Filippo Spreafico1, Davide Biasoni2, Salvatore Lo Vullo3, Lorenza Gandola4, Paolo D'Angelo5, Monica Terenziani6, Maurizio Bianchi7, Massimo Provenzi8, Paolo Indolfi9, Andrea Pession10, Marilina Nantron11, Andrea Di Cataldo12, Carlo Morosi4, Daniela Perotti13, Serena Catania6, Franca Fossati Bellani6, Paola Collini14. 1. Pediatric Oncology Unit, Department of Hematology and Pediatric Hematology-Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. Electronic address: filippo.spreafico@istitutotumori.mi.it. 2. Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 3. Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 4. Department of Radiology and Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 5. Pediatric Hematology and Oncology Unit, Ospedale dei Bambini G. di Cristina, Palermo, Italy. 6. Pediatric Oncology Unit, Department of Hematology and Pediatric Hematology-Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 7. Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Torino, Italy. 8. Pediatric Unit, Ospedali Riuniti Bergamo, Bergamo, Italy. 9. Pediatric Oncology, Pediatric Department, II University, Napoli, Italy. 10. Pediatric Hematology and Oncology Unit "Lalla Seràgnoli," Bologna University, Bologna, Italy. 11. Department of Hematology and Oncology, Istituto G. Gaslini, Genova, Italy. 12. Pediatric Hematology and Oncology, Catania University, Catania, Italy. 13. Department of Predictive & Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 14. Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Abstract
PURPOSE: TW2003, the third Italian prospective study on Wilms tumor, aimed to improve survival in patients with stage III-IV tumors, de-escalate therapy for stage I-II nonanaplastic tumors, refine the risk stratification of therapy, and develop a national infrastructure for biobanking and central pathology review. MATERIALS AND METHODS: TW2003 recruited children 18 years old or younger with primary intrarenal tumors. Local physicians chose nephrectomy with or without preoperative chemotherapy as the initial treatment based on the risk of unsafe and/or incomplete immediate surgery. The main drivers for adjuvant therapy were tumor stage and diffuse anaplasia. A new risk stratification schema was investigated, incorporating patient age, reason for stage III designation and completeness of lung nodule response in stage IV disease. RESULTS: We report on 453 patients with unilateral Wilms tumor. Preoperative chemotherapy was administered to 42% of patients. The 5-year event-free survival and overall survival rates were 89.1% (95% CI 83.6-94.9) and 97.0% (93.7-100) for stage I; 85.1% (79.6-91.1) and 94.0% (90.1-98.1) for stage II (160); 82.7% (75.3-90.8) and 90.9% (85.0-97.1) for stage III (101); and 72.1% (61.9-84.0) and 82.5% (73.1-93.1) for stage IV (69), respectively. On multivariable analysis only anaplasia was significant for event-free survival (HR 2.68, 95% CI 1.48-4.86, p=0.001; bias corrected c-index 0.580) and overall survival (HR 5.29, 95% CI 2.52-11.12, p <0.001; bias corrected c-index 0.697). CONCLUSIONS: The survival rates achieved and the proposed risk stratification schema provide a basis for future comparisons of Wilms tumor treatment burden and patient outcome.
PURPOSE: TW2003, the third Italian prospective study on Wilms tumor, aimed to improve survival in patients with stage III-IV tumors, de-escalate therapy for stage I-II nonanaplastic tumors, refine the risk stratification of therapy, and develop a national infrastructure for biobanking and central pathology review. MATERIALS AND METHODS: TW2003 recruited children 18 years old or younger with primary intrarenal tumors. Local physicians chose nephrectomy with or without preoperative chemotherapy as the initial treatment based on the risk of unsafe and/or incomplete immediate surgery. The main drivers for adjuvant therapy were tumor stage and diffuse anaplasia. A new risk stratification schema was investigated, incorporating patient age, reason for stage III designation and completeness of lung nodule response in stage IV disease. RESULTS: We report on 453 patients with unilateral Wilms tumor. Preoperative chemotherapy was administered to 42% of patients. The 5-year event-free survival and overall survival rates were 89.1% (95% CI 83.6-94.9) and 97.0% (93.7-100) for stage I; 85.1% (79.6-91.1) and 94.0% (90.1-98.1) for stage II (160); 82.7% (75.3-90.8) and 90.9% (85.0-97.1) for stage III (101); and 72.1% (61.9-84.0) and 82.5% (73.1-93.1) for stage IV (69), respectively. On multivariable analysis only anaplasia was significant for event-free survival (HR 2.68, 95% CI 1.48-4.86, p=0.001; bias corrected c-index 0.580) and overall survival (HR 5.29, 95% CI 2.52-11.12, p <0.001; bias corrected c-index 0.697). CONCLUSIONS: The survival rates achieved and the proposed risk stratification schema provide a basis for future comparisons of Wilms tumor treatment burden and patient outcome.
Authors: J A Hol; M I Lopez-Yurda; H Van Tinteren; M Van Grotel; J Godzinski; G Vujanic; F Oldenburger; B De Camargo; G L Ramírez-Villar; C Bergeron; K Pritchard-Jones; N Graf; M M Van den Heuvel-Eibrink Journal: PLoS One Date: 2019-08-19 Impact factor: 3.240