Andrea Necchi1, Salvatore Lo Vullo2, Marco Bregni3, Giovanni Rosti4, Luigi Mariani2, Daniele Raggi2, Patrizia Giannatempo2, Simona Secondino4, Kathrin Schumacher5, Christophe Massard6, Edward Kanfer7, Karin Oechsle8, Daniele Laszlo9, Mariagrazia Michieli10, Norbert Ifrah11, Melanie Mercier11, Martina Crysandt12, Patrick Wuchter13, Arnon Nagler14, Anders Wahlin15, Massimo Martino16, Manuela Badoglio17, Paolo Pedrazzoli4, Francesco Lanza18. 1. Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. Electronic address: andrea.necchi@istitutotumori.mi.it. 2. Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 3. Medical Oncology, Azienda Ospedaliera di Busto Arsizio, Busto Arsizio, Italy. 4. Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 5. UKGM-Marburg Klinik for Hematology and Oncology, Marburg, Germany. 6. Gustave Roussy, Institut de cancérologie, Villejuif, France. 7. Imperial College, Hammersmith Hospital, London, United Kingdom. 8. Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. 9. European Institute of Oncology, Milano, Italy. 10. Centro di Riferimento Oncologico, Aviano, Italy. 11. Centre Hospitalier Universitaire (CHU), Angers, France. 12. University Hospital of Aachen, Aachen, Germany. 13. Universitätsklinikum Heidelberg, Heidelberg, Germany. 14. Chaim Sheba Medical Center, Tel-Hashomer, Israel. 15. Umeå University Hospital, Umeå, Sweden. 16. Azienda Ospedaliera BMM, Reggio Calabria, Italy. 17. EBMT Study Office, EBMT, Paris, France. 18. Istituti Ospitalieri di Cremona, Cremona, Italy.
Abstract
BACKGROUND: The optimal management of advanced seminoma that relapses after chemotherapy remains unknown. We retrospectively analyzed outcomes with the use of high-dose chemotherapy (HDCT). PATIENTS AND METHODS: Eligibility included adult male patients with pure seminomatous histology and treatment with salvage HDCT. Data of patients who received HDCT from 13 European Society for Blood and Marrow Transplantation (EBMT) centers were used. Multivariable Cox analyses evaluated the association of prespecified factors (line of treatment, prior radiotherapy, and chemosensitivity according to standard definition), with progression-free (PFS) and overall survival (OS). The prognostic ability of the model was assessed through the concordance statistic. RESULTS: From December 2002 to December 2012, 46 cases were identified. Median age was 38 years (interquartile range, 35-46 years). HDCT was provided as second-line therapy (n = 14, 30.4%) and in third-line or beyond third-line therapy (n = 20, 43.5%; 12 had missing information). Sixteen patients (34.8%) received paraortic and/or iliac radiotherapy, and 10 (21.7%) had disease that was cisplatin refractory or absolutely refractory. Median follow-up was 22 months (interquartile range, 8-56). On multivariable Cox analysis, refractory disease was a significantly negative prognostic factor for both PFS (hazard ratio, 6.04; 95% confidence interval, 1.86-19.64) and OS (hazard ratio, 3.93; 95% confidence interval, 1.07-14.45), while prior radiotherapy trended to significance for both. The c index was 0.74 and 0.66 for PFS and OS, respectively. The small numbers and the lack of any comparison with conventional-dose chemotherapy are major study limitations. CONCLUSION: Despite our small sample size, this retrospective analysis suggested that HDCT may represent a valuable therapeutic option for patients with a pure seminoma after standard-dose chemotherapy failure. Our observation requires validation through a prospective study.
BACKGROUND: The optimal management of advanced seminoma that relapses after chemotherapy remains unknown. We retrospectively analyzed outcomes with the use of high-dose chemotherapy (HDCT). PATIENTS AND METHODS: Eligibility included adult male patients with pure seminomatous histology and treatment with salvage HDCT. Data of patients who received HDCT from 13 European Society for Blood and Marrow Transplantation (EBMT) centers were used. Multivariable Cox analyses evaluated the association of prespecified factors (line of treatment, prior radiotherapy, and chemosensitivity according to standard definition), with progression-free (PFS) and overall survival (OS). The prognostic ability of the model was assessed through the concordance statistic. RESULTS: From December 2002 to December 2012, 46 cases were identified. Median age was 38 years (interquartile range, 35-46 years). HDCT was provided as second-line therapy (n = 14, 30.4%) and in third-line or beyond third-line therapy (n = 20, 43.5%; 12 had missing information). Sixteen patients (34.8%) received paraortic and/or iliac radiotherapy, and 10 (21.7%) had disease that was cisplatin refractory or absolutely refractory. Median follow-up was 22 months (interquartile range, 8-56). On multivariable Cox analysis, refractory disease was a significantly negative prognostic factor for both PFS (hazard ratio, 6.04; 95% confidence interval, 1.86-19.64) and OS (hazard ratio, 3.93; 95% confidence interval, 1.07-14.45), while prior radiotherapy trended to significance for both. The c index was 0.74 and 0.66 for PFS and OS, respectively. The small numbers and the lack of any comparison with conventional-dose chemotherapy are major study limitations. CONCLUSION: Despite our small sample size, this retrospective analysis suggested that HDCT may represent a valuable therapeutic option for patients with a pure seminoma after standard-dose chemotherapy failure. Our observation requires validation through a prospective study.