Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis
Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS)....
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/2/381 |
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| author | Rodolfo Sacco Daryl Ramai Raffaella Tortora Giovan Giuseppe di Costanzo Michela Emma Burlone Mario Pirisi Piera Federico Bruno Daniele Marianna Silletta Paolo Gallo Caterina Cocuzza Maurizio Russello Giuseppe Cabibbo Gabriele Rancatore Silvia Cesario Gianluca Masi Luca Marzi Andrea Mega Alessandro Granito Giulia Pieri Edoardo G. Giannini Rosa Paolillo Gennaro Gadaleta-Caldarola Vincenzo Dadduzio Guido Giordano Luca Giacomelli Simonetta Papa Matteo Renzulli Marcello Maida Michele Ghidini Mauro Borzio Antonio Facciorusso |
| author_facet | Rodolfo Sacco Daryl Ramai Raffaella Tortora Giovan Giuseppe di Costanzo Michela Emma Burlone Mario Pirisi Piera Federico Bruno Daniele Marianna Silletta Paolo Gallo Caterina Cocuzza Maurizio Russello Giuseppe Cabibbo Gabriele Rancatore Silvia Cesario Gianluca Masi Luca Marzi Andrea Mega Alessandro Granito Giulia Pieri Edoardo G. Giannini Rosa Paolillo Gennaro Gadaleta-Caldarola Vincenzo Dadduzio Guido Giordano Luca Giacomelli Simonetta Papa Matteo Renzulli Marcello Maida Michele Ghidini Mauro Borzio Antonio Facciorusso |
| author_sort | Rodolfo Sacco |
| collection | DOAJ |
| description | Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed. Actuarial survival estimates were computed using the Kaplan–Meier method and compared with the log-rank test. We performed an event-based counterfactual mediation analysis to estimate direct (chronic inflammation and immunosuppression), indirect (tobacco smoking, alcohol use, illicit drug abuse with injections), and the total effect of viral etiology on OS. Results were expressed as hazard ratio (HR) and 95% CI. Results: Median OS was 21 months (95% CI: 20–23) in the group with other etiologies and 15 months (14–16) in the group with viral etiology (<i>p</i> < 0.0001). The total effect of viral etiology was associated with OS (HR 2.76, 1.32–5.21), and it was mainly explained by the pure direct effect of viral etiology (HR 2.74, 1.15–4.45). By contrast, its total indirect effect was not associated with poorer survival (HR 1.05, 0.82–2.13). These results were confirmed when considering tobacco, alcohol consumption, or injection drug abuse as potential mediators. Median progression-free survival was 9 months (8–10) in patients with other etiologies and 6 months (5–7) in patients with viral etiology (<i>p</i> < 0.0001). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Patients affected by HCC with nonviral etiology treated with lenvatinib exhibit longer survival than those with viral etiology. This finding may have relevance in the treatment decision-making process. |
| first_indexed | 2024-03-09T13:18:59Z |
| format | Article |
| id | doaj.art-f7dfb3e4727f4ae783e4eece2d571cc2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:18:59Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f7dfb3e4727f4ae783e4eece2d571cc22023-11-30T21:33:04ZengMDPI AGCancers2072-66942023-01-0115238110.3390/cancers15020381Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation AnalysisRodolfo Sacco0Daryl Ramai1Raffaella Tortora2Giovan Giuseppe di Costanzo3Michela Emma Burlone4Mario Pirisi5Piera Federico6Bruno Daniele7Marianna Silletta8Paolo Gallo9Caterina Cocuzza10Maurizio Russello11Giuseppe Cabibbo12Gabriele Rancatore13Silvia Cesario14Gianluca Masi15Luca Marzi16Andrea Mega17Alessandro Granito18Giulia Pieri19Edoardo G. Giannini20Rosa Paolillo21Gennaro Gadaleta-Caldarola22Vincenzo Dadduzio23Guido Giordano24Luca Giacomelli25Simonetta Papa26Matteo Renzulli27Marcello Maida28Michele Ghidini29Mauro Borzio30Antonio Facciorusso31Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, ItalyGastroenterology and Hepatology, University of Utah, Salt Lake City, UT 84112, USALiver Unit, Department of Transplantation, Cardarelli Hospital, 80100 Naples, ItalyLiver Unit, Department of Transplantation, Cardarelli Hospital, 80100 Naples, ItalyDepartment of Internal Medicine, AOU “Maggiore Della Carità”, 28100 Novara, ItalyDepartment of Internal Medicine, AOU “Maggiore Della Carità”, 28100 Novara, ItalyMedical Oncology Unit, Ospedale del Mare, 80100 Naples, ItalyMedical Oncology Unit, Ospedale del Mare, 80100 Naples, ItalyDivision of Medical Oncology, Policlinico Universitario Campus Bio-Medico, 00128 Rome, ItalyClinical Medicine and Hepatology Unit, Campus Bio-Medico University, 00128 Rome, ItalyLiver Unit, ARNAS Garibaldi-Nesima, 95100 Catania, ItalyLiver Unit, ARNAS Garibaldi-Nesima, 95100 Catania, ItalySection of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90121 Palermo, ItalySection of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90121 Palermo, ItalyUnit of Medical Oncology, AOU Pisana, Santa Chiara Hospital, 56121 Pisa, ItalyUnit of Medical Oncology, AOU Pisana, Santa Chiara Hospital, 56121 Pisa, ItalyGastroenterology Unit, Bolzano Regional Hospital, 39100 Bolzano, ItalyGastroenterology Unit, Bolzano Regional Hospital, 39100 Bolzano, ItalyDivision of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, S. Orsola-Malpighi Hospital, IRCCS AOU di Bologna, 40121 Bologna, ItalyGastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16100 Genova, ItalyGastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16100 Genova, ItalyGastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, ItalyMedical Oncology Unit, Mons. A.R. Dimiccoli Hospital, 76121 Barletta, ItalyMedical Oncology Unit, Mons. A.R. Dimiccoli Hospital, 76121 Barletta, ItalyMedical Oncology and Biomolecular Therapy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, ItalyPolistudium SRL, 20135 Milan, ItalyPolistudium SRL, 20135 Milan, ItalyDepartment of Radiology, IRCCS AOU di Bologna, 40121 Bologna, ItalyGastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital, 93100 Caltanissetta, ItalyDivision of Medical Oncology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20100 Milano, ItalyGastroenterologia ed Endoscopia Digestiva, Centro Diagnostico Italiano, 20100 Milan, ItalyGastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, ItalyBackground: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed. Actuarial survival estimates were computed using the Kaplan–Meier method and compared with the log-rank test. We performed an event-based counterfactual mediation analysis to estimate direct (chronic inflammation and immunosuppression), indirect (tobacco smoking, alcohol use, illicit drug abuse with injections), and the total effect of viral etiology on OS. Results were expressed as hazard ratio (HR) and 95% CI. Results: Median OS was 21 months (95% CI: 20–23) in the group with other etiologies and 15 months (14–16) in the group with viral etiology (<i>p</i> < 0.0001). The total effect of viral etiology was associated with OS (HR 2.76, 1.32–5.21), and it was mainly explained by the pure direct effect of viral etiology (HR 2.74, 1.15–4.45). By contrast, its total indirect effect was not associated with poorer survival (HR 1.05, 0.82–2.13). These results were confirmed when considering tobacco, alcohol consumption, or injection drug abuse as potential mediators. Median progression-free survival was 9 months (8–10) in patients with other etiologies and 6 months (5–7) in patients with viral etiology (<i>p</i> < 0.0001). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Patients affected by HCC with nonviral etiology treated with lenvatinib exhibit longer survival than those with viral etiology. This finding may have relevance in the treatment decision-making process.https://www.mdpi.com/2072-6694/15/2/381HCCsurvivalprogressionliver cancermediation analysisviral etiology |
| spellingShingle | Rodolfo Sacco Daryl Ramai Raffaella Tortora Giovan Giuseppe di Costanzo Michela Emma Burlone Mario Pirisi Piera Federico Bruno Daniele Marianna Silletta Paolo Gallo Caterina Cocuzza Maurizio Russello Giuseppe Cabibbo Gabriele Rancatore Silvia Cesario Gianluca Masi Luca Marzi Andrea Mega Alessandro Granito Giulia Pieri Edoardo G. Giannini Rosa Paolillo Gennaro Gadaleta-Caldarola Vincenzo Dadduzio Guido Giordano Luca Giacomelli Simonetta Papa Matteo Renzulli Marcello Maida Michele Ghidini Mauro Borzio Antonio Facciorusso Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis Cancers HCC survival progression liver cancer mediation analysis viral etiology |
| title | Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis |
| title_full | Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis |
| title_fullStr | Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis |
| title_full_unstemmed | Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis |
| title_short | Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis |
| title_sort | role of etiology in hepatocellular carcinoma patients treated with lenvatinib a counterfactual event based mediation analysis |
| topic | HCC survival progression liver cancer mediation analysis viral etiology |
| url | https://www.mdpi.com/2072-6694/15/2/381 |
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