-off: May 2022) using PubMed and Cochrane CENTRAL databases. Medical professionals advised on the search strategies. RESULTS: Study heterogeneity limited the evidence and inferences from the 36 publications reviewed. While increased baseline levels of serum cytokeratin 19 fragment antigen (CYFRA21-1) and carcinoembryonic antigen (CEA) may predict IT response, results for TT were less clear. For monitoring IT-treated patients, STM panels (including CYFRA21-1, CEA, and neuron-specific enolase) may surpass the power of single analyses to predict non-response. CYFRA21-1 measurement could aid in monitoring TT-treated patients, but the value of CEA in this context requires further investigation. Overall, baseline and dynamic changes in individual or combined STM levels have potential utility to predict treatment outcome and for monitoring of patients with advanced lung cancer. CONCLUSIONS: In advanced lung cancer, STMs provide additional relevant clinical information by predicting treatment outcome, but further standardization and validation is warranted. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Combined use of CYFRA 21-1 and CA 125 predicts survival of patients with metastatic NSCLC and stable disease in IMpower150.
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Mang, Anika, Zou, Wei, Rolny, Vinzent, Reck, Martin, Cigoianu, Daniel, Schulze, Katja, Holdenrieder, Stefan, Socinski, Mark A., Shames, David S., Wehnl, Birgit, and Patil, Namrata S.
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OVERALL survival ,NON-small-cell lung carcinoma ,TUMOR markers - Abstract
BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and stable disease (SD) have an unmet clinical need to help guide early treatment adjustments. OBJECTIVE: To evaluate the potential of tumor biomarkers to inform on survival outcomes in NSCLC SD patients. METHODS: This post hoc analysis included 480 patients from the IMpower150 study with metastatic NSCLC, treated with chemotherapy, atezolizumab and bevacizumab combinations, who had SD at first CT scan (post-treatment initiation). Patients were stratified into high- and low-risk groups (overall survival [OS] and progression-free survival [PFS] outcomes) based on serum tumor biomarker levels. RESULTS: The CYFRA 21-1 and CA 125 biomarker combination predicted OS and PFS in patients with SD. Risk of death was ~4-fold higher for the biomarker-stratified high-risk versus low-risk SD patients (hazard ratio [HR] 3.80; 95% confidence interval [CI] 3.02–4.78; p < 0.0001). OS in patients with the low- and high-risk SD was comparable to that in patients with the CT-defined partial response (PR; HR 1.10; 95% CI 0.898–1.34) and progressive disease (PD) (HR 1.05; 95% CI 0.621–1.77), respectively. The findings were similar with PFS, and consistent across treatment arms. CONCLUSIONS: Biomarker testing shows potential for providing prognostic information to help direct treatment in NSCLC patients with SD. Prospective clinical studies are warranted. ClinicalTrials.gov: NCT02366143 [ABSTRACT FROM AUTHOR]
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- 2024
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29. CYFRA 21-1, CA 125 and CEA provide additional prognostic value in NSCLC patients with stable disease at first CT scan.
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Muley, Thomas, Schneider, Mark A., Meister, Michael, Thomas, Michael, Heußel, Claus Peter, Kriegsmann, Mark, Holdenrieder, Stefan, Wehnl, Birgit, Rolny, Vinzent, Mang, Anika, Gerber, Rebecca, and Herth, Felix
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COMPUTED tomography ,PROGNOSIS ,NON-small-cell lung carcinoma ,IMMUNE checkpoint inhibitors ,PROTEIN-tyrosine kinase inhibitors - Abstract
BACKGROUND: Serum tumor markers (STM) may complement imaging and provide additional clinical information for patients with non-small cell lung cancer (NSCLC). OBJECTIVE: To determine whether STMs can predict outcomes in patients with stable disease (SD) after initial treatment. METHODS: This single-center, prospective, observational trial enrolled 395 patients with stage III/IV treatment-naïve NSCLC; of which 263 patients were included in this analysis. Computed Tomography (CT) scans were performed and STMs measured before and after initial treatment (two cycles of chemotherapy and/or an immune checkpoint inhibitor or tyrosine kinase inhibitor); analyses were based on CT and STM measurements obtained at first CT performed after cycle 2 only PFS and OS were analyzed by Kaplan-Meier curves and Cox-proportional hazard models. RESULTS: When patients with SD (n = 100) were split into high- and low-risk groups based on CYFRA 21-1, CEA and CA 125 measurements using an optimized cut-off, a 4-fold increase risk of progression or death was estimated for high- vs low-risk SD patients (PFS, HR 4.17; OS, 3.99; both p < 0.0001). Outcomes were similar between patients with high-risk SD or progressive disease (n = 35) (OS, HR 1.17) and between patients with low-risk SD or partial response (n = 128) (PFS, HR 0.98; OS, 1.14). CONCLUSIONS: STMs can provide further guidance in patients with indeterminate CT responses by separating them into high- and low-risk groups for future PFS and OS events. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Auf die Datenaufbereitung kommt es an.
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Trulson, Inga, Klawonn, Frank, Holdenrieder, Stefan, and Hoffmann, Georg
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MACHINE learning ,CLINICAL pathology ,ARTIFICIAL intelligence in medicine ,ONCOLOGY ,DIAGNOSIS - Abstract
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- 2024
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