Cardiac angiosarcoma represents a notably rare and aggressive form of soft tissue sarcoma that originates in the heart. Characterized by rapid growth and a propensity for early metastasis, diagnosing this condition presents significant challenges. Due to its uncommon nature, a standardized treatment protocol remains elusive. While surgical intervention appears to offer the most promising outcomes for localized tumors, its feasibility is often limited by the intricate anatomy of the heart and the extent of tumor invasion. In cases where surgery is not immediately viable, upfront chemoradiotherapy emerges as a valuable alternative, potentially reducing tumor size and facilitating subsequent surgical resection. This article delves into the complexities of Cardiac Angiosarcoma Diagnosis, drawing upon a compelling case study showcasing a patient who achieved a complete metabolic and pathological response following upfront chemoradiotherapy with paclitaxel, ultimately undergoing successful surgery. This approach highlights a potential treatment paradigm for individuals facing this rare and challenging malignancy.
The Diagnostic Challenges of Cardiac Angiosarcoma
Early diagnosis of cardiac angiosarcoma is frequently hampered by its non-specific initial symptoms. Patients may present with a range of vague complaints, often mimicking more common cardiac conditions. This diagnostic ambiguity can lead to delays in appropriate management, underscoring the critical need for heightened clinical awareness and advanced diagnostic strategies. As the disease progresses, more pronounced manifestations may arise, including right heart failure, myocardial rupture, and cardiac tamponade, further complicating the clinical picture. A multi-faceted diagnostic approach is essential for accurate identification, often incorporating echocardiography, computed tomography (CT), cardiac magnetic resonance imaging (MRI), and positron emission tomography (PET) CT scans to comprehensively assess the presence, extent, and characteristics of the tumor.
Case Presentation: A Successful Treatment Strategy
We present the case of a 46-year-old woman in good general health, a non-smoker with a history of hypertension, Hashimoto’s thyroiditis, and factor V Leiden deficiency. Her initial presentation at the Royal Adelaide Hospital involved symptoms suggestive of pericarditis, including fevers, dyspnea, and cough. Initial echocardiography revealed a pericardial effusion, but no cardiac mass was detected at this stage. Following anti-inflammatory therapy, her symptoms subsided, and she was discharged. However, she returned three months later with a recurrence of symptoms, now including chest pain, dysphagia, dyspnea, and night sweats. This time, an echocardiogram revealed a right atrial mass, prompting further investigation. CT and cardiac MRI confirmed a substantial 7 × 11 × 10 cm mass within the right atrium, encasing the right coronary artery (Fig. 1). A PET scan demonstrated significant fluorodeoxyglucose avidity, indicative of malignancy, without evidence of distant spread. While initial biopsy results were inconclusive, a repeat biopsy definitively confirmed the diagnosis of cardiac angiosarcoma (Fig. 2).
Therapeutic Intervention: Chemoradiotherapy and Surgical Resection
Considering the tumor’s location and involvement of critical cardiac structures, primary surgical resection was deemed to carry a high risk of technical complications. Therefore, a strategy of upfront chemoradiotherapy was adopted to potentially reduce tumor size and improve the feasibility of subsequent surgery. The patient underwent concurrent chemoradiotherapy, receiving 60 Gy of radiation in 30 fractions alongside weekly paclitaxel (80 mg/m2). She completed a total of 18 cycles of weekly paclitaxel. This treatment course was complicated by esophagitis requiring nutritional support and a brief hospitalization for radiation pneumonitis, which resolved with dexamethasone.
Post-chemoradiotherapy cardiac MRI demonstrated a reduction in tumor size. A follow-up PET scan revealed a significant decrease in tumor metabolic activity, indicating a complete metabolic response with only minimal residual activity (Fig. 3).
Following multidisciplinary evaluation at Cleveland Clinic, surgical resection was deemed appropriate. Intraoperatively, the tumor was found to be largely necrotic and avascular, occupying the entire right atrium. The mass was resected with a small margin of atrial wall, carefully preserving the tricuspid annulus, right coronary artery, and right ventricle. The resulting defect was reconstructed using a bovine pericardial patch. Post-operative recovery was complicated by a recurrent pleural effusion, which was managed with chest drainage, and the patient otherwise recovered well.
Favorable Outcome and Follow-Up
Pathological examination of the resected tumor confirmed a complete pathological response, with only necrotic tumor tissue surrounded by normal myocardium and fibrosis. At the most recent follow-up, five months post-surgery and eight months post-chemoradiotherapy, the patient remained asymptomatic, with only mild residual dysphagia as a treatment-related toxicity.
Discussion: Advancing Cardiac Angiosarcoma Diagnosis and Treatment
Primary cardiac tumors are exceedingly rare, with the majority being benign. Among malignant primary cardiac tumors, cardiac angiosarcoma is the most prevalent. Its aggressive nature and propensity for local recurrence and distant metastases contribute to a poor prognosis. The rapid infiltrative growth pattern can lead to life-threatening emergencies such as pericardial effusion, cardiac tamponade, and myocardial rupture. This case underscores the diagnostic challenges posed by the non-specific symptoms of cardiac angiosarcoma, which can contribute to delayed diagnosis and treatment initiation.
Significant advancements in imaging modalities have improved the ability to diagnose cardiac tumors. While echocardiography remains a valuable initial diagnostic tool, cardiac MRI offers superior delineation of tumor location, size, and local extent. CT and PET scans play crucial roles in detecting distant metastatic disease and assessing treatment response.
Given the rarity of cardiac angiosarcoma, a definitive standard treatment approach is lacking. Current evidence primarily stems from retrospective case series and case reports, often encompassing heterogeneous patient populations. Surgical resection, when feasible, is generally considered the cornerstone of treatment for localized disease, associated with improved long-term survival. However, the technical complexity of cardiac surgery, particularly in these challenging tumor locations, often limits surgical options. The rapid progression of the disease further complicates surgical planning, rendering some patients ineligible for resection.
Combined modality therapies, integrating chemotherapy and radiotherapy, have emerged as a promising strategy to enhance outcomes in cardiac angiosarcoma. Neoadjuvant chemotherapy aims to downstage tumors, facilitating radical surgical resection. Paclitaxel, among other chemotherapeutic agents, has demonstrated efficacy in treating angiosarcomas at various sites. Notably, in the ANGIOTAX phase II study, paclitaxel demonstrated a median overall survival of 8 months in patients with unresectable angiosarcoma, with a subset achieving partial responses that enabled curative-intent surgery.
This case report presents, to our knowledge, the first documented instance of a complete metabolic and pathologic response to upfront chemoradiotherapy with paclitaxel followed by surgery in cardiac angiosarcoma. The observed complete metabolic response on PET scan post-chemoradiotherapy and the absence of viable tumor at surgery highlight the potential of this approach. Surgical resection was pursued based on the patient’s favorable response to chemoradiotherapy, the tumor’s necrotic nature, symptom relief, and the feasibility of resection without extensive right ventricle removal. The patient’s favorable post-operative course, without tumor recurrence at five months, further supports the efficacy of this combined modality treatment strategy.
Upfront chemoradiotherapy with weekly paclitaxel, followed by surgical resection, represents a potentially effective treatment paradigm for cardiac angiosarcoma, capable of inducing significant pathological responses. However, prospective studies are warranted to validate these findings and further refine treatment protocols for this rare and aggressive malignancy.
Funding
No financial support to disclose.
Conflict of interest
The authors declare that there are no conflicts of interest.
Acknowledgments
Laura Sullivan, International Nurse Coordinator, Cleveland Clinic.
Footnotes
Appendix A Supplementary material related to this article can be found, in the online version, at https://doi.org/10.1016/j.jccase.2020.04.010.
Appendix A. Supplementary data
The following are Supplementary data to this article:
mmc1.docx (53.5KB, docx)
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