Discussion
We present an extremely rare example of successful use of multimodal therapy and excellent survival outcome in an adolescent patient with an aggressive primary cardiac UPS. Because of non-specificity of symptoms and rarity of these UPS, they are often difficult to diagnose preoperatively and are missed occasionally.5, 6 The majority are presumed to be benign myxomas and the suspicion of sarcomas arises at the time of operation due to its invasive nature. Abnormal pre-operative imaging features (immobility of the mass, neovascularity, multicentricity, calcification and invasion into the heart structures) should raise the suspicion for a cardiac sarcoma.6Given the difficulty of biopsy in cardiac tumors, a presumptive diagnosis must be made based on radiologic appearance with surgery undertaken to provide both definitive diagnosis and therapy. Patients with localized disease amenable to complete resection experienced longer survival compared to incompletely resected disease.7-9However, UPSs are aggressive and locally invasive tumors, frequently making complete surgical excision unfeasible, leading to a poor prognosis.9, 10
Due to the lack of large of representative pediatric case-series, there is no uniform approach to treating these patients, and the benefits of adjuvant therapy are unclear.11-13 First-line adjuvant treatment generally usually consists of chemotherapy with doxorubicin and ifosfamide.13 Data on the role of radiation therapy (RT) in cardiac sarcoma management are also sparse.14,15 There is widespread fear among oncologists to use high RT doses to large volumes of the heart due to the significant concerns for increased risks of cardiac toxicities, including pericarditis, cardiomyopathy, coronary artery and valvular injury that may be irreversible16. All modern advances in RT planning and delivery including IMRT, respiratory gating and Cine imaging patient immobilization techniques have been used in this patient.
Based on older retrospective and heterogeneous adult case series, sarcomas of the heart are aggressive tumors with frequent tumor recurrence (45%) and metastases (72%) and most patients die within 12–16 months after diagnosis. In more recent series, survival is slightly prolonged but only for patients who underwent complete resection in referral centers. 16, 17 Very few pediatric cases are reported and long term survival in pediatric and adolescent patients is extremely uncommon.18-19 A case of disseminated metastatic undifferentiated sarcoma in a 13 year old was reported who could not undergo complete resection and after multiple rounds of chemotherapy succumbed to widespread disease .21 Another 12‐year‐old boy with metastatic primary UPS of the left atrium died 41 days after diagnosis.22 A pediatric patient with cardiac undifferentiated sarcoma had good response to oral etoposide, followed by complete resection. 23 This report has currently surpassed the median survival rates cited in literature for a patient even after complete resection of the tumor.
The advent of molecular analysis and targeted therapy offers some promise. MDM2 regulates the cell cycle by inhibiting the tumor suppressor p53, through ubiquitin-mediated degradation and transcriptional suppression. When upregulated, MDM2 results in aberrant cellular proliferation.24 In recent years, a number of small molecule inhibitors of MDM2 have been developed which function to stabilize p53 activity and present a promising option for recurrent disease .24
This rare case illustrates two crucial aspects of cardiac tumors in pediatric patients: they can masquerade as other conditions and modern aggressive multidisciplinary management of these tumors can result in long-term good quality survival. Longer-term follow up is required to determine the incidence of late toxicities of these treatments including cardiac, pulmonary and secondary malignancies.
Disclosures: Authors have no disclosures.
References
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