Table 2.

Summary of preclinical and clinical studies investigating the potential of using nanoparticles to enhance the pathologic response of sarcomas treated with radiotherapy.

Study Type [Refs.]	Nanoparticles Used/ Study Design	Main Findings
Preclinical [44]	12 nm gold nanoparticles decorated with polyethylene glycol (P-GNPs). In vitro/in vivo experiments irradiating with low-energy X-ray beams. HT1080 fibrosarcoma and U2OS osteosarcoma human sarcoma cell lines.	RT + P-GNP increased the density of double-strand breaks (DSBs) 1.6 times compared to RT only. RT + P-GNP reduced clonogenic survival of tumor cells compared to RT only, with dose-enhancement ratios of 1.08 and 1.16 for the HT1080 and U2OS, respectively. Mice treated with RT + P-GNP exhibited significantly improved tumor regression, and long-term survival was observed in one third of the mice in this group compared to none in the RT only group.
Preclinical [45]	NBTXR3 50 nm hafnium oxide. In vitro/in vivo experiments irradiating with high-energy photon beams HT1080 fibrosarcoma and A673. Ewing human sarcoma cell lines.	Broad persistence and dispersion of NBTXR3 in tumor cells, with little or no diffusion into the extracellular space. Marked decrease of the clonogenic surviving fraction of tumor cells in the RT + NBTXR3 group, with dose-enhancement factors of 1.4 and 1.8 for the 6 MV and Co-60 photon beams, respectively. Two-fold increase in tumor doubling time associated with tumor growth inhibition of 82% for RT + NBTXR3 group, versus 72% for RT only. Median survival time increased to 31 days for the RT + NBTXR3 group compared to 25 days for the RT only.
Clinical, phase 1 first in human trial, [46]	NBTXR3 50 nm hafnium oxide. Preoperative RT (50 Gy in 25 fractions) of patients with histologically confirmed locally advanced soft tissue sarcoma of the extremity or trunk wall. Treated patients: 22.	A single intratumoral injection of NBTXR3, equivalent to 10% of the tumor volume, was feasible and well-tolerated with manageable toxicity. NBTXR3 remained stable within the tumor volume and did not leak to the surrounding tissue or bloodstream. RT + NBTXR3 showed median decrease in the maximal tumor diameter of 29% and a median change in volume of -40%
Clinical phase 2/3 trial, [47,48,49]	NBTXR3 50 nm hafnium oxide. Preoperative RT of patients with histologically confirmed locally advanced soft tissue sarcoma of the extremity or trunk wall. Treated patients: 176.	RT + NBTXR3 group had a pCR of 19% versus 9% in the RT only group (p = 0.047). Higher percentage of R0 resections in the RT + NBTXR3 group (81%) compared to the RT only group (66%; p = 0.030) The 2-year cumulative rate of local recurrence was 12.0% and 7.1% in the RT + NBTXR3 and RT only group, respectively. The 2-year cumulative rate of distant recurrence was 33.3% and 26.2% in the RT + NBTXR3 and RT only group, respectively.