Katerina Kopeckova
@fnmotol.cz
Dept. of Oncology
Motol University Hospital
RESEARCH INTERESTS
Rare cancer- lymphoma, thyroid cancer, sarcoma , immunooncology
Scopus Publications
Scopus Publications
Iva Benesova, Linda Capkova, Andrej Ozaniak, Pavel Pacas, Katerina Kopeckova, Dominika Galova, Robert Lischke, Tomas Buchler, and Zuzana Ozaniak Strizova
Springer Science and Business Media LLC
Abstract Purpose The CD47 molecule, often referred to as the “do not eat me” signal, is frequently overexpressed in tumor cells. This signaling pathway limits phagocytosis by macrophages. Our objective was to determine CD47 abundance in various soft tissue sarcomas (STS) to investigate whether it could serve as a potential evasion mechanism for tumor cells. Additionally, we aimed to assess the prognostic value of CD47 expression by examining its association with different clinicopathological factors. This study aimed to elucidate the significance of CD47 in the context of emerging anti-tumor targeting approaches. Methods In this retrospective study, formalin-fixed paraffine-embedded (FFPE) tumor tissues of 55 treatment-naïve patients were evaluated by immunohistochemistry for the abundance of CD47 molecule on tumor cells. The categorization of CD47 positivity was as follows: 0 (no staining of tumor cells), 1 + (less than 1/3 of tumor area positive), 2 + (between 1/3 and 2/3 of tumor area positive), and 3 + (more than 2/3 of tumor area positive for CD47). Next, we compared CD47 abundance between different tumor grades (G1–3). We used Kaplan–Meier survival curves with log-rank test to analyze the differences in survival between patients with different CD47 expression. Moreover, we performed Cox proportional hazards regression model to evaluate the clinical significance of CD47. Results CD47 is widely prevalent across distinct STS subtypes. More than 80% of high grade undifferentiated pleiomorphic sarcoma (UPS), 70% of myxofibrosarcoma (MFS) and more than 60% of liposarcoma (LPS) samples displayed a pattern of moderate-to-diffuse positivity. This phenomenon remains consistent regardless of the tumor grade. However, there was a tendency for higher CD47 expression levels in the G3 group compared to the combined G1 + G2 groups when all LPS, MFS, and UPS were analyzed together. No significant associations were observed between CD47 abundance, death, and metastatic status. Additionally, high CD47 expression was associated with a statistically significant increase in progression-free survival in the studied cohort of patients. Conclusion This study highlights the potential of the CD47 molecule as a promising immunotherapeutic target in STS, particularly given its elevated expression levels in diverse sarcoma types. Our data showed a notable trend linking CD47 expression to tumor grade, while also suggesting an interesting correlation between enhanced abundance of CD47 expression and a reduced hazard risk of disease progression. Although these findings shed light on different roles of CD47 in STS, further research is crucial to assess its potential in clinical settings.
Petr Holý, Viktor Hlaváč, Karolína Šeborová, Simona Šůsová, Tereza Tesařová, Lukáš Rob, Martin Hruda, Jiří Bouda, Alena Bartáková, Marcela Mrhalová,et al.
Wiley
AbstractHigh‐grade serous ovarian carcinoma (HGSC) is the most common subtype of ovarian cancer and is among the most fatal gynecological malignancies worldwide, due to late diagnosis at advanced stages and frequent therapy resistance. In 47 HGSC patients, we assessed somatic and germline genetic variability of a custom panel of 144 known or suspected HGSC‐related genes by high‐coverage targeted DNA sequencing to identify the genetic determinants associated with resistance to platinum‐based therapy. In the germline, the most mutated genes were DNAH14 (17%), RAD51B (17%), CFTR (13%), BRCA1 (11%), and RAD51 (11%). Somatically, the most mutated gene was TP53 (98%), followed by CSMD1/2/3 (19/19/36%), and CFTR (23%). Results were compared with those from whole exome sequencing of a similar set of 35 HGSC patients. Somatic variants in TP53 were also validated using GENIE data of 1287 HGSC samples. Our approach showed increased prevalence of high impact somatic and germline mutations, especially those affecting splice sites of TP53, compared to validation datasets. Furthermore, nonsense TP53 somatic mutations were negatively associated with patient survival. Elevated TP53 transcript levels were associated with platinum resistance and presence of TP53 missense mutations, while decreased TP53 levels were found in tumors carrying mutations with predicted high impact, which was confirmed in The Cancer Genome Atlas data (n = 260). Targeted DNA sequencing of TP53 combined with transcript quantification may contribute to the concept of precision oncology of HGSC. Future studies should explore targeting the p53 pathway based on specific mutation types and co‐analyze the expression and mutational profiles of other key cancer genes.
Julien Hadoux, Rossella Elisei, Marcia S. Brose, Ana O. Hoff, Bruce G. Robinson, Ming Gao, Barbara Jarzab, Pavel Isaev, Katerina Kopeckova, Jonathan Wadsley,et al.
Massachusetts Medical Society
BACKGROUND
Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear.
METHODS
We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician's choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment. The primary end point in the protocol-specified interim efficacy analysis was progression-free survival, assessed by blinded independent central review. Crossover to selpercatinib was permitted among patients in the control group after disease progression. Treatment failure-free survival, assessed by blinded independent central review, was a secondary, alpha-controlled end point that was to be tested only if progression-free survival was significant. Among the other secondary end points were overall response and safety.
RESULTS
A total of 291 patients underwent randomization. At a median follow-up of 12 months, median progression-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 16.8 months (95% confidence interval [CI], 12.2 to 25.1) in the control group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.16 to 0.48; P<0.001). Progression-free survival at 12 months was 86.8% (95% CI, 79.8 to 91.6) in the selpercatinib group and 65.7% (95% CI, 51.9 to 76.4) in the control group. Median treatment failure-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 13.9 months in the control group (hazard ratio for disease progression, discontinuation due to treatment-related adverse events, or death, 0.25; 95% CI, 0.15 to 0.42; P<0.001). Treatment failure-free survival at 12 months was 86.2% (95% CI, 79.1 to 91.0) in the selpercatinib group and 62.1% (95% CI, 48.9 to 72.8) in the control group. The overall response was 69.4% (95% CI, 62.4 to 75.8) in the selpercatinib group and 38.8% (95% CI, 29.1 to 49.2) in the control group. Adverse events led to a dose reduction in 38.9% of the patients in the selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively.
CONCLUSIONS
Selpercatinib treatment resulted in superior progression-free survival and treatment failure-free survival as compared with cabozantinib or vandetanib in patients with RET-mutant medullary thyroid cancer. (Funded by Loxo Oncology, a subsidiary of Eli Lilly; LIBRETTO-531 ClinicalTrials.gov number, NCT04211337.).
Lenka Šlegerová and Kateřina Kopečková
Elsevier BV
David Belada, Katerina Kopeckova, Juan Miguel Bergua Burgues, Don Stevens, Marc André, ERNESTO PEREZ PERSONA, Petra Pichler, Philipp B. Staber, Marek Trněný, Johannes Duell,et al.
American Society of Hematology
Anti-CD19 immunotherapy tafasitamab in combination with lenalidomide is used in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant. Open-label, phase 1b, First-MIND study assessed safety and preliminary efficacy of tafasitamab + R-CHOP ± lenalidomide as first-line therapy in patients with DLBCL. Adults with newly-diagnosed, untreated DLBCL (ECOG PS 0-2, IPI 2-5), were randomly assigned to RCHOP+tafasitamab (Arm T) or R-CHOP+tafasitamab+lenalidomide (Arm T/L) for six cycles. Primary endpoint was safety; secondary endpoints included overall response rate (ORR) and complete response (CR) rate at end of treatment (EoT). From Dec2019-Aug2020, 83 patients were screened, 66 treated (n=33 per arm). All patients had ≥1 treatment-emergent adverse event, mostly grade 1/2. Grade ≥3 neutropenia and thrombocytopenia occurred in 57.6% and 12.1% of patients (Arm T), and 84.8% and 36.4% (Arm T/L). Non-hematologic toxicities occurred at similar rates between arms. Mean relative dose intensity of R-CHOP was 89% or higher in both arms. ORR at EoT was 75.8% (CR 72.7%) in Arm T and 81.8% (CR 66.7%) in Arm T/L; best ORR across visits was 90.0% and 93.9%. Eighteen-month duration of response and duration of CR rates were 72.7% and 74.5% (Arm T), and 78.7% and 86.5% (Arm T/L); 24-month progression-free survival and overall survival rates were 72.7% and 90.3% (Arm T), and 76.8% and 93.8% (Arm T/L). Manageable safety and promising signals of efficacy were observed in both arms. Potential benefit of adding tafasitamab+lenalidomide to R-CHOP is being investigated in phase 3 frontMIND (NCT04824092).
Petr Holý, Veronika Brynychová, Karolína Šeborová, Vojtěch Haničinec, Renata Koževnikovová, Markéta Trnková, David Vrána, Jiří Gatěk, Kateřina Kopečková, Marcela Mrhalová,et al.
Wiley
Oxysterols, oxidized derivatives of cholesterol, act in breast cancer (BC) as selective estrogen receptor modulators and affect cholesterol homeostasis, drug transport, nuclear and cell receptors, and other signaling proteins. Using data from three highly overlapping sets of patients (N = 162 in total) with early‐stage estrogen‐receptor‐positive luminal BC—high‐coverage targeted DNA sequencing (113 genes), mRNA sequencing, and full micro‐RNA (miRNA) transcriptome microarrays—we describe complex oxysterol‐related interaction (correlation) networks, with validation in public datasets (n = 538) and 11 databases. The ESR1‐CH25H‐INSIG1‐ABCA9 axis was the most prominent, interconnected through miR‐125b‐5p, miR‐99a‐5p, miR‐100‐5p, miR‐143‐3p, miR‐199b‐5p, miR‐376a‐3p, and miR‐376c‐3p. Mutations in SC5D, CYP46A1, and its functionally linked gene set were associated with multiple differentially expressed oxysterol‐related genes. STARD5 was upregulated in patients with positive lymph node status. High expression of hsa‐miR‐19b‐3p was weakly associated with poor survival. This is the first study of oxysterol‐related genes in BC that combines DNA, mRNA, and miRNA multiomics with detailed clinical data. Future studies should provide links between intratumoral oxysterol signaling depicted here, circulating oxysterol levels, and therapy outcomes, enabling eventual clinical exploitation of present findings.
Joan Prades, Annalisa Trama, Paolo G Casali, Jean-Francois Emile, Nathalie Gaspar, Ramunas Janavicius, Rasa Jančiauskienė, Sakari Karjalainen, Katerina Kopeckova, Liisa Pylkkänen,et al.
Oxford University Press (OUP)
Abstract Background As a system of European Reference Networks (ERNs) emerges, the differences in quality of care for patients with rare cancers may increase at national level. We aimed to elucidate the processes and healthcare planning principles through which the reference centres (RCs) for rare cancers are embedded in national health systems. Methods We used a multiple case-study design based on the experiences of Czechia, Finland, France, Italy, Lithuania and Spain. Using sarcoma as an example of rare cancer, 52 semi-structured interviews were conducted during on-site visits, including a multidisciplinary group of professionals, Ministry of Health professionals, patient representatives and European policymakers. Results The comparative analysis showed substantial heterogeneity in the processes for formalizing RCs’ status and in their levels of integration in the different health systems, but two models (centre-based and the network-based) can be envisaged at national level. RCs for rare cancers were legally established only in France and Spain. Expert clinicians cooperate in a structured way, using network mechanisms, in France and Italy, and these countries, plus Finland and Lithuania, had a referral system to facilitate patients’ access from non-expert centres to RCs. Seven key healthcare planning principles in instituting RCs at the national level were identified. Conclusions The conditions governing patient access to treatment centres—whether RCs or not—are decided at the national level. It is advisable to progressively align the European and national levels so that the RCs that participate in the ERNs also play a significant role at the national level.
Jiří Kubeš, Vladimír Vondráček, Michal Andrlik, Matěj Navrátil, Silvia Sláviková, Daniel Klika, Alexandra Haas, Kateřina Dědečková, Kateřina Kopečková, Barbora Ondrová,et al.
Wiley
Glomus jugulare tumours (GJT) are benign tumours that arise locally and destructively in the base of the skull and can be successfully treated with radiotherapy. Patients have a long‐life expectancy and the late effects of radiotherapy can be serious. Proton radiotherapy reduces doses to critical organs and can reduce late side effects of radiotherapy. The aim of this study was to report feasibility and early clinical results of 12 patients treated using proton therapy.
Ivona Krus, Veronika Brynychová, Viktor Hlaváč, Radka Václavíková, Maria Kováčová, Renata Koževnikovová, Katerina Kopečková, Jannis Tornikidis, David Vrána, Jiří Gatěk,et al.
Springer Science and Business Media LLC
Richard Greil, Katerina Kopeckova, Luca Arcaini, Aasim Amin, Katrien de Graaf, and Anna-Maria Jegg
Elsevier BV
David Belada, Katerina Kopeckova, Juan Miguel Bergua Burgues, Don Stevens, Grzegorz S. Nowakowski, Maeve Waldron-Lynch, Nira Hadar, Johannes Weirather, Charlotte Lässig, Derek Blair,et al.
Elsevier BV
Petr Holý, Viktor Hlaváč, Pavel Ostašov, Veronika Brynychová, Renata Koževnikovová, Markéta Trnková, Kateřina Kopečková, Soňa Měšťáková, Marcela Mrhalová, and Pavel Souček
Elsevier BV
P.G. Casali, J.Y. Blay, N. Abecassis, J. Bajpai, S. Bauer, R. Biagini, S. Bielack, S. Bonvalot, I. Boukovinas, J.V.M.G. Bovee,et al.
Elsevier BV
S.J. Strauss, A.M. Frezza, N. Abecassis, J. Bajpai, S. Bauer, R. Biagini, S. Bielack, J.Y. Blay, S. Bolle, S. Bonvalot,et al.
Elsevier BV
A. Gronchi, A.B. Miah, A.P. Dei Tos, N. Abecassis, J. Bajpai, S. Bauer, R. Biagini, S. Bielack, J.Y. Blay, S. Bolle,et al.
Elsevier BV
J.-Y. Blay, P. Casali, C. Bouvier, C. Dehais, I. Galloway, J. Gietema, J. Halámková, N. Hindi, A. Idbaih, E. Kinloch,et al.
Elsevier BV
Andrea Cumova, Veronika Vymetalkova, Alena Opattova, Veronika Bouskova, Barbara Pardini, Katerina Kopeckova, Renata Kozevnikovova, Katerina Lickova, Miloslav Ambrus, Ludmila Vodickova,et al.
Oxford University Press (OUP)
AbstractBreast cancer (BC) is the most frequent malignancy in women accounting for approximately 2 million new cases worldwide annually. Several genetic, epigenetic and environmental factors are known to be involved in BC development and progression, including alterations in post-transcriptional gene regulation mediated by microRNAs (miRNAs). Single nucleotide polymorphisms (SNPs) located in miRNA binding sites (miRSNPs) in 3′-untranslated regions of target genes may affect miRNA-binding affinity and consequently modulate gene expression. We have previously reported a significant association of miRSNPs in the SMUG1 and NEIL2 genes with overall survival in colorectal cancer patients. SMUG1 and NEIL2 are DNA glycosylases involved in base excision DNA repair. Assuming that certain genetic traits are common for solid tumours, we have investigated wherever variations in SMUG1 and NEIL2 genes display an association with BC risk, prognosis, and therapy response in a group of 673 BC patients and 675 healthy female controls. Patients with TC genotype of NEIL2 rs6997097 and receiving only hormonal therapy displayed markedly shorter overall survival (HR = 4.15, 95% CI = 1.7–10.16, P = 0.002) and disease-free survival (HR = 2.56, 95% CI = 1.5–5.7, P = 0.02). Our results suggest that regulation of base excision repair glycosylases operated by miRNAs may modulate the prognosis of hormonally treated BC.
Viktor Hlaváč, Radka Václavíková, Veronika Brynychová, Pavel Ostašov, Renata Koževnikovová, Katerina Kopečková, David Vrána, Jiří Gatěk, and Pavel Souček
MDPI AG
Breast cancer is the most frequent cancer in the female population worldwide. The role of germline genetic variability in cytochromes P450 (CYP) in breast cancer prognosis and individualized therapy awaits detailed elucidation. In the present study, we used the next-generation sequencing to assess associations of germline variants in the coding and regulatory sequences of all human CYP genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). A total of 22 prioritized variants associating with a response or survival in the above evaluation phase were then analyzed by allelic discrimination in the large confirmation set (n = 802). Associations of variants in CYP1B1, CYP4F12, CYP4X1, and TBXAS1 with the response to the neoadjuvant cytotoxic chemotherapy were replicated by the confirmation phase. However, just association of variant rs17102977 in CYP4X1 passed the correction for multiple testing and can be considered clinically and statistically validated. Replicated associations for variants in CYP4X1, CYP24A1, and CYP26B1 with disease-free survival of all patients or patients stratified to subgroups according to therapy type have not passed a false discovery rate test. Although statistically not confirmed by the present study, the role of CYP genes in breast cancer prognosis should not be ruled out. In conclusion, the present study brings replicated association of variant rs17102977 in CYP4X1 with the response of patients to the neoadjuvant cytotoxic chemotherapy and warrants further research of genetic variation CYPs in breast cancer.
Robert Pytlík, Blanka Vacková, Eva Konířová, Marie Trnková, Petra Blahovcová, David Pohlreich, Kamila Polgárová, Pavel Klener, Kateřina Benešová, Kateřina Kopečková,et al.
Springer Science and Business Media LLC
Viktor Hlavac, Radka Vaclavikova, Veronika Brynychova, Pavel Dvorak, Katerina Elsnerova, Renata Kozevnikovova, Karel Raus, Katerina Kopeckova, Sona Mestakova, David Vrana,et al.
Springer Science and Business Media LLC
Viktor Hlaváč, Radka Václavíková, Veronika Brynychová, Renata Koževnikovová, Katerina Kopečková, David Vrána, Jiří Gatěk, and Pavel Souček
MDPI AG
Breast cancer is the most common cancer in women in the world. The role of germline genetic variability in ATP-binding cassette (ABC) transporters in cancer chemoresistance and prognosis still needs to be elucidated. We used next-generation sequencing to assess associations of germline variants in coding and regulatory sequences of all human ABC genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). A total of 43 prioritized variants associating with response or survival in the above testing phase were then analyzed by allelic discrimination in the large validation set (n = 802). Variants in ABCA4, ABCA9, ABCA12, ABCB5, ABCC5, ABCC8, ABCC11, and ABCD4 associated with response and variants in ABCA7, ABCA13, ABCC4, and ABCG8 with survival of the patients. No association passed a false discovery rate test, however, the rs17822931 (Gly180Arg) in ABCC11, associating with response, and the synonymous rs17548783 in ABCA13 (survival) have a strong support in the literature and are, thus, interesting for further research. Although replicated associations have not reached robust statistical significance, the role of ABC transporters in breast cancer should not be ruled out. Future research and careful validation of findings will be essential for assessment of genetic variation which was not in the focus of this study, e.g., non-coding sequences, copy numbers, and structural variations together with somatic mutations.
Alexandr Poprach, Milos Holanek, Renata Chloupkova, Radek Lakomy, Michal Stanik, Ondrej Fiala, Bohuslav Melichar, Katerina Kopeckova, Milada Zemanova, Igor Kiss,et al.
MDPI AG
The role of cytoreductive nephrectomy (CN) in treatment of locally advanced or metastatic renal cell carcinoma (mRCC) in the era of targeted therapies (TT) is still not clearly defined. The study population consisted of 730 patients with synchronous mRCC. The RenIS (Renal carcinoma Information System) registry was used as the data source. The CN/TT cohort included patients having CN within 3 months from the mRCC diagnosis and subsequently being treated with TT, while the TT cohort included patients receiving TT upfront. Median progression-free survival from the first intervention was 6.7 months in the TT arm and 9.3 months in the CN/TT patients (p < 0.001). Median overall survival was 14.2 and 27.2 months, respectively (p < 0.001). Liver metastasis, high-grade tumor, absence of CN, non-clear cell histology, and MSKCC (Memorial Sloan-Kettering Cancer Center) poor prognosis status were associated with adverse treatment outcomes. According to the results of this retrospective study, patients who underwent CN and subsequently were treated with TT had better outcomes compared to patients treated with upfront TT. The results of the study support the use of CN in the treatment algorithm for mRCC.
Christian Rolfo, Nicolas Isambert, Antoine Italiano, L. Rhoda Molife, Jan H.M. Schellens, Jean‐Yves Blay, Thomas Decaens, Rebecca Kristeleit, Olivier Rosmorduc, Regina Demlova,et al.
Wiley
Olaparib, a potent oral poly(ADP‐ribose) polymerase inhibitor, is partially hepatically cleared. We investigated the pharmacokinetics (PK) and safety of olaparib in patients with mild or moderate hepatic impairment to provide dosing recommendations.
Patrick Schöffski, Olivier Mir, Bernd Kasper, Zsuzsanna Papai, Jean-Yves Blay, Antoine Italiano, Charlotte Benson, Katerina Kopeckova, Nasim Ali, Palma Dileo,et al.
Elsevier BV