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1. Clear Improvement in Real-World Chronic Myeloid Leukemia Survival: A Comparison With Randomized Controlled Trials

Author

Vener, C., Rossi, S., Minicozzi, P., Marcos-Gragera, R., Poirel, H. A., Maynadie, M., Troussard, X., Pravettoni, G., De Angelis, R., Sant, M., Hackl, M., Van Eycken, E., Valerianova, Z., Sekerija, M., Pavlou, P., Dusek, L., Storm, H., Magi, M., Innos, K., Malila, N., Pitkaniemi, J., Velten, M., Bouvier, A. M., Jooste, V., Guizard, A. V., Launoy, G., Yonli, S. D., Woronoff, A. S., Nousbaum, J. B., Coureau, G., Monnereau, A., Baldi, I., Hammas, K., Tretarre, B., Colonna, M., Plouvier, S., D'Almeida, T., Molinie, F., Cowppli-Bony, A., Bara, S., Schvartz, C., Defossez, G., Lapotre-Ledoux, B., Grosclaude, P., Luttmann, S., Stabenow, R., Nennecke, A., Kieschke, J., Zeissig, S., Holleczek, B., Katalinic, A., Birgisson, H., Murray, D., Walsh, P. M., Mazzoleni, G., Vittadello, F., Cuccaro, F., Galasso, R., Sampietro, G., Rosso, S., Magoni, M., Ferrante, M., Sardo, A. S., Gambino, M. L., Ballotari, P., Giacomazzi, E., Ferretti, S., Caldarella, A., Manneschi, G., Gatta, G., Baili, P., Berrino, F., Botta, L., Trama, A., Lillini, R., Bernasconi, A., Bonfarnuzzo, S., Didone, F., Lasalvia, P., Del Monego, G., Magri, M. C., Buratti, L., Serraino, D., Dal Maso, L., Capocaccia, R., Demuru, E., Di Benedetto, C., Santaquilani, M., Venanzi, S., Filiberti, R. A., Iacovacci, S., Gennaro, V., Russo, A. G., Spagnoli, G., D'Oro, L. C., Fusco, M., Vitale, M. F., Usala, M., Vitale, F., Michiara, M., Chiranda, G., Cascone, G., Spata, E., Mangone, L., Falcini, F., Cavallo, R., Piras, D., Madeddu, A., Bella, F., Fanetti, A. C., Minerba, S., Candela, G., Scuderi, T., Rizzello, R. V., Stracci, F., Tagliabue, G., Rugge, M., Brustolin, A., Pildava, S., Smailyte, G., Azzopardi, M., Johannesen, T. B., Didkowska, J., Wojciechowska, U., Bielska-Lasota, M., Pais, A., Pontes, J. L., Miranda, A., Diba, C. S., Zadnik, V., Zagar, T., Escudero, C. S. -C., Sureda, P. F., de Munain, A. L., De-La-cruz, M., Rojas, M. D., Aleman, A., Vizcaino, A., Sanchez, M. J., Chirlaque, M. D., Eslava, M. G., Ardanaz, E., Galceran, J., Carulla, M., Bergeron, Y., Bouchardy, C., Mousavi, S. M., Bordoni, A., Visser, O., Rashbass, J., Gavin, A., Morrison, D., and Huws, D. W.

Subjects
Cancer Research, Survival, real-world data, randomized controlled trials (RCTs), tyrosine kinase inhibitor (TKI), population-based studies, Tyrosine kinase inhibitor (TKI), Randomized controlled trials (RCTs), survival, Real-world data, Europe, Oncology, cancer registries, chronic myeloid leukemia (CML), Chronic myeloid leukemia (CML), Cancer registries, Population-based studies
Abstract

This study was funded by the Compagnia di San Paolo, the Cariplo Foundation and the European Commission (grant number 801520 HP-JA-2017, Innovative Partnership for Action Against Cancer, iPAAC Joint Action). The sources of the funding played no role in designing the study, collecting, analyzing, or interpreting the data, writing the report, or deciding whether or not to submit the article for publication. This research was (partially) funded by Italian Ministry of Health "Ricerca Corrente" funds. Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15-64 years) diagnosed in 2000-2006 vs. 2007-2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there.

Published
2022
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2. Long-term survival and cure fraction estimates for childhood cancer in Europe (EUROCARE-6): results from a population-based study

Author

Laura Botta, Gemma Gatta, Riccardo Capocaccia, Charles Stiller, Adela Cañete, Luigino Dal Maso, Kaire Innos, Ana Mihor, Friederike Erdmann, Claudia Spix, Brigitte Lacour, Rafael Marcos-Gragera, Deirdre Murray, Silvia Rossi, Monika Hackl, Elizabeth Van Eycken, Nancy Van Damme, Zdravka Valerianova, Mario Sekerija, Vasos Scoutellas, Anna Demetriou, Ladislav Dušek, Denisa Krejci, Hans Storm, Margit Mägi, Keiu Paapsi, Nea Malila, Janne Pitkäniemi, Valerie Jooste, Jacqueline Clavel, Claire Poulalhon, Emmanuel Desandes, Alain Monnereau, Alexander Katalinic, Eleni Petridou, Georgios Markozannes, Miklos Garami, Helgi Birgisson, Paul M Walsh, Guido Mazzoleni, Fabio Vittadello, Francesco Cuccaro, Rocco Galasso, Giuseppe Sampietro, Stefano Rosso, Cinzia Gasparotto, Giovanni Maifredi, Margherita Ferrante, Antonina Torrisi, Antonella Sutera Sardo, Maria Letizia Gambino, Monica Lanzoni, Paola Ballotari, Erica Giacomazzi, Stefano Ferretti, Adele Caldarella, Gianfranco Manneschi, Milena Sant, Paolo Baili, Franco Berrino, Annalisa Trama, Roberto Lillini, Alice Bernasconi, Simone Bonfarnuzzo, Claudia Vener, Fabio Didonè, Paolo Lasalvia, Giulia Del Monego, Lucia Buratti, Diego Serraino, Martina Taborelli, Roberta De Angelis, Elena Demuru, Corrado Di Benedetto, Mariano Santaquilani, Serenella Venanzi, Marco Tallon, Luca Boni, Silvia Iacovacci, Antonio Giampiero Russo, Federico Gervasi, Gianbattista Spagnoli, Luca Cavalieri d'Oro, Mario Fusco, Maria Francesca Vitale, Mario Usala, Francesco Vitale, Maria Michiara, Giorgio Chiranda, Carlotta Sacerdote, Milena Maule, Giuseppe Cascone, Eugenia Spata, Lucia Mangone, Fabio Falcini, Rossella Cavallo, Daniela Piras, Ylenia Dinaro, Marine Castaing, Anna Clara Fanetti, Sante Minerba, Giuseppina Candela, Tiziana Scuderi, Roberto Vito Rizzello, Fabrizio Stracci, Giovanna Tagliabue, Massimo Rugge, Angelita Brustolin, Santa Pildava, Giedre Smailyte, Miriam Azzopardi, Tom Børge Johannesen, Joanna Didkowska, Urszula Wojciechowska, Magdalena Bielska-Lasota, Ana Pais, Ana Maria Ferreira, Maria José Bento, Ana Miranda, Chakameh Safaei Diba, Vesna Zadnik, Tina Zagar, Carmen Sánchez-Contador Escudero, Paula Franch Sureda, Arantza Lopez de Munain, Marta De-La-Cruz, Marìa Dolores Rojas, Araceli Aleman, Ana Vizcaino, Fernando Almela, Arantza Sanvisens, Maria Josè Sanchez, Maria Dolores Chirlaque, Antonia Sanchez-Gil, Marcela Guevara, Eva Ardanaz, Adela Cañete-Nieto, Rafael Peris-Bonet, Jaume Galceran, Maria Carulla, Claudia Kuehni, Shelagh Redmond, Otto Visser, Henrike Karim-Kos, Sarah Stevens, Anna Gavin, David Morrison, Dyfed Wyn Huws, Botta, L, Gatta, G, Capocaccia, R, Stiller, C, Canete, A, Dal Maso, L, Innos, K, Mihor, A, Erdmann, F, Spix, C, Lacour, B, Marcos-Gragera, R, Murray, D, Rossi, S, Hackl, M, Van Eycken, E, Van Damme, N, Valerianova, Z, Sekerija, M, Scoutellas, V, Demetriou, A, Dusek, L, Krejci, D, Storm, H, Magi, M, Paapsi, K, Malila, N, Pitkaniemi, J, Jooste, V, Clavel, J, Poulalhon, C, Desandes, E, Monnereau, A, Katalinic, A, Petridou, E, Markozannes, G, Garami, M, Birgisson, H, Walsh, P, Mazzoleni, G, Vittadello, F, Cuccaro, F, Galasso, R, Sampietro, G, Rosso, S, Gasparotto, C, Maifredi, G, Ferrante, M, Torrisi, A, Sutera Sardo, A, Gambino, M, Lanzoni, M, Ballotari, P, Giacomazzi, E, Ferretti, S, Caldarella, A, Manneschi, G, Sant, M, Baili, P, Berrino, F, Trama, A, Lillini, R, Bernasconi, A, Bonfarnuzzo, S, Vener, C, Didone, F, Lasalvia, P, Del Monego, G, Buratti, L, Serraino, D, Taborelli, M, De Angelis, R, Demuru, E, Di Benedetto, C, Santaquilani, M, Venanzi, S, Tallon, M, Boni, L, Iacovacci, S, Russo, A, Gervasi, F, Spagnoli, G, Cavalieri d'Oro, L, Fusco, M, Vitale, M, Usala, M, Vitale, F, Michiara, M, Chiranda, G, Sacerdote, C, Maule, M, Cascone, G, Spata, E, Mangone, L, Falcini, F, Cavallo, R, Piras, D, Dinaro, Y, Castaing, M, Fanetti, A, Minerba, S, Candela, G, Scuderi, T, Rizzello, R, Stracci, F, Tagliabue, G, Rugge, M, Brustolin, A, Pildava, S, Smailyte, G, Azzopardi, M, Johannesen, T, Didkowska, J, Wojciechowska, U, Bielska-Lasota, M, Pais, A, Ferreira, A, Bento, M, Miranda, A, Safaei Diba, C, Zadnik, V, Zagar, T, Sanchez-Contador Escudero, C, Franch Sureda, P, Lopez de Munain, A, De-La-Cruz, M, Rojas, M, Aleman, A, Vizcaino, A, Almela, F, Sanvisens, A, Sanchez, M, Chirlaque, M, Sanchez-Gil, A, Guevara, M, Ardanaz, E, Canete-Nieto, A, Peris-Bonet, R, Galceran, J, Carulla, M, Kuehni, C, Redmond, S, Visser, O, Karim-Kos, H, Stevens, S, Gavin, A, Morrison, D, and Huws, D

Subjects
Retinal Neoplasms, Retinoblastoma, Bone Neoplasms, Sarcoma, Ewing, EUROCARE-6, survival, Burkitt Lymphoma, population-based cancer registrie, Europe, Oncology, Humans, cure fraction, childhood cancer, EUROCARE, Child, chidlhood cancer
Abstract

Background: The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer. Methods: In this population-based study, we analysed 135 847 children (aged 0–14 years) diagnosed during 2000–13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival. Findings: 5-year survival for all childhood cancer combined in Europe in 2010–14 was 81% (95% CI 81–82), showing an increase of three percentage points compared with 2004–06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60–79] to 87% [77–93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010–13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73–75) in 1998–2001 to 80% (79–81) in 2010–13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74–100) for retinoblastoma to 60% (58–63) for CNS tumours and reached 90% (95% CI 87–93) for lymphoid leukaemia and 70% (67–73) for acute myeloid leukaemia. Interpretation: Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care. Funding: European Commission.

Published
2022

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