방사선의학 웹진

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Abstract

​Purpose:

This phase I study aimed to determine the recommended dose (RD), safety profile, and feasibility of a procedure combining intratumoral injection of hafnium oxide nanoparticles (NBTXR3; a radioenhancer) and external beam radiotherapy (EBRT) for preoperative treatment of adults with locally advanced soft tissue sarcoma (STS).

Experimental Design:

Patients had a preoperative indication of EBRT for STS of the extremity or trunk. Baseline tumor volume (TV) was calculated by MRI. NBTXR3 was injected percutaneously into tumors at 53.3 g/L. Dose escalation was based on four levels equivalent to 2.5%, 5%, 10%, and 20% of baseline TV. NBTXR3 was visualized in the tumor 24 hours postinjection, and EBRT was initiated (50 Gy over 5 weeks). Surgery was performed 6 to 8 weeks after EBRT completion.

Results: 

Twenty-two patients completed NBTXR3 injection, EBRT, and surgery and were followed for a median 22 months (range, 6-40). At NBTXR3 20% of TV, two dose-limiting toxicities occurred: injection-site pain and postoperative scar necrosis. The RD was defined as 10%. No leakage of NBTXR3 into surrounding tissues occurred; intratumor NBTXR3 levels were maintained during radiotherapy. At the RD, median tumor shrinkage was 40% (range 71% shrinkage, 22% increase); median percentage of residual viable tumor cells was 26% (range, 10%-90%). Patients receiving 20% of TV demonstrated pathologic complete responses. Seven grade 3 adverse events occurred, which were reversible.

Conclusions:

A single intratumoral injection of NBTXR3 at 10% of TV with preoperative EBRT was technically feasible with manageable toxicity; clinical activity was observed.  

Author information

Bonvalot S1, Le Pechoux C2, De Baere T2, Kantor G3, Buy X3, Stoeckle E3, Terrier P2, Sargos P3, Coindre JM3, Lassau N2, Ait Sarkouh R4, Dimitriu M4, Borghi E4, Levy L4, Deutsch E2, Soria JC2.

1 Institut Curie, PSL Research University, Paris, France. sylvie.bonvalot@curie.fr.

2 Gustave Roussy Cancer Campus, Villejuif, France.

3 Institut Bergonié, Bordeaux, France.

4 Nanobiotix, Paris, France.​ ​