This study describes the short- and long-term outcomes of successful LT treatment in patients with HCC-PVTT following TAE in combination with SBRT. PVTT, as a common complication in patients with advanced-stage HCC, is closely related to intrahepatic metastasis and recurrence after surgical resection and results in poor prognosis [15]. The prognosis of patients with HCC-PVTT is much worse than that of patients with HCC without PVTT, which may be related to the high risk of tumor aggressiveness. In addition, the progression of PVTT may be related to liver reserve insufficiency and portal hypertension. Therefore, previous studies showed that based on varying tumor grades, liver function status, and treatment approaches, the mOS only ranged from 3–16.4 months [16, 17].
For HCC patients beyond LT indications, down-staging treatments are often employed to assess candidates with HCC exceeding Milan criteria for LT. Furthermore, LT outcomes, following successful down-staging, significantly surpass those observed in patients not undergoing LT [18, 19]. TACE is often utilized as a local treatment for unresectable or non-transplantable HCC, offering a survival advantage over best supportive care [19]. This is the preferred locoregional therapy for down-staging, typically administered transarterially. Prospective studies from multiple continents[3, 10, 11] have demonstrated the safety and efficacy of external RT for HCC, and accumulating evidence has demonstrated that RT has local effects on PVTT in patients with HCC. SBRT has been investigated as a research hotspot for providing a higher biologically effective dose. Encouraging results have indicated that SBRT has a high rate of local control and is safe to use in patients with HCC[20, 21].
Numerous clinical studies have reported improved HCC patient outcomes using TACE + RT combination therapy compared to TACE alone, and numerous clinical studies have reported improved outcomes using TACE + RT combination therapy compared to TACE [22–24] or RT alone[25]. Li Ke. et al. [25, 26] found that in patients with HCC-PVTT treated with TACE + RT, response rates ranged from 39.6–88.7%, 1-year survival rates from 25.0–62.4%, and median survival time from 9.7–15.8 months. These outcomes are more favorable compared to those of TACE alone. These results suggest that TACE + RT for HCC-PVTT is more effective and may prolong the survival of these patients.
In our retrospective analysis, the 12-, 18-, 24-, 36- and 60-month actuarial patient survival rates at the time of LT were 100%, 88.23%, 64.70%, 47.06%, and 17.65%, respectively. The mOS was 37 months, and the survival time was significantly longer than that of the other treatments. After LT, eight patients (47.06%) remained in complete remission, eight patients (47.05%) were stable, and nine patients (52.94%) progressed. Our results suggest that TAE + SBRT + LT had better clinical outcomes than RT、TACE or TACE + RT for primary liver cancer with PVTT with median survival time from 9.7–15.8 months [25–27]. The survival time of HCC-PVT was significantly prolonged who received the treatment of TAE + SBRT + LT.
Assessing the treatment response after radiation-based therapy is particularly challenging, as arterial enhancement and washout can persist for several months with increasing rates of necrosis over time. Alternative approaches for the treatment of residual and/or recurrent tumors often include thermal ablation and stereotactic body radiotherapy, depending on the size and location of the tumor(s) and the adequacy of hepatic function for additional locoregional therapy [19]. Our retrospective analysis showed that SBRT combined with TAE to control PVTT, followed by LT, had a better short-term therapeutic effect than did other treatment methods. Seventeen HCC-PVTT patients were classified as stage III, with 15 of these patients at TNM stage IIIB and all presenting with Child–Pugh grade A-B. All 17 patients exhibited advanced tumor stages and compromised general health. Notably, three individuals achieved a survival period exceeding 5 years post-transplantation, remaining tumor-free, and being clinically cured. From the diagnosis of HCC to August 31, 2023, the 5-year survival rate of the 17 patients was 50%, and the longest survival time was 8.4 years. Five patients survived after LT and were followed up for less than 3 years; thus, the current statistical OS may be low.
The OS of some LT patients with recurrence and metastasis was found to be better than that of cirrhotic patients following multidisciplinary treatment. This improvement may be attributable to LT addressing not only the tumor but also the underlying liver cirrhosis. Post-LT, patients often experience an enhancement in liver function and achieve a Child–Pugh classification of grade A [5]. Rather than using expanded criteria, down-staging strategies are increasingly being used to select a subgroup of patients beyond the Milan criteria who have favorable biology for LT based on their response to locoregional therapy[5, 28]. Moreover, Li et al.'s [26] study suggested that the combination of TACE and RT is more suitable for patients with unresectable HCC with PVTT stages II and III, a finding that has not been thoroughly explored previously. Our analysis further supports that TAE combined with CK-SBRT in the treatment of HCC-PVTT achieved better down-staging treatment, which could be employed to select patients with HCC beyond the Milan Criteria for LT.
Our study has some limitations. First, it was a retrospective study, which may have led to selection bias in our study population. In addition, certain patients were observed to undergo a brief follow-up period. Therefore, to validate our observations on the potential advantages and safety of SBRT coupled with TAE in patients with HCC-PVTT preceding LT, a prospective randomized trial involving a larger cohort is warranted.