Partial splenic embolization plus antitumor therapy for treating patients with hepatocellular carcinoma and splenomegaly: a case series study
Highlight box
Key findings
• This study showed the outcomes when partial splenic embolization (PSE) was administered in combination with various antitumor therapies in patients with hepatocellular carcinoma (HCC) and splenomegaly. Platelet counts increased in most patients by day 7 post-procedure, with response rates ranging from 33% to 100% among patients receiving different treatment strategies. The median duration of thrombocytopenia remission was observed to be greater than 10 months, while the median progression-free survival (PFS) ranged from 4.5 to 21 months. Splenic region pain was commonly observed, but no PSE-related mortality was reported.
What is known and what is new?
• An association has been noted between thrombocytopenia and poorer prognosis in patients with HCC and splenomegaly, with some studies reporting outcomes of PSE combined with transarterial chemoembolization (TACE).
• This study provides initial data on PSE used concurrently with newer systemic agents, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), documenting platelet response and survival parameters across these treatment combinations.
What is the implication, and what should change now?
• The findings of this study indicate that combining PSE with various antitumor treatment regimens in patients with HCC and splenomegaly may represent a strategy that balances efficacy, safety, convenience, and cost-effectiveness. These findings contribute to the existing literature but are preliminary in nature. Additional investigation through randomized controlled trials is needed to further evaluate the applicability of these observations before conclusions can be drawn concerning clinical practice.
Introduction
According to the GLOBOCAN 2022 data, primary liver cancer ranks as the sixth most commonly diagnosed malignancy and the third leading cause of cancer-related mortality worldwide, with 865,000 new cases (accounting for 4.3% of all new cancer cases) and 758,000 deaths (representing 7.8% of all cancer-related deaths) in 2022. Liver cancer consists predominantly of hepatocellular carcinoma (HCC) (75–85% of cases) (1), and more than 85% of HCC cases are complicated by comorbid liver cirrhosis (2). Cirrhosis can induce portal hypertension, which elevates the portal venous pressure gradient and leads to splenomegaly (typically defined as a spleen diameter exceeding 13 cm), ultimately resulting in thrombocytopenia (3), the occurrence of which has been associated with poorer overall survival in patients with HCC (4).
The combination of partial splenic embolization (PSE) with transarterial chemoembolization (TACE) or systemic therapy may potentially improve survival outcomes and has demonstrated an acceptable safety profile in patients with HCC accompanied by splenomegaly (5). The combination of interventional therapy with systemic treatment, along with that of targeted agents with immunotherapy, has become a mainstay in the management of HCC (6-9). However, there have been no reports to date on the combined use of PSE with these treatment strategies. This study thus aimed to evaluate the effect of PSE on p4latelet elevation and survival outcomes in patients who had undergone interventional therapy, tyrosine kinase inhibitor (TKI) treatment, or immune checkpoint inhibitor (ICI) therapy. We present this article in accordance with the AME Case Series and PROCESS reporting checklists (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-1070/rc).
Case presentation
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Publication of this case series was waived from patients consent according to the ethics committee of Dalian Public Health Clinical Center.
Patients
The inclusion criteria for patients were as follows: (I) a clinical or pathological diagnosis of HCC; (II) presentation of splenomegaly (defined as a spleen diameter ≥13 cm); (III) administration of at least one PSE procedure at the Interventional and Radiation Therapy Center of Dalian Public Health Clinical Center between January 2020 and February 2025; (IV) administration of at least one of TACE, hepatic arterial infusion chemotherapy (HAIC), radiofrequency ablation (RFA), TKIs, or ICIs; (V) has complete medical records at our center or agrees to provide follow-up information. Meanwhile, the exclusion criteria were as follows: (I) refusal to participate in the study; (II) concurrent untreated malignancies other than HCC; and (III) incomplete medical records at the center due to either refusal to provide additional data or loss to follow-up.
Procedure for PSE
Preoperative preparation
(I) Comprehensive preoperative evaluations were performed, including imaging studies [chest computed tomography (CT) or contrast-enhanced abdominal CT or magnetic resonance imaging (MRI)] and laboratory tests. (II) For patients with comorbidities such as hypertension or diabetes, blood pressure and glycemic levels were optimized to minimize perioperative cardiovascular risk. (III) Iodine and antibiotic allergy tests were conducted. (IV) Detailed explanations of the procedure, potential complications, and precautions were provided to patients and their families. Informed consent was obtained after concerns were addressed. (V) Patients were instructed to fast for 6–8 hours before the procedure.
Equipment and materials
The following equipment and materials were used: a digital subtraction angiography system (Philips, Amsterdam, the Netherlands); disposable compression hemostatic devices; chemotherapeutic agents including fluorouracil (Jiangsu Hengrui Pharmaceuticals, Lianyungang, China) and epirubicin (Pfizer, New York, NY, USA); the contrast agent iodixanol (Jiangsu Hengrui Pharmaceuticals); embolic materials including ethiodized poppyseed oil and gelatin sponge particles (Hangzhou Ailikang Medical Technology, Hangzhou, China); and catheter systems consisting of a 5F-Right Hepatic (RH) catheter, 5F a femoral sheath, a puncture needle, and a 2.7F microcatheter (Hunan Aipute Medical Equipment, Xiangxiang, China).
TACE and PSE procedure
The patient was placed in the supine position on the digital subtraction angiography table. After standard disinfection and draping, local anesthesia with lidocaine was administered. The femoral artery was punctured via the Seldinger technique, which was followed by the placement of a 5F sheath. A 5F-RH catheter was introduced for angiography. Mesenteric arteriography was conducted via catheterization of the superior mesenteric artery to evaluate accessory hepatic arteries and portal vein status. Subsequently, celiac trunk angiography was performed to assess hepatic and splenic arterial anatomy and identify any variants. For tumor embolization, a microcatheter was superselectively advanced into the tumor-feeding arteries. Under fluoroscopic guidance to prevent reflux, an emulsion consisting of ethiodized poppyseed oil (X mL), fluorouracil (X+2 mL), and epirubicin (10 mg) was slowly injected, with X≤10. Intermittent flushing was conducted with 1% lidocaine. Embolization was completed via the suspension of gelatin sponge particles (350–560 µm) in 10 mL of saline and 10 mL of iodixanol. The mixture was injected until stasis was confirmed on postembolization angiography. For splenic embolization, the RH catheter was repositioned into the splenic artery. After the absence of branches supplying the pancreas or gastrointestinal tract were confirmed, 6–8 mL of the gelatin sponge suspension was slowly injected; the total volume did not exceed 10 mL (≤1/2 bottle), and the target splenic embolization area was 30–40% and not beyond 50% with the aim of enhancing patient safety. Postoperatively, oral antibiotics were administered for 5–7 days for infection prophylaxis.
Outcomes
The platelet response rate (PRR) at ≥7 days after PSE was defined as the proportion of patients whose first platelet count measurement at or beyond 7 days postprocedure increase by ≥10×109/L as compared to baseline. The PRR within 3–6 days was defined as the proportion of patients with a platelet count increase of ≥10×109/L within 3–6 days post-PSE. Duration of thrombocytopenia remission (DoTR) was defined as the time from PSE until a platelet count decrease to within 10×109/L of baseline. Progression-free survival (PFS) was defined as the time from initiation of first antitumor therapy to disease progression or death from any cause, with PSE being performed during this period. The primary endpoint was the PRR at ≥7 days in the cohort receiving interventional therapy combined with systemic therapy and PSE. The secondary endpoint was the PRR at ≥7 days in cohorts not included in the primary endpoint analysis. In addition, secondary endpoints included the PRR within 3–6 days, DoTR, and PFS across all cohorts.
Statistical analysis
The patients enrolled in this study were assigned to different cohorts based on their antitumor treatment regimens. Statistical analysis in this study was exclusively descriptive in nature. Categorical variables are expressed as frequencies and percentages, and discrete variables are expressed as medians with interquartile ranges. For time-to-event data, the Kaplan-Meier method was employed to estimate median survival times. All statistical computations and data visualization were performed with R software version 4.4.2 (The R Foundation for Statistical Computing, Vienna, Austria).
Results
Between January 2020 and February 2025, a total of 270 patients were treated in the Department of Interventional Medicine at Dalian Public Health Clinical Center. Among them, 155 patients underwent PSE. Of these, 86 had incomplete or unavailable medical records, and 19 received PSE as a standalone procedure. A total of 50 patients were included in this study.
This study evaluated nine treatment strategies: TACE + TKI + ICIs + PSE, TACE + HAIC + TKI + PSE, TACE + RFA + TKI + PSE, TACE + TKI + PSE, TKI + ICI + PSE, TACE + PSE, RFA + PSE, TKI + PSE, and RFA + TKI (Table 1 and Table S1). The TACE + PSE cohort had the largest sample size (n=13), while all other cohorts contained fewer than 10 patients. Only one patient received RFA + TKI, and this case was excluded from the final statistical analysis. Male participants constituted the majority in most cohorts, except for the TACE + PSE (38.5%) and TKI + PSE (50.0%) cohorts. The proportion of patients with hepatitis B virus-related cirrhosis was 80% or higher across all cohorts. Additionally, over 75% of patients in each cohort had an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Clinical stages were variably distributed among the cohorts. The median spleen diameter ranged from 14.35 to 15.2 cm in cohorts receiving interventional therapy combined with systemic treatment and from 16 to 17.2 cm in those receiving either interventional therapy or systemic therapy alone.
Table 1
| Characteristics | TACE + TKI + ICI + PSE (n=5) | TACE + HAIC + TKI + PSE (n=3) | TACE + RFA + TKI PSE (n=4) | TACE + TKI + PSE (n=9) |
|---|---|---|---|---|
| Sex, n (%) | ||||
| Male | 4 (80.0) | 2 (66.7) | 3 (75.0) | 8 (88.9) |
| Female | 1 (20.0) | 1 (33.3) | 1 (25.0) | 1 (11.1) |
| Age (years), median [IQR] | 58 [52.5–67] | 61 [54–66] | 52 [47–60] | 68 [63–71.5] |
| Types of liver cirrhosis, n (%) | ||||
| Hepatitis B virus | 4 (80.0) | 3 (100.0) | 4 (100.0) | 7 (77.8) |
| Hepatitis C virus | 1 (20.0) | 0 | 0 | 1 (11.1) |
| Cryptogenic | 0 | 0 | 0 | 1 (11.1) |
| Autoimmune | 0 | 0 | 0 | 0 |
| Mixed type | 0 | 0 | 0 | 0 |
| Clinical stage, n (%) | ||||
| Ia | 0 | 0 | 2 (50.0) | 1 (11.1) |
| Ib | 0 | 0 | 0 | 2 (22.2) |
| IIa | 0 | 0 | 1 (25.0) | 0 |
| IIb | 0 | 0 | 1 (25.0) | 4 (44.4) |
| IIIa | 3 (60.0) | 3 (100.0) | 0 | 1 (11.1) |
| IIIb | 2 (40.0) | 0 | 0 | 1 (11.1) |
| ECOG PS score, n (%) | ||||
| 1 | 5 (100.0) | 3 (100.0) | 4 (100.0) | 8 (88.9) |
| 2 | 0 | 0 | 0 | 1 (11.1) |
| Child-Pugh score, n (%) | ||||
| 5 | 0 | 0 | 1 (25.0) | 1 (11.1) |
| 6 | 3 (60.0) | 2 (66.7) | 1 (25.0) | 3 (33.3) |
| 7 | 2 (40.0) | 0 | 2 (50.0) | 3 (33.3) |
| 8 | 0 | 1 (33.3) | 0 | 2 (22.2) |
| 9 | 0 | 0 | 0 | 0 |
| Diameter of spleen (cm), median [IQR] | 15.2 [13.6–16.4] | 14.5 [13.4–15.4] | 14.35 [13.35–15.85] | 15.2 [13.35–18.25] |
| System therapy, n (%) | ||||
| Sorafenib | 0 | 0 | 0 | 4 (44.4) |
| Lenvatinib | 4 (80.0) | 3 (100.0) | 2 (50.0) | 4 (44.4) |
| Donafenib | 0 | 0 | 1 (25.0) | 0 |
| Regorafenib | 1 (20.0) | 0 | 2 (50.0) | 1 (11.1) |
| Apatinib | 0 | 0 | 1 (25.0) | 0 |
ECOG PS, Eastern Cooperative Oncology Group performance status; HAIC, hepatic arterial infusion chemotherapy; ICI, immune checkpoint inhibitor; IQR, interquartile range; PSE, partial splenic embolization; RFA, radiofrequency ablation; TACE, transarterial chemoembolization; TKI, tyrosine kinase inhibitor.
As shown in Table 2, the PRR at ≥7 days post-PSE was 100% in the TACE + TKI + ICI + PSE cohort, 33.33% in the TACE + HAIC + TKI + PSE cohort, 50% in the TACE + RFA + TKI + PSE cohort, and 77.78% in the TACE + TKI + PSE cohort; the corresponding PRR during the 3–6 days post-PSE was 40%, 33.33%, 50%, and 33.33%, respectively. The PRR at ≥7 days post-PSE was 100% in the TKI + ICI + PSE cohort, 76.92% in the TACE + PSE cohort, 55.56% in the RFA + PSE cohort, and 100% in the TKI + PSE cohort (Table S2). The corresponding PRR during the 3–6 days post-PSE was 0%, 46.15%, 44.44%, and 50%, respectively. Trends in platelet count changes for each cohort are illustrated in Figures 1,2 and Figures S1,S2.
Table 2
| Outcome | TACE + TKI + ICI + PSE (n=5) | TACE + HAIC + TKI + PSE (n=3) | TACE + RFA + TKI + PSE (n=4) | TACE + TKI + PSE (n=9) |
|---|---|---|---|---|
| Platelet response rate at ≥7 days†, n (%) | 5 (100.0) | 1 (33.33) | 2 (50.0) | 7 (77.78) |
| Platelet response rate at 3–6 days‡, n (%) | 2 (40.0) | 1 (33.33) | 2 (50.0) | 3 (33.33) |
†, defined as the proportion of patients whose first platelet count measurement at or beyond 7 days post-PSE showed an increase of ≥10×109/L compared to baseline. ‡, defined as the proportion of patients with a platelet count increase of ≥10×109/L within 3–6 days post-PSE. HAIC, hepatic arterial infusion chemotherapy; ICI, immune checkpoint inhibitor; PSE, partial splenic embolization; RFA, radiofrequency ablation; TACE, transarterial chemoembolization; TKI, tyrosine kinase inhibitor.
The DoTR was 19.0 months [95% confidence interval (CI): 19.0–not available] in the TACE + TKI + ICI + PSE cohort, 11.0 months (95% CI: 6.0–not available) in the TACE + HAIC + TKI + PSE cohort, 28.5 months (95% CI: 8.0–not available) in the TACE + RFA + TKI + PSE cohort, and 13.0 months (95% CI: 8.0–not available) in the TACE + TKI + PSE cohort (Figure 3). As shown in Figure S3, the DoTR was 10.0 months (95% CI: 10.0–not available) in the TKI + ICI + PSE cohort, 23.0 months (95% CI: 22.0–not available) in the TACE + PSE cohort, 11.0 months (95% CI: 11.0–not available) in the RFA + PSE cohort, and 22.0 months (95% CI: 7.0–not available) in the TKI + PSE cohort.
The PFS was 9.0 months (95% CI: 6.0–not available) in the TACE + TKI + ICI + PSE cohort, 5.0 months (95% CI: 4.0–not available) in the TACE + HAIC + TKI + PSE cohort, 4.5 months (95% CI: 3.0–not available) in the TACE + RFA + TKI + PSE cohort, and 7.0 months (95% CI: 5.0–not available) in the TACE + TKI + PSE cohort (Figure 4). As shown in Figure S4, the PFS was 5.0 months (95% CI: 5.0–not available) in the TKI + ICI + PSE cohort, 6.0 months (95% CI: 5.0–not available) in the TACE + PSE cohort, 21.0 months (95% CI: 10.0–not available) in the RFA + PSE cohort, and 13.5 months (95% CI: 2.0–not available) in the TKI + PSE cohort.
The incidences of splenic region pain for all cohorts were as follows: 100% in the TACE + TKI + ICI + PSE cohort, TACE + HAIC + TKI + PSE, and TACE + RFA + TKI + PSE cohort; 88.89% in the TACE + TKI + PSE cohort; 50% in the TKI + ICI + PSE cohort; 84.62% in the TACE + PSE cohort; 55.56% in the RFA + PSE cohort; and 25.0% in the TKI + PSE cohort. No PSE-related mortality was observed. The incidences of fever for all cohorts were as follows: 100% in the TACE + TKI + ICI + PSE cohort and TACE + RFA + TKI + PSE cohort; 77.78% in the TACE + TKI + PSE cohort; 33.33% in the TACE + HAIC + TKI + PSE cohort. As all patients underwent combined hepatic embolization and splenic embolization, post-procedural fever was primarily attributed to post-embolization syndrome following liver-directed therapy.
Discussion
This study yielded four principal findings. First, when PSE was combined with interventional and/or systemic therapy in patients with HCC and splenomegaly, platelet counts increased in nearly all patients by day 7 after the procedure, although the response varied considerably between 3 and 6 days. Second, the median duration of platelet remission exceeded 10 months across all cohorts. Third, the median PFS was at least 4.5 months in all treatment cohorts. Fourth, splenic region pain was the most common complication, but no fatal adverse events were reported.
To our knowledge, this is the first clinical study to evaluate both platelet count elevation and survival outcomes following PSE combined with interventional and/or systemic therapy in patients with HCC and splenomegaly. Our research examined nearly all major treatment modalities for HCC and individually analyzed the platelet response and survival outcomes associated with their combination with PSE.
This study involved several limitations that should be addressed. First, the overall small sample size led to a limited number of patients in each treatment cohort, potentially undermining the robustness of the reported outcomes. Second, the considerable heterogeneity across cohorts, coupled with the small sample size, confined the analysis to descriptive statistics and precluded meaningful between-group comparisons at this stage.
Avatrombopag, a thrombopoietin receptor agonist approved in China for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) scheduled for invasive procedures, demonstrated a significantly higher response rate in patients without CLD than in those with CLD (100% vs. 76.4%; P=0.01) (10). In patients with HCC and splenomegaly, TACE plus PSE yielded a significantly longer median PFS compared to TACE alone (19.4 vs. 9.5 months; P=0.02), with PSE identified as an independent protective factor (hazard ratio =0.508; P=0.01) (11). The PRR in our study was comparable to that reported for avatrombopag, while the median PFS appeared relatively shorter compared with similar studies that reported above —a difference that may be attributable to variations in the study population characteristics.
Based on current evidence, PSE combined with interventional and/or systemic therapy appears to be a safe and effective approach for treating patients with HCC and splenomegaly.
Conclusions
PSE combined with interventional and/or systemic therapy shows modest efficacy and a favorable safety profile in patients with HCC and splenomegaly. This approach may alleviate the financial burden associated with long-term thrombopoietin medication, can be performed concurrently with TACE, and demonstrates favorable patient tolerance. Further validation through large, well-designed randomized controlled trials is necessary to confirm these findings.
Acknowledgments
The authors acknowledge Yang Wang (a medical writer from Suzhou Suncadia Biopharmaceuticals Co., Ltd.) for writing assistance and technical editing.
Footnote
Reporting Checklist: The authors have completed the AME Case Series and PROCESS reporting checklists. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-1070/rc
Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-1070/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-1070/coif). The authors report that this article received writing support from Yang Wang, a medical writer at Suzhou Suncadia Biopharmaceuticals Co., Ltd. The authors have no other 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 study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Publication of this case series was waived from patients consent according to the ethics committee of Dalian Public Health Clinical Center.
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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(English Language Editor: J. Gray)
