Table 2.

Key trials investigating SBRT as a bridge to OLT in patients with HCC

Study info	Design	Sample size	CP Classification	Radiotherapy dose	Survival and local control	Drop out rate	Conclusions and special considerations
Sandroussi et al. 2009 [17]	Prospective pilot study	n = 10	CP-A5: 4 (40%) CP-B7: 3 (30%) CP-B8: 1 (10%) CP-98: 1 (10%) CP-C10: 1 (10%)	Median dose: 33 Gy in 5-6 fractions)	Median follow-up: 8 months *Radiographic response rate: PR: 70% SD: 20% One patient received only 1 fraction before undergoing OLT.	Two patients were de-listed (20%) due to progression of disease outside the treated field and died (lung metastasis; new HCC within untreated segment of liver)	All patients who completed SBRT course had a PR. No grade ≥ 3 acute toxicities CRT did not make transplantation more difficult, nor did it have an adverse effect on the outcome following transplantation.
O’Connor et al. 2012 [18]	Retrospective	n = 10 patients with a total of 11 tumors	CP-A: 7 (70%) CP-B: 2 (20%) CP-C: 1 (10%)	Median dose = 51 Gy in 3 fractions	Median follow-up: 62 months *Radiographic response rate at 5 months: PR: 10% SD: 50% 40% of patients underwent OLT before 3 months Pathologic complete response: 3 tumors (27%) 5-year OS: 100% 5-year DFS: 100%	No patients (0%) treated with SBRT dropped off the waitlist due to progression	Four patients experienced acute toxicity, no grade ≥ 3 acute toxicities
Mannina et al. 2016 [19]	Retrospective	n = 38 patients with a total of 51 tumors	CP-A: 17 (45%) CP-B7: 21 (55%)	Median dose in CP-A patients: 9-14 Gy in 3-5 fractions Median dose in CP-B7 patients: 8 Gy in 5 fractions	Median follow-up: 4.8 years since OLT *Pathologic response rate: 68% CR: 20 tumors (45%) PR: 10 tumors (23%) SD: 14 tumors (32%) Local recurrence: 9 (24%) Death: 10 (26%) 3-year OS: 77% 3-year DFS: 74%	No patients (0%) treated with SBRT dropped off the waitlist due to progression	PVT in 16% CP score changes from pre-SBRT baseline until pre-OLT: A→A: 34% A→B: 8% A→C: 3% B→A: 8% B→B: 29% B→C: 18%
Moore et al. 2017 [20]	Retrospective	n = 23 patients, 16/23 patients treated with SBRT as a bridge to transplant	CP-A: 13 CP-B: 10	Median Dose = 54 Gy	Median follow-up: 12 months *Pathologic response rate: CR: 3 patients (27.3%) PR: 6 patients (54.5%) SD: 2 patients (18.2%) 11 out of the 16 eligible patients underwent successful OLT Median OS and PFS of transplanted patients not reached OS range: 2.0–53.7+ months PFS > 54 months at time of publication	No patients (0%) treated with SBRT dropped off the waitlist due to progression. Remaining 5 patients were awaiting transplant and without disease progression.	Median OS and PFS of non-transplanted patients = 23 months and 14.0 months respectively One patient developed RILD. No other patients experienced decompensation at 12 weeks post-SBRT
Garg et al. 2020 [21•]	Retrospective	n = 20 patients	CP-A5: 5 (25%) CP-A6: 5 (25%) CP-B7: 3 (15%) CP-B8: 3 (15%) CP-B9: 2 (10%) CP-C10: 2 (10%)	Median dose: 50 Gy in 5 fractions	Median follow-up: 42.4 months in patients who underwent OLT *Radiographic response rate (n = 21): CR: 16 (76%) PR: 5 (24%) *Pathologic response rate (n = 26): CR: 16 tumors (62%) PR: 10 tumors (38%) Complete clinical response: 76%	Six patients (6/27, 22%) were de-listed: 4 passed away, 2 patients progressed beyond Milan (one developed diffuse carcinomatosis of liver; progression elsewhere in the liver)	No significant correlation between pathologic CR and increasing tumor size (OR = 0.95, 95% CI 0.595–1.53) or equivalent dose in 2 Gy fractions (OR = 1.03, 95% CI 0.984–1.07) Four patients (20%) experienced progression of CP score after SBRT

HCC hepatocellular carcinoma, CP Child-Pugh score, SBRT stereotactic body radiotherapy, LC local control, PFS progression-free survival, OS overall survival, OLT orthotopic liver transplant, GTV gross tumor volume, CR complete response, PR partial response, SD stable disease, PD progressive disease, PVT portal venous thrombosis

*Response to treatment per RECIST guidelines [22]