title: Preoperative chemo-radiation therapy for localised retroperitoneal sarcoma: a phase I-II study from the Italian Sarcoma Group.
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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  This is a pure academic trial. No funding sources contributed to it.
authors: Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: alessandro.gronchi@istitutotumori.mi.it.
authors: Alessandro
authors: A
authors: Gronchi
authors: Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano, Italy.
authors: Antonino
authors: A
authors: De Paoli
authors: Department of Epidemiology, Biostatistics and Clinical Trials, IRCCS S. Martino, IST, Genova, Italy.
authors: Carla
authors: C
authors: Dani
authors: Department of Epidemiology, Biostatistics and Clinical Trials, IRCCS S. Martino, IST, Genova, Italy.
authors: Domenico Franco
authors: DF
authors: Merlo
authors: Department of Surgery, Istituto Clinico Humanitas, Milan, Italy.
authors: Vittorio
authors: V
authors: Quagliuolo
authors: Department of Cancer Medicine, Institute for Cancer Research and Treatment at Candiolo, Torino, Italy.
authors: Giovanni
authors: G
authors: Grignani
authors: Department of Surgery, Centro di Riferimento Oncologico, Aviano, Italy.
authors: Giulio
authors: G
authors: Bertola
authors: Department of Radiation Oncology, Istituto Clinico Humanitas, Milan, Italy.
authors: Piera
authors: P
authors: Navarria
authors: Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors: Claudia
authors: C
authors: Sangalli
authors: Department of Cancer Medicine, Centro di Riferimento Oncologico, Aviano, Italy.
authors: Angela
authors: A
authors: Buonadonna
authors: Department of Cancer Medicine, Istituto Clinico Humanitas, Milan, Italy.
authors: Rita
authors: R
authors: De Sanctis
authors: Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors: Roberta
authors: R
authors: Sanfilippo
authors: Department of Pathology, Treviso General Hospital, Treviso, Italy.
authors: Angelo Paolo
authors: AP
authors: Dei Tos
authors: Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors: Silvia
authors: S
authors: Stacchiotti
authors: Department of Epidemiology, Biostatistics and Clinical Trials, IRCCS S. Martino, IST, Genova, Italy.
authors: Laura
authors: L
authors: Giorello
authors: Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors: Marco
authors: M
authors: Fiore
authors: Department of Epidemiology, Biostatistics and Clinical Trials, IRCCS S. Martino, IST, Genova, Italy.
authors: Paolo
authors: P
authors: Bruzzi
authors: Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors: Paolo Giovanni
authors: PG
authors: Casali
mesh_terms: D000368:Aged; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D007558:Italy; D008875:Middle Aged; D011300:Preoperative Care / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D012186:Retroperitoneal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012509:Sarcoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis
chemical_list: D007069:Ifosfamide
keywords: Chemotherapy; Radiation therapy; Retroperitoneal sarcoma; Soft tissue sarcoma