Résumé
Purpose: Stereotactic body radiation therapy (SBRT) is a common treatment for unresectable liver cancers; however, delivering ablative doses while minimizing normal tissue toxicity is challenging. NBTXR3, a novel radioenhancer, demonstrated enhanced radiation therapy (RT) efficacy with minimal toxicity in healthy tissue. We evaluated NBTXR3 intratumoral injection followed by SBRT for hepatocellular carcinoma (HCC) or liver metastases. Methods and Materials: This phase 1, multicenter, dose-escalation trial enrolled adults with unresectable HCC or liver metastases. Five dose levels of NBTXR3 were evaluated (3 + 3 design): 10%, 15%, 22%, 33% and 42% of gross tumor volume (GTV) determined by magnetic resonance imaging. Patients received RT (15 Gy pound 3 or 10 Gy pound 5 over 5-15 days) starting 1 to 5 days after NBTXR3 injection. Primary endpoints included: incidence of early dose-limiting toxicities (DLTs) and determination of the recommended phase 2 dose (RP2D) of NBTXR3. Results: Between December 2015 and May 2020, 26 liver lesions in 23 patients with HCC (17 lesions in 15 patients) or liver metastases (9 lesions in 8 patients) were treated. No early DLTs were reported, and the maximum tolerated dose was not reached. The RP2D of NBTXR3 was 42% of GTV. During the treatment period, 6 patients experienced grade >= 3 toxicities; none were NBTXR3-related, one was RT-related (grade 3 fatigue), and 2 were injection procedure-related (grade 3 abdominal pain). During the follow-up period, 2 patients experienced treatment-related grade >= 3 AEs (grade 3 bile duct stenosis related to cancer/RT/NBTXR3, and grade 3 anemia related to cancer/RT/underlying liver disease). No treatment-related deaths were reported. The 12-week objective response rate in treated lesions was 58.3% (7/12) in patients with HCC, and 50.0% (4/8) in patients with liver metastases. Conclusions: NBTXR3 + RT has a manageable safety profile with no DLTs identified during dose escalation. The RP2D for treatment of HCC or liver metastases is 42% of GTV. Future studies will further evaluate efficacy. (c) 2025 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).