Search Results and Study Evaluation
After eliminating duplicates and screening abstracts, 14 articles were assessed for eligibility. A total of seven articles were identified to be eligible for this study. Six comparative studies were included in the quantitative analysis. Four studies (three retrospective studies, one prospective cohort study) directly compared the outcomes of SBRT versus TACE, while two retrospective studies compared TACE + SBRT versus TACE alone. One phase III RCT compared TACE + SBRT versus TACE/TAE + further TACE/TAE and was included in the qualitative analysis. Full details of the inclusion process and PRISMA flow chart can be found in Fig. 1. The characteristics of the included studies comparing SBRT versus TACE and TACE + SBRT versus TACE+/- further TACE are summarized in Tables 1 and 2, respectively.
Critical Appraisal Results
All seven studies were found to have sound methodological quality, clearly-stated objectives, and relevant background discussion on the topic. They had well-defined, measurable outcomes with clinically meaningful results. The study population in the included articles generally fit the inclusion criteria of the review. The RCT of Comito et al. included patients with advanced HCC, but the subgroup analysis revealed that the impact of BCLC stage on outcomes was not significant. Due to the retrospective nature of most of the studies, some had missing information. Some of the studies had relatively small population sizes.
Table 1
Characteristics of studies included in the review (SBRT versus TACE)
Study | Type of Study | Country | Median Follow-up (months) | Total Number of Patients | Inclusion Criteria | Median Age (years) | SBRT Dose (Gy) | TACE Agent | Treatment Intent | Other Interventions |
Mohamed et al., 2016 [14] | Retrospective review | USA (University of Rochester Medical Center) | 41 | 60 Number of lesions treated: 79 SBRT: 24 TACE: 37 | BCLC A; Listed for liver transplant | 57.5 | 50 (45–60) in 5 fractions | Cisplatin Doxorubicin | Bridge to liver transplant | RFA Y90 |
Sapisochin et al., 2017 [15] | Retrospective review | Canada (Toronto General Hospital) | 47.2 | 406 SBRT: 30 TACE: 79 | Listed for liver transplant | SBRT: 60.4 TACE: 57.6 | 36 (30–40) in 6 fractions | Doxorubicin 75–150 mg/m2 | Bridge to liver transplant | RFA |
Su et al., 2020 [16] | Retrospective review | China (Guangxi Medical University Cancer Hospital, Rui Kang Hospital) | SBRT: 35 TACE: 32 | 326 SBRT:167 TACE: 159 | BCLC A | SBRT: 56 TACE: 52 | 28–50 In 1–5 fractions | Oxaliplatin or Lobaplatin or Cisplatin (20–100mg), Pharmorubicin or Pirarubicin (10–40 mg) | Definitive | None |
Wong et al. 2021 [17] | Prospective cohort | Hong Kong (Queen Mary Hospital) | 42 | 150 SBRT: 40 TACE: 59 | Listed for liver transplant | SBRT: 59.6 TACE: 58.1 | 50 (35–50) in 5 fractions | Cisplatin (maximum dose 30mg) | Bridge to liver transplant | Retrospective control: TACE and HIFU |
Table 2
Characteristics of studies included in the review (SBRT + TACE versus TACE +/- further TACE)
Study | Type of Study | Country | Median Follow-up (months) | Total Number of Patients | Staging Characteristics/ Inclusion Criteria | Median Age (years) | Median SBRT Dose (Gy) | TACE Agent | Treatment Intent | Other interventions |
Honda et al. 2012 [18] | Retrospective review | Japan (Hiroshima University Hospital) | SBRT + TACE: 12.3 TACE alone: 30.2 | TACE + SBRT: 30 TACE alone: 38 | - HCC nodule < 30mm in diameter - CTP score < 7 | SBRT + TACE: 70 TACE alone: 73 | 48–60 In 4 or 8 fractions | Miriplatin (median dose: 27mg), Cisplatin (median dose: 25 mg) | Definitive | None |
Jun et al. 2018 [19] | Retrospective review | South Korea | Not specified | TACE + SBRT: 85 TACE alone: 85 | - HCC nodule < 50mm in diameter - <3 lesions - CP class A or B - BCLC A | SBRT + TACE: 62 TACE alone: 62 | 40–60 (median:55) in 3–5 fractions | Doxorubicin (50mg/m2) | Definitive | None |
Comito et al. 2022 [20] | Phase III RCT | Italy | 20 | SBRT: 21 Further TACE: 19 | - BCLC A or B | 75 | 60Gy in 3–6 fractions | Epirubicin (50mg) | Salvage treatment after TACE failure | None |
3.3. Survival Outcomes Comparing Sbrt Versus Tace
Four eligible articles compared SBRT versus TACE and evaluated the 3- and 5-year OS and RFS. A total of 237 patients in the SBRT group and 297 patients in the TACE group were included in the 3-year analysis. For the 5-year pooled data, 220 patients were included in the SBRT group versus 274 in the TACE group. Forest plots for the pooled analyses are presented in Figs. 2 and 3.
An OS benefit was seen at 3 years (OR 1.67, 95% CI 1.17–2.39, p = 0.005) which persisted after 5 years (OR 1.53, 95% CI 1.06–2.39, p = 0.02). There was no heterogeneity in the pooled data.
RFS benefit was also seen at 3 years (OR 2.06, 95% CI 1.03–4.11, p = 0.04) which likewise persisted after 5 years (OR 2.35, 95% CI 1.47–3.75, p = 0.0004). Substantial heterogeneity was seen in the 3-year pooled sample and was analyzed by the random effects model.
3.4 Survival Outcomes Comparing Tace + sbrt Versus Tace Alone
Two articles evaluated the 3-year OS and LC of patients treated with TACE + SBRT compared to those who received TACE alone (Fig. 4). For the OS analysis, a total of 61 patients were included in the TACE + SBRT group versus 136 patients in the TACE alone group. Pooled analysis showed significantly improved 3-year OS in the TACE + SBRT group (OR 5.47, 95% CI 2.47–12.11, p < 0.0001). No significant heterogeneity was found in this pooled sample (I2 = 0%, p = 0.72).
For the LC analysis, 79 patients were included in the TACE + SBRT group versus 135 patients in the TACE alone group. The results showed a statistically significant improvement in LC in favor of the TACE + SBRT group (OR: 21.05, 95% CI 5.01–88.39, p = < 0.0001). There was no heterogeneity in the pooled data (I2 = 12%, p = 0.29).
3.5 Survival Outcomes Of Sbrt Versus Further Tace/tae After Incomplete Response To Tace/tae
An Italian, single-center, phase III RCT evaluated the benefit of adding SBRT versus further TACE/TAE after an incomplete response to TACE/TAE [20]. Forty patients with BCLC A-B were enrolled, 21 in the SBRT group and 19 in the exclusive TACE group. Primary endpoint was 1-year LC while 1-year progression-free survival (PFS), distant RFS, and OS were the secondary endpoints.
Significantly higher LC rates were seen with the use of SBRT versus TACE with 1 year LC rates of 84% versus 23% (median not reached versus 8 months, p = 0.0002, HR: 0.15, 95% CI 0.04–0.4), respectively. Patients treated with SBRT experienced significantly longer PFS in comparison with patients treated with TACE (median 9 versus 4 months, p = 0.016). Median OS was 31 months in the SBRT arm and 30 months in the TACE arm (p = 0.472). OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. Distant RFS was similar between both groups.
The impact of BCLC stage on outcomes was not significant. Fifteen percent of the population had BCLC A stage HCC. Median LC was not reached in patients with BCLC A stage compared to 11 months with BCLC B. The median PFS for BCLC A and B was 7 months and 5 months while the median OS was 30 months and 29 months, respectively.