Stereotactic Body Radiotherapy versus Radiofrequency Ablation as Initial Treatment of Small Hepatocellular Carcinoma

doi:10.21203/rs.3.rs-1463763/v1

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Research Article

Stereotactic Body Radiotherapy versus Radiofrequency Ablation as Initial Treatment of Small Hepatocellular Carcinoma

https://doi.org/10.21203/rs.3.rs-1463763/v1

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posted 29 Mar, 2022

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Background/Aim: Resection or ablative therapy is not indicated for many patients with hepatocellular carcinoma (HCC) because of advanced cirrhosis or the tumor location. Stereotactic body radiotherapy (SBRT) may be an alternative treatment for these patients. This study compared the therapeutic effects of radiofrequency ablation (RFA) and SBRT in patients with small (≤ 3 cm) HCCs.

Methods: Data of HCC patients who underwent SBRT or RFA as an initial treatment at four tertiary referral hospitals between March 2011 and February 2017 were reviewed. The patient inclusion criteria were a single nodule measuring ≤ 3 cm in size and not suitable for resection.

Results: SBRT and RFA were performed for 72 (SBRT group) and 134 (RFA group) patients, respectively. The 1-, 3- and 5-year overall survival (OS) rates were 97.0%, 80.3%, and 80.3%, respectively, in the SBRT group compared with 98.5%, 83.9%, and 80.8%, respectively, in the RFA group, with no significant differences between the groups (P = 0.81). The estimated five-year local control (LC) rate was 68.1% in the SBRT group and 73.1% in the RFA group (P = 0.81). In the SBRT group analysis, both SBRT alone (n=34) and SBRT combined with transarterial chemoembolization (n=38) showed no difference with RFA in OS (p = 0.72) or LC rate (p = 0.95).

Conclusion: SBRT is an effective and safe treatment method for small HCCs, with survival and tumor recurrence rates similar to those of RFA.

Hepatocellular carcinoma

Stereotactic body radiotherapy

Radiofrequency ablation

Transarterial chemoembolization

Initial treatment

Survival rate

Local control rate

Progression-free survival rate

Liver toxicity

Child-Pugh

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide.¹ Resection, transplantation, and radiofrequency ablation (RFA) are the standard treatments for early-stage HCC. However, many patients are not indicated for resection because of advanced cirrhosis and a poor general condition. Also, RFA could not be performed in patients with a difficult location of the tumor and an elevated risk of bleeding. In these cases, transarterial chemoembolization (TACE) is usually performed even in early-stage HCC.² However, TACE has a low response rate (26–35%) and a high recurrence rate compared with curative treatments.^3,4

In recent decades, stereotactic body radiotherapy (SBRT) has increasingly been used to treat tumors not suited for surgery or RFA. The development of radiation technology has improved the accuracy of targeting and delivering high-dose radiation, increasing the treatment response rate while simultaneously reducing the side effects.⁵ With the improvements in radiation techniques, favorable outcomes have been noted with good local control (LC) rates for HCC patients who are not eligible for curative treatment^6–9. Especially, SBRT has an excellent LC rate (more than 90%) for small (≤ 3 cm) HCC.^10,11

Currently, SBRT is not recommended as an initial treatment for HCC due to a lack of evidence.² Therefore, SBRT is performed as palliative therapy for patients who are not candidates for surgery or other initial treatments, although SBRT has a high LC rate. Recently, several studies have suggested that SBRT could be an alternative to RFA for treating HCC patients.^7,10,12 However, few studies have compared SBRT and RFA for HCC patients as an initial treatment.^13–15 The aim of this study was to compare the effects and overall survival (OS) of SBRT and RFA as an initial treatment and to evaluate the therapeutic effects of SBRT in patients with HCC ≤ 3 cm.

2.1 Patients

Data of HCC patients who underwent SBRT or RFA as an initial treatment between March 2011 and February 2017 were reviewed at four tertiary referral hospitals (Soonchunhyang University Seoul, Bucheon, Cheonan Hospital and Gangneung Asan Medical Center). Patients meeting the inclusion criteria were selected: 1) tumor size ≤ 3 cm in the long diameter and 2) not suitable for resection. The exclusion criteria were: 1) previous treatment with resection, radiofrequency ablation, or TACE; 2) extrahepatic metastasis; and 3) vascular invasion or portal vein tumor thrombosis. The diagnosis of HCC was made with dynamic imaging techniques.¹⁶

Seventy-two patients were treated with SBRT (SBRT alone or SBRT combined with TACE), while 134 patients were treated with RFA. SBRT alone was defined as no other treatment combined with SBRT. In treatment of SBRT combined with TACE, SBRT was performed within 2 months after TACE. The selection criteria for TACE and SBRT were mainly determined by considering tumor vascularity, hepatic angiography, accessibility, risk of bleeding or liver toxicity. This study was approved by the Institutional Review Board of Soonchunhyang University Seoul, Bucheon, Cheonan Hospital, and Gangneung Asan Medical Center, and written informed consent was waived because of its retrospective design.

2.2 SBRT procedure

SBRT was performed at Gangneung Asan Medical Center using the TrueBeam medical linear accelerator (Varian Medical Systems, Palo Alto, CA, USA), Soonchunhyang University Cheonan using the Novalis TX (Varian Medical Systems and BrainLab), Soonchunhyang University Seoul Hospital using the CyberKnife Radiosurgery System (Accuray Incorporated, Sunnyvale, CA) and Soonchunhyang University Bucheon using the TomoTherapy device (Madison, WI, USA). SBRT was performed alone or on viable tumors that showed an incomplete response after the first TACE. The patient was fixed in the supine position with the arms placed above the head. Four-dimensional (4D) CT scanning was performed for all plans. Gross tumor volume (GTV) was measured based on the end-expiratory phase for the 4D-CT images with multi-phase MR images. The internal target volume (ITV) was defined as extension based on movement within the gating phase (30–70%) from the GTV. The planning target volume (PTV) was set as the volume with a 5 mm margin added to the ITV. A total dose of 40–60 Gy (median, 55 Gy) was delivered to the PTV in three to five fractions over 3 consecutive days.¹⁷

2.3 TACE procedure

TACE was performed through the path from the common femoral artery to the feeder blood vessels of the hepatic segment by using an angiographic catheter. A mixture of intra-arterial adriamycin (50 mg/m²) and lipiodol (5 to 10 mL) with gel foam embolization was used at Soonchunhyang University Seoul, Cheoan, Bucheon Hospital and Gangeung Asan Hospital.¹⁸

2.4 RFA procedure

RFA was performed with the patient under conscious sedation and local anesthesia under ultrasound guidance. A single electrode with a cooled tip (RF Medical Co, Korea) was used for tumor ablation at Soonchunhyang University Seoul, Cheoan, Bucheon Hospital and Gangeung Asan Hospital. The RFA current was elevated to 20 W/min starting from 60 W to deliver the maximum power using the automatic impedance control method and a 200 W generator (RF Medical Co., Korea) for 8 to 18 minutes.

2.5 Liver toxicity evaluation

Liver toxicity was defined as worsening of the Child-Pugh (CP) score by 2 or more within 3 months or elevated liver transaminases more than five times the upper normal limit after treatment.¹⁹

2.6 Assessment

The primary endpoint was a comparison of the OS between the SBRT and RFA groups. The secondary endpoint was a comparison of LC and progression-free survival (PFS) between the groups. All patients were followed up every 1 to 3 months. All patients underwent physical examinations, complete blood cell counts, biochemical profiles, tumor markers, and three-phasic CT or magnetic resonance imaging (MRI) scans at every follow-up visit. Complications were assessed according to version 4 of the Common Terminology Criteria for Adverse Events version 5.0.

2.7 Statistical analysis

The OS, PFS and LC in each treatment group were estimated using the Kaplan-Meier method and log-rank test. OS was calculated from the date of diagnosis until the date of final follow-up or death. PFS was estimated from the date of initial treatment until the date of extra- and/or intrahepatic disease progression, recurrence, or death. LC was defined as the absence of progressive disease (PD) within the PTV as per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as observed on multiphasic CT or MRI. Lesions that developed or progressed outside the PTV in the liver or lymph nodes were scored as regional PD and those that developed in other organs as distant PD. Survival and control times were calculated from the start of SBRT or RFA. Time to progression and survival were evaluated with the Kaplan-Meier method. A Cox proportional-hazards model was used to evaluate the factors influencing the OS rates.

To reduce the impact of treatment selection bias and potential confounding in this observational study, the inverse probability of treatment weighting (IPTW) method based on propensity score (PPS) analysis was used. With that technique, weights for patients receiving SBRT were the inverse of the propensity score, and weights for patients not receiving RFA were the inverse of 1-the propensity score. The propensity score was estimated after two treatments as the dependent variable by multiple logistic regression analysis that included all of the variables in Table 1. Absolute standardized differences (ASD) were used to diagnose the balance after the propensity analysis. All ASDs after IPTW were < 0.2. The risks of clinical endpoints were compared using the IPTW-weighted Cox model with a robust standard error. A P-value of < 0.05 was considered significant. All statistical analyses were performed using the SPSS statistical package (version 18.0; SPSS Inc., Chicago, IL, USA).

Table 1

Baseline characteristics
					IPTW
	SBRT	RFA	P-value	Stddiff	SBRT	RFA	weighted Stddiff
	(n = 72)	(n = 134)	P-value	Stddiff	(n = 72)	(n = 134)	weighted Stddiff
Age (years)	62.75 ± 10.84	60.34 ± 10.38	0.120	0.227	60.3 ± 11.68	60.91 ± 10.69	0.055
Sex (male/female)	46/26	102/32	0.063	0.269	71.87/28.13	71.12/28.88	0.017
Etiology n(%)
Alcoholic	18 (25.00)	30 (22.39)	0.940	0.092	21.28	22.20	0.057
HBV	41 (56.94)	82 (61.19)			63.55	61.15
HCV	9 (12.50)	16 (11.94)			11.01	11.61
Others	4 (5.56)	6 (4.48)			4.16	5.04
Liver cirrhosis n(%)	68 (94.44)	124 (92.54)	0.774	0.077	95.33	93.67	0.073
Child-Pugh score	5.57 ± 0.9	5.66 ± 1.05	0.702	0.097	5.6 ± 0.88	5.64 ± 1.01	0.047
Baseline total bilirubin level (mg/dL)	1.05 ± 0.87	0.88 ± 0.55	0.104	0.241	0.96 ± 0.71	0.94 ± 0.62	0.037
Baseline serum albumin level (g/L)	3.83 ± 0.54	3.85 ± 0.6	0.754	0.046	3.82 ± 0.55	3.83 ± 0.58	0.014
Platelet count (105/mm³) (SD)	122.38 ± 57.37	131.81 ± 67.72	0.419	0.150	129.33 ± 62.42	128.6 ± 68.41	0.011
Baseline ALT level (IU/L)	28.03 ± 19.53	35.33 ± 41.74	0.302	0.224	29.67 ± 20.88	32.42 ± 36.29	0.093
Tumor size	1.71 ± 0.64	1.63 ± 0.53	0.617	0.137	1.66 ± 0.62	1.66 ± 0.54	0.009
AFP (median, IQR)	5.9 (3, 25.85)	7.51 (2.96, 30.9)	0.553	0.181	6.5 (3.4, 31.7)	7 (2.94, 30.9)	0.116
HBV, hepatitis B virus; HCV, hepatitis C virus; AFP; alpha-fetoprotein; ALT, alanine aminotransferase; SD, standard deviation; IQR, interquartile range.

3.1 Baseline characteristics

Baseline characteristics of the study population are summarized in Table 1. A total of 206 consecutive patients received a first-time diagnosis of HCC in our four centers, comprising 72 subjects who underwent SBRT and 134 who underwent RFA for the treatment of HCC. The mean diameter of the HCC was not significantly different between the SBRT group and the RFA group (1.71 ± 0.64 cm vs. 1.63 ± 0.53 cm, P = 0.617). The median AFP level was 5.9 (3 to 25.85) and 7.51 (2.96 to 30.9) for the SBRT group and the RFA group, respectively (P = 0.553). The mean Child-Pugh score was 5.57 ± 0.9 and 5.66 ± 1.05 for the SBRT group and the RFA group, respectively (P = 0.702).

3.2 Outcomes of SBRT and RFA

The 1-, 3- and 5-year OS rates were not significantly different between the SBRT and RFA groups (97.0%, 80.3% and 80.3%, respectively, vs. 98.5%, 83.9%, and 80.8%, respectively; P = 0.81) (Fig. 1A). The 1-, 3- and 5-year LC rates in the SBRT group were 95.5%, 73.0% and 68.1%, compared to 91.6%, 73.1% and 73.1% in the RFA group, respectively (P = 0.81) (Fig. 1B). The 1-, 3- and 5-year recurrence-free survival (RFS) rates in the SBRT group were 84.7%, 60.7% and 39.8%, compared to 84.7%, 60.7% and 39.8% in the RFA group, respectively (P = 0.51) (Fig. 1C).

3.3 Prognostic factors for overall survival

In the Cox proportional hazard model, tumor size (hazard ratio [HR] = 1.973, 95% CI 1.043–3.732, P = 0.037) and CP class (HR = 2.613, 95% CI 1.135–6.016, P = 0.024) were independent prognostic factors affecting the OS in multivariate analysis. Antiviral treatment was not associated with OS (P = 0.979) (Table 2).

Table 2

Prognostic factors for overall survival
Variable	Univariate analysis			Multivariate analysis
	HR	95% CI	P value	HR	95%CI	P value
Treatment (RFA/SBRT)	0.989	0.432–2.264	0.979
Sex, male/female	1.657	0.783–3.505	0.186
Tumor size	1.965	1.056–3.657	0.033	1.973	1.043–3.732	0.037
Child-Pugh class B/A	2.668	1.161–6.130	0.021	2.613	1.135–6.016	0.024
Age	1.029	0.991–1.068	0.138
AFP (ng/mL) ≥ 20/<20	1.532	0.513–4.579	0.445
HR, hazard ratio; CI, confidence interval; SBRT, stereotactic body radiation therapy; RFA, Radiofrequency ablation; AFP, a-fetoprotein

3.4 Outcomes of SBRT alone and SBRT-TACE

We performed subgroup analysis for SBRT group. SBRT group is divided to SBRT alone group and SBRT-TACE group. In SBRT alone group, 34 patients received SBRT alone and 38 received SBRT combined with TACE in SBRT-TACE group.

Table 3 is baseline characteristics of the SBRT alone group. After PPS matching, baseline characteristics were not significantly different between SBRT alone group and RFA group. The 1- and 3-year OS rates were not significantly different between the SBRT alone group and the RFA group (97.1% and 72.8%, respectively vs. 98.5% and 83.9%; P = 0.72) (Fig. 2A). The 1- and 3-year LC rates in the SBRT alone group were 97.1% and 56.4%, compared to 91.6% and 73.1% in the RFA group, respectively (P = 0.95) (Fig. 2B). The 1- and 3-year RFS rates in the SBRT alone group were 93.8% and 44.5%, compared to 83.8% and 55.2% in the RFA group, respectively (P = 0.26) (Fig. 2C).

Table 3

Baseline characteristics of SBRT alone
					IPTW
	SBRT alone	RFA	P-value	Stddiff	SBRT alone	RFA	weighted Stddiff
	(n = 34)	(n = 134)	P-value	Stddiff	(n = 34)	(n = 134)	weighted Stddiff
Age (years)	62.94 ± 10.9	60.34 ± 10.38	0.199	0.244	60.84 ± 10.51	60.69 ± 12.92	0.012
Sex (male/female)	22/12	102/32	0.176	0.252	25/9	99/35	0.025
Etiology n(%)			0.731	0.199			0.090
Alcoholic	8 (23.53)	30 (22.39)			7 (19.45)	30 (22.43)
HBV	20 (58.82)	82 (61.19)			22 (64.9)	82 (61.21)
HCV	3 (8.82)	16 (11.94)			4 (11.37)	15 (11.23)
Others	3 (8.82)	6 (4.48)			1 (4.27)	7 (5.13)
Liver cirrhosis n(%)	32 (94.12)	124 (92.54)	1.000	0.063	32 (95)	125 (92.97)	0.085
Child-Pugh score	5.5 ± 0.9	5.66 ± 1.05	0.504	0.168	5.52 ± 0.77	5.62 ± 1.01	0.116
Baseline total bilirubin level (mg/dL)	1.11 ± 1.07	0.88 ± 0.55	0.140	0.268	0.91 ± 0.68	0.91 ± 0.58	0.001
Baseline serum albumin level (g/L)	3.9 ± 0.56	3.85 ± 0.6	0.650	0.089	3.82 ± 0.59	3.85 ± 0.59	0.063
Platelet count (105/mm³) (SD)	129.03 ± 59.35	131.81 ± 67.72	0.907	0.044	133.12 ± 60.09	132.8 ± 69.71	0.005
Baseline ALT level (IU/L)	26.12 ± 18.62	35.33 ± 41.74	0.161	0.285	32.1 ± 23.97	33.52 ± 38.62	0.044
Tumor size	1.41 ± 0.42	1.63 ± 0.53	0.029	0.453	1.56 ± 0.45	1.59 ± 0.53	0.066
AFP (median, IQR)	4.8 (2.83–21.87)	7.51 (2.96, 30.9)	0.429	0.186	6.09 (3.42, 98.16)	7.51 (2.94, 31.2)	0.089
HBV, hepatitis B virus; HCV, hepatitis C virus; AFP; alpha-fetoprotein; ALT, alanine aminotransferase; SD, standard deviation; IQR, interquartile range.

In subgroup analysis for SBRT-TACE, there were no differences between SBRT-TACE group and RFA group in baseline characteristic after PPS matching. (Supplementary Table 1) The 1-, 3- and 5-year OS rates (P = 0.90, Fig. 3A), LC rates (P = 0.68, Fig. 3B) and RFS rates (P = 0.99, Fig. 3C) were not significantly different between the SBRT-TACE group and the RFA group, respectively.

3.5 Liver toxicity

The rate of liver toxicity after treatment was higher in the SBRT group than in the RFA group (17.5% vs. 3.7%; P = 0.022) (Supplementary Table 2). In the CP class A subgroup, the rate of liver toxicity was not significantly different between the two groups (P = 0.199). The rate of liver toxicity was significantly higher in the SBRT group (23.1%) than in the RFA group (0%) in the CP class B subgroup (P = 0.031).

SBRT has not been performed as an initial treatment, although it has good therapeutic effects in small HCC. In this multicenter study, we compared the initial therapeutic outcome of SBRT and RFA in HCC ≤ 3 cm. SBRT provided comparable OS, LC, and PFS rates to RFA. The rate of liver toxicity in CP A class patients was not significantly different between SBRT and RFA. Furthermore, in subgroup analysis, both SBRT alone group and SBRT-TACE group had similar OS, LC and PFS rates to RFA. These results showed that SBRT could be an effective treatment for HCC patients who were not eligible for RFA as an initial treatment and also suggests that SBRT could be performed alone without combination therapy with TACE

Tumor size is one of the most important factors for local tumor control after SBRT.^{6,7,10,20−22} In this study, SBRT produced good LC rates (95.5% at 1-year) for patients with ≤ 3 cm HCC. Previous studies showed high LC rates in patients with ≤ 5 cm HCC. A phase II study of SBRT for HCC ≤ 5 cm reported favorable LC rates at 2-years (100%) and 5-years (97.1%).²⁰ Retrospective studies of patients with HCC ≤ 5 cm reported 1-year LC rates of 90.9%, 99% and 2-year LC rates of 84.1%, 91%, respectively. ^7,21 In a Japanese study that performed SBRT on HCC ≤ 4 cm, the 3-year LC rate was 96.3%.⁶ Yoon et al. reported that the 3-year LC rate was 93.3% in patients with tumors between 2.1-3 cm and 100% in patients with tumors ≤ 2 cm.¹⁰ A recent meta-analysis reported that SBRT had high LC rates (96% at 1-year, 91% at 3-years) in patients with HCC less than 6 cm.²² Therefore, it might be reasonable that SBRT has a good LC rate in small HCCs, especially below 3 cm.

In the current study, SBRT achieved similar OS and LC rates to RFA as an initial treatment for HCC. Several studies also reported comparable outcomes to patients with HCC undergoing SBRT and RFA.^{13–15, 23,24} However, SBRT was not performed as an initial treatment in most of these studies.^13–15 Also, these studies included HCC patients with a wide range of tumor sizes and multiple tumor lesions.^13,15,24 In a large cohort study, treatment with RFA had superior survival compared with SBRT for patients with stage I or II HCC.²³ However, this study used data from the National Cancer Database, and there was no available clinical information such as the baseline liver function or the LC rate, which could affect the survival rate. Recently, a multinational study comparing RFA and SBRT suggested that SBRT could be an effective alternative to RFA for unresectable HCC.¹³ However, in that study, the enrolled patients had various tumor sizes, multiple tumor lesions and a history of prior treatments. Other previous studies reported that the therapeutic outcome of SBRT was equivalent to that of the RFA group, but these studies also included patients who received prior liver-directed treatment before SBRT.^14,15 Compared to prior studies, our study included only patients with a single and small (≤ 3 cm) HC who received SBRT as their initial treatment. These results suggest that SBRT can be performed as initial treatment in HCC patients who are not eligible for RFA.

In practice, SBRT is usually performed as a salvage treatment after incomplete TACE.²⁵ However, recent studies have shown that SBRT alone provides good LC rates.^6–11 In our subgroup analysis, we found the same results, that the OS and LC rates with SBRT alone and SBRT-TACE for small HCC (≤ 3 cm) were not different from those of RFA. Kimura et al. suggested that SBRT alone and SBRT-TACE provide similar 2-year OS and local progression-free survival for HCC ≤ 5 cm.²⁶ Previous studies showed that both SBRT alone or SBRT combined with TACE have similar LC rates, greater than 90%. SBRT alone for HCC tumors smaller than 5 cm had 1-year LC rates of 90.9 ~ 99% and 2-year LC rates of 84.1 ~ 100%.^7,20,21 LC rates of SBRT-TACE for small HCC (≤ 5 cm) were reported to be 1-year 91.1% and 93.6% and 3-years of 89.9%.^27,28 Therefore, we suggest that SBRT alone could be an effective treatment modality for small HCC.

We analyzed the differences in liver toxicity after SBRT or RFA. For CP-A, liver toxicity did not show a statistical difference between groups. However, in CP-B, the incidence of a worsening CP score or increased transaminase levels was slightly higher for SBRT. Previous studies have reported that SBRT is safe in CP-A patients but CP-B patients can experience severe radiation-induced liver damage.^29,30 Also, our previous study showed that RILD after SBRT was tolerable in patients with CP-A.¹⁷ Therefore, SBRT is a safe option for patients with small HCC and CP-A.

This study has a few limitations. First, this study is retrospective. Additional well-controlled randomized trials are necessary to validate its findings. Second, this study is a multicenter study, with variations in devices used across multiple institutions. All procedures were performed by different staff members at different hospitals. However, there were no differences in the treatment methods or response evaluation of HCC among the four hospitals.

SBRT is an effective and safe treatment method for small HCCs, with survival and tumor recurrence rates similar to those of RFA. SBRT may be an effective initial treatment for small HCC (≤ 3 cm) when RFA is not feasible.

HCC, hepatocellular carcinoma; SBRT, stereotactic body radiotherapy; RFA, radiofrequency ablation; LC, local control; TACE, transarterial chemoembolization; OS, overall survival; 4D, Four-dimensional; GVT, gross tumor volume; ITV, internal target volume; PTV, planning target volume; CP, Child-Pugh; PFS, progression-free survival; MRI, magnetic resonance imaging; PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumors; IPTW, inverse probability of treatment weighting; PSS, propensity score; ASD, absolute standardized differences; RFS, recurrence-free survival; HR, hazard ratio.

Acknowledgements:

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government(MIST) (2020R1A2C1008097).

Data Availability:

The datasets generated or analyzed during the current study are available from the corresponding author on reasonable request.

Animal research:

Not applicable.

Ethics approval:

The study protocol was performed in accordance with the ethical standards of the institution and the 1964 Helsinki Declaration. The Institutional Review Boards of Soonchunhyang University Seoul, Bucheon, Cheonan Hospital and the Gangneung Asan Medical Center approved this study.

Consent to participate:

The requirement for written informed consent waived because of its retrospective nature.

Consent to publish:

Not applicable.

Clinical trials registration:

Not applicable.

Conflict of interest:

All the authors declare no potential conflicts of interest pertinent to this manuscript.

Funding:

This study was supported by grants from the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (2019M3E5D1A02069065)

Authors’ contributions:

G.J. Cheon1: Data acquisition/interpretation, statistical analysis; H.S. Shin2: Data interpretation, statistical analysis, draft writing; B.G. Jun3: Data acquisition/interpretation, statistical analysis/supervision, draft revision; J.J. Yoo4: Data acquisition; S.G. Kim4: Data acquisition; Y.S. Kim4: Data acquisition; S.W. Jeong5: Data acquisition; J.Y. Jang5: Data acquisition; H.S. Kim6: Data acquisition; K.T. Suk7: Data acquisition; D.J. Kim7: Data acquisition; S.H. Lee6: Study concept, design, and supervision, manuscript revision.

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Stereotactic Body Radiotherapy versus Radiofrequency Ablation as Initial Treatment of Small Hepatocellular Carcinoma

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Abstract

Figures

1. Introduction

2. Methods

2.1 Patients

2.2 SBRT procedure

2.3 TACE procedure

2.4 RFA procedure

2.5 Liver toxicity evaluation

2.6 Assessment

2.7 Statistical analysis

3. Results

3.1 Baseline characteristics

3.2 Outcomes of SBRT and RFA

3.3 Prognostic factors for overall survival

3.4 Outcomes of SBRT alone and SBRT-TACE

3.5 Liver toxicity

4. Discussion

5. Conclusion

Abbreviations

Statements & Declarations

References

Supplementary Files

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