Alessandro Gronchi1, Antonino De Paoli2, Carla Dani3, Domenico Franco Merlo3, Vittorio Quagliuolo4, Giovanni Grignani5, Giulio Bertola6, Piera Navarria7, Claudia Sangalli8, Angela Buonadonna9, Rita De Sanctis10, Roberta Sanfilippo11, Angelo Paolo Dei Tos12, Silvia Stacchiotti11, Laura Giorello3, Marco Fiore13, Paolo Bruzzi3, Paolo Giovanni Casali11. 1. Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: alessandro.gronchi@istitutotumori.mi.it. 2. Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano, Italy. 3. Department of Epidemiology, Biostatistics and Clinical Trials, IRCCS S. Martino, IST, Genova, Italy. 4. Department of Surgery, Istituto Clinico Humanitas, Milan, Italy. 5. Department of Cancer Medicine, Institute for Cancer Research and Treatment at Candiolo, Torino, Italy. 6. Department of Surgery, Centro di Riferimento Oncologico, Aviano, Italy. 7. Department of Radiation Oncology, Istituto Clinico Humanitas, Milan, Italy. 8. Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 9. Department of Cancer Medicine, Centro di Riferimento Oncologico, Aviano, Italy. 10. Department of Cancer Medicine, Istituto Clinico Humanitas, Milan, Italy. 11. Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 12. Department of Pathology, Treviso General Hospital, Treviso, Italy. 13. Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract
BACKGROUND: To study feasibility, safety and activity of the combination of high-dose long-infusion ifosfamide (HLI) and radiotherapy (RT) as preoperative treatment for resectable localised retroperitoneal sarcoma (RPS). METHODS: Patients received three cycles of HLI (14 g/m2). RT was started in combination with second cycle and administered up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. Primary end-point was 3-year relapse free survival (RFS). The trial is registered with ITASARC_∗II_2004_003. FINDINGS: Between December 2003 and 2010, 83 patients were recruited. Main histological subtypes were well differentiated liposarcoma (19/83, 23%), dedifferentiated liposarcoma (26/83, 31%), leiomyosarcoma (14/83, 17%). Median tumour size was 120 mm (interquartile (IQ) range=82-160). The overall preoperative treatment was completed in 60 patients. Chemotherapy (CT) was completed in 65, while RT in 73. Four patients progressed before surgery and were not operated. 79 patients underwent surgery. At a median follow-up of 4.8 years (IQ range = 3-6.1), 23 and 15 patients developed local recurrence (LR) and distant metastases (DM); 30 patients died of disease. 3 and 5-year RFS and overall survival were 0.56 (90% confidence interval (CI): 0.45, 0.65) and 0.44 (90% CI: 0.27, 0.48), and 0.74 (90% CI: 0.62, 0.81) and 0.59 (90% CI: 0.33, 0.58). Crude cumulative incidence of LR and DM at 5 years were 0.37 (standard error (SE): 0.06) and 0.26 (SE: 0.06). INTERPRETATION: The combination of preoperative HLI and RT was feasible in two thirds of patients, while preoperative RT could be completed in most (73/83). Although a systemic coverage can be added to RT when this is felt to be appropriate, the ongoing international phase III trial is exploring the role of RT alone. FUNDING: This is a pure academic trial. No funding sources contributed to it.
BACKGROUND: To study feasibility, safety and activity of the combination of high-dose long-infusion ifosfamide (HLI) and radiotherapy (RT) as preoperative treatment for resectable localised retroperitoneal sarcoma (RPS). METHODS:Patients received three cycles of HLI (14 g/m2). RT was started in combination with second cycle and administered up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. Primary end-point was 3-year relapse free survival (RFS). The trial is registered with ITASARC_∗II_2004_003. FINDINGS: Between December 2003 and 2010, 83 patients were recruited. Main histological subtypes were well differentiated liposarcoma (19/83, 23%), dedifferentiated liposarcoma (26/83, 31%), leiomyosarcoma (14/83, 17%). Median tumour size was 120 mm (interquartile (IQ) range=82-160). The overall preoperative treatment was completed in 60 patients. Chemotherapy (CT) was completed in 65, while RT in 73. Four patients progressed before surgery and were not operated. 79 patients underwent surgery. At a median follow-up of 4.8 years (IQ range = 3-6.1), 23 and 15 patients developed local recurrence (LR) and distant metastases (DM); 30 patients died of disease. 3 and 5-year RFS and overall survival were 0.56 (90% confidence interval (CI): 0.45, 0.65) and 0.44 (90% CI: 0.27, 0.48), and 0.74 (90% CI: 0.62, 0.81) and 0.59 (90% CI: 0.33, 0.58). Crude cumulative incidence of LR and DM at 5 years were 0.37 (standard error (SE): 0.06) and 0.26 (SE: 0.06). INTERPRETATION: The combination of preoperative HLI and RT was feasible in two thirds of patients, while preoperative RT could be completed in most (73/83). Although a systemic coverage can be added to RT when this is felt to be appropriate, the ongoing international phase III trial is exploring the role of RT alone. FUNDING: This is a pure academic trial. No funding sources contributed to it.
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