Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

Abstract

BackgroundPrimary cardiac angiosarcomas are rare, but they are the most aggressive type of primary cardiac neoplasms. When patients do present, it is with advanced pulmonary and/or cardiac symptoms. Therefore, many times the correct diagnosis is not made at the time of initial presentation. These patients have metastatic disease and the vast majority of these patients die within a few months after diagnosis. Currently the treatment choices are limited and there are no targeted therapies available.Case presentationA 56-year-old male presented with shortness of breath, night sweats, and productive cough for a month. Workup revealed pericardial effusion and multiple bilateral pulmonary nodules suspicious for metastatic disease. Transthoracic echocardiogram showed a large pericardial effusion and a large mass in the base of the right atrium. Results of biopsy of bilateral lung nodules established a diagnosis of primary cardiac angiosarcoma. Aggressive pulmonary disease caused rapid deterioration; the patient went on hospice and subsequently died. Whole exome sequencing of the patient’s postmortem tumor revealed a novel KDR (G681R) mutation, and focal high-level amplification at chromosome 1q encompassing MDM4, a negative regulator of TP53.ConclusionMutations in KDR have been reported previously in angiosarcomas. Previous studies also demonstrated that KDR mutants with constitutive KDR activation could be inhibited with specific KDR inhibitors in vitro. Thus, patients harboring activating KDR mutations could be candidates for treatment with KDR-specific inhibitors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3000-z) contains supplementary material, which is available to authorized users.

Metastatic Cardiac Angiosarcoma to the Lung, Spine, and Brain: A Case Report and Review of the Literature

“…They discovered the patient had a KDR mutation, a vascular-specific tyrosine kinase receptor, resulting in its overactivation. 50 KDR mutations in angiosarcoma patients has been reported to have a 10% incidence and the whole exome sequencing study supported the potential clinical efficacy of a KDR inhibitor. 51 Other genomic studies have demonstrated an upregulation of p53, Ras, BRCA, PTEN, and MYC in angiosarcomas.…”

A Patient Presenting with Cardiac Tamponade and the Challenges of Finding Its Cause: A Cardiac Angiosarcoma

“…Primary pericardial neoplasms are rare entities with estimated prevalence of 0.001 to 0.007% based on mostly case series studies [ 1 , 2 ]. Mesothelioma is the most common malignancy followed by different subtypes of sarcomas and lymphoma [ 1 ].…”

“…Cardiac transplantation is not currently recommended due to poor survival benefit in few studies [ 8 ], except for very selected group of patients with subsequent immunotherapy [ 9 ]. Genome sequencing of the tumor in attempt to target gene therapy against vascular-specific receptor tyrosine kinases is currently being studied [ 2 ]. The optimal treatment strategy remains to be discovered.…”

Mathematical model predicts response to chemotherapy in advanced non-resectable non-small cell lung cancer patients treated with platinum-based doublet

“…We performed model simulations using the following protocols: 1) maximum-tolerated dose schedule, 2) maximum-tolerated dose schedule with drug holiday, 3) metronomic therapy schedule, and 4) metronomic therapy with drug holiday. Graphically, the schedules are presented in Fig 5. The maximum-tolerated dose (MTD) therapy is simulated as follows [39]. The virtual patient after diagnosis and without time delay is treated with three cycles of cisplatinum with dose 80mg/m 2 and 21 days' time interval between each two consecutive cycles.…”