Hepatic arterial infusion chemotherapy combined with targeted immunotherapy and anticoagulation for hepatocellular carcinoma with right atrial tumor thrombus: a case report
Case Report

Hepatic arterial infusion chemotherapy combined with targeted immunotherapy and anticoagulation for hepatocellular carcinoma with right atrial tumor thrombus: a case report

Hang Li1#, Si-Yuan Weng1#, Wen-Di Kang1, Jun-Qing Xi1, Zhen-Tao Yan2, Zheng-Qiang Yang1

1Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 2Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang, China

Contributions: (I) Conception and design: H Li, SY Weng, ZQ Yang; (II) Administrative support: ZQ Yang; (III) Provision of study materials or patients: WD Kang, ZT Yan; (IV) Collection and assembly of data: H Li, WD Kang, ZT Yan, JQ Xi; (V) Data analysis and interpretation: H Li, SY Weng, JQ Xi, ZQ Yang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work.

Correspondence to: Zheng-Qiang Yang, PhD. Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17#, Chaoyang District, Beijing 100021, China. Email: yangzq@cicams.ac.cn.

Background: Hepatocellular carcinoma (HCC) with right atrial tumor thrombus (RATT) carries a poor prognosis with limited therapeutic options. This case report demonstrates that multimodal therapy combining hepatic arterial infusion chemotherapy (HAIC), targeted immunotherapy, and anticoagulation can achieve durable clinical responses in this challenging condition.

Case Description: We describe two male patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) and RATT. The first case, a 67-year-old man, presented with extensive tumor thrombus extending to the right atrium. He was treated with a combination of HAIC (FOLFOX), lenvatinib, pembrolizumab, and nadroparin anticoagulation. Follow-up imaging after two months showed complete radiographic resolution of the RATT and marked regression of the intrahepatic lesion. The second case, a 63-year-old man with a history of hepatitis B, developed RATT after progressing on initial systemic therapies. He was subsequently treated with seven cycles of HAIC (FOLFOX) combined with sintilimab, bevacizumab, and peri-procedural anticoagulation. This resulted in a substantial reduction of the intracardiac thrombus. This patient maintained stable disease for 4 years since his initial HCC diagnosis, with the RATT remaining stable for 3 years.

Conclusions: Multimodal therapy integrating HAIC with targeted immunotherapy and anticoagulation achieved exceptional tumor control in these HCC-RATT cases. This approach warrants further investigation to optimize protocols and improve outcomes in this difficult-to-treat population.

Keywords: Hepatocellular carcinoma (HCC); hepatic arterial infusion chemotherapy (HAIC); immunotherapy; right atrial tumor thrombus (RATT); case report

Received: 24 July 2025; Accepted: 16 October 2025; Published online: 16 January 2026.

doi: 10.21037/tgh-25-100

Highlight box

Key findings

• Two patients with advanced hepatocellular carcinoma (HCC) complicated by right atrial tumor thrombus (RATT) were treated with a multimodal regimen combining hepatic arterial infusion chemotherapy (HAIC), targeted therapy, immunotherapy, and anticoagulation.

• The first patient achieved complete radiographic resolution of RATT within two months after receiving HAIC (FOLFOX), lenvatinib, pembrolizumab, and anticoagulation.

• The second patient, after progression on initial systemic therapy, achieved substantial RATT reduction with HAIC, sintilimab, bevacizumab, and anticoagulation, maintaining stable disease for 4 years with RATT stable for 3 years.

What is known and what is new?

• HCC with RATT is rare (1.4–3.5% of cases) with extremely poor prognosis (median survival 2–5 months untreated). Most patients are ineligible for curative surgery.

• This case report demonstrates that combining HAIC with targeted immunotherapy and anticoagulation can achieve durable tumor control, with outcomes substantially exceeding historical data.

What is the implication, and what should change now?

• This multimodal strategy represents a promising option for surgically ineligible HCC-RATT patients.

• Larger prospective studies are needed to validate efficacy, optimize protocols, and define patient selection criteria.

Introduction

Hepatocellular carcinoma (HCC) ranks as the sixth most common cancer and the third leading cause of cancer-related mortality globally (1). A hallmark of advanced HCC is the propensity for vascular invasion. Tumor thrombi commonly occur in the portal venous system, but extension into the hepatic veins, inferior vena cava (IVC) or right atrial tumor thrombus (RATT) is much rarer (2). Advanced HCC frequently demonstrates vascular invasion, with extension into the right atrium as RATT occurring in 1.4–3.5% of cases (3,4). When present, intracardiac tumor thrombus portends a dismal prognosis: median survival without treatment has been reported as only 2–5 months in historical series (5,6). Effective management of HCC with RATT is extremely challenging. Surgical resection with thrombectomy offers the only potential cure, with a median post-operative survival of approximately 1 year in selected patients (7). Most patients are ineligible due to advanced liver dysfunction or extensive disease burden (7-9). Similarly, although transarterial chemoembolization (TACE) demonstrates efficacy for intrahepatic tumor control, its applicability is limited in patients with extensive vascular invasion due to the risks of hepatic decompensation and incomplete thrombus resolution (10). Initial combination strategies, such as TACE combined with chemotherapy, external beam radiotherapy (EBRT), or sorafenib, demonstrated superior efficacy over monotherapy (11,12). Recently, the integration of systemic and local treatments has further improved patient outcomes. For instance, TACE combined with lenvatinib and sintilimab achieved a median overall survival (OS) of 17.3 months (13).

Hepatic arterial infusion chemotherapy (HAIC) has emerged as a valuable treatment modality for advanced HCC, particularly in cases with vascular invasion (14,15). Several studies have demonstrated improved response rates and survival outcomes with HAIC compared to conventional systemic therapy in HCC with vascular invasion (15,16). Zhong et al. showed that for patients with IVC or RATT, median OS was only about 7 months with either targeted immunotherapy combination or HAIC alone, but combining both in a triple regimen significantly extended median OS to approximately 18 months (17). But literature on integrated multimodal approaches for HCC-RATT remains sparse. This report presents two patients with HCC-RATT who received an innovative multimodal regimen consisting of HAIC, targeted immunotherapy, and anticoagulation therapy, achieving profound and durable clinical remission. We explore the potential synergistic mechanisms underlying this combination strategy. We present this article in accordance with the CARE reporting checklist (available at https://tgh.amegroups.com/article/view/10.21037/tgh-25-100/rc).

Case presentation

All procedures performed in this article were in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (No. 25/336 - 4616). Written informed consent was obtained from the patients for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Case 1

A 67-year-old man was admitted with progressive abdominal distension and worsening abdominal pain. Baseline laboratory tests revealed impaired hepatic function [aspartate aminotransferase (AST) 138.2 U/L; albumin 37.5 g/L], a mildly elevated α-fetoprotein level (AFP 6.70 ng/mL), and a markedly increased D-dimer concentration (68.37 mg/L FEU) (Table 1). Contrast-enhanced imaging together with percutaneous biopsy confirmed HCC complicated by extensive tumor thrombus involving the portal vein, hepatic veins, inferior vena cava, and extending into the right atrium (T4N0M0, Barcelona Clinic Liver Cancer stage C). The patient also had cirrhosis, splenomegaly, severe oesophageal varices, and ascites. Nadroparin calcium was started for anticoagulation (4,100 IU subcutaneously every 12 h). After initial stabilization and improvement of the D-dimer level, he underwent HAIC with FOLFOX (oxaliplatin 120 mg, leucovorin 400 mg, fluorouracil 2,000 mg), followed by systemic therapy combining lenvatinib (8 mg orally once daily) and pembrolizumab (200 mg intravenously every three weeks). Two months later, follow-up imaging demonstrated marked regression of the primary hepatic lesion and complete resolution of the right-atrial tumor thrombus (Figure 1).

Table 1

Patient characteristics and treatment outcomes

Variables Case 1 Case 2
Age (years) 67 63
Sex Male Male
ECOG Performance Status 0 0
Etiology None HBV with 2-year history of cirrhosis
Comorbidities Diabetes mellitus Hypertension (130/90 mmHg)
Child-Pugh score/grade 5, A 5, A
ALT (U/L) 48.5 15.2
AST (U/L) 48.5 18.1
Total bilirubin (μmol/L) 21.6 11.8
Albumin (g/L) 37.5 53.1
Creatinine (μmol/L) 69.8 Not reported
INR 1.10 0.93
aPTT (seconds) 25.8 33.8
Fibrinogen (g/L) 3.28 5.00
D-dimer (mg/L FEU) 68.37 0.74
ALBI Score −2.31 −3.81
WBC count (×109/L) 5.48 7.87
Platelet count (×109/L) 134 180
BCLC Stage C C
Clinical TNM Stage (AJCC) T4N0M0 T4N0M0
AFP (ng/mL) 6.7 72
Tumor location Left lobe of liver, IVC, RA Right lobe of liver, IVC, RA
Number of lesions 2 1
Tumor size (cm) 1.9×1.3 7.7×4.7
Extrahepatic metastasis None None
Tumor thrombus type III III
Pathology HCC HCC
HAIC regimen
   Oxaliplatin (mg) 120 130
   Leucovorin (mg) 400 600
   5-fluorouracil (mg) 2,000 2,000
Number of HAIC cycles 1 7
Targeted therapy Lenvatinib 8 mg Bevacizumab 700 mg
Immunotherapy Pembrolizumab 200 mg Sintilimab 200 mg
Anticoagulation therapy Nadroparin calcium 4,100 IU q12h for 3–7 days following each procedure Nadroparin calcium 3,800 IU q12h for 3–7 days following each procedure
Response (RECIST 1.1) PR SD
Response (mRECIST) CR PR
Adverse events Grade 1 pain Grade 1 nausea
Grade 2 Pulmonary embolism Grade 2 Pain

AFP, alpha-fetoprotein; AJCC, American Joint Committee on Cancer; ALBI, albumin-bilirubin; ALT, alanine aminotransferase; aPTT, activated partial thromboplastin time; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; CR, complete response; ECOG, Eastern Cooperative Oncology Group; HAIC, hepatic arterial infusion chemotherapy; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; INR, international normalized ratio; IVC, inferior vena cava; mRECIST, modified RECIST; PR, partial response; RA, right atrium; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; TNM, tumor-node-metastasis; WBC, white blood cell.

Figure 1 Serial contrast-enhanced MRI and tumor response assessment in Case 1. (A) Serial contrast-enhanced MRI from October 2024 to April 2025. The images demonstrate a significant reduction in the size and enhancement of the primary hepatic lesion (arrows) and the associated cardiac tumor thrombus (arrowheads) over the treatment period. (B) Temporal changes in maximum tumor diameter measured by RECIST 1.1 and mRECIST criteria. mRECIST, modified RECIST; MRI, magnetic resonance imaging; RECIST, Response Evaluation Criteria in Solid Tumors.

Case 2

A 63-year-old man with a 20-year history of chronic hepatitis B had been receiving long-term oral nucleos(t)ide analogue therapy. At routine follow-up on 29 May 2021, his serum AFP level was found to be elevated (Table 1). Contrast-enhanced abdominal magnetic resonance imaging (MRI) performed on 16 June 2021 revealed an irregular mass occupying the right hepatic lobe and abutting the inferior vena cava. Tumor thrombi were present in the right hepatic vein and the right posterior branch of the portal vein, and a satellite nodule was seen in segment VIII; no extra-hepatic disease was detected. Ultrasound-guided percutaneous biopsy on 25 June 2021 confirmed poorly differentiated HCC (Edmondson-Steiner grade III). From 8 July 2021, the patient received sintilimab 200 mg intravenously every 3 weeks (day 1) combined with lenvatinib 12 mg orally once daily. After two cycles, radiological assessment demonstrated progressive disease. On 19 August 2021 treatment was switched to sintilimab 200 mg plus bevacizumab 700 mg intravenously every 3 weeks. Despite therapy, follow-up imaging in June 2022 showed cranial extension of the tumor thrombus along the inferior vena cava into the right atrium. Between August 2022 and August 2023, the patient underwent seven sessions of FOLFOX-based HAIC: oxaliplatin 85 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; and a 5-fluorouracil 400 mg/m2 intravenous bolus on day 1 followed by a 2,400 mg/m2 continuous infusion over 46 hours. This local therapy was administered in combination with his ongoing systemic treatment of sintilimab (200 mg) and bevacizumab (700 mg) every three weeks. Furthermore, each HAIC cycle was accompanied by a one-week course of peri-procedural anticoagulation with nadroparin calcium (3,800 IU subcutaneously every 12 hours). MRI in June 2023 demonstrated substantial regression of the right-atrial tumor thrombus, and both the intrahepatic primary lesion and residual thrombi fulfilled the criteria for stable disease (SD). During continued surveillance, the disease remained radiologically stable without new distant metastases. At the most recent assessment in June 2025, the hepatic mass and intracardiac thrombus were still classified as SD (Figure 2).

Figure 2 Serial contrast-enhanced MRI, tumor response, and AFP trends in Case 2. (A) Serial contrast-enhanced MRI images from baseline (February 2022) through long-term follow-up (June 2025) demonstrating sustained tumor control. The primary hepatic tumor (arrows) and tumor thrombus in the right atrium (arrowheads) show progressive regression and prolonged disease stability throughout the treatment course. (B) Temporal changes in maximum tumor diameter measured by RECIST 1.1 and mRECIST criteria, showing initial tumor reduction followed by sustained disease control. (C) Serial AFP trends demonstrating marked decline from elevated baseline levels to near-normal range, correlating with radiographic tumor response. AFP, alpha-fetoprotein; mRECIST, modified RECIST; MRI, magnetic resonance imaging; RECIST, Response Evaluation Criteria in Solid Tumors.

Discussion

Advanced HCC typically metastasizes to the lungs, bones, brain, and adrenal glands. Due to the activation of hemostatic mechanisms, vascular invasion and tumor thrombosis are prominent features in most cases of advanced HCC (18,19). The incidence of vascular invasion increases with tumor size, with a reported rate of 82% in patients with serum AFP levels >1,000 ng/mL and tumor diameter >5 cm (20). HCC with RATT is an uncommon but life-threatening presentation, seen in approximately 1–4% of HCC cases (7).

Given that clinical data focusing exclusively on HCC with RATT is scarce, many studies analyze a combined population of patients with tumor thrombus in HCC-IVC/RATT. Surgical resection, though potentially curative, is only feasible for a small subset of patients and yields a median OS of approximately 1.02 to 2.47 years, with a high rate of recurrence (median recurrence-free survival 0.44–0.54 years) (7). For unresectable cases, local therapies have been widely used. Radiotherapy has been reported to achieve a median OS ranging from 12.6 to 17.4 months, while TACE monotherapy results in a median OS of 10.9 months (21-23). Systemic or HAIC has shown a median OS of 7.9 to 15.4 months (3,22). These figures represent the baseline efficacy of single-modality or dual-combination therapies and underscore the severe challenge posed by this disease. More recent combination therapies have established a higher benchmark. As mentioned, TACE combined with lenvatinib and sintilimab pushed the median OS to 17.3 months (24). The HAIC combined with targeted immunotherapy triple-therapy regimen achieved a median OS of approximately 18 months in the challenging IVC/RATT population (17).

This study reports that two patients with HCC-RATT underwent a highly aggressive multimodal regimen. The first patient achieved complete radiographic resolution of the atrial thrombus and dramatic shrinkage of the liver tumor. The second patient has maintained SD for 4 years since initial diagnosis and remains under active surveillance. The intracardiac thrombus has remained stable for 3 years since its appearance. These outcomes are highly unusual for HCC-RATT and suggest a possible synergistic effect of the combined therapy approach.

Several important limitations must be acknowledged. This small case series of two patients cannot establish definitive efficacy or safety profiles, and the findings require validation in larger, prospective studies. Patient selection bias may have contributed to favorable outcomes—both patients had preserved liver function (Child-Pugh A), good performance status (Eastern Cooperative Oncology Group 0), and absence of extrahepatic metastases, which may not be representative of the broader RATT population. The optimal sequencing, dosing, duration, and specific agents for each component of the quadruple-modality therapy remain undefined and require systematic investigation. The relative contribution of anticoagulation specifically in achieving these outcomes cannot be isolated from the other therapeutic interventions. Longer follow-up is needed to assess the durability of responses, potential late recurrences, and cumulative toxicities.

Conclusions

For patients with HCC-RATT, a multimodal therapeutic approach integrating HAIC with targeted therapy, immunotherapy, and anticoagulation represents a promising and effective strategy for achieving sustained clinical benefit.

Acknowledgments

We are deeply grateful to the patients and their family for their participation in this study and for providing biological samples.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tgh.amegroups.com/article/view/10.21037/tgh-25-100/rc

Peer Review File: Available at https://tgh.amegroups.com/article/view/10.21037/tgh-25-100/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-25-100/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this article were in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (No. 25/336 - 4616). Written informed consent was obtained from the patients for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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doi: 10.21037/tgh-25-100
Cite this article as: Li H, Weng SY, Kang WD, Xi JQ, Yan ZT, Yang ZQ. Hepatic arterial infusion chemotherapy combined with targeted immunotherapy and anticoagulation for hepatocellular carcinoma with right atrial tumor thrombus: a case report. Transl Gastroenterol Hepatol 2026;11:35.

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