Table 1.
Selected Series of Stereotactic Body Radiotherapy (SBRT) for Hepatocellular Carcinoma (HCC)
| Author | Year | N | Tumour Size Median (Range) | Dose | LC | OS | Toxicity | Comments |
|---|---|---|---|---|---|---|---|---|
| Kwon et al23 | 2010 | 42 | Median volume= 15.4 cc (3.0–81.8 cc) | 30–39 Gy/3# to 75–80% isodose | 3-yr LC=68% | 3-yr OS=59% | One patient died with extrahepatic metastasis and radiation-induced hepatic failure | Cyberknife; no planned therapy, eg TACE, prior to SBRT |
| Choi et al25 | 2008; retrospective | 22 (+9 with PVT) | Median volume= 23.5cc (3.6–57.3 cc) | 30–39 Gy/3# to 75–80% of target volume | Overall Response rate= 83% | Median OS= 12m (of small HCC alone) | 10% progression of CP;3% Grade 3 liver enzyme toxicity | Cyberknife; small HCC were treated with SBRT alone (lesions with PVT underwent SBRT+TACE) |
| Jang et al26 | 2013; retrospective | 74 (+8 with PVT) | Median size=3 cm (1–7 cm) | Median 51 Gy in 3# (33–60Gy) | 2-yr LC=87% | 2-yr OS=63% | 6%-> Grade 3 GI toxicity; 7%- deterioration of CP score by >2. | Unsuitable for surgery/local ablation/had incomplete response to TACE (all patients underwent TACE, although not planned); LINAC-based SBRT; Dose response threshold at 45–54 Gy EQD2 |
| Yoon SM et al29 | 2013 | 93 | Median size=2 cm (1–6 cm) | 30–60Gy in 3–4 # | 3-yr LC=92% | 3-yr OS=54% | 6.5% ≥Grade 3 hepatic | LINAC based SBRT-static conformal, no planned TACE |
| Sanuki et al27 | 2014; retrospective | 185 | Median size=2.4–2.7 cm (0.8–5 cm) | 35Gy/5# 40Gy/5# |
3-yr LC=91% | 3-yr OS=70% | Acute toxicities ≥ Grade 3 observed in 13.0% patients; 10.3% patients had worsening of CP score by 2 points. 2 patients had grade 5 liver failure | 2 cohorts- dose as per size; no planned TACE |
| Qiu et al33 | 2018; retrospective | 93; 86% no PVT | Median sum of longest diameter= 4.4 cm (2.9–5.8) | 50–60 Gy/5-10# | At median follow up of 4 months, 94% had CR,PR or SD | Median OS =9 m | Adverse events ≥ Grade 3 were 10% | 46% Child-Pugh Class B or C; no planned therapy/TACE |
| Jeong Y30 | 2018; retrospective | 119 | Median size=1.7 cm (0.8–6 cm) | 30–60Gy in 3–4# | 3-yr LC=97% | 3-yr OS= 84% | 2% acute ≥Grade 3 hepatic non-classic RILD; 6% worsening of CP≥2; 2% ≥Grade 3 late biliary strictures | LINAC based respiratory gated VMAT; no planned therapy/TACE |
| Liu et al34 | 2020; retrospective | 59 (BCLC O/A) out of 96 | Median size=3.8 cm (1.5–17 cm) | Median BED10 =86 Gy | FFLP at 18 months was 94% for BCLC 0/A | 1-yr OS= 95% for BCLC O/A | 7% increase in CP score >1 within 3 months of SBRT. Clinical toxicities grade ≥2-20%. | No UVA or MVA; no planned therapy/TACE |
| Yeung et al35 | 2019; retrospective | 31 | Median size=3.3 cm (1.3–5 cm) | 45 Gy/3-5# | 1-year LC= 94% | 1-yr OS=84% | 19% worsened CP score by>2 points; 32% > Grade 3 toxicities | Child-Pugh Class A or B, with small HCCs measuring ≤5 cm; On UVA, small tumour size predicted for improved overall survival (P = 0.01); no planned therapy/TACE |
| Mathew et al28 | 2020; retrospective | 297; ineligible or recurrent/residual after RFA/TACE; CP A/B/C=76/20/2 | Median size=2.7cm (0.5–18.1cm) | 27–60 Gy/3-6# | 3-yr LRR=13% | 3-yr OS= 39% | Worsening of CP score by ≥2 points three months after SBRT in 16%. | Liver transplant after downstaging post SBRT in 25 patients, CP A liver function, AFP ≤ 10 ng/mL, and ECOG status 0 significantly improved OS; no planned TACE |
| Kimura et al31 | 2020; prospective | 36 (target 60; closed early due to poor accrual) | Median size=2.3 cm (1–5 cm) | 40 Gy/5# | 3-yr LC= 90% | 3-yr OS=78% | ≥Grade 3 toxicities= 11% | Previously untreated solitary HCC |
| Loi et al32 | 2020; retrospective | 128 (BCLC Class A/B=31%/56%) | Median size= 3 cm (1.4–9.9 cm) | Median BED10=103 Gy/3-10#; Range=30–75 Gy in 3–10 # | 2-yr LC= 78% | 2-yr OS=58% (whole cohort; separately NA) | Acute Grade 3 Toxicity- acute liver failure and ascites in 1 pt. | In BCLC stage A-B disease (n=112), LC associated with improved OS (median 30 months vs not reached, p=0.036) |
| Park et al36 | 2020; retrospective | 290 (BCLC Class A=86%) | Median size=1.7 cm | Median 45 Gy in 3 −4# (Range 30–60 Gy/3-4 #) | 5-yr LC= 91% | 5-yr OS= 44.9% | ≥Grade 3 hepatic toxicities=2.3%; 5.5% had decline in CP score of >2 | MVA showed tumour size (< or > 3 cm) and serum albumin significantly associated with tumor LC. |
Abbreviations: HCC, hepatocellular carcinoma; LC, local control; OS, overall survival; PVT, portal vein thrombosis; CP, Child-Pugh; LINAC, linear accelerator; SBRT, stereotactic body radiotherapy; RFA, radiofrequency ablation; TACE, transarterial chemoembolization; CR, complete response; PR, partial response; SD, stable disease; RILD, radiation induced liver disease; FFLP, freedom from local progression; UVA, univariate analysis; MVA, multivariate analysis; VMAT, volumetric modulated arc therapy; AFP, alpha-fetoprotein; ECOG, Eastern Co-operative Oncology Group; HCC, hepatocellular carcinoma; BCLC, Barcelona Clinic Liver Cancer classification; Gy, Gray; EQD2, equivalent dose in 2 Gy fractions; #, fractions; BED10, biologically effective dose with alpha/beta ratio of 10; m, month; yr, year.