External beam and stereotactic radiation in the treatment of fibrolamellar carcinoma.

Abstract

e16137 Background: Fibrolamellar Carcinoma (FLC) is an extremely rare (< 50 cases/year US), distinct type of primary liver cancer, unrelated to hepatocellular carcinoma (HCC), affecting healthy children and young adults that often presents at an advanced stage. Surgery is the only known cure, but is only possible in half of patients, and, even with surgery, there is an 80% relapse rate. Loco-regional therapies can make surgery possible or replace surgery, allow systemic therapy time to work, and prolong life. However because of the paucity of data and the common misunderstanding of treating FLC as a “variant of hepatocellular carcinoma (HCC)” it is often assumed to be radio-resistant. For example, the 2021 NCCN Guidelines give no specific recommendations for radiation in FLC but classifying FLC as a “variant of HCC'' recommend 25 1.8Gy fractions (45Gy) with a boost to 50-60 Gy for external beam radiation(EBRT) and 3-5 10Gy fractions for stereotactic body radiation (SBRT). In their HCC reviews, the New England Journal of Medicine (2020), ASCO (2019), and the Fibrolamellar Cancer Summit (2017) do not discuss radiation. This is the largest collection of FLC patients treated with radiation in the literature to date and will hopefully inform clinicians of the option to use radiotherapy in this difficult to treat cancer. Methods: We reviewed the literature for cases of FLC treated with radiation after 2000. With IRB approval, (ORA#19071603), we collected data on all Rush FLC patients treated with radiation. Descriptive statistics were used to characterize this group of patients. Results: We found 29 instances of EBRT or SBRT treating FLC: 3 case reports, 21 of our patients (two had multiple (2 and 4) distinct treatments). Of these 24 (13F/10M/1 Unknown), median age at diagnosis/start of treatment 17(11-40)/23(13-45) underwent radiation with a median dose of 36 Gy (20-50). Ten of 27 were considered “palliative” treatments. High fraction therapy (> 10 fractions) was used 9 times while low fraction therapy (≤ 10 fractions) 16. Biological Equivalent Dose median was 0.36108(0.2008-0.505). Six patients were treated concurrently with nivolumab. Mean prior systemic therapies was 2.6 (0-10) and 5 patients received prior radiation. Fourteen patients underwent SBRT, 10 conventional, 2 IMRT, and 2 unknown. Best response by RECIST 1.1 of the 27 instances with outcome data, was 21 CR, 2 PR, 2 PD, and 2 SD, for a objective response rate (CR + PR) of 85% and a cancer control rate (CR + PR + SD) of 93% at a median follow up of 13 months. In 18 out of 29 instances (62%), surgery was avoided after radiation. Late recurrence was noted in 2 out of 26 instances (8%). Conclusions: FLC is a rare disease lacking radiation guidelines. Our data strongly suggest radiotherapy can be effective with a variety of doses and strategies. We hope our report will encourage clinicians to consider EMRT/SBRT as part of a multi-modal approach to this difficult to treat cancer.