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1. Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations

Author

Incorvaia, Lorena, Monteiro, Fernando Sabino Marques, Massari, Francesco, Park, Se Hoon, Roviello, Giandomenico, Fiala, Ondřej, Myint, Zin W., Kucharz, Jakub, Molina-Cerrillo, Javier, Santini, Daniele, Buttner, Thomas, Poprach, Alexandr, Kopecky, Jindrich, Zeppellini, Annalisa, Pichler, Martin, Buchler, Tomas, Pichler, Renate, Facchini, Gaetano, Fay, Andre Poisl, Soares, Andrey, Manneh, Ray, Iezzi, Laura, Kuronya, Zsofia, Russo, Antonio, Bourlon, Maria T., Bhuva, Dipen, Ansari, Jawaher, Kanesvaran, Ravindran, Grande, Enrique, Buti, Sebastiano, and Santoni, Matteo

Published
2024
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6. Corrigendum: Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms

Author

Grünwald, Viktor, primary, Powles, Thomas, additional, Eto, Masatoshi, additional, Kopyltsov, Evgeny, additional, Rha, Sun Young, additional, Porta, Camillo, additional, Motzer, Robert, additional, Hutson, Thomas E., additional, Méndez-Vidal, María José, additional, Hong, Sung-Hoo, additional, Winquist, Eric, additional, Goh, Jeffrey C., additional, Maroto, Pablo, additional, Buchler, Tomas, additional, Takagi, Toshio, additional, Burgents, Joseph E., additional, Perini, Rodolfo, additional, He, Cixin, additional, Okpara, Chinyere E., additional, McKenzie, Jodi, additional, and Choueiri, Toni K., additional

Published
2024
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7. Association of the combined parameters including the frequency of primary cilia, PD-L1, Smoothened protein, membranous β-catenin and cytoplasmic β-catenin expression with the outcome of patients with clear cell renal cell carcinoma

Author

Rozsypalova, Aneta, primary, Rosova, Blanka, additional, Filipova, Alzbeta, additional, Nikolov, Dimitar Hadzi, additional, Chloupkova, Renata, additional, Richter, Igor, additional, Zachoval, Roman, additional, Matej, Radoslav, additional, Melichar, Bohuslav, additional, Buchler, Tomas, additional, and Dvorak, Josef, additional

Published
2024
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9. Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms.

Author

Grünwald, Viktor, Powles, Thomas, Masatoshi Eto, Kopyltsov, Evgeny, Sun Young Rha, Porta, Camillo, Motzer, Robert, Hutson, Thomas E., José Méndez-Vidal, María, Sung-Hoo Hong, Winquist, Eric, Goh, Jeffrey C., Maroto, Pablo, Buchler, Tomas, Toshio Takagi, Burgents, Joseph E., Perini, Rodolfo, Cixin He, Okpara, Chinyere E., and McKenzie, Jodi

Subjects
SUNITINIB, RENAL cell carcinoma, BONE metastasis, THERAPEUTICS, TREATMENT effectiveness, PROGRESSION-free survival
Abstract

Introduction: The phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features. Methods: In CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology. Results: In all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern. Conclusion: Efficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Spontaneous Regression of Metastatic Renal Cell Carcinoma after SARS-CoV-2 Infection: A Report of Two Cases

Author

Buchler, Tomas, Fiser, Lukas, Benesova, Jaroslava, Jirickova, Hana, and Votrubova, Jana

Subjects
renal cell carcinoma, SARS-CoV-2, COVID-19, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Case Report, innate immunity, spontaneous regression, RC254-282
Abstract

Spontaneous regression of metastatic renal cell carcinoma (mRCC) is a rare event, often associated with an activation of innate immunity by various triggers. SARS-CoV-2 infection induces a strong inflammatory response in some patients and a cytokine storm is one of the main causes of severe morbidity and mortality associated with the virus. Here, we describe two cases of patients with histologically and radiologically proven mRCC whose treatment was delayed due to COVID-19 and who experienced spontaneous tumour regression following the infection. Both patients reported here had predominantly pulmonary and mediastinal involvement and underwent nephrectomy. The interval between the diagnosis of COVID-19 and the detection of tumour regression was 3 and 4 months, respectively. Although approved vaccines and other measures are clearly the best way to prevent COVID-19-associated morbidity and mortality in cancer patients, we hypothesize that innate immunity activation by the infection can contribute to tumour regression in special circumstances.

Published
2021

13. Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms.

Author

Grünwald, Viktor, Powles, Thomas, Masatoshi Eto, Kopyltsov, Evgeny, Sun Young Rha, Porta, Camillo, Motzer, Robert, Hutson, Thomas E., José Méndez-Vidal, María, Sung-Hoo Hong, Winquist, Eric, Goh, Jeffrey C., Maroto, Pablo, Buchler, Tomas, Toshio Takagi, Burgents, Joseph E., Perini, Rodolfo, Cixin He, Okpara, Chinyere E., and McKenzie, Jodi

Subjects
SUNITINIB, BONE metastasis, THERAPEUTICS, TREATMENT effectiveness, PROGRESSION-free survival
Abstract

Introduction: The phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features. Methods: In CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology. Results: In all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern. Conclusion: Efficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Adjuvant PD-1 and PD-L1 Inhibitors and Relapse-Free Survival in Cancer Patients: The MOUSEION-04 Study

Author

Rizzo, Alessandro, primary, Mollica, Veronica, additional, Marchetti, Andrea, additional, Nuvola, Giacomo, additional, Rosellini, Matteo, additional, Tassinari, Elisa, additional, Molina-Cerrillo, Javier, additional, Myint, Zin W., additional, Buchler, Tomas, additional, Monteiro, Fernando Sabino Marques, additional, Grande, Enrique, additional, Santoni, Matteo, additional, and Massari, Francesco, additional

Published
2022
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17. Single-course bleomycin, etoposide, and cisplatin (1xBEP) as adjuvant treatment in testicular nonseminoma clinical stage 1: outcome, safety, and risk factors for relapse in a population-based study

Author

Dieckmann, Klaus-Peter, Pokrivcak, Tomas, Geczi, Lajos, Niehaus, David, Dralle-Filiz, Inken, Matthies, Cord, Dienes, Tamas, Zschaebitz, Stefanie, Paffenholz, Pia, Gschliesser, Tanja, Pichler, Renate, Mego, Michal, Bader, Pia, Zengerling, Friedemann, Heinzelbecker, Julia, Krausewitz, Philipp, Krege, Susanne, Aurilio, Gaetano, Aksoy, Cem, Hentrich, Marcus, Seidel, Christoph, Toerzsoek, Peter, Nestler, Tim, Majewski, Matthaeus, Hiester, Andreas, Buchler, Tomas, Vallet, Sonia, Studentova, Hana, Schoenburg, Sandra, Niedersuess-Beke, Dora, Ring, Julia, Trenti, Emanuela, Heidenreich, Axel, Wuelfing, Christian, Isbarn, Hendrik, Pichlmeier, Uwe, Pichler, Martin, Dieckmann, Klaus-Peter, Pokrivcak, Tomas, Geczi, Lajos, Niehaus, David, Dralle-Filiz, Inken, Matthies, Cord, Dienes, Tamas, Zschaebitz, Stefanie, Paffenholz, Pia, Gschliesser, Tanja, Pichler, Renate, Mego, Michal, Bader, Pia, Zengerling, Friedemann, Heinzelbecker, Julia, Krausewitz, Philipp, Krege, Susanne, Aurilio, Gaetano, Aksoy, Cem, Hentrich, Marcus, Seidel, Christoph, Toerzsoek, Peter, Nestler, Tim, Majewski, Matthaeus, Hiester, Andreas, Buchler, Tomas, Vallet, Sonia, Studentova, Hana, Schoenburg, Sandra, Niedersuess-Beke, Dora, Ring, Julia, Trenti, Emanuela, Heidenreich, Axel, Wuelfing, Christian, Isbarn, Hendrik, Pichlmeier, Uwe, and Pichler, Martin

Abstract

Introduction: Clinical stage 1 (CS1) nonseminomatous (NS) germ cell tumors involve a 30% probability of relapse upon surveillance. Adjuvant chemotherapy with one course of bleomycin, etoposide, and cisplatin (1xBEP) can reduce this risk to <5%. However, 1xBEP results are based solely on five controlled trials from high-volume centers. We analyzed the outcome in a real-life population. Patients and Methods: In a multicentric international study, 423 NS CS1 patients receiving 1xBEP were retrospectively evaluated. Median follow-up was 37 (range, 6-89) months. Primary end points were relapse-free and overall survival evaluated after 5 years. We also looked at associations of relapse with clinico-pathological factors using stratified Kaplan-Meier methods and Cox regression models. Treatment modality and outcome of recurrences were analyzed descriptively. Results: The 5-year relapse-free survival rate was 96.2%. Thirteen patients (3.1%; 95% confidence interval, 1.65-5.04%) relapsed after a median time of 13 months, of which 10 were salvaged (77%). Relapses were mostly confined to retroperitoneal nodes. Three patients succumbed, two to disease progression and one to toxicity of chemotherapy. Pathological stage >pT2 was significantly associated with relapse rate. Conclusion: The relapse rate of 3.1% found in this population of NS CS1 patients treated with 1xBEP at the routine care level was not inferior to the median rate of 2.3% reported from a meta-analysis of controlled trials. Also, the cure rate of relapses of 77% is consistent with the previously reported rate of 80%. This study clearly shows that the 1xBEP regimen represents a safe treatment for NS CS1 patients.

Published
2022

21. Patients with metastatic renal cell carcinoma treated with cabozantinib in the Czech Republic: analysis of four cancer centers

Author

Richter, Igor, primary, Poprach, Alexandr, additional, Zemankova, Anezka, additional, Buchler, Tomas, additional, Bartos, Jiri, additional, Samal, Vladimir, additional, Studentova, Hana, additional, Rozsypalova, Aneta, additional, Dvorak, Josef, additional, Brom, Ondrej, additional, and Melichar, Bohuslav, additional

Published
2022
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24. Evaluating Alternative Ramucirumab Doses as a Single Agent or with Paclitaxel in Second-Line Treatment of Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma: Results from Two Randomized, Open-Label, Phase II Studies

Author

Shah, Manish A., primary, Udrea, Anghel Adrian, additional, Bondarenko, Igor, additional, Mansoor, Was, additional, Sánchez, Raquel Guardeño, additional, Sarosiek, Tomasz, additional, Bozzarelli, Silvia, additional, Schenker, Michael, additional, Gomez-Martin, Carlos, additional, Morgan, Carys, additional, Özgüroğlu, Mustafa, additional, Pikiel, Joanna, additional, Kalofonos, Haralabos P., additional, Wojcik, Elzbieta, additional, Buchler, Tomas, additional, Swinson, Daniel, additional, Cicin, Irfan, additional, Joseph, Mano, additional, Vynnychenko, Ihor, additional, Luft, Alexander Valerievich, additional, Enzinger, Peter C., additional, Salek, Tomas, additional, Papandreou, Christos, additional, Tournigand, Christophe, additional, Maiello, Evaristo, additional, Wei, Ran, additional, Ferry, David, additional, Gao, Ling, additional, Oliveira, Joana M., additional, and Ajani, Jaffer A., additional

Published
2022
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25. Single-course bleomycin, etoposide, and cisplatin (1xBEP) as adjuvant treatment in testicular nonseminoma clinical stage 1: outcome, safety, and risk factors for relapse in a population-based study

Author

Dieckmann, Klaus-Peter, primary, Pokrivcak, Tomas, additional, Geczi, Lajos, additional, Niehaus, David, additional, Dralle-Filiz, Inken, additional, Matthies, Cord, additional, Dienes, Tamas, additional, Zschäbitz, Stefanie, additional, Paffenholz, Pia, additional, Gschliesser, Tanja, additional, Pichler, Renate, additional, Mego, Michal, additional, Bader, Pia, additional, Zengerling, Friedemann, additional, Heinzelbecker, Julia, additional, Krausewitz, Philipp, additional, Krege, Susanne, additional, Aurilio, Gaetano, additional, Aksoy, Cem, additional, Hentrich, Marcus, additional, Seidel, Christoph, additional, Törzsök, Péter, additional, Nestler, Tim, additional, Majewski, Matthaeus, additional, Hiester, Andreas, additional, Buchler, Tomas, additional, Vallet, Sonia, additional, Studentova, Hana, additional, Schönburg, Sandra, additional, Niedersüß-Beke, Dora, additional, Ring, Julia, additional, Trenti, Emanuela, additional, Heidenreich, Axel, additional, Wülfing, Christian, additional, Isbarn, Hendrik, additional, Pichlmeier, Uwe, additional, and Pichler, Martin, additional

Published
2022
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32. Mutational landscape of plasma cell-free DNA identifies molecular features associated with therapeutic response in patients with colon cancer. A pilot study

Author

Cervena, Klara, primary, Pardini, Barbara, additional, Urbanova, Marketa, additional, Vodenkova, Sona, additional, Eva, Pazourkova, additional, Veskrnova, Veronika, additional, Levy, Miroslav, additional, Buchler, Tomas, additional, Mokrejs, Martin, additional, Naccarati, Alessio, additional, Vodicka, Pavel, additional, and Vymetalkova, Veronika, additional

Published
2021
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33. Regorafenib for Metastatic Colorectal Cancer: An Analysis of a Registry-Based Cohort of 555 Patients

Author

Novakova-Jiresova, Alena, Kopeckova, Katerina, Boublikova, Ludmila, Chloupkova, Renata, Melichar, Bohuslav, Petruzelka, Lubos, Finek, Jindrich, Fiala, Ondrej, Grell, Peter, Batko, Stanislav, Linke, Zdenek, Kiss, Igor, Prausova, Jana, and Buchler, Tomas

Subjects
Cancer Management and Research, outcome analysis, colorectal cancer, regorafenib, registry, survival, Original Research
Abstract

Alena Novakova-Jiresova,1 Katerina Kopeckova,2 Ludmila Boublikova,1 Renata Chloupkova,3 Bohuslav Melichar,4 Lubos Petruzelka,5 Jindrich Finek,6 Ondrej Fiala,6,7 Peter Grell,8 Stanislav Batko,2 Zdenek Linke,2 Igor Kiss,8 Jana Prausova,2 Tomas Buchler1 1Department of Oncology, First Faculty of Medicine and Thomayer Hospital, Charles University, Prague, Czech Republic; 2Department of Oncology, University Hospital in Motol, Charles University, Prague, Czech Republic; 3Institute of Biostatistics and Analysis, Faculty of Medicine, Masaryk University, Brno, Czech Republic; 4Department of Oncology, Palacky University Medical and Teaching Hospital, Olomouc, Czech Republic; 5Department of Oncology, General Faculty Hospital, Charles University, Prague, Czech Republic; 6Department of Oncology and Radiotherapy, Medical School and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic; 7Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic; 8Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech RepublicCorrespondence: Tomas BuchlerDepartment of Oncology, First Faculty of Medicine and Thomayer Hospital, Charles University, Videnska 800, Prague 140 59, Czech RepublicTel +420-261-082-637Fax +420-261-082-522Email tomas.buchler@ftn.czPurpose: Regorafenib is an oral multikinase inhibitor approved for the therapy of previously treated metastatic colorectal carcinoma (mCRC). The aim of the present study was to analyze the outcomes of treatment with regorafenib in real-world clinical practice based on data from a national registry.Methods: The CORECT registry, the Czech non-interventional database of patients with mCRC treated with targeted agents, searched for patients with metastatic CRC treated with regorafenib. In total, 555 evaluable patients were identified.Results: The median age at diagnosis was 61.7 years. All patients had disease progression on or after previous systemic treatment. Most patients were treated with an initial dose of 160 mg daily (n = 463; 83.6%). The median duration of treatment was 2.7 months (range 0.0– 23.4 months). By the data cut-off date, 472 patients (85%) had completed treatment with regorafenib and were evaluable for treatment response evaluation. Partial response was reported in 13 patients (2.8%) and disease stabilization in 130 patients (27.5%). Median progression-free survival (PFS) and overall survival (OS) were 3.5 months (95% confidence interval [CI] 3.2– 3.7 months) and 9.3 months (95% CI 8.3– 10.3 months), respectively. The 6-month OS rate was 67.7% (95% CI 63.4– 72.1%). Multivariable analysis showed that female gender, longer interval from diagnosis of metastatic disease, M0 stage at diagnosis, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0 were associated with longer PFS, while higher body-mass index (BMI), longer interval from diagnosis of metastatic disease, and ECOG PS of 0 were associated with longer OS.Conclusion: OS of patients treated with regorafenib in the real-world clinical practice in this cohort exceeded that reported in randomized trials. Regorafenib is a safe and active treatment option for a subgroup of patients with mCRC who are progressing after other systemic therapies and maintain good performance status.Keywords: colorectal cancer, regorafenib, registry, survival, outcome analysis

Published
2020

34. The Association of Baseline Serum Tumour Markers with Outcome of Patients with Metastatic Colorectal Cancer Treated with Anti-EGFR Monoclonal Antibodies in the First Line

Author

Fiala, Ondrej, Hosek, Petr, Sorejs, Ondrej, Liska, Vaclav, Buchler, Tomas, Poprach, Alexandr, Kucera, Radek, Topolcan, Ondrej, Sedivcova, Monika, and Finek, Jindrich

Subjects
tumor markers, serum carcinoembryonic antigen, cetuximab, thymidine kinase, colorectal cancer, panitumumab, chemotherapy, carbohydrate antigen 19-9, tissue polypeptide specific antigen, Research Paper
Abstract

The measurement of serum tumour markers is a simple and non-invasive method for assessing the response to systemic therapies in metastatic colorectal cancer (mCRC) and estimation of prognosis. The aim of our retrospective study was to evaluate the association of baseline serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), thymidine kinase (TK) and tissue polypeptide specific antigen (TPS) with outcome of patients with mCRC treated with combination of chemotherapy and monoclonal antibodies against epidermal growth factor receptor (anti-EGFR mAbs) in the first line. In our study, the cohort included 102 patients treated with therapy based on anti-EGFR mAbs between years 2011 and 2017 at Department of Oncology and Radiotherapy, Medical School and University Hospital in Pilsen, Czech Republic. Serum samples were collected within one month before the initiation of treatment. In multivariate Cox analysis that included serum tumour markers and clinical baseline parameters show that high baseline serum CA 19-9 was significantly associated with worse progression-free survival (HR=1.871, p=0.0330) and also overall survival (HR=3.903, p=0.0006). We have not demonstrated association of baseline levels of CEA, TK and TPS with patients' outcome. CA 19-9 is commonly used serum tumour marker which is simple and readily available and its candidate prognostic importance in the setting of anti-EGFR therapy deserves to be studied in prospective trials.

Published
2018

37. Genetic variations in microRNA-binding sites of solute carrier transporter genes as predictors of clinical outcome in colorectal cancer

Author

Bendova, Petra, primary, Pardini, Barbara, additional, Susova, Simona, additional, Rosendorf, Jachym, additional, Levy, Miloslav, additional, Skrobanek, Pavel, additional, Buchler, Tomas, additional, Kral, Jan, additional, Liska, Vaclav, additional, Vodickova, Ludmila, additional, Landi, Stefano, additional, Soucek, Pavel, additional, Naccarati, Alessio, additional, Vodicka, Pavel, additional, and Vymetalkova, Veronika, additional

Published
2020
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38. Cytoreductive Nephrectomy and Overall Survival of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy—Data from the National Renis Registry

Author

Poprach, Alexandr, primary, Holanek, Milos, additional, Chloupkova, Renata, additional, Lakomy, Radek, additional, Stanik, Michal, additional, Fiala, Ondrej, additional, Melichar, Bohuslav, additional, Kopeckova, Katerina, additional, Zemanova, Milada, additional, Kiss, Igor, additional, Penka, Igor, additional, Bohosova, Julia, additional, and Buchler, Tomas, additional

Published
2020
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41. Outcomes According to MSKCC Risk Score with Focus on the Intermediate-Risk Group in Metastatic Renal Cell Carcinoma Patients Treated with First-Line Sunitinib: A Retrospective Analysis of 2390 Patients

Author

Fiala, Ondrej, primary, Finek, Jindrich, additional, Poprach, Alexandr, additional, Melichar, Bohuslav, additional, Kopecký, Jindrich, additional, Zemanova, Milada, additional, Kopeckova, Katerina, additional, Mlcoch, Tomas, additional, Dolezal, Tomas, additional, Capkova, Lenka, additional, and Buchler, Tomas, additional

Published
2020
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42. Incidental Use of Beta-Blockers Is Associated with Outcome of Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Based Therapy: A Single-Institution Retrospective Analysis of 514 Patients

Author

Fiala, Ondrej, Ostasov, Pavel, Sorejs, Ondrej, Liska, Vaclav, Buchler, Tomas, Poprach, Alexandr, and Finek, Jindrich

Subjects
hypertension, beta-blocker, outcome, colorectal cancer, bevacizumab
Abstract

Background: Beta-adrenergic signalling plays an important role in several cancer-related processes, including angiogenesis. The impact of beta-blocker use on prognosis of cancer patients treated with antiangiogenic agents is unclear. The aim of this study was to evaluate the association between the incidental use of beta-blockers and the outcomes of patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-based therapy. Methods: Clinical data from 514 mCRC patients treated with bevacizumab between 2005 and 2019 were analysed retrospectively. The association of progression-free survival (PFS) and overall survival (OS) with the incidental use of beta-blockers and other common antihypertensive drugs was assessed. Results: The median PFS and OS for patients using beta-blockers was 11.40 (95% confidence interval (CI) 10.10&ndash, 13.61) months and 26.8 (95% CI 22.2&ndash, 32.2) months compared with 8.30 (95% CI 7.80&ndash, 9.57) and 21.0 (95% CI 17.8&ndash, 23.8) months for patients not using beta-blockers (p = 0.006 and p = 0.009, respectively). In the Cox multivariate analysis, the use of beta-blockers was a significant factor predicting both PFS (hazard ratio (HR) = 0.763 (95% CI 0.606&ndash, 0.960), p = 0.021) and OS (HR = 0.730 (95% CI 0.560&ndash, 0.951), p = 0.020). Conclusions: The results of the present retrospective study suggest that there is a significant association between the use of beta-blockers and favourable outcomes of mCRC patients treated with bevacizumab-based therapy.

Published
2019
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43. Expression quantitative trait loci in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients

Author

Vymetalkova, Veronika, primary, Rosa, Fabio, primary, Susova, Simona, primary, Bendova, Petra, primary, Levy, Miroslav, primary, Buchler, Tomas, primary, Kral, Jan, primary, Bartu, Linda, primary, Vodickova, Ludmila, primary, Hughes, David J, primary, Soucek, Pavel, primary, Naccarati, Alessio, primary, Kumar, Rajiv, primary, Vodicka, Pavel, primary, and Pardini, Barbara, primary

Published
2020
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44. Impact of Hormone Receptor Status on the Behaviour of HER2+ Breast Cancer

Author

KOLAROVA, IVETA, primary, DUSEK, LADISLAV, additional, RYSKA, ALES, additional, ODRAZKA, KAREK, additional, DOLEZEL, MARTIN, additional, VANASEK, JAROSLAV, additional, MELICHAR, BOHUSLAV, additional, PETERA, JIRI, additional, BUCHLER, TOMAS, additional, VOSMIK, MILAN, additional, PETRAKOVA, KATARINA, additional, TERAROVA, PETRA, additional, VILASOVA, ZDENA, additional, and JARKOVSKY, JIRI, additional

Published
2020
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45. Tumour devascularisation as a potential immunotherapeutic strategy

Author

Buchler, Tomas, Vasek, Pavel, Spisek, Radek, Skrobanek, Pavel, and Horejsi, Vaclav

Subjects
lcsh:Immunologic diseases. Allergy, biochemical phenomena, metabolism, and nutrition, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, environment and public health, tumour ligation, enzymes and coenzymes (carbohydrates), health occupations, cancer, Point-of-View, Immunotherapy, ischaemia, lcsh:RC581-607, devascularisation
Abstract

Complete tumour devascularisation (CTD) is a surgical technique which entails the complete disruption by ligation or cutting of afferent and efferent tumour vasculature which remains in situ. In some animal models, CTD induces immune responses that lead to regression of distant metastases and protective immunity.

Published
2018

48. Molecular Basis of Cisplatin Resistance in Testicular Germ Cell Tumors

Author

Bakardjieva-Mihaylova, Violeta, primary, Skvarova Kramarzova, Karolina, additional, Slamova, Martina, additional, Svaton, Michael, additional, Rejlova, Katerina, additional, Zaliova, Marketa, additional, Dobiasova, Alena, additional, Fiser, Karel, additional, Stuchly, Jan, additional, Grega, Marek, additional, Rosova, Blanka, additional, Zachoval, Roman, additional, Klezl, Petr, additional, Eis, Vaclav, additional, Kindlova, Eva, additional, Buchler, Tomas, additional, Trka, Jan, additional, and Boublikova, Ludmila, additional

Published
2019
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49. Genetic variations in microRNA-binding sites of solute carrier transporter genes as predictors of clinical outcome in colorectal cancer.

Author

Bendova, Petra, Pardini, Barbara, Susova, Simona, Rosendorf, Jachym, Levy, Miloslav, Skrobanek, Pavel, Buchler, Tomas, Kral, Jan, Liska, Vaclav, Vodickova, Ludmila, Landi, Stefano, Soucek, Pavel, Naccarati, Alessio, Vodicka, Pavel, and Vymetalkova, Veronika

Subjects
COLORECTAL cancer, GENES, TREATMENT effectiveness, PROGNOSIS, MESSENGER RNA
Abstract

One of the principal mechanisms of chemotherapy resistance in highly frequent solid tumors, such as colorectal cancer (CRC), is the decreased activity of drug transport into tumor cells due to low expression of important membrane proteins, such as solute carrier (SLC) transporters. Sequence complementarity is a major determinant for target gene recognition by microRNAs (miRNAs). Single-nucleotide polymorphisms (SNPs) in target sequences transcribed into messenger RNA may therefore alter miRNA binding to these regions by either creating a new site or destroying an existing one. miRSNPs may explain the modulation of expression levels in association with increased/decreased susceptibility to common diseases as well as in chemoresistance and the consequent inter-individual variability in drug response. In the present study, we investigated whether miRSNPs in SLC transporter genes may modulate CRC susceptibility and patient's survival. Using an in silico approach for functional predictions, we analyzed 26 miRSNPs in 9 SLC genes in a cohort of 1368 CRC cases and 698 controls from the Czech Republic. After correcting for multiple tests, we found several miRSNPs significantly associated with patient's survival. SNPs in SLCO3A1 , SLC22A2 and SLC22A3 genes were defined as prognostic factors in the classification and regression tree analysis. In contrast, we did not observe any significant association between miRSNPs and CRC risk. To the best of our knowledge, this is the first study investigating miRSNPs potentially affecting miRNA binding to SLC transporter genes and their impact on CRC susceptibility or patient's prognosis. [ABSTRACT FROM AUTHOR]

Published
2021
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