Survival after the diagnosis of de novo malignancy in liver transplant recipients
Corresponding Author
Martina Taborelli
Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute IRCCS, Aviano, Italy
Correspondence to: Martina Taborelli, Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, via Franco Gallini 2, 33081 Aviano (PN), Italy, E-mail: [email protected]; Tel.: +39-0434-659187; Fax: +39-0434-659231Search for more papers by this authorPierluca Piselli
Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
Search for more papers by this authorGiuseppe Maria Ettorre
Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Italy
Search for more papers by this authorUmberto Baccarani
Department of Medicine, University of Udine, Udine, Italy
Search for more papers by this authorPatrizia Burra
Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
Search for more papers by this authorAugusto Lauro
Liver and Multiorgan Transplant Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy
Search for more papers by this authorLaura Galatioto
Department of Gastroenterology and Hepatology, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center, Palermo, Italy
Search for more papers by this authorMaria Rendina
Department of Emergency and Organ Transplantation, Section of Gastroenterology, University Hospital, Bari, Italy
Search for more papers by this authorSarah Shalaby
Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
Search for more papers by this authorRaffaella Petrara
Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
Search for more papers by this authorFrancesco Nudo
Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy
Search for more papers by this authorLuca Toti
UOC Transplant Unit, Department of Surgery, Tor Vergata University, Rome, Italy
Search for more papers by this authorGiovanni Fantola
Department of Surgery, General and Hepatic Transplantation Surgery Unit, A.O.B. Brotzu, Cagliari, Italy
Search for more papers by this authorClaudia Cimaglia
Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
Search for more papers by this authorAlessandro Agresta
Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
Search for more papers by this authorGiovanni Vennarecci
Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Italy
Search for more papers by this authorAntonio Daniele Pinna
Liver and Multiorgan Transplant Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy
Search for more papers by this authorSalvatore Gruttadauria
Department of Gastroenterology and Hepatology, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center, Palermo, Italy
Search for more papers by this authorAndrea Risaliti
Department of Medicine, University of Udine, Udine, Italy
Search for more papers by this authorAlfredo Di Leo
Department of Emergency and Organ Transplantation, Section of Gastroenterology, University Hospital, Bari, Italy
Search for more papers by this authorMassimo Rossi
Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy
Search for more papers by this authorGiuseppe Tisone
UOC Transplant Unit, Department of Surgery, Tor Vergata University, Rome, Italy
Search for more papers by this authorFausto Zamboni
Department of Surgery, General and Hepatic Transplantation Surgery Unit, A.O.B. Brotzu, Cagliari, Italy
Search for more papers by this authorDiego Serraino
Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute IRCCS, Aviano, Italy
Search for more papers by this authorfor the Italian Transplant and Cancer Cohort Study
Others of the Italian Transplant & Cancer Cohort Study: Giacomo Zanus, Stefano Zanini, Paolo Rigotti (Padua University Hospital, Padua, Italy); Francesco Paolo Schena, Giuseppe Grandaliano, Marco Fiorentino, (University Hospital, Bari, Italy); Paolo Di Gioia, Sara Pellegrini, Chiara Zanfi, Maria Piera Scolari, Sergio Stefoni, Paola Todeschini, Laura Panicali, Chiara Valentini (“S. Orsola-Malpighi” Hospital, Bologna); Gian Luigi Adani, Dario Lorenzin (Udine University, Udine, Italy); Marco Colasanti, Manuela Coco, Fabrizio Ettorre, Roberto Santoro, Lucia Miglioresi (S. Camillo Hospital, Rome, Italy); Gianluca Mennini (Umberto I Policlinic, Rome, Italy); Annachiara Casella, Laura Fazzolari, Daniele Sforza, Giuseppe Iaria, Carlo Gazia, Chiara Belardi (Tor Vergata University, Rome, Italy); Gianpiero D'Offizi, Ubaldo Visco Comandini, Raffaella Lionetti, Marzia Montalbano, Chiara Taibi (INMI “L. Spallanzani”, Rome, Italy); Gian Benedetto Piredda, Maria Benigna Michittu, Maria Gavina Murgia, Bruno Onano (“Brotzu” Hospital, Cagliari, Italy); Lucia Fratino, Luigino Dal Maso, Paolo De Paoli, Diana Verdirosi, Emanuela Vaccher (CRO Aviano National Cancer Institute, Aviano, Italy); Francesco Pisani, Antonio Famulari, Federica Delreno, Samuele Iesari, Linda De Luca (University of L'Aquila, L'Aquila, Italy); Maurizio Iaria, Enzo Capocasale, Elena Cremaschi (Parma University Hospital); Silvio Sandrini, Francesca Valerio, Valentina Mazzucotelli, Nicola Bossini, Gisella Setti (Spedali Civili of Brescia, Brescia, Italy); Massimiliano Veroux, Pierfrancesco Veroux, Giuseppe Giuffrida, Alessia Giaquinta, Domenico Zerbo (Policlinico of Catania, Catania, Italy); Ghil Busnach, Laura Di Leo, Maria Luisa Perrino, Marialuisa Querques, Valeriana Colombo, Maria Chiara Sghirlanzoni (“Niguarda Ca' Granda” Hospital, Milan, Italy); Piergiorgio Messa, Antonio Leoni (“Maggiore-Mangiagalli” Hospital, Milan, Italy); Vito Sparacino, Flavia Caputo, Barbara Buscemi (Policlinico of Palermo, Palermo, Italy); Franco Citterio, Gionata Spagnoletti, Maria Paola Salerno, Evaldo Favi (Policlinico “A. Gemelli”, Rome, Italy); Giuseppe Paolo Segoloni, Luigi Biancone, Antonio Lavacca (“Molinette” Hospital, Turin, Italy); Maria Cristina Maresca, Carmelo Cascone, Bice Virgilio (Treviso Hospital, Treviso, Italy); Donato Donati, Fiorella Dossi, Andrea Fontanella, Andrea Ambrosini, Marco Di Cicco (“Ospedale di Circolo”, Varese, Italy).Search for more papers by this authorCorresponding Author
Martina Taborelli
Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute IRCCS, Aviano, Italy
Correspondence to: Martina Taborelli, Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, via Franco Gallini 2, 33081 Aviano (PN), Italy, E-mail: [email protected]; Tel.: +39-0434-659187; Fax: +39-0434-659231Search for more papers by this authorPierluca Piselli
Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
Search for more papers by this authorGiuseppe Maria Ettorre
Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Italy
Search for more papers by this authorUmberto Baccarani
Department of Medicine, University of Udine, Udine, Italy
Search for more papers by this authorPatrizia Burra
Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
Search for more papers by this authorAugusto Lauro
Liver and Multiorgan Transplant Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy
Search for more papers by this authorLaura Galatioto
Department of Gastroenterology and Hepatology, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center, Palermo, Italy
Search for more papers by this authorMaria Rendina
Department of Emergency and Organ Transplantation, Section of Gastroenterology, University Hospital, Bari, Italy
Search for more papers by this authorSarah Shalaby
Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
Search for more papers by this authorRaffaella Petrara
Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
Search for more papers by this authorFrancesco Nudo
Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy
Search for more papers by this authorLuca Toti
UOC Transplant Unit, Department of Surgery, Tor Vergata University, Rome, Italy
Search for more papers by this authorGiovanni Fantola
Department of Surgery, General and Hepatic Transplantation Surgery Unit, A.O.B. Brotzu, Cagliari, Italy
Search for more papers by this authorClaudia Cimaglia
Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
Search for more papers by this authorAlessandro Agresta
Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
Search for more papers by this authorGiovanni Vennarecci
Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Italy
Search for more papers by this authorAntonio Daniele Pinna
Liver and Multiorgan Transplant Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy
Search for more papers by this authorSalvatore Gruttadauria
Department of Gastroenterology and Hepatology, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center, Palermo, Italy
Search for more papers by this authorAndrea Risaliti
Department of Medicine, University of Udine, Udine, Italy
Search for more papers by this authorAlfredo Di Leo
Department of Emergency and Organ Transplantation, Section of Gastroenterology, University Hospital, Bari, Italy
Search for more papers by this authorMassimo Rossi
Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy
Search for more papers by this authorGiuseppe Tisone
UOC Transplant Unit, Department of Surgery, Tor Vergata University, Rome, Italy
Search for more papers by this authorFausto Zamboni
Department of Surgery, General and Hepatic Transplantation Surgery Unit, A.O.B. Brotzu, Cagliari, Italy
Search for more papers by this authorDiego Serraino
Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute IRCCS, Aviano, Italy
Search for more papers by this authorfor the Italian Transplant and Cancer Cohort Study
Others of the Italian Transplant & Cancer Cohort Study: Giacomo Zanus, Stefano Zanini, Paolo Rigotti (Padua University Hospital, Padua, Italy); Francesco Paolo Schena, Giuseppe Grandaliano, Marco Fiorentino, (University Hospital, Bari, Italy); Paolo Di Gioia, Sara Pellegrini, Chiara Zanfi, Maria Piera Scolari, Sergio Stefoni, Paola Todeschini, Laura Panicali, Chiara Valentini (“S. Orsola-Malpighi” Hospital, Bologna); Gian Luigi Adani, Dario Lorenzin (Udine University, Udine, Italy); Marco Colasanti, Manuela Coco, Fabrizio Ettorre, Roberto Santoro, Lucia Miglioresi (S. Camillo Hospital, Rome, Italy); Gianluca Mennini (Umberto I Policlinic, Rome, Italy); Annachiara Casella, Laura Fazzolari, Daniele Sforza, Giuseppe Iaria, Carlo Gazia, Chiara Belardi (Tor Vergata University, Rome, Italy); Gianpiero D'Offizi, Ubaldo Visco Comandini, Raffaella Lionetti, Marzia Montalbano, Chiara Taibi (INMI “L. Spallanzani”, Rome, Italy); Gian Benedetto Piredda, Maria Benigna Michittu, Maria Gavina Murgia, Bruno Onano (“Brotzu” Hospital, Cagliari, Italy); Lucia Fratino, Luigino Dal Maso, Paolo De Paoli, Diana Verdirosi, Emanuela Vaccher (CRO Aviano National Cancer Institute, Aviano, Italy); Francesco Pisani, Antonio Famulari, Federica Delreno, Samuele Iesari, Linda De Luca (University of L'Aquila, L'Aquila, Italy); Maurizio Iaria, Enzo Capocasale, Elena Cremaschi (Parma University Hospital); Silvio Sandrini, Francesca Valerio, Valentina Mazzucotelli, Nicola Bossini, Gisella Setti (Spedali Civili of Brescia, Brescia, Italy); Massimiliano Veroux, Pierfrancesco Veroux, Giuseppe Giuffrida, Alessia Giaquinta, Domenico Zerbo (Policlinico of Catania, Catania, Italy); Ghil Busnach, Laura Di Leo, Maria Luisa Perrino, Marialuisa Querques, Valeriana Colombo, Maria Chiara Sghirlanzoni (“Niguarda Ca' Granda” Hospital, Milan, Italy); Piergiorgio Messa, Antonio Leoni (“Maggiore-Mangiagalli” Hospital, Milan, Italy); Vito Sparacino, Flavia Caputo, Barbara Buscemi (Policlinico of Palermo, Palermo, Italy); Franco Citterio, Gionata Spagnoletti, Maria Paola Salerno, Evaldo Favi (Policlinico “A. Gemelli”, Rome, Italy); Giuseppe Paolo Segoloni, Luigi Biancone, Antonio Lavacca (“Molinette” Hospital, Turin, Italy); Maria Cristina Maresca, Carmelo Cascone, Bice Virgilio (Treviso Hospital, Treviso, Italy); Donato Donati, Fiorella Dossi, Andrea Fontanella, Andrea Ambrosini, Marco Di Cicco (“Ospedale di Circolo”, Varese, Italy).Search for more papers by this authorAbstract
In the setting of liver transplant (LT), the survival after the diagnosis of de novo malignancies (DNMs) has been poorly investigated. In this study, we assessed the impact of DNMs on survival of LT recipients as compared to corresponding LT recipients without DNM. A nested case–control study was conducted in a cohort of 2,818 LT recipients enrolled in nine Italian centres between 1985 and 2014. Cases were 244 LT recipients who developed DNMs after LT. For each case, two controls matched for gender, age, and year at transplant were selected by incidence density sampling among cohort members without DNM. The survival probabilities were estimated using the Kaplan–Meier method. Hazard ratios (HRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. The all-cancer 10-year survival was 43% in cases versus 70% in controls (HR = 4.66; 95% CI: 3.17–6.85). Survival was impaired in cases for all the most frequent cancer types, including lung (HR = 37.13; 95% CI: 4.98–276.74), non-Hodgkin lymphoma (HR = 6.57; 95% CI: 2.15–20.01), head and neck (HR = 4.65; 95% CI: 1.81–11.95), and colon-rectum (HR = 3.61; 95% CI: 1.08–12.07). The survival gap was observed for both early and late mortality, although the effect was more pronounced in the first year after cancer diagnosis. No significant differences in survival emerged for Kaposi's sarcoma and nonmelanoma skin cancers. The survival gap herein quantified included a broad range of malignancies following LT and prompts close monitoring during the post-transplant follow-up to ensure early cancer diagnosis and to improve survival.
Abstract
What's new?
Solid-organ transplant recipients are at higher risk of developing several cancer types compared with the general population. The prognostic impact of de novo malignancies (DNMs) in these patients remain poorly investigated, however. This study shows the detrimental effect of DNMs on survival of liver transplant (LT) recipients as compared to matched LT recipients without DNM. The all-cancer 10-year survival was 43% versus 70% in controls. This pattern was consistent for all the most frequent cancer types, except Kaposi's sarcoma and nonmelanoma skin cancer. The findings call for close post-transplant follow-up to detect tumors at earlier stages when treatments are more effective.
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