Dynamic Contrast Enhanced MRI Reveals Acute Changes in Vascular Permeability/Perfusion Following Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma

Abstract

The purpose of this pilot study was to evaluate acute tumor vasculature changes in hepatocellular carcinoma (HCC) using dynamic contrast enhanced MRI (DCE-MRI) following stereotactic body radiation therapy (SBRT). Patients with unresectable HCC based on multiphase imaging and treated with SBRT were eligible. Patients were required to have Child-Turcotte-Pugh A/B liver disease with 1-3 lesions amenable to SBRT with a tumor size ≤ 15 cm (single lesion or sum of lesions). A baseline MRI was performed within 2 weeks prior to the first fraction of SBRT. SBRT was delivered using a 2 or 3 arc volumetric arc therapy plan with 6 or 10 MV photons with a dose of 7.5 Gy. Following SBRT, post-treatment imaging was performed by either 6 or 24 hours after the first fraction. All research MRI scans were performed with a 3T whole-body MRI. DCE-MRI was performed with 60 dynamic cycles at a temporal resolution of 6 seconds. Contrast infusion (Gadobenate, 0.5 mL/sec) was initiated at the 10th dynamic cycle. DCE-MRI data were analyzed with the modified Brix’s pharmacokinetic model. The uni-directional exchange rate constants kep (interstitial space to blood plasma) and kpe (blood plasma to interstitial space) were reported as measures of vascular permeability/perfusion. Statistical analysis was performed using the Wilcoxon rank sum test. Eight patients (7 male/1 female) were enrolled with a median age of 65 years (range 48-79). Ten tumors were evaluated and treated with a median tumor size of 5.9 cm (range 1.6-12 cm). Five patients (7 tumors) completed post-treatment imaging between 20-24 hours post-SBRT while the remaining 3 patients (3 tumors) completed post-SBRT imaging 2-6 hours after treatment. Pharmacokinetic analysis of DCE-MRI revealed significant changes in tumor permeability/perfusion after a single fraction of SBRT. The exchange rate kpe showed a rapid increase within 6 hours post-SBRT (median 1005%, range 115∼1030%) followed by a subsequent decrease by 24 hours (median -24%, range -75∼17%, P=0.02). A similar trend was also observed for kep. However, it was of smaller magnitude and did not reach statistical significance (an initial increase in the 6-hour time window: median 105%, range -50∼218%; and a subsequent return to near baseline by 24 hours post-treatment: median 1%, range -29∼155%; P=0.7). Our preliminary results suggest that SBRT may trigger a rapid increase in tumor permeability/perfusion within 6 hours of radiation therapy delivery. The magnitude of this effect is subsequently diminished or reversed by 24 hours post-treatment. This 6-hour time window may provide an opportunity for better accessibility and efficacy when delivering chemotherapy or molecularly targeted agents in conjunction with moderate SBRT doses.