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

BMC Cancer

Falk Roeder⁷  Alexis Ulrich³  Gregor Habl⁵  Matthias Uhl⁵  Ladan Saleh-Ebrahimi⁷  Peter E Huber⁵  Daniela Schulz-Ertner⁶  Anna V Nikoghosyan⁴  Ingo Alldinger³  Robert Krempien⁴  Gunhild Mechtersheimer²  Frank W Hensley⁵  Juergen Debus⁵  Marc Bischof¹ 

[1] Department of Radiation Oncology, SLK Clinic, Heilbronn, Germany

[2] Institute of Pathology, University of Heidelberg, Heidelberg, Germany

[3] Department of Surgery, University of Heidelberg, Heidelberg, Germany

[4] Department of Radiation Oncology, Helios Clinic, Berlin-Buch, Germany

[5] Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany

[6] Department of Radiation Oncology, Markus Clinic, Frankfurt, Germany

[7] Department of Radiation Oncology, University of Munich (LMU), Munich, Germany

Others  :  1121299
DOI  :  10.1186/1471-2407-14-617

 received in 2014-05-20, accepted in 2014-08-20,  发布年份 2014

【 摘 要 】

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.

Conclusion

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.

Trial registration

NCT01566123.

【 授权许可】

   
2014 Roeder et al.; licensee BioMed Central Ltd.

【 图 表 】

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