Search

Your search keyword '"Wege, Henning"' showing total 12 results
Start Over Author "Wege, Henning" Publication Type Electronic Resources
12 results on '"Wege, Henning"'

1. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score

Author

Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Himmelsbach, Vera, Schulze, Kornelius, von Felden, Johann, Frundt, Thorben W., Stadler, Marc, Heinzl, Harald, Shmanko, Kateryna, Spahn, Stephan, Radu, Pompilia, Siebenhuener, Alexander R., Mertens, Joachim C., Rahbari, Nuh N., Kuetting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias P., Teufel, Andreas, De Dosso, Sara, Pinato, David J., Pressiani, Tiziana, Meischl, Tobias, Balcar, Lorenz, Mueller, Christian, Mandorfer, Mattias, Reiberger, Thomas, Trauner, Michael, Personeni, Nicola, Rimassa, Lorenza, Bitzer, Michael, Trojan, Joerg, Weinmann, Arndt, Wege, Henning, Dufour, Jean-Francois, Peck-Radosavljevic, Markus, Vogel, Arndt, Pinter, Matthias, Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Himmelsbach, Vera, Schulze, Kornelius, von Felden, Johann, Frundt, Thorben W., Stadler, Marc, Heinzl, Harald, Shmanko, Kateryna, Spahn, Stephan, Radu, Pompilia, Siebenhuener, Alexander R., Mertens, Joachim C., Rahbari, Nuh N., Kuetting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias P., Teufel, Andreas, De Dosso, Sara, Pinato, David J., Pressiani, Tiziana, Meischl, Tobias, Balcar, Lorenz, Mueller, Christian, Mandorfer, Mattias, Reiberger, Thomas, Trauner, Michael, Personeni, Nicola, Rimassa, Lorenza, Bitzer, Michael, Trojan, Joerg, Weinmann, Arndt, Wege, Henning, Dufour, Jean-Francois, Peck-Radosavljevic, Markus, Vogel, Arndt, and Pinter, Matthias

Abstract

Background & Aims: Immunotherapy with atezolizumab plus bevacizumab represents the new standard of care in systemic front-line treatment of hepatocellular carcinoma (HCC). However, biomarkers that predict treatment success and survival remain an unmet need. Methods: Patients with HCC put on PD-(L)1-based immunotherapy were included in a training set (n = 190; 6 European centers) and a validation set (n = 102; 8 European centers). We investigated the prognostic value of baseline variables on overall survival using a Cox model in the training set and developed the easily applicable CRAFITY (CRP and AFP in ImmunoTherapY) score. The score was validated in the independent, external cohort, and evaluated in a cohort of patients treated with sor- afenib (n = 204). Results: Baseline serum alpha-fetoprotein >= 100 ng/ml (hazard ratio [HR] 1.7; p = 0.007) and C-reactive protein >= 1 mg/dl (HR, 1.7; p = 0.007) were identified as independent prognostic factors in multivariable analysis and were used to develop the CRAFITY score. Patients who fulfilled no criterion (0 points; CRAFITY-low) had the longest median overall survival (27.6 (95% CI 19.5-35.8) months), followed by those fulfilling 1 criterion (1 point; CRAFITY-intermediate; 11.3 (95% CI 8.0-14.6) months), and patients meeting both criteria (2 points; CRAFITY-high; 6.4 (95% CI 4.8-8.1) months; p <0.001). Additionally, best radiological response (complete response/partial response/stable disease/ progressive disease) was significantly better in patients with lower CRAFITY score (CRAFITY-low: 9%/20%/52%/20% vs. CRAFITY-intermediate: 3%/25%/36%/36% vs. CRAFITY-high: 2%/ 15%/22%/61%; p = 0.003). These results were confirmed in the independent validation set and in different subgroups, including Child-Pugh A and B, performance status 0 and >= 1 and first-line and later lines. In the sorafenib cohort, CRAFITY was associated with survival, but not radiological response. Conclusions: The CRAFITY score is associated with survival

Published
2022

2. Atezolizumab and bevacizumab with transarterial chemoembolization in hepatocellular carcinoma: the DEMAND trial protocol

Author

Ben Khaled, Najib, Seidensticker, Max, Ricke, Jens, Mayerle, Julia, Oehrle, Bettina, Roessler, Daniel, Teupser, Daniel, Ehmer, Ursula, Bitzer, Michael, Waldschmidt, Dirk, Fuchs, Martin, Reuken, Philipp A., Lange, Christian M., Wege, Henning, Kandulski, Arne, Dechene, Alexander, Venerito, Marino, Berres, Marie-Luise, Luedde, Tom, Kubisch, Ilja, Reiter, Florian P., De Toni, Enrico N., Ben Khaled, Najib, Seidensticker, Max, Ricke, Jens, Mayerle, Julia, Oehrle, Bettina, Roessler, Daniel, Teupser, Daniel, Ehmer, Ursula, Bitzer, Michael, Waldschmidt, Dirk, Fuchs, Martin, Reuken, Philipp A., Lange, Christian M., Wege, Henning, Kandulski, Arne, Dechene, Alexander, Venerito, Marino, Berres, Marie-Luise, Luedde, Tom, Kubisch, Ilja, Reiter, Florian P., and De Toni, Enrico N.

Abstract

The combination of the anti-PD-L1 antibody atezolizumab and the anti-VEGF bevacizumab is the first approved immunotherapeutic regimen for first-line therapy in patients with unresectable hepatocellular carcinoma (HCC), currently approved in more than 80 countries. The efficacy and tolerability of this regimen suggest that the use of atezolizumab bevacizumab could be extended to the treatment of patients with intermediate-stage HCC in combination with transarterial chemoembolization (TACE). The authors describe the rationale and design of the DEMAND study. This investigator-initiated, multicenter, randomized phase 2 study is the first trial to evaluate the safety and efficacy of atezolizumab bevacizumab prior to or in combination with TACE in patients with intermediate-stage HCC. The primary end point is the 24-month survival rate; secondary end points include objective response rate, progression-free survival, safety and quality of life.

Published
2022

3. Atezolizumab and bevacizumab with transarterial chemoembolization in hepatocellular carcinoma: The DEMAND randomized phase II clinical trial

Author

De Toni, Enrico N., Kubisch, Ilja, Ben Khaled, Najib, Ricke, Jens, Mayerle, Julia, Ehmer, Ursula, Waldschmidt, Dirk, Roessler, Daniel Christoph, Oehrle, Bettina, Bitzer, Michael, Kandulski, Arne, Reuken, Philipp A., Wege, Henning, Seidensticker, Max, De Toni, Enrico N., Kubisch, Ilja, Ben Khaled, Najib, Ricke, Jens, Mayerle, Julia, Ehmer, Ursula, Waldschmidt, Dirk, Roessler, Daniel Christoph, Oehrle, Bettina, Bitzer, Michael, Kandulski, Arne, Reuken, Philipp A., Wege, Henning, and Seidensticker, Max

Published
2022

4. NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Author

Pfister, Dominik, Nunez, Nicolas Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Mueller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jorn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D'Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jorg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rossler, Fabian, Siebenhuner, Alexander, De Dosso, Sara, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Mueller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kutting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, Ruiz de Galarreta, Marina, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., Heikenwalder, Mathias, Pfister, Dominik, Nunez, Nicolas Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Mueller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jorn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D'Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jorg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rossler, Fabian, Siebenhuner, Alexander, De Dosso, Sara, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Mueller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kutting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, Ruiz de Galarreta, Marina, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., and Heikenwalder, Mathias

Abstract

Hepatocellular carcinoma (HCC) can have viral or non-viral causes(1-5). Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need(6,7). Here we report the progressive accumulation of exhausted, unconventionally activated CD8(+)PD1(+) T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8(+)PD1(+) T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8(+)PD1(+)CXCR6(+), TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8(+) T cells or TNF neutralization, suggesting that CD8(+) T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8(+)PD1(+) T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of pa

Published
2021

5. NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Author

Pfister, Dominik, Nunez, Nicolas Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Muller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jorn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D'Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jorg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rossler, Fabian, Siebenhuner, Alexander, De Dosso, Sara, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Muller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kutting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, de Galarreta, Marina Ruiz, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., Heikenwalder, Mathias, Pfister, Dominik, Nunez, Nicolas Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Muller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jorn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D'Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jorg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rossler, Fabian, Siebenhuner, Alexander, De Dosso, Sara, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Muller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kutting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, de Galarreta, Marina Ruiz, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., and Heikenwalder, Mathias

Abstract

Hepatocellular carcinoma (HCC) can have viral or non-viral causes(1-5). Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need(6,7). Here we report the progressive accumulation of exhausted, unconventionally activated CD8(+)PD1(+) T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8(+)PD1(+) T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASHHCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8(+)PD1(+)CXCR6(+), TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8(+) T cells or TNF neutralization, suggesting that CD8(+) T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8(+)PD1(+) T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of

Published
2021

6. Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life Cohort

Author

Finkelmeier, Fabian, Scheiner, Bernhard, Leyh, Catherine, Best, Jan, Fruendt, Thorben Wilhelm, Czauderna, Carolin, Beutel, Alica, Bettinger, Dominik, WeiSS, Johannes, Meischl, Tobias, Kuetting, Fabian, Waldschmidt, Dirk-Thomas, Radu, Pompilia, Schultheiss, Michael, Peiffer, Kai-Henrik, Ettrich, Thomas J., Weinmann, Arndt, Wege, Henning, Venerito, Marino, Dufour, Jean-Francois, Lange, Christian M., Pinter, Matthias, Waidmann, Oliver, Finkelmeier, Fabian, Scheiner, Bernhard, Leyh, Catherine, Best, Jan, Fruendt, Thorben Wilhelm, Czauderna, Carolin, Beutel, Alica, Bettinger, Dominik, WeiSS, Johannes, Meischl, Tobias, Kuetting, Fabian, Waldschmidt, Dirk-Thomas, Radu, Pompilia, Schultheiss, Michael, Peiffer, Kai-Henrik, Ettrich, Thomas J., Weinmann, Arndt, Wege, Henning, Venerito, Marino, Dufour, Jean-Francois, Lange, Christian M., Pinter, Matthias, and Waidmann, Oliver

Abstract

Background and Aims: The multikinase inhibitor cabozantinib has been approved for hepatocellular carcinoma (HCC) previously treated with sorafenib. We report safety and efficacy data of an international, multicenter, real-life cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 11 centers in Austria, Switzerland, and Germany. Patients' characteristics, adverse events, duration of treatment and overall survival (OS) data were analyzed until April 1, 2020. Results: Eighty-eight patients from 11 centers were included. The predominant underlying liver diseases were NAFLD/NASH in 26 (30%) and hepatitis C infection in 21 (24%) patients. Seventy-eight patients (89%) were classified as Barcelona clinic liver cancer (BCLC) stage C. Sixty patients (68%) were Child-Pugh A, whereas 22 (25%) were Child-Pugh B, respectively. Cabozantinib was used as systemic second- and third-line or later treatment in 41 (47%) and 46 (52%) patients, respectively. The following best responses under cabozantinib were documented: partial response in 6 (7%), stable disease in 28 (32%), and progressive disease in 28 (32%) patients, respectively. Fifty-two patients (59%) died during follow-up. The median OS from start of cabozantinib treatment was 7.0 months in the entire cohort and 9.7 months in Child-Pugh A patients, while Child-Pugh B patients had a median OS of 3.4 months, respectively. Thirty-seven (42%) patients fulfilled the CELESTIAL inclusion and exclusion criteria, showing a median OS of 11.1 months. Most common adverse events were fatigue (15.6%) and diarrhea (15.6%). Conclusion: Cabozantinib treatment was effective, safe, and feasible in patients with advanced HCC in patients with compensated cirrhosis. Patients in the real-life setting had more advanced liver disease - in which 25% of patients were Child-Pugh B. However, OS in patients with Child-Pugh A cirrhosis was similar to

Published
2021

7. NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Author

Pfister, Dominik, Nunez, Nicolas Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Mueller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jorn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D'Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jorg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rossler, Fabian, Siebenhuner, Alexander, De Dosso, Sara, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Mueller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kutting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, Ruiz de Galarreta, Marina, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., Heikenwalder, Mathias, Pfister, Dominik, Nunez, Nicolas Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Mueller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jorn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D'Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jorg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rossler, Fabian, Siebenhuner, Alexander, De Dosso, Sara, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Mueller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kutting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, Ruiz de Galarreta, Marina, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., and Heikenwalder, Mathias

Abstract

Hepatocellular carcinoma (HCC) can have viral or non-viral causes(1-5). Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need(6,7). Here we report the progressive accumulation of exhausted, unconventionally activated CD8(+)PD1(+) T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8(+)PD1(+) T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8(+)PD1(+)CXCR6(+), TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8(+) T cells or TNF neutralization, suggesting that CD8(+) T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8(+)PD1(+) T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of pa

Published
2021

8. NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Author

Pfister, Dominik, Nunez, Nicolas Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Muller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jorn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D'Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jorg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rossler, Fabian, Siebenhuner, Alexander, De Dosso, Sara, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Muller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kutting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, de Galarreta, Marina Ruiz, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., Heikenwalder, Mathias, Pfister, Dominik, Nunez, Nicolas Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Muller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jorn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D'Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jorg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rossler, Fabian, Siebenhuner, Alexander, De Dosso, Sara, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Muller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kutting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, de Galarreta, Marina Ruiz, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., and Heikenwalder, Mathias

Abstract

Hepatocellular carcinoma (HCC) can have viral or non-viral causes(1-5). Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need(6,7). Here we report the progressive accumulation of exhausted, unconventionally activated CD8(+)PD1(+) T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8(+)PD1(+) T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASHHCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8(+)PD1(+)CXCR6(+), TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8(+) T cells or TNF neutralization, suggesting that CD8(+) T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8(+)PD1(+) T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of

Published
2021

9. Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life Cohort

Author

Finkelmeier, Fabian, Scheiner, Bernhard, Leyh, Catherine, Best, Jan, Fruendt, Thorben Wilhelm, Czauderna, Carolin, Beutel, Alica, Bettinger, Dominik, WeiSS, Johannes, Meischl, Tobias, Kuetting, Fabian, Waldschmidt, Dirk-Thomas, Radu, Pompilia, Schultheiss, Michael, Peiffer, Kai-Henrik, Ettrich, Thomas J., Weinmann, Arndt, Wege, Henning, Venerito, Marino, Dufour, Jean-Francois, Lange, Christian M., Pinter, Matthias, Waidmann, Oliver, Finkelmeier, Fabian, Scheiner, Bernhard, Leyh, Catherine, Best, Jan, Fruendt, Thorben Wilhelm, Czauderna, Carolin, Beutel, Alica, Bettinger, Dominik, WeiSS, Johannes, Meischl, Tobias, Kuetting, Fabian, Waldschmidt, Dirk-Thomas, Radu, Pompilia, Schultheiss, Michael, Peiffer, Kai-Henrik, Ettrich, Thomas J., Weinmann, Arndt, Wege, Henning, Venerito, Marino, Dufour, Jean-Francois, Lange, Christian M., Pinter, Matthias, and Waidmann, Oliver

Abstract

Background and Aims: The multikinase inhibitor cabozantinib has been approved for hepatocellular carcinoma (HCC) previously treated with sorafenib. We report safety and efficacy data of an international, multicenter, real-life cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 11 centers in Austria, Switzerland, and Germany. Patients' characteristics, adverse events, duration of treatment and overall survival (OS) data were analyzed until April 1, 2020. Results: Eighty-eight patients from 11 centers were included. The predominant underlying liver diseases were NAFLD/NASH in 26 (30%) and hepatitis C infection in 21 (24%) patients. Seventy-eight patients (89%) were classified as Barcelona clinic liver cancer (BCLC) stage C. Sixty patients (68%) were Child-Pugh A, whereas 22 (25%) were Child-Pugh B, respectively. Cabozantinib was used as systemic second- and third-line or later treatment in 41 (47%) and 46 (52%) patients, respectively. The following best responses under cabozantinib were documented: partial response in 6 (7%), stable disease in 28 (32%), and progressive disease in 28 (32%) patients, respectively. Fifty-two patients (59%) died during follow-up. The median OS from start of cabozantinib treatment was 7.0 months in the entire cohort and 9.7 months in Child-Pugh A patients, while Child-Pugh B patients had a median OS of 3.4 months, respectively. Thirty-seven (42%) patients fulfilled the CELESTIAL inclusion and exclusion criteria, showing a median OS of 11.1 months. Most common adverse events were fatigue (15.6%) and diarrhea (15.6%). Conclusion: Cabozantinib treatment was effective, safe, and feasible in patients with advanced HCC in patients with compensated cirrhosis. Patients in the real-life setting had more advanced liver disease - in which 25% of patients were Child-Pugh B. However, OS in patients with Child-Pugh A cirrhosis was similar to

Published
2021

10. Assessing the impact of COVID-19 on liver cancer management (CERO-19)

Author

Muñoz-Martínez, Sergio, Sapena, Victor, Forner, Alejandro, Nault, Jean-Charles, Sapisochin, Gonzalo, Rimassa, Lorenza, Sangro, Bruno, Bruix, Jordi, Sanduzzi-Zamparelli, Marco, Hołówko, Wacław, El Kassas, Mohamed, Mocan, Tudor, Bouattour, Mohamed, Merle, Philippe, Hoogwater, Frederik J.H., Alqahtani, Saleh A., Reeves, Helen L., Pinato, David J., Giorgakis, Emmanouil, Meyer, Tim, Villadsen, Gerda Elisabeth, Wege, Henning, Salati, Massimiliano, Mínguez, Beatriz, Di Costanzo, Giovan Giuseppe, Roderburg, Christoph, Tacke, Frank, Varela, María, Galle, Peter R., Alvares-da-Silva, Mario Reis, Trojan, Jörg, Bridgewater, John, Cabibbo, Giuseppe, Toso, Christian, Lachenmayer, Anja, Casadei-Gardini, Andrea, Toyoda, Hidenori, Lüdde, Tom, Villani, Rosanna, Matilla Peña, Ana María, Guedes Leal, Cassia Regina, Ronzoni, Monica, Delgado, Manuel, Perelló, Christie, Pascual, Sonia, Lledó, José Luis, Argemi, Josepmaria, Basu, Bristi, da Fonseca, Leonardo, Acevedo, Juan, Siebenhüner, Alexander R., Braconi, Chiara, Meyers, Brandon M., Granito, Alessandro, Sala, Margarita, Rodríguez-Lope, Carlos, Blaise, Lorraine, Romero-Gómez, Manuel, Piñero, Federico, Gomez, Dhanny, Mello, Vivianne, Camargo Pinheiro Alves, Rogerio, França, Alex, Branco, Fernanda, Brandi, Giovanni, Pereira, Gustavo, Coll, Susanna, Guarino, María, Benítez, Carlos, Anders, Maria Margarita, Bandi, Juan C., Vergara, Mercedes, Calvo, Mariona, Peck-Radosavljevic, Markus, García-Juárez, Ignacio, Cardinale, Vincenzo, Lozano, Mar, Gambato, Martina, Okolicsanyi, Stefano, Morales- Arraez, Dalia, Elvevi, Alessandra, Muñoz, Alberto E., Lué, Alberto, Iavarone, Massimo, Reig, María, Muñoz-Martínez, Sergio, Sapena, Victor, Forner, Alejandro, Nault, Jean-Charles, Sapisochin, Gonzalo, Rimassa, Lorenza, Sangro, Bruno, Bruix, Jordi, Sanduzzi-Zamparelli, Marco, Hołówko, Wacław, El Kassas, Mohamed, Mocan, Tudor, Bouattour, Mohamed, Merle, Philippe, Hoogwater, Frederik J.H., Alqahtani, Saleh A., Reeves, Helen L., Pinato, David J., Giorgakis, Emmanouil, Meyer, Tim, Villadsen, Gerda Elisabeth, Wege, Henning, Salati, Massimiliano, Mínguez, Beatriz, Di Costanzo, Giovan Giuseppe, Roderburg, Christoph, Tacke, Frank, Varela, María, Galle, Peter R., Alvares-da-Silva, Mario Reis, Trojan, Jörg, Bridgewater, John, Cabibbo, Giuseppe, Toso, Christian, Lachenmayer, Anja, Casadei-Gardini, Andrea, Toyoda, Hidenori, Lüdde, Tom, Villani, Rosanna, Matilla Peña, Ana María, Guedes Leal, Cassia Regina, Ronzoni, Monica, Delgado, Manuel, Perelló, Christie, Pascual, Sonia, Lledó, José Luis, Argemi, Josepmaria, Basu, Bristi, da Fonseca, Leonardo, Acevedo, Juan, Siebenhüner, Alexander R., Braconi, Chiara, Meyers, Brandon M., Granito, Alessandro, Sala, Margarita, Rodríguez-Lope, Carlos, Blaise, Lorraine, Romero-Gómez, Manuel, Piñero, Federico, Gomez, Dhanny, Mello, Vivianne, Camargo Pinheiro Alves, Rogerio, França, Alex, Branco, Fernanda, Brandi, Giovanni, Pereira, Gustavo, Coll, Susanna, Guarino, María, Benítez, Carlos, Anders, Maria Margarita, Bandi, Juan C., Vergara, Mercedes, Calvo, Mariona, Peck-Radosavljevic, Markus, García-Juárez, Ignacio, Cardinale, Vincenzo, Lozano, Mar, Gambato, Martina, Okolicsanyi, Stefano, Morales- Arraez, Dalia, Elvevi, Alessandra, Muñoz, Alberto E., Lué, Alberto, Iavarone, Massimo, and Reig, María

Abstract

[Background & Aims] The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic., [Methods] An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave., [Results] Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37)., [Conclusions] The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making., [Lay summary] The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

Published
2021

11. Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial.

Author

UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Merle, Philippe, Blanc, Jean-Frederic, Phelip, Jean-Marc, Pelletier, Gilles, Bronowicki, Jean-Pierre, Touchefeu, Yann, Pageaux, Georges, Gerolami, René, Habersetzer, François, Nguyen-Khac, Eric, Casadei-Gardini, Andrea, Borbath, Ivan, Tran, Albert, Wege, Henning, Saad, Amr Shafik, Colombo, Massimo, Abergel, Armand, Richou, Carine, Waked, Imam, Yee, Nelson S, Molé, Audrey, Attali, Pierre, Le Boulicaut, Julie, Vasseur, Bérangère, RELIVE Investigators, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Merle, Philippe, Blanc, Jean-Frederic, Phelip, Jean-Marc, Pelletier, Gilles, Bronowicki, Jean-Pierre, Touchefeu, Yann, Pageaux, Georges, Gerolami, René, Habersetzer, François, Nguyen-Khac, Eric, Casadei-Gardini, Andrea, Borbath, Ivan, Tran, Albert, Wege, Henning, Saad, Amr Shafik, Colombo, Massimo, Abergel, Armand, Richou, Carine, Waked, Imam, Yee, Nelson S, Molé, Audrey, Attali, Pierre, Le Boulicaut, Julie, Vasseur, Bérangère, and RELIVE Investigators

Abstract

BACKGROUND: Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. METHODS: We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m2 doxorubicin-loaded nanoparticles (30 mg/m2 group), 20 mg/m2 doxorubicin-loaded nanoparticles (20 mg/m2 group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01655693. FINDINGS: Between June 15, 2012, and Jan 27, 2017, 541 patients were screened, of whom 144 were excluded and 397 were randomly assigned to one of the groups (133 to the 30 mg/m2 group; 130 to the 20 mg/m2 group; and 134 to the control group). Median follow-up was 22·7 months (IQR 11·2-34·9). After pooling the doxorubicin groups for the efficacy analysis, median overall survival was 9·1 months (95% CI 8·1-10·4) in the pooled doxorubicin-loaded nanoparticles group and 9·0 months (7·1-11·8) in the control group (HR 1·00 [95% CI 0·78-1·28], two-sided p=0·99). 227 (94%) of 242 patients who received doxorubicin-loaded nanoparticles and 100 (75%) of 134 patients in the control group had at least one treatment-emergent adverse event. The most common drug-related grade 3 or 4 tr

Published
2019

12. Correction: Genetic Variants in PNPLA3 and TM6SF2 Predispose to the Development of Hepatocellular Carcinoma in Individuals With Alcohol-Related Cirrhosis.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Stickel, Felix, Buch, Stephan, Nischalke, Hans Dieter, Weiss, Karl Heinz, Gotthardt, Daniel, Fischer, Janett, Rosendahl, Jonas, Marot, Astrid, Elamly, Mona, Casper, Markus, Lammert, Frank, McQuillin, Andrew, Zopf, Steffen, Spengler, Ulrich, Marhenke, Silke, Kirstein, Martha M, Vogel, Arndt, Eyer, Florian, von Felden, Johann, Wege, Henning, Buch, Thorsten, Schafmayer, Clemens, Braun, Felix, Deltenre, Pierre, Berg, Thomas, Morgan, Marsha Y, Hampe, Jochen, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Stickel, Felix, Buch, Stephan, Nischalke, Hans Dieter, Weiss, Karl Heinz, Gotthardt, Daniel, Fischer, Janett, Rosendahl, Jonas, Marot, Astrid, Elamly, Mona, Casper, Markus, Lammert, Frank, McQuillin, Andrew, Zopf, Steffen, Spengler, Ulrich, Marhenke, Silke, Kirstein, Martha M, Vogel, Arndt, Eyer, Florian, von Felden, Johann, Wege, Henning, Buch, Thorsten, Schafmayer, Clemens, Braun, Felix, Deltenre, Pierre, Berg, Thomas, Morgan, Marsha Y, and Hampe, Jochen

Abstract

Author Pierre Deltenre, MD should appear in the author list in position 25, between Felix Braun and Thomas Berg. He should also have a PhD degree added to his name.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results