Emerging curative-intent minimally-invasive therapies for hepatocellular carcinoma

Table 1 Outcomes for curative-intent therapies in hepatocellular carcinoma within Milan criteria

Modality	Overall survival at 5 yr (%)	Local tumor progression at 2 yr (%)	Local tumor progression at 5 yr (%)	Disease-free survival at 5 yr (%)
Transplant	≥ 70[21]	NDA	Cumulative recurrence < 15[22]	> 70[23]
Resection	60-80[24-26]	NDA	Resection margin recurrence 1-7[27-29]	38-54[26,27,30]
Ablation ≤ 3 cm	44-69[13,25,31]	2-16[28,29,32]	9.7-22[13,33,34]	14-46[25,27]
TARE ≤ 3 cm	75[35]	2.4-6.1[36,37]	NDA	NDA
Ablation ≤ 5 cm	49-72[27,38,39]	6-9[40,41]	3-14[12,31,40]	50-59[27,40]
TARE ≤ 5 cm	57[35]	6.1-10[37,42]	28 for ≤ 5 cm[35]	NDA

While ablation is recommended for lesions < 3 cm, data for lesions up to 5cm is also included. Ablation studies included patients who were not surgical candidates. Data is derived from studies that included solitary and multiple lesions. Resection outcomes are limited to patients with Child-Pugh A liver function, while all other modalities include patients with Child-Pugh A and B. Data for transarterial radio-embolization should be considered preliminary. Included papers were published within the last ten years. NDA: No data available; TARE: Transarterial radio-embolization.

Table 2 Comparing key features of the LEGACY study and DOSISPHERE trial

	LEGACY	DOSISPHERE
Study design	Multi-center single-arm retrospective study	Multicenter randomized control phase ii trial
Objective	To assess clinical outcomes of Y-90 glass microsphere treatment in patients with unresectable solitary HCC lesions	To compare clinical outcomes of lobar TARE using 120 Gy (SDA) versus > 205 Gy (PDA) in patients with intermediate/advanced HCC
Inclusion criteria	Unresectable solitary lesions (≤ 8 cm); BCLC A or C (ECOG 0-1); Child-Pugh score A	≥ 1 unresectable lesion ≥ 7 cm; BCLC A, B, or C
Exclusion criteria	Patients with vascular or extrahepatic disease, significant ascites, encephalopathy, or prior LRT, LT, resection, or systemic therapy	Patients with micro-aggregate albumin (MAA) studies demonstrating poor tumor targeting
Overall survival	At 3 yr, 86.6% for patients treated with TARE alone (median dose 410 Gy) and 92.8% for patients who down-staged via TARE	Overall survival was improved in the personalized dosimetry group (26.6 mo vs 10.7 mo)
Downstaging	21% successfully down-staged to LT; 6.8% to resection.	36% patients in the PDA group and 3.5% (1/28) in the SDA group down-staged to resection1

¹Including patients with portal vein tumor thrombus.

HCC: Hepatocellular carcinoma; BCLC: Barcelona clinic liver criteria; LRT: Locoregional therapy; LT: Liver transplant; PDA: Personalized dosimetry group; SDA: Standardized dosimetry group; TARE: Transarterial radio-embolization.