Maura Massimino1, Francesco Barretta2, Piergiorgio Modena3, Pascal Johann4, Paolo Ferroli5, Manila Antonelli6, Lorenza Gandola7, Maria Luisa Garrè8, Daniele Bertin9, Angela Mastronuzzi10, Maurizio Mascarin11, Lucia Quaglietta12, Elisabetta Viscardi13, Iacopo Sardi14, Antonio Ruggiero15, Luna Boschetti1, Marzia Giagnacovo3, Veronica Biassoni1, Elisabetta Schiavello1, Luisa Chiapparini16, Alessandra Erbetta16, Anna Mussano17, Carlo Giussani18, Rosa Maria Mura19, Salvina Barra20, Giovanni Scarzello21, Giuseppe Scimone22,23, Andrea Carai24, Felice Giangaspero6, Francesca Romana Buttarelli25. 1. Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 2. Medical Statistics, Biometry and Bioinformatics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 3. Laboratory of Genetics, S. Anna General Hospital, Como, Italy. 4. Hopp-Children's Cancer Center Heidelberg KiTZ, German Cancer Research Center DKFZ, German Cancer Consortium DKTK, Heidelberg, Germany. 5. Neurosurgery Unit, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 6. Department of Radiological, Oncological, and Anatomo-Pathological Sciences, La Sapienza University, Rome, Italy. 7. Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 8. Neuroncology and Neurosurgery Unit, Istituto Giannina Gaslini, Genova, Italy. 9. Pediatric Onco-Hematology Unit, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Torino, Italy. 10. Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, Rome, Italy. 11. Department of Pediatric Radiotherapy, CRO, Aviano, Italy. 12. Pediatric Oncology Unit, Ospedale Santobono-Pausilipon, Napoli, Italy. 13. Pediatric Oncology Unit, Padova University, Padova, Italy. 14. Department of Neuroncology, Ospedale Pediatrico Meyer, Firenze, Italy. 15. Pediatric Oncology Unit, Policlinico A. Gemelli, Roma, Italy. 16. Radiology Unit, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 17. Radiotherapy Unit, Department of Oncology, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Torino, Italy. 18. Neurosurgery Unit, Università Bicocca, Monza, Italy. 19. Pediatric Oncology Unit, AO Brotzu, Cagliari, Italy. 20. Pediatric Radiotherapy and Special Techniques Unit, Ospedale Policlinico San Martino, Genova, Italy. 21. Radiotherapy Unit, Istituto Oncologico del Veneto-IOV IRCCS, Padova, Italy. 22. Radiotherapy Unit, Azienda Ospedaliera Universitaria S. Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy. 23. Neuropathology Laboratory IRCCS Neuromed, Pozzilli, Italy. 24. Department of Neurosciences, Neurosurgery Unit, Ospedale Pediatrico Bambino Gesù, Rome, Italy. 25. Department of Neurology and Psychiatry, La Sapienza University, Rome, Italy.
Abstract
BACKGROUND: More than 40% of patients with intracranial ependymoma need a salvage treatment within 5 years after diagnosis, and no standard treatment is available as yet. We report the outcome after first relapse of 64 patients treated within the 2nd AIEOP protocol. METHODS: We considered relapse sites and treatments, that is, various combinations of complete/incomplete surgery, if followed by standard or hypofractionated radiotherapy (RT) ± chemotherapy (CT). Molecular analyses were available for 38/64 samples obtained at first diagnosis. Of the 64 cases, 55 were suitable for subsequent analyses. RESULTS: The median follow-up was 147 months after diagnosis, 84 months after first relapse, 5-year EFS/OS were 26.2%/30.8% (median EFS/OS 13/32 months) after relapse. For patients with a local relapse (LR), the 5-year cumulative incidence of second LRs was 51.6%, with a 5-year event-specific probability of being LR-free of 40.0%. Tumor site/grade, need for shunting, age above/below 3 years, molecular subgroup at diagnosis, had no influence on outcomes. Due to variation in the RT dose/fractionation used and the subgroup sizes, it was not possible to assess the impact of the different RT modalities. Multivariable analyses identified completion of surgery, the absence of symptoms at relapse, and female sex as prognostically favorable. Tumors with a 1q gain carried a higher cumulative incidence of dissemination after first relapse. CONCLUSIONS: Survival after recurrence was significantly influenced by symptoms and completeness of surgery. Only a homogeneous protocol with well-posed, randomized questions could clarify the numerous issues, orient salvage treatment, and ameliorate prognosis for this group of patients.
BACKGROUND: More than 40% of patients with intracranial ependymoma need a salvage treatment within 5 years after diagnosis, and no standard treatment is available as yet. We report the outcome after first relapse of 64 patients treated within the 2nd AIEOP protocol. METHODS: We considered relapse sites and treatments, that is, various combinations of complete/incomplete surgery, if followed by standard or hypofractionated radiotherapy (RT) ± chemotherapy (CT). Molecular analyses were available for 38/64 samples obtained at first diagnosis. Of the 64 cases, 55 were suitable for subsequent analyses. RESULTS: The median follow-up was 147 months after diagnosis, 84 months after first relapse, 5-year EFS/OS were 26.2%/30.8% (median EFS/OS 13/32 months) after relapse. For patients with a local relapse (LR), the 5-year cumulative incidence of second LRs was 51.6%, with a 5-year event-specific probability of being LR-free of 40.0%. Tumor site/grade, need for shunting, age above/below 3 years, molecular subgroup at diagnosis, had no influence on outcomes. Due to variation in the RT dose/fractionation used and the subgroup sizes, it was not possible to assess the impact of the different RT modalities. Multivariable analyses identified completion of surgery, the absence of symptoms at relapse, and female sex as prognostically favorable. Tumors with a 1q gain carried a higher cumulative incidence of dissemination after first relapse. CONCLUSIONS: Survival after recurrence was significantly influenced by symptoms and completeness of surgery. Only a homogeneous protocol with well-posed, randomized questions could clarify the numerous issues, orient salvage treatment, and ameliorate prognosis for this group of patients.
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