Background
Retrospective intention-to-treat analysis (Toronto General Hospital). 379 patients listed for liver transplantation for HCC and treated with bridging therapy: SBRT (n=36), TACE (n=99), or RFA (n=244) from 2004 to 2014. Goal: compare SBRT vs TACE vs RFA as bridge to transplant in terms of dropout rate, post-transplant outcomes, and survival.
Interventions and follow up
Arm A: SBRT bridging — 24–54 Gy in 6 fractions (median)
Arm B: TACE bridging
Arm C: RFA bridging
Primary endpoint: Dropout rate from transplant waitlist; post-transplant OS and tumor recurrence
mFollow up: Up to 10 years from listing
Arm B: TACE bridging
Arm C: RFA bridging
Primary endpoint: Dropout rate from transplant waitlist; post-transplant OS and tumor recurrence
mFollow up: Up to 10 years from listing
Results
Dropout rate: 16.7% (SBRT) vs 20.2% (TACE) vs 16.8% (RFA), P=.7 — not significant
5-year OS (from listing): 61% (SBRT) vs 56% (TACE) vs 61% (RFA), P=.4
5-year OS (from transplant): 75% (SBRT) vs 69% (TACE) vs 73% (RFA), P=.7
Tumor necrosis in explant: More complete necrosis with RFA than SBRT (P<.05)
5-year OS (from listing): 61% (SBRT) vs 56% (TACE) vs 61% (RFA), P=.4
5-year OS (from transplant): 75% (SBRT) vs 69% (TACE) vs 73% (RFA), P=.7
Tumor necrosis in explant: More complete necrosis with RFA than SBRT (P<.05)
Adverse events
Main adverse events: No significant difference in postoperative complications between groups. SBRT was non-invasive and did not increase surgical complexity. Comparable post-transplant morbidity across bridging modalities.
Conclusions
SBRT achieves equivalent dropout rates from the transplant waiting list and equivalent post-transplant survival compared to TACE and RFA in HCC patients awaiting liver transplantation, establishing SBRT as a safe and effective bridging therapy alternative for patients not suitable for or failing TACE/RFA.
Key Limitations
Key Limitations: Retrospective design with non-random treatment assignment — SBRT patients may have had tumors less amenable to TACE/RFA (central location, poor access), introducing selection bias. SBRT arm is much smaller (n=36) than TACE or RFA arms. Tumor necrosis was greater with RFA, but post-transplant outcomes were similar ��� biological significance of residual viable tumor after SBRT vs complete necrosis after RFA remains unclear. Long accrual period with evolving SBRT techniques across 10 years.
Clinical Context
This study is a key reference supporting SBRT as a bridge-to-transplant option for HCC. The finding that tumor necrosis is less complete with SBRT than RFA but post-transplant outcomes are identical suggests that pathologic necrosis is not the primary driver of transplant benefit. SBRT is now recommended as a bridging option in NCCN and AASLD guidelines, particularly for tumors in central locations, adjacent to vessels, or in patients with bleeding risk precluding RFA or TACE.
References