LAUSR

One complication of hepatocellular carcinoma (HCC), portal vein thrombosis (PVT), portends a particularly poor prognosis and typically excludes patients from transplant or resection eligibility [1]. While current guidelines recommend effective treatment with tyrosine kinase inhibitors, they are associated with toxicities and eventual drug discontinuation. Recently, immunotherapies (IOs) have received considerable attention supported by the notion of a survival tail: the concept that a small subset of patients achieves a markedly prolonged survival with a given treatment [2]. In 2020, KEYNOTE-240 showed that pembrolizumab, another IO, produced a similar tail in the second-line treatment of advanced HCC, with a 19.4% progression-free survival at 12 months [3]. Yttrium-90 (Y90) radioembolization is a therapy achieving comparable median survival to sorafenib in PVT patients with fewer adverse events [4]. However, in select cases, a median survival of 32 months has been observed in Y90-treated PVT patients [5]. At our institution, we have also observed a prolonged survival tail with the use of Y90. Of 185 patients with locally advanced HCC with PVT receiving Y90, 34 (18%) exhibited a survival of C18 months [6]. This cohort had a relatively heterogeneous set of baseline demographics and tumor characteristics. The majority were Child–Pugh (CP) Class A (20, 59%), while 14 were CP Class B (41%). PVT location varied: 10 patients segmental (29%), 14 lobar (41%), and 10 main (29%). Seventeen patients had multifocal tumor (50%), while 17 exhibited solitary tumor (50%). Median size of index tumor was 6.4 (range 1.5–14.4) cm. Notably, toxicities were minimal, with 2 of 34 patients (6%) experiencing grade 3 albumin or bilirubin toxicities within 60 days, and 4 (12%) within the first year. No patients experienced grade 4 toxicities. The median number of Y90 treatments was 2. 9 patients (26%) received sorafenib after their first Y90, with 5 discontinuing due to adverse events. Six patients (18%) exhibited exceptional responses to Y90, leading to liver transplantation in 5, and surgical resection in 1. Four of these 6 patients survived[5 additional years following curative therapy. The median overall survival in our 34 patients with durable responses and long survival tail was 29 months (CI 22–51) (Fig. 1). While the prognosis of HCC patients with PVT has historically been bleak, there are a growing number of treatments available. Compared to traditional multi-tyrosine kinase inhibitors recommended by most guidelines, Y90 is an FDA-approved outpatient treatment that, in a manner similar to IOs, leads to a long survival tail in advanced-stage HCC patients with PVT. Our institutional data show that 34 PVT patients treated with Y90 achieved a markedly prolonged survival of C18 months; this observation is not unique to IOs. Additionally, Y90 has the potential to downstage these patients traditionally excluded from curative treatments to transplant or resection. This downstaging outcome following IOs has not been reported in a patient series to date. In conclusion, the narrative of a subgroup of patients exhibiting prolonged survival should not be reserved solely for IOs. Y90 should still be considered a key primary treatment option for localized advanced HCC and PVT, since it too has the potential to create sustained, durable & Riad Salem [email protected]