title: Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis.
abstract: BACKGROUND
  To report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123).
  
  
  METHODS
  Between 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45-50 Gy to PTV and 50-56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12 Gy). Primary endpoint was 5-year-LC, secondary endpoints included PFS, OS, resectability, and acute/late toxicity. The majority of patients showed high grade lesions (FNCLCC G1:18%, G2:52%, G3:30%), predominantly liposarcomas (70%). Median tumor size was 15 cm (6-31).
  
  
  RESULTS
  Median follow-up was 33 months (5-75). Neoadjuvant IMRT was performed as planned (median dose 50 Gy, 26-55) in all except 2 pts (93%). Gross total resection was feasible in all except one patient. Final margin status was R0 in 6 (22%) and R1 in 20 pts (74%). Contiguous-organ resection was needed in all grossly resected patients. IOERT was performed in 23 pts (85%) with a median dose of 12 Gy (10-20 Gy).We observed 7 local recurrences, transferring into estimated 3- and 5-year-LC rates of 72%. Two were located outside the EBRT area and two were observed after more than 5 years. Locally recurrent situation had a significantly negative impact on local control. Distant failure was found in 8 pts, resulting in 3- and 5-year-DC rates of 63%. Patients with leiomyosarcoma had a significantly increased risk of distant failure. Estimated 3- and 5-year-rates were 40% for PFS and 74% for OS. Severe acute toxicity (grade 3) was present in 4 pts (15%). Severe postoperative complications were found in 9 pts (33%), of whom 2 finally died after multiple re-interventions. Severe late toxicity (grade 3) was scored in 6% of surviving patients after 1 year and none after 2 years.
  
  
  CONCLUSIONS
  Combination of neoadjuvant IMRT, surgery and IOERT is feasible with acceptable toxicity and yields good results in terms of LC and OS in patients with high-risk retroperitoneal sarcomas. Long term follow-up seems mandatory given the observation of late recurrences. Accrual of patients will be continued with extended follow-up.
  
  
  BACKGROUND
  NCT01566123.
authors.affiliation: Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. F.Roeder@dkfz.de.
authors.forename: Falk
authors.initials: F
authors.lastname: Roeder
authors.forename: Alexis
authors.initials: A
authors.lastname: Ulrich
authors.forename: Gregor
authors.initials: G
authors.lastname: Habl
authors.forename: Matthias
authors.initials: M
authors.lastname: Uhl
authors.forename: Ladan
authors.initials: L
authors.lastname: Saleh-Ebrahimi
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
authors.forename: Daniela
authors.initials: D
authors.lastname: Schulz-Ertner
authors.forename: Anna V
authors.initials: AV
authors.lastname: Nikoghosyan
authors.forename: Ingo
authors.initials: I
authors.lastname: Alldinger
authors.forename: Robert
authors.initials: R
authors.lastname: Krempien
authors.forename: Gunhild
authors.initials: G
authors.lastname: Mechtersheimer
authors.forename: Frank W
authors.initials: FW
authors.lastname: Hensley
authors.forename: Juergen
authors.initials: J
authors.lastname: Debus
authors.forename: Marc
authors.initials: M
authors.lastname: Bischof
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011300:Preoperative Care; D018714:Radiotherapy, Adjuvant / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012186:Retroperitoneal Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D012509:Sarcoma / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D016019:Survival Analysis; D016896:Treatment Outcome