Transarterial chemoembolization for inoperable primary cardiac angiosarcoma: a description of two cases and literature analysis

Introduction

Angiosarcomas, an infrequent subtype of soft-tissue sarcomas, arise from vascular or lymphatic endothelial cells, constituting less than 1% of all sarcomas (1). While they can manifest in various soft tissue structures or viscera, their prevalence is most pronounced in the head and neck region. However, angiosarcomas directly originating from major blood vessels or the heart are exceedingly rare, with few documented case reports (2).

Historically, surgical resection has been the cornerstone of post-diagnostic treatment for cardiac angiosarcoma. For patients with inoperable, locally advanced, or metastatic angiosarcomas, palliative chemotherapy has emerged as the preferred treatment. Paclitaxel-containing regimens are the most frequently used regimen for angiosarcomas (3). Additionally, doxorubicin, liposomal doxorubicin, ifosfamide, vinorelbine, and gemcitabine play a crucial role in non-paclitaxel regimens (1,2,4). However, due to the cardiac toxicity and limited efficacy of these drugs, chemotherapy is restricted. Thoracic radiotherapy is not recommended due to its acute and chronic toxicity to the heart (5).

In this report, we present two exceptional cases of primary cardiac angiosarcoma diagnosed noperable by conventional surgical or chemoradiotherapy approaches. After multidisciplinary discussion, the patients underwent transarterial chemoembolization (TACE), an innovative treatment for cardiac tumors (6). The remarkable success of this unconventional approach provides and highlights a promising avenue for the existing treatment dilemmas for complex cardiac tumors.

Case presentation

Case 1

A 36-year-old female patient presented with persistent chest pain and elevated heart rate, and was bedridden. The patient also experienced fatigue, bilateral lower extremity edema, and distended neck veins for over eight months. Exploratory thoracotomy, enhanced computed tomography (CT), and Doppler ultrasound revealed the presence of a right atrial tumor accompanied by pericardial effusion (Figure 1A-1C), and highly differentiated angiosarcoma was diagnosed using immunohistochemical markers (including CD31, CD34, ERG, and FLI-1) (Figure 1D,1E, Figures S1,S2). The angiosarcoma was assessed as unresectable by the surgeons. Radiotherapists and oncologists also concluded that it had a high risk of potential post-radiotherapy risk of cardiac rupture, heart failure, and chemotherapeutic resistance. Thus, the patient abstained from tumor treatment in the preceding months.

Figure 1.

Inoperable primary cardiac sarcoma: gross appearance, CT imaging, immunohistochemistry, TACE therapy, and follow-up. (A) A photograph from exploratory thoracotomy. The tumor has invaded the pericardium, with membranous adhesions and an intriguing separation pattern from the visceral wall of the heart, affecting both upper, lower vena cava and atrioventricular groove. (B) The enhanced CT scan image of the cardiac tumor (indicated by the white snow pattern). (C) Three-dimensional reconstruction of enhanced heart CT scan of the cardiac tumor (indicated by the white snow pattern). The tumor was positive for immunohistochemical staining of paraffin-embedded tissue with anti-ERG (D) and anti-CD34 (E) antibodies. The secondary antibody used was HRP goat anti-rabbit IgG. Signal was developed using a 3,3'-DAB substrate kit. The sample is counterstained with hematoxylin. Images were captured using the Leica DMi8 Inverted Microscopes. (F) Posteroanterior DSA image of left internal mammary arteriogram shows tumor staining supplied by several small branches of the left internal mammary artery (arrows). (G) Posteroanterior internal mammary arteriogram shows the main blood supply from the branches of the right internal mammary artery (arrows). (H) Posteroanterior inferior phrenic artery arteriogram shows little blood supply from the upward branch of the right inferior phrenic artery (arrow). The embolization site is shown by the white arrow. (I) The latest enhanced heart CT scan during follow-up. The tumor site indicated by the white snow pattern. 3,3'-DAB, 3,3'-diaminobenzidine; CT, computerized tomography; DSA, digital subtraction angiography; HRP, horseradish peroxidase; LCX, left circumflex artery; LP, left pulmonary artery; RA, right atrium; RCA, right coronary artery; TACE, transarterial chemoembolization.

After a multidisciplinary discussion, the patient opted for TACE. The procedure was performed via the right femoral artery under local anesthesia. Angiography showed that the internal mammary arteries and the right inferior phrenic artery, but not the bronchial arteries, supplied blood to the cardiac angiosarcoma. Subsequently, a 2.7-F microcatheter was used to deliver 200 mg paclitaxel followed by 150–300 µm gelatin sponge until intra-arterial flow stasis of the left internal mammary artery, right internal mammary artery, and right inferior phrenic artery (Figure 1F-1H, white arrow denoted). Rigorous perioperative monitoring of the patient’s physiological parameters was performed because of the interconnected vascular anastomoses between the tumor-feeding arteries and arteries that nourished healthy organs and tissues. One month later, a secondary TACE procedure was performed as some residual tumor tissue was still active. After two sessions of TACE, the patient experienced pain relief [visual analogue scale (VAS) score =0], steady heart rate (85 bpm) and function [ejection fraction (EF) =72%], and an Eastern Cooperative Oncology Group (ECOG) score of 0 to 1. At five-month follow-up, the enhanced CT scan revealed the disappearance of pericardial effusion and a significant reduction in tumor volume (Figure 1I). With 14 months of clinical follow-up, the patient’s symptoms remained in remission, and the CT scan showed no disease progression.

Case 2

Two years ago, a 40-year-old patient presented to the emergency department with a history of dyspnea for six months, without fever, cough, or chest pain. External CT revealed a cardiac tumor (Figure 2A) with lung metastasis (Figure 2B). The maximum cross-section of the right atrial mass was 5.7 cm × 3.3 cm. The left ventricle had an EF of 44%. Pericardial effusion had a maximum depth of 1.3 cm and pleural effusion had a maximum depth of 2.5 cm. The patient had a heart rate of 125 bpm, a blood pressure of 107/65 mmHg, and an oxygen saturation of 92%. A biopsy confirmed the diagnosis of angiosarcoma.

Figure 2.

Cardiac sarcoma with pulmonary metastasis: CT images and interventional treatment process before and after TACE. (A) The enhanced CT scan image of the cardiac tumor (indicated by the white snow pattern). (B) The initial enhanced CT scan revealed the lung metastasis. (C) The enhanced CT scan revealed the rapid progression of lung lesions within a week. (D) Posteroanterior left bronchial artery arteriogram shows the main blood supply from the branches of the left bronchial artery (arrow). (E) Posteroanterior right bronchial artery arteriogram shows the partial blood supply from several branches of the right bronchial artery (arrow). (F) Posteroanterior right internal mammary artery arteriogram shows limited blood supply from the small branches of the right bronchial artery (arrow). (G) The CT scan revealed a reduction in pulmonary metastatic nodules after four weeks of TACE. (H) The right atrial mass in the CT scans after four weeks of TACE (indicated by the white snow pattern). (I) The CT scans revealed that the pulmonary nodules were significantly decreased after two months of TACE. (J) The right atrial mass in the CT scans after two months of TACE (indicated by the white snow pattern). (K) The CT scans revealed that all lung metastases had regressed after four months of TACE. (L) The right atrial mass in the CT scans after four months of TACE (indicated by the white snow pattern). CT, computerized tomography; TACE, transarterial chemoembolization.

Within a week, the patient experienced increased breathing difficulty, elevated heart rate, and low oxygen saturation, which led to an emergency visit (heart rate, 140 bpm; oxygen saturation, 89%). Repeat CT showed rapid progression of the lung lesions (Figure 2C). Following a multidisciplinary consultation, the patient underwent emergency digital subtraction angiography (DSA) guided bronchial artery and right internal mammary artery chemoembolization using paclitaxel and gelatin sponge granules (the procedures were similar to those described in case one, Figure 2D-2F). After the procedure, the patient’s heart rate decreased to 81 beats/min, oxygen saturation improved to 97%, and EF increased to 67%.

Four weeks later, ultrasonography showed no pericardial effusion, and the depth of the pleural effusion was reduced to 2 cm. CT scans revealed a reduction in pulmonary metastatic nodules (Figure 2G) and a decrease in the size of the heart tumor (Figure 2H). Subsequently, the patient received a combination of paclitaxel, bevacizumab, and pembrolizumab, with regular follow-up. Two months later, the pulmonary nodules significantly decreased in size (Figure 2I) and the right atrial mass decreased to 2.3 cm × 1.9 cm (Figure 2J). Four months later, all lung metastases regressed (Figure 2K) and the diameter of the right atrial mass was immeasurable (Figure 2L). Since then, the patient was asymptomatic and maintained monotherapy with pembrolizumab for 1.5 years.

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. Written informed consent was obtained from the patients for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Primary cardiac tumors are exceedingly rare, representing a minute fraction of cardiac pathologies, with an estimated prevalence of 0.017–0.019% (7). Among these cases, malignant tumors account for a quarter, with sarcomas emerging as the predominant subtype, notably angiosarcomas, posing significant challenges. Typically localized in the right heart (8), particularly the right atrium, cardiac sarcomas, including angiosarcomas, often remain asymptomatic until they reach an advanced stage. Characterized by infiltrative growth, these tumors can encroach upon cardiac structures, leading to complications, such as obstruction, right heart failure, and pericardial involvement. Regrettably, owing to their insidious progression, many of these cases present with metastases at the time of diagnosis, thereby limiting treatment options (9).

Cardiac angiosarcoma, typified by aggressive infiltrative growth, has the poorest prognosis among cardiac tumors (10), with a one-year survival rate of approximately 35% and a median survival of only 5.2 months (11). The primary cardiac site has been confirmed to be an independent adverse prognostic factor for survival (12). Immunohistochemistry plays a pivotal role in establishing the diagnosis by leveraging endothelial cell markers to identify abnormal malignant endothelial cells characteristic of angiosarcoma. Abnormal, pleomorphic, and malignant endothelial cells are observed under a microscope (13). The combined use of endothelial cell markers, including von Willebrand factor, Ulex europaeus agglutinin 1, and CD31, is useful for diagnosing angiosarcoma (14).

In case 1, the patient’s journey began with chest pain and pericardial effusions. An exploratory thoracotomy proved to be an inoperable tumor. The patient had already lost the possibility of surgical treatment, and because of the toxicity and risk of chemoradiotherapy of the heart, the patient almost had no options. According to the patient’s choice, an unprecedented application of interventional infusion embolization chemotherapy of the heart was performed, offering hope in a therapeutically limited landscape. The treatment had a great achievement, with more than one year of progression-free time since the last TACE treatment.

Case 2 addresses another situation of cardiac angiosarcoma, in which the patient was initially diagnosed with an advanced stage of extensive metastasis and developed tumor emergencies such as heart failure, expiratory failure, and tachycardia after losing surgical indications and responding to first-line chemotherapy. We performed transbronchial artery and right internal mammary artery chemoembolization in the emergency, and the cardiac and respiratory symptoms were controlled immediately after surgery. After combining with systemic treatment such as immunotherapy, the patient’s condition was further improved and the tumor continued to shrink. This may be related to the fact that TACE, as a local treatment of metastases, can mediate tumor antigen release and enhance the effectiveness of systemic immunotherapy as reported in the literature (15-17). This suggests that TACE can be used as a means of tumor treatment and symptom control in case of metastases in which the primary site has lost treatment.

Due to the rarity of angiosarcomas, the choice of chemotherapy drug relies on the clinical experience of the attending physician. According to retrospective studies, paclitaxel is most commonly administered as first-line therapy, with a median progression-free survival (PFS) of 4.5 months (4,18). Therefore, paclitaxel was the preferred drug for arterial infusion chemotherapy in TACE in our cases. We will continue to follow up with these two patients.

Cardiac tumors remain a realm of limited research, and surgery remains a fundamental therapeutic approach. Vascular interventional therapies, such as arterial perfusion and embolization, have introduced an innovative avenue to cardiac tumors. By delivering drugs and embolizers directly to the tumor site, vascular intervention offers targeted treatment with reduced trauma and side effects, enhancing effectiveness, while enabling real-time assessment.

Still, there are some risks in TACE for cardiac tumors: (I) ectopic embolism; (II) abnormal vascular anatomy, for example, it would heighten risks if there is communication between the internal mammary artery and coronary arteries; (III) drug cardiac toxicity, allergy to angiography media, and vascular spasm during embolism process; (IV) embolism in non-coronary arteries; (V) wound infection and bleeding. Due to these risks, preoperative angiography should be applied to identify tumor nutrition supplying vessels, with continuous cardiac function monitoring during the operation, and precision management of wounds after the operation. Also, for the operation, there are many strict requirements of anatomy, tumor treatment, or vascular intervention experience. Although fraught with risks due to cardiac intricacies, interventional therapies hold promise for addressing these challenging tumors.

Conclusions

This report presented two exceptional cases of inoperable primary cardiac angiosarcoma managed with TACE. Supported by compelling corroborative evidence from positron emission tomography-computed tomography (PET-CT) and enhanced CT scans, the patients’ condition showed marked and encouraging improvement. The combination of advanced imaging, interventional techniques, and clinical experience offers promise for the future management of complex cardiac tumors.

Supplementary

The article’s supplementary files as

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. Written informed consent was obtained from the patients for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.