Downstaging of Hepatocellular Carcinoma Outside Milan Criteria Using SBRT

Abstract

Orthotopic liver transplantation (OLT) offers the potential for cure in patients (pts) with hepatocellular carcinoma (HCC) who meet Milan criteria. Many pts are outside of Milan at diagnosis or after subsequent progression. Prior studies have shown that downstaging with local therapies can facilitate successful OLT leading to prolonged disease free survival. Stereotactic body radiotherapy (SBRT) is an established local therapy for HCC, though data for this specific indication is limited. From a survey of a large single institution database, the present study therefore reports on outcomes of patients treated with SBRT with the intention of downstaging to facilitate OLT. We surveyed our IRB-approved prospective liver SBRT data registry for pts not meeting Milan criteria and treated with the intention of downstaging. The primary outcome was undergoing OLT. Overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan Meier methods. Time to transplant, as well as local, liver, and extrahepatic failure, were estimated with cumulative incidence functions. 14 pts treated between 2010 and 2018 met criteria for analysis. Median follow up was 27 months and 7 pts were alive at time of analysis. Most were male (n=11), and median age was 60. Median KPS was 80 (range 60-90). 5 pts were Child-Pugh (CP) A, 3 CP B, and 6 CP C. Median size of the largest single lesion was 4.2 cm (1.8 - 6.8 cm). The most common reason for not meeting Milan criteria was multiple lesions larger than 3 cm (n=8). Median AFP at time of SBRT was 40 (3 - 3255). 11 pts (79%) had undergone prior liver directed therapy. Pts were treated a median of 6.5 months after diagnosis. Median dose was 40 Gy, and median number of fractions was 5. There were no local failures. 11 pts (79%) were successfully downstaged to within Milan Criteria after SBRT. 5 pts (36%) had subsequent disease progression within the liver, 2 of whom were successfully salvaged and proceeded to transplant. 2 pts became ineligible for OLT due to extrahepatic failure. In total, 7 pts (50%) underwent OLT at a median 3.6 months after SBRT. Percent necrosis was reported for 5 pts, 4 (80%) of whom had greater than 67%. 2 pts (29%) had recurrence after OLT, one with metastases to lung and the other with solitary recurrence in the transplanted liver. Median OS was 33.0 months for all pts, 14.5 months in pts not undergoing OLT, and not reached for those who did undergo OLT. No pts developed radiation induced liver disease. SBRT provides excellent local control and high rates of radiographic downstaging, however progression within the liver is common. Despite this significant risk, a sizeable number of patients are able to proceed to transplant and achieve prolonged survival. SBRT should be considered for patients requiring downstaging to meet transplant criteria.