Author information
- 1Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute; 460 W. 10th Ave Columbus OH 43210; USA.
- 2Department of Radiology, The Ohio State University Wexner Medical Center; 395 W. 12 Ave; Columbus, OH 43210 USA.
- 3Department of Biomedical Informatics, The Ohio State University College of Medicine; 320 Lincoln Tower, 1800 Cannon Drive, Columbus OH 43210; USA.
- 4Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute; 460 W. 10th Ave Columbus OH 43210; USA. Electronic address: Terence.Williams@osumc.edu.
Abstract
Background: Despite the survival benefit of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), a majority of tumors recur, attributed to hypovascularity and treatment resistance. Preclinical studies show that moderate radiation doses induce changes in tumor permeability and perfusion, suggesting an opportunity for TACE sensitization by radiation. In this prospective phase I trial, we evaluated the feasibility, safety, tolerability, response, and functional magnetic resonance imaging (MRI) changes associated with single-fraction SBRT followed by TACE within 24 hours.
Materials/methods: Patients with HCC, 1-3 lesions, Childs-Pugh A/B liver function, and no major vascular invasion were enrolled. The primary objective was to establish the feasibility of single-dose SBRT (7.5 or 10 Gy) followed by TACE within 24 hours. Secondary endpoints included safety, tolerability, perfusional changes via functional MRI, overall response rate (ORR), clinical benefit rate (CBR), freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS).
Results: Sixteen patients were enrolled, and 13 received SBRT and TACE. Median follow up was 15.3 months. Best overall ORR and CBR were and 76.9% and 92.3%, respectively. The 1- and 3-month ORR was 76.9% and 69.2%, respectively, and 1- and 3-month CBR was 92.3% and 69.2%, respectively. Median OS, PFS, and FFLP were 14.0, 5.2, and 5.9 months, respectively. Crude rates of grade 1+ and grade 2+ toxicity were 85% and 38%, respectively. No grade 3-4 toxicities were recorded. One grade 5 toxicity occurred due to hemorrhage 4 days after TACE. On dynamic contrast enhanced (DCE)-MRI, the transfer rate constant from blood plasma to extracellular extravascular space (kpe) increased within 6 hours post-SBRT, but decreased by 24 hours.
Conclusions: We hypothesized a strategy of SBRT preceding TACE for the purpose of enhancing TACE delivery and efficacy, and tested this strategy in a small pilot study. We found that single-dose SBRT followed by TACE within 24 hours is feasible and tolerable. DCE-MRI revealed acute changes in tumor permeability/perfusion after SBRT. Additional studies are needed to establish the safety and efficacy of this combination, and the effects of SBRT on the HCC microenvironment.