Phase 1 Study of Stereotactic Body Radiation Therapy for Liver Tumors Utilizing an MRI-Guided Tri-Co Teletherapy System

Abstract

The primary objective of this phase I study was to assess the feasibility of utilizing a commercially available MRI-guided tri-60Co teletherapy (MRI-guided tri-co60-RT) system for liver SBRT, as determined by the ability to create treatment plans considered dosimetrically comparable to those that could be delivered with a linear accelerator (LINAC). Secondary objectives included determining tumor local control (LC) and the frequency of acute grade 2-5 gastrointestinal toxicity as determined by CTCAE (version 4). Eligible patients had metastatic lesions from another primary site (up to 5 lesions), primary hepatocellular carcinoma, or cholangiocarcinoma and were referred to radiation oncology for liver SBRT. Histologic confirmation of metastases was encouraged but not required. For patients with a single lesion, dose/fractionation regimens included 15 Gy x 3, 16 Gy x 3, and 18 Gy x 3. For patients with multiple lesions, dose/fractionation regimens included 8 Gy x 5, 10 Gy x 5, and 12 Gy x 5. Determination of dose schedule was based on achieving the highest dose while meeting protocol specified normal tissue constraints (adapted from RTOG 1112). LC was defined as stable disease, partial response, or complete response on imaging. Imaging follow-up was based on PET/CT or MRI imaging every 3 months per standard-of-care. Sixteen patients were enrolled on our study from July 2015 to September 2016. Four had HCC, two had cholangiocarcinoma, and ten had hepatic metastases. Eleven patients had a single lesion. Overall, 15 of 16 patients (93.8%) had MRI-guided tri-60Co-RT plans that met our dosimetric constraints. The patient who did not have an acceptable MRI-guided tri-60Co-RT plan also did not have an acceptable LINAC-based plan, so was excluded from the study and treated with a dose-reduced schedule. Twenty lesions were treated in total. The median biologically effective dose (BED, assuming a/b=10) used to treat single lesions was 151 Gy. Among plans in which multiple lesions were treated, the median BED per lesion was 132 Gy. The mean gross tumor volume (GTV) for single lesions was 24.1 ml; when multiple lesions were treated, the mean GTV for each lesion was 8.2 ml. At a median imaging follow-up of 5.8 months, LC was 100%. At a median clinical follow-up of 7.2 months, no grade 2 or higher GI toxicities were seen. Nearly all patients referred to radiation oncology at our institution for liver SBRT were eligible to receive MRI-guided tri-60Co-RT at ablative doses, as defined by having treatment plans that met adapted RTOG 1112 constraints. LC at a median imaging follow-up of nearly 6 months was 100%, and no grade 2 or higher GI toxicities were seen. Future studies will investigate the ability of the MRI-guided RT system to reduce treatment planning margins and safely allow further dose escalation.