Background: This study was designed to assess patterns of recurrence and long-term outcomes of patients undergoing surgery for localized retroperitoneal sarcoma (RPS) after neoadjuvant high dose long-infusion ifosfamide (HLI) and radiotherapy (RT). Methods: Patients received three cycles of HLI (14 g/m2). RT was started in combination with II cycle up to a total dose of 50.4 Gy. Surgery was scheduled 4–6 weeks after the end of RT. The primary endpoint was relapse-free survival (RFS) after surgery. Secondary endpoints were overall survival (OS), crude cumulative incidence of local recurrence (CCI-LR), and distant metastases (CCI-DM). For patients who relapsed, progression-free survival (PFS) and post-relapse OS were estimated. The trial was registered with ITASARC_*II_2004_003. Results: Between 2003 and 2010, 83 patients were recruited. At a median follow-up of 91.7 months, 42 (56%) of 75 operated patients developed LR (n = 27) or DM (n = 10) or both LR and DM (n = 5) relapse. Seven-year RFS was 46.6% [95% confidence interval (CI) 29.6–52.4]. Thirty-two patients died. Seven-year OS rate was 63.2% (95% CI 42.7–66.0). The corresponding CCI of LR and DM were 37.4% [standard error (SE) 5.5%] and 20.0% (SE 12.6%), respectively. The only factor significantly associated with LR was FNCLCC grading, whereas histological subtype resulted associated with DM. At recurrence, 24 patients (57%) underwent surgery. Two-year post-relapse PFS and OS rates for patients developing LR or DM were 14.8, 41.0, 27.3, and 63.6%, respectively. Conclusions: LR after neoadjuvant CT-RT for RPS were predominantly infield. While almost one half of relapsed patients underwent further surgery, prognosis was poor.
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