Efficacy and safety of stereotactic body radiotherapy for hepatocellular carcinoma with tumor thrombus in right atrium: a two-center retrospective review

Abstract

Background

We sought to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma with tumor thrombus in right atrium (RATT).

Methods

HCC patients with RATT treated with SBRT at two institutions between June 2017 to July 2023 were analyzed. SBRT was generated to target the RATT. The primary endpoint was local control (LC) rate and incidence of SBRT-related pulmonary embolism (PE). The second endpoint were progression-free survival (PFS) and overall survival (OS) rate. Kaplan-Meier method was used to estimate PFS and OS. Univariate and multivariate analysis were used to identify predictors of survival.

Results

Twenty-two HCC patients with RATT underwent SBRT were analyzed. The median follow-up was 7.8 months. At one-month post-SBRT, 2 (9.5%) achieved complete response (CR), 13 (61.9%) achieved partial response (PR), and 6 (28.6%) patients were stable disease (SD). At three months post-SBRT, imaging assessments were available for 12 patients, demonstrating an improved response rate, with 4 patients (33.3%) achieving CR, 6 patients (50.0%) demonstrating PR, and 2 patients (16.7%) exhibiting SD. Pulmonary embolism (PE) was observed in two cases. One patient developed PE after receiving two fractions of SBRT, while the other experienced PE eight months post-SBRT. Median PFS was 3.3 months, while median OS was 7.8 months. The 3-month, 6-month, 9-month and 12-month overall survival rate was 77.3%, 54.5%, 45.5% and 31.8%, respectively. The 3-month, 6-month, 9-month and 12-month progression-free survival rate was 50.0%, 31.8%, 27.3% and 18.2%, respectively. Multivariate analysis identified that Child-Pugh score, prior TACE and immunotherapy history before SBRT were predictors of survival.

Conclusions

In the largest case series of SBRT for RATT to date, SBRT achieved high local control with low rates of severe toxicity, suggesting SBRT is a safe and efficient treatment option for HCC patients with RATT.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13014-025-02698-5.

Introduction

Hepatocellular carcinoma (HCC) is a prevalent primary liver malignancy, often associated with vascular invasion, including tumor thrombus formation in the portal vein, inferior vena cava (IVC), and, less commonly, the right atrium (RA) [1]. The occurrence of tumor thrombus extending into the RA is relatively rare with a reported incidence of 1.4–3.5% but signifies an advanced disease stage with a particularly poor prognosis [2, 3]. Patients with RA involvement are at increased risk of severe complications such as pulmonary embolism (PE) and heart failure, contributing to limited survival outcomes [4].

The prognosis for patients with RATT remains dismal, with median overall survival (OS) often reported in the range of 2 to 5 months if untreated [5, 6]. Traditional treatment options for HCC with RA tumor thrombus (RATT) are limited and often yield suboptimal results. Although systemic therapy is the only standard treatment recommended by guidelines [7], other treatment modalities are explored including surgery, radiotherapy, etc. in some centers [8, 9]. Surgical resection, while potentially beneficial, is technically challenging due to the complexity of the procedure and the patient’s compromised hepatic function. Moreover, surgery carries significant risks, including intraoperative complications and postoperative mortality [10]. Systemic therapies, such as tyrosine kinase inhibitors and immunotherapy, have shown limited efficacy in managing advanced HCC with vascular invasion.

Stereotactic body radiotherapy (SBRT) has emerged as a promising non-invasive treatment modality for HCC, particularly in cases involving vascular invasion. SBRT delivers high doses of radiation with precision, minimizing damage to surrounding healthy tissues. Recent studies have demonstrated the efficacy of SBRT in managing HCC with portal vein tumor thrombus and inferior vena cava (IVC) tumor thrombus, suggesting potential applicability in cases with RA involvement [9, 11].

However, the application of SBRT specifically for RATT remains underexplored, with limited data available. This study aims to evaluate the efficacy and safety of SBRT in treating HCC patients with RATT, providing insights into its potential as a viable therapeutic option for this challenging condition.

Methods

Study design and population

A retrospective study was conducted to analyze the efficacy and safety of SBRT to RATT. All patients diagnosed as having HCC with RATT and who underwent SBRT at two institutions between June 2017 to July 2023 were included in the study. The diagnosis of HCC was established either histopathologically or clinically, with the latter based on elevated serum alpha-fetoprotein (AFP) levels combined with characteristic imaging features on computed tomography (CT) and/or magnetic resonance imaging (MRI), in accordance with established diagnostic criteria. The presence of RATT was determined by imaging studies either CT or MRI showing tumor thrombus entering the right atrium. Staging was assigned according to the American Joint Committee on Cancer (AJCC) Staging Manual, 8th edition [12]. Given the retrospective design of this study, informed consent was waived, and the study received approval from the Institutional Review Board of two hospitals (2025 − 0531).

Study objectives and data collection

The primary objective of the study was to assess the local control (LC) rate and incidence of SBRT-related adverse events, especially PE. Post-SBRT follow-up was scheduled at 1, 3, 6, 9, 12-month post-SBRT by CT or MRI with contrast. Local response was defined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) [13]. The local response was classified into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), with the specific definitions as follows: CR: No enhancement of all lesions in the arterial phase; PR: A reduction of at least 30% in the sum of the diameters of contrast-enhanced lesions in the arterial phase; PD: An increase of at least 20% in the sum of the diameters of contrast-enhanced lesions in the arterial phase; SD: Cases that do not meet the criteria for PR or PD. The objective response rate (ORR) includes the total number of CR and PR cases. SBRT-related PE was defined as PE within 2 weeks after SBRT.

Secondary outcomes included progression-free survival (PFS) and overall survival (OS) rate at 1, 3, 6, 9, 12-month post-SBRT. PFS was determined using the date of any progression or death from any cause, with those lost from follow-up censored. OS was determined using the date of death from any cause, or until the date of last follow-up.

All data were obtained from the institution-wide electronic medical record (EMR), as well as the radiation oncology department-specific EMR.

SBRT technique

SBRT was done via linear accelerator (Varian, USA) or Cyberknife, an image-guided frameless stereotactic robotic radiosurgery system (Accuray Corporation, Sunnyvale, CA, USA). For SBRT via linear accelerator, the patient was immobilized using a vacuum cushion and a stereotactic body frame, with abdominal compression applied to control respiratory motion. A four-dimensional contrast-enhanced CT scan with a slice thickness of 2.5 mm was performed using a CT simulator (Light Speed RT, GE). The visible tumor thrombus in the RA and IVC was defined as the gross tumor volume (GTV). Meanwhile, intrahepatic lesions located within 1 cm of the right atrium and IVC were included in the GTV; lesions beyond this range were excluded. The internal target volume (ITV) was defined as the fusion of GTVs from all scan phases. The planning target volume (PTV) was created by expanding the ITV margin by 5 mm. For SBRT via Cyberknife with X-sight spine tracking system, patients were immobilized in a supine position with arms by their sides using vacuum bags. Enhanced CT scan was performed with a slice thickness of 1.5 mm at least 10 cm above and below the tumor. The gross tumor volume (GTV) was defined as a radiographic lesion based on contrast-enhanced CT, MRI or fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans. The PTV was created by expanding the GTV margin by 3–5 mm.

Organs at risk (OARs) included the liver, esophagus, stomach, duodenum, jejunum/ileum, colon, kidneys, spinal cord, and heart. The normal liver volume was defined as the total liver volume minus the GTV. The dose constraint for the PTV was set at 90-110% of the prescription dose. Dose constraints for the OARs were defined as follows:

1. Normal liver: The mean dose limits for patients without cirrhosis, Child-Pugh A, and Child-Pugh B were 15–18 Gy, 13–15 Gy, and 8–10 Gy, respectively.

2. Esophagus: Dmax < 35 Gy, V19.5 < 5 cc.

3. Stomach: Dmax ≤ 35 Gy, V26.5 < 10 cc.

4. Duodenum: Dmax < 26 Gy, V18.5 < 5 cc.

5. Jejunum/Ileum: Dmax ≤ 32 Gy, V20 < 30 cc.

6. Colon: Dmax < 35 Gy, V28.5 < 20 cc.

7. Bilateral kidneys: Dmean ≤ 18 Gy.

8. Spinal cord: Dmax ≤ 23 Gy.

9. Heart: Dmax ≤ 38 Gy, V32 < 15 cc.

Data analysis

Descriptive statistics were generated using medians with interquartile ranges for continuous variables, while frequencies or proportions were used for categorical variables. The Kaplan-Meier method was used to analyze PFS and OS. Univariate analyses were conducted to identify variables associated with overall survival. Variables found to be statistically significant were subsequently included in a multivariate Cox proportional hazards regression model to determine independent prognostic factors. A P-value of < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS software (version 26.0; SPSS Inc., Chicago). Time origin for all time-to-event analyses was day 1 of SBRT.

Results

A total of 22 patients, including 19 from The Second Affiliated Hospital, Zhejiang University School of Medicine and 3 from The First Affiliated Hospital of Naval Medical University, underwent SBRT for RATT, with baseline characteristics summarized in Table 1. The median follow-up duration was 7.8 months (range: 2.0–52.9 months). Of these patients, histopathological confirmation of HCC was available in 5 cases. The remaining 17 patients (77.3%) were diagnosed clinically, based on elevated serum alpha-fetoprotein (AFP) levels in conjunction with characteristic findings on CT and/or MRI. 14 patients (63.6%) had a Child-Pugh score of A, while 8 (36.4%) had a score of B. In terms of disease stage, 11 patients (50.0%) were classified as stage IIIB, 1 patient (4.5%) as stage IIIA, 2 patients (9.1%) as stage IVA, and 8 patients (36.4%) as stage IVB. Metastatic involvement included portal vein tumor thrombus in 10 patients (45.5%), abdominal lymph node metastases in 6 patients (27.3%) and distant metastases in 8 patients (36.4%) including 7 lung metastasis, 2 bone metastasis and 1 superior mediastinum metastasis. Most patients had undergone prior systemic or local treatments before SBRT, including radiofrequency ablation (RFA, 4.5%), transcatheter arterial chemoembolization (TACE, 54.5%), radiotherapy (RT, 9.1%), targeted therapy (27.3%), immunotherapy (18.2%), surgery (9.1%), and radioactive seed implantation (9.1%). 18 patients (81.8%) had lesions outside the target. Additionally, 5 patients (22.7%) received concurrent sorafenib treatment during SBRT.

Table 1.

Baseline clinical characteristics at time of SBRT (n = 22)

Variable	n	Characteristics
Median follow-up time (mo, median and range)	22	7.82 (2, 52.93)
Age (y, median and range)	22	57 (39, 75)
Sex
Male	19	86.4%
Female	3	13.6%
ECOG
0–1	22	100%
2–3	0	0%
Center
1#	19	86.4
2#	3	13.6
Diagnosis of HCC
Histopathological	5	22.7
Clinical	17	77.3
Child-Pugh scoring
A	14	63.6
B	8	36.4
C	0	0.0
TNM stage
IIIA	1	4.5%
IIIB	11	50.0%
IVA	2	9.1%
IVB	8	36.4%
Portal vein tumor thrombus
yes	10	45.5%
no	12	54.5%
Abdominal lymph nodes metastasis
yes	6	27.3%
no	16	72.7%
Distant metastasis
Lung	7	31.8%
Bone	2	9.1%
Superior mediastinum	1	4.5%
no	14	63.6%
Local or systemic therapy history
RFA	1	4.5%
TACE	12	54.5%
Radiotherapy	2	9.1%
Targeted therapy	6	27.3%
Immunotherapy	4	18.2%
Surgery	2	9.1%
Radioactive elements	2	9.1%
Lesions outside the target area
yes	18	81.8%
no	4	18.2%
Concurrent Sorafenib
yes	5	22.7%
no	17	77.3%

Abbreviations: ECOG = Eastern Cooperative Oncology Group; RAF = radiofrequency ablation; TACE = transcatheter arterial chemoembolization

SBRT dosimetry is described in Supplementary Table 1. The most prescribed dose fractionation was 4000 cGy in 5 fractions (72.7%), followed by 4500 cGy in 5 fractions (13.6%). The median maximum diameter of target lesion was 9.4 (IQR, 6.9–11.5) cm. The median volume of ITV and PTV were 127.2 cc and 183.1 cc, respectively. The liver volume excluding the PTV was 1519.1 cc (IQR, 997.8–1912.0 cc), while the maximum dose to the heart (Dmax) was 3886.1 cGy (IQR, 3537.7–4224.9 cGy).

The local control outcomes of the target lesion following SBRT are summarized in Table 2. At one month post-SBRT, 21 patients underwent CT or MRI, revealing CR in 2 patients (9.5%), PR in 13 patients (61.9%), and SD in 6 patients (28.6%). At three months post-SBRT, imaging was performed in 12 patients, with 4 patients (33.3%) achieving CR, 6 patients (50.0%) demonstrating PR, and 2 patients (16.7%) exhibiting SD. At six months post-SBRT, 13 patients underwent CT or MRI, showing CR in 5 patients (38.5%), PR in 6 patients (46.2%), and SD in 2 patients (15.4%). At nine months post-SBRT, among the 4 patients evaluated, 2 patients (50.0%) achieved CR, 1 patient (25.0%) demonstrated PR, and 1 patient (25.0%) exhibited SD. At twelve months post-SBRT, 3 patients underwent imaging, with 1 patient (33.3%) achieving CR, 1 patient (33.3%) demonstrating PR, and 1 patient (33.3%) exhibiting SD. Additionally, the typical images of an HCC patient with RATT demonstrating a CR after SBRT was shown in Fig. 1.

Table 2.

Local control after SBRT (n = 22)

	n		n	%
Local response
1-month	21	CR	2	9.5%
		PR	13	61.9%
		SD	6	28.6%
		PD	0	0.0%
3-month	12	CR	4	33.3%
		PR	6	50.0%
		SD	2	16.7%
		PD	0	0.0%
6-month	13	CR	5	38.5%
		PR	6	46.2%
		SD	2	15.4%
		PD	0	0.0%
9-month	4	CR	2	50.0%
		PR	1	25.0%
		SD	1	25.0%
		PD	0	0.0%
12-month	3	CR	1	33.3%
		PR	1	33.3%
		SD	1	33.3%
		PD	0	0.0%

Abbreviations: CR = complete remission; PR = partial remission; SD = stable disease; PD = progression disease

Fig. 1.

An HCC patient with RATT demonstrating a CR after SBRT. (A, B) Pre-treatment MRI shows a tumor thrombus in the right atrium (white circle). (C, D) Radiotherapy planning contrast-enhanced CT in axial and coronal views, showing SBRT treatment plan isodose curves; red represents PTV, yellow represents 4000 cGy (prescription dose for PTV is 40 Gy). (E) One month after treatment, follow-up contrast-enhanced MRI shows that the enhanced lesion and filling defect have almost disappeared (white circle). (F-H) At 3, 6, 9 months post-treatment, the lesion has achieved CR (white circle). HCC, hepatocellular carcinoma; RATT, tumor thrombus in right atrium; CR, complete response; SBRT, stereotactic body radiotherapy; PTV, planning tumor volume

Among the 22 patients who underwent SBRT, two developed grade 4 pulmonary embolism (PE). Additionally, one patient experienced grade 1 pericarditis, two developed grade 1 radiation pneumonitis, and two had grade 1 liver dysfunction; no other adverse events of grade 2 or higher were observed (Table 3). Notably, pulmonary embolism (PE) was observed in two cases, as detailed in Table 4. One patient developed PE after receiving two fractions of SBRT, while the other experienced PE eight months post-SBRT. Given the extended interval between treatment and event, the latter case was not considered attributable to SBRT. Accordingly, the incidence of SBRT-related PE was 4.5%. Patient #1 was a 39-year-old male diagnosed with stage IIIB hepatocellular carcinoma (HCC) and a Child-Pugh score of A. He received a prescribed dose of 4000 cGy in five fractions. The maximum diameter of the target lesion was 9.5 cm, with planning target volume (PTV) measuring 166.1 cc. The maximum dose (Dmax) and mean dose (Dmean) to the PTV were 4780 cGy and 4290 cGy, respectively. The patient developed shortness of breath after two fractions, and contrast-enhanced CT confirmed the presence of PE. He was subsequently treated with medical therapy, which led to symptom resolution. However, he succumbed to tumor progression two months later. Patient #2 was a 64-year-old female diagnosed with stage IIIB HCC and a Child-Pugh score of A. She received a prescribed dose of 3600 cGy in eight fractions. The maximum diameter of the target lesion was 3.5 cm, with a PTV of 10.6 cc. The PTV Dmax and Dmean were 4170 cGy and 3951 cGy, respectively. She completed all eight fractions without complications and subsequently received sorafenib as adjuvant therapy. However, 2.1 months later, disease progression was noted in intrahepatic lesions, for which she underwent two sessions of TACE while continuing sorafenib. At eight months post-SBRT, she developed PE and ultimately succumbed to PE and disease progression, with an overall survival of 8.4 months.

Table 3.

Post-SBRT adverse events (n = 22)

	Grade 1	Grade 2	Grade 3	Grade 4	Grade 5
Ischemic heart disease	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Pericarditis	1 (4.5%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Radiation pneumonitis	2 (9.1%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Liver dysfunction	2 (9.1%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Pulmonary embolism	0 (0%)	0 (0%)	0 (0%)	2 (9.1%)	0 (0%)

Table 4.

Details of PE after SBRT

Patient	Age	Time	Toxicity	Dosimetric details	Clinical outcome
1#	39	Acute (Day2)	PE	40 Gy in 5fx PTV 166.1 cc, Dmax 47.8 Gy, Dmean 42.9 Gy	Cease SBRT after 2fx Medical treatment for PE OS: 2 months
2#	64	8 months post-SBRT	PE	36 Gy in 8fx PTV 10.6 cc, Dmax 41.7 Gy, Dmean 39.5 Gy	Finished 8fx Medical treatment for PE Sorafenib for half a year intrahepatic lesion progression OS: 8.4 months

Abbreviations: PE = pulmonary embolism; SBRT = stereotactic body radiation therapy; PTV = planning target volume; OS = overall survival

Progression-free survival (PFS) and overall survival (OS) outcomes are illustrated in Supplementary Fig. 1. The median time to progression following SBRT was 3.3 months. The PFS rates at specific time points post-SBRT were 50% at 3 months, 31.8% at 6 months, 27.3% at 9 months, and 18.2% at 12 months. The median OS for the cohort was 7.8 months. The overall survival rates were 77.3% at 3 months post-SBRT, 54.5% at 6 months, 45.5% at 9 months, and 31.8% at 12 months.

Factors associated with survival outcomes are presented in Table 5. Univariate analysis identified a Child-Pugh score of A, a maximum target lesion diameter of < 9.4 cm, and a history of TACE prior to SBRT as significant positive prognostic factors for survival. In contrast, a history of immunotherapy prior to SBRT was associated with poorer survival outcomes. These significant variables were subsequently entered into multivariate analysis. Multivariate analysis further confirmed that a Child-Pugh score of A, prior TACE, and prior immunotherapy were independent predictors of survival.

Table 5.

Analysis of prognostic factors for survival

Factor	N	Median survival (IQR)	Univariate	Multivariate
Sex			0.128
Male	19	9.5 (3.1, 13.7)
Female	3	4.2 (2.2, 8.4)
Age			0.520
< 57	11	4.3 (2.6, NA)
>=57	11	9.5 (4.2, 12.0)
Child-Pugh			0.026	0.025
A	14	9.5 (4.2, NA)
B	8	3.4 (2.5, 4.7)
Abdominal lymph node metastasis			0.737
yes	6	3.4 (3.1, 12.7)
no	16	8.4 (2.6, 13.7)
Distant metastasis			0.245
yes	14	4.2 (2.5, 12.0)
no	8	8.4 (3.4, NA)
Max diameter			0.031	0.129
< 9.38 cm	11	9.5 (4.7, NA)
>=9.38 cm	11	3.4 (2.2, 12.0)
ITV volume			0.176
< 127.15 cc	11	9.5 (2.6, NA)
>=127.15 cc	11	4.7 (3.1, 12.0)
Targeted therapy history			0.814
yes	6	3.1 (2.5, NA)
no	16	8.4 (3.4, 12.7)
Prior TACE			0.006	0.012
yes	12	12.0 (4.7, NA)
no	10	3.1 (2.5, 9.5)
Prior Immunotherapy			0.041	0.014
yes	4	3.1 (1.5, 4.2)
no	18	9.5 (3.4, NA)
Radiation dose			0.339
< 40 Gy	2	8.4 (NA)
>=40 Gy	20	4.7 (2.6, 12.7)
Adjuvant therapy after SBRT			0.690
yes	18	7.2 (3.1, 13.7)
no	4	3.4 (1.8, 9.5)
Response to SBRT			0.224
CR + PR	15	4.7 (3.1, 12.0)
SD	7	8.4 (2.0, NA)

Abbreviations: ITV = internal target volume; TACE = transarterial chemoembolization; SBRT = stereotactic body radiation therapy; CR = complete remission; PR = partial remission; SD = stable disease

Discussion

The management of HCC with RATT poses significant clinical challenges due to the advanced nature of the disease and the limited efficacy of conventional treatments. Our study demonstrates that SBRT offers a promising therapeutic approach, achieving favorable local control and survival outcomes with an acceptable safety profile.

In our study, the CR rate was 9.5% and the PR rate was 61.9% at one month following SBRT. At three months post-treatment, the CR rate increased to 33.3%, while the PR rate was 50.0%, resulting in an ORR of 71.4% and 83.3% at one and three months, respectively. Meanwhile, the local control rate achieved 100% at one and three months, respectively. These findings are promising, particularly when compared to other therapeutic approaches. Systemic therapies have generally demonstrated limited efficacy in achieving substantial tumor regression in HCC with vascular invasion. Among alternative treatments, TACE remains the most commonly utilized procedure for these patients. A study evaluating the efficacy of TACE in combination with lenvatinib and sintilimab reported an ORR of 48.3% in patients with IVC tumor thrombus or RATT [14]. Similarly, hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and PD-1 inhibitors achieved a response rate of 68.7% in patients with inferior vena vava tumor thrombus (IVCTT) or RATT [15]. Furthermore, a meta-analysis of external beam radiotherapy (EBRT) reported a pooled ORR of 59.2% (95% CI: 39.0–76.7%) [16]. Moreover, particle therapies such as proton and carbon ion beam therapy, which represent the most advanced forms of radiotherapy, have demonstrated promising local control in HCC patients with IVCTT. Sekino et al. reported a CR of IVCTT in 7 out of 21 patients (33.3%) following particle therapy [17]. In another cohort of 17 patients, 100% local control was achieved despite the absence of CR [18]. In comparison, the ORR and local control achieved in our SBRT study were similarly favorable, highlighting SBRT as a competitive non-invasive option in this challenging clinical context.

As well known, PE is the most risky and deadly complication of RATT. In our study, two cases developed PE with the incidence of 9.1%. one patient developed SBRT-related PE which happened after two fraction and the other developed PE 8 months post-SBRT, which we think it is more related with disease or other reasons such as deep vein thrombosis rather than SBRT induced. This finding is noteworthy, considering that HCC patients with RA tumor thrombus are inherently at high risk for PE due to tumor embolization. Although the incidence of PE in patients with HCC complicated by tumor thrombus extending into the RA is not well-defined due to its rarity, previous reports have highlighted the occurrence of PE in such patients, underscoring the need for vigilant monitoring. A case report described a 61-year-old male with HCC and a mobile RA thrombus who developed bilateral pulmonary artery embolism [19]. Another report detailed a 49-year-old man with HCC and tumor thrombus extending into the RA, complicated by PE [20]. Additionally, a study highlighted that significant pulmonary tumor embolism occurred in 3 (43%) of the 7 HCCs with evidence of major hepatic vein and IVC invasion [21]. Given the inherent risk of PE in HCC patients with vascular invasion, the relatively low incidence of PE observed in our study suggests that SBRT does not substantially increase this risk.

HCC patients with tumor thrombus extending into the IVC or RA generally have a poor prognosis, with a median survival of approximately 4.5 to 5 months in the absence of intervention [6]. For patients with RATT, survival outcomes may be even worse. In the present study, the median OS was 7.8 months, with 31.8% (7/22) of patients surviving beyond 12 months and 13.6% (3/22) exceeding 50 months. These outcomes are comparable to those reported for surgical resection. A review of 19 cases in which patients underwent surgical resection demonstrated a postoperative survival range of 18 days to 56 months, with a median survival of 11 months [22]. Additionally, a recent study examining HCC patients with tumor thrombus in the IVC or RA who underwent surgical resection reported a median survival of 1.02 years for those with RATT [8]. No specific survival data are available for HCC patients with RATT receiving non-surgical treatments. Existing studies primarily include patients with tumor thrombus in the IVC and/or RA. One study evaluating the efficacy of SBRT in this patient population reported OS rates of 80.0% at 6 months, 60.0% at 12 months, 33.3% at 18 months, and 26.7% at 24 months [9]. Additionally, the combination of hepatic arterial infusion chemotherapy with lenvatinib and PD-1 inhibitors was shown to improve median OS from 14.4 months to 22.2 months compared to lenvatinib and PD-1 inhibitors alone in patients with tumor thrombus in the IVC and/or RA [15]. While these survival outcomes appear superior to those observed in our study, it is important to note that the majority of patients in the referenced studies had tumor thrombi located in the IVC rather than the RA, which may have contributed to the observed differences in survival. Our findings indicates that SBRT may provide a survival benefit for patients who are not candidates for surgical intervention. This survival benefit may be attributed to the effective local control achieved with SBRT, potentially reducing the risk of life-threatening complications such as PE and heart failure.

In terms of predictors of survival, multivariate analysis revealed that a Child-Pugh score of A, prior TACE, and prior immunotherapy were independent predictors of survival. Liver function plays a crucial role in the prognosis of HCC patients, especially those with advanced disease and vascular invasion. Patients with preserved hepatic function (Child-Pugh A) demonstrated significantly better survival than those with impaired liver function. This aligns with prior studies showing that hepatic reserve is a key determinant of treatment tolerance and overall prognosis in HCC [23]. Patients with Child-Pugh B or C often have limited treatment options due to increased risk of hepatic decompensation, which may explain their worse survival outcomes. Moreover, TACE is a widely used locoregional therapy for intermediate to advanced HCC. Our findings suggest that patients who had undergone prior TACE had better survival, potentially due to better liver function and performance status. Moreover, TACE may delay progression and reduce tumor burden, allowing subsequent treatments such as SBRT or systemic therapies to be more effective. Additionally, TACE has been reported to induce tumor necrosis and enhance the immunogenicity of HCC, which could contribute to improved responses to immunotherapy or radiation [24]. However, in our study, prior immunotherapy was associated with worse overall survival. This paradoxical finding could be attributed to several factors. First, patients receiving immunotherapy may represent a subgroup with more advanced or aggressive disease, as immunotherapy is often considered for patients with extrahepatic spread, vascular invasion, or those refractory to locoregional therapies. The worse survival in these patients might reflect the underlying tumor burden and poor prognosis rather than a direct negative effect of immunotherapy itself. Second, the small sample size of only four patients receiving immunotherapy limits the statistical power of our findings. Given the heterogeneity in treatment regimens, immune checkpoint inhibitors used, and patient selection criteria, larger studies are required to clarify the impact of prior immunotherapy on outcomes in this setting.

Furthermore, our study did not demonstrate a statistically significant survival benefit from adjuvant therapies following SBRT, including TACE, immunotherapy, and targeted therapy, in HCC patients with RATT. However, we observed a trend toward improved survival, suggesting that adjuvant or systemic therapies may still play a role in prolonging outcomes, despite the lack of definitive statistical significance. This finding is likely influenced by the limited sample size, which reduces the power to detect significant differences. One key observation in our study was that most patients experienced disease progression outside the irradiated target lesion. This highlights a major challenge in managing advanced HCC with RATT—while SBRT provides excellent local control, it does not address microscopic or metastatic disease beyond the radiation field. This pattern of progression underscores the need for effective systemic or adjuvant therapies to control distant tumor spread and improve overall survival.

Conclusions

In conclusion, our study suggests that SBRT is a safe and effective treatment option for HCC patients with RATT, offering favorable local control and survival outcomes with a low incidence of PE. These findings contribute to the growing body of evidence supporting the use of SBRT in managing advanced HCC with right atrium invasion and highlight the need for further research to optimize treatment strategies for this challenging condition.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Abbreviations

SBRT

Stereotactic Body Radiotherapy

HCC

Hepatocellular Carcinoma

RATT

Right Atrium Tumor Thrombus

PE

Pulmonary Embolism

LC

Local Control

PFS

Progression-Free Survival

OS

Overall Survival

CR

Complete Response

PR

Partial Response

SD

Stable Disease

TACE

Transarterial Chemoembolization

IVC

Inferior Vena Cava

IVCTT

Inferior Vena Cava Tumor Thrombus

GTV

Gross Tumor Volume

ITV

Internal Target Volume

PTV

Planning Target Volume

Author contributions

Yongjie Shui, Huojun Zhang and Qichun Wei were the principal investigators of this study and conceived the research design. Yongjie Shui, Jia Yang, Xianzhi Zhao, Yang Yang, Chunshan Yu, Dongjun Dai, Liang Chen, Haiyan Chen, Di Chen, Xia Li, Lihong Liu, Qiaoying Tian and Yinglu Guo contributed to data collection. Yongjie Shui and Jia Yang analyzed the data and prepared the figures. The manuscript was primarily drafted by Jia Yang. Qichun Wei critically reviewed the manuscript.

Funding

J.Y. receives funding from the National Natural Science Foundation of China (No. 82203078) and the Natural Science Foundation of Zhejiang Province (No. LQ22H160030). Q.W. receives funding from the National Key Research and Development Program of China (No. 2022YFE0107800) and National Natural Science Foundation of China (No. 82473234).

Data availability

Research data are stored in an institutional repository and will be shared upon request to the corresponding author.

Declarations

Ethics approval and consent to participate

This two-center study was approved by the Institutional Review Boards of The Second Affiliated Hospital, Zhejiang University School of Medicine and The First Affiliated Hospital of Naval Medical University (2025 − 0531). Written informed consent was deemed unnecessary due to the study’s retrospective design.

Consent for publication

Not applicable.

Clinical trial number

Not applicable.

Competing interests

The authors declare no competing interests.