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
Mené sur 27 patients atteints d'un sarcome rétropéritonéal primitif ou récidivant traité entre 2007 et 2013 (durée médiane de suivi : 33 mois), cet essai de phase I/II évalue l'efficacité, du point de vue du contrôle local, de la survie sans progression et de la survie globale à 3 et 5 ans, et la toxicité d'une radiothérapie néoadjuvante avec modulation d'intensité et escalade de dose en combinaison avec une radiothérapie intra-opératoire
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 45-50Gy to PTV and 50-56Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12Gy). 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 50Gy, 26-55) in all except 2pts (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 23pts (85 %) with a median dose of 12Gy (10-20Gy). 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 8pts, 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 4pts (15 %). Severe postoperative complications were found in 9pts (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.