A 45 year old man patient with stage IVA thymic carcinoma was enrolled on a phase II study of sunitinib (50 mg daily) [1] four weeks after disease progression on first-line chemotherapy with cisplatin, doxorubicin, cyclophosphamide (PAC), and belinostat [2]. Molecular profiling of his tumor revealed only a p53 gene mutation (c-Kit was wild-type) [3].
Baseline chest computed tomography (CT), prior to sunitinib, showed a mediastinal mass with compression of the proximal right main pulmonary artery (Figure 1A), and direct invasion of pericardium. Three weeks after initiation of sunitinib, patient reported increased left shoulder pain, cough, nausea, vomiting, and a palpable soft and fluctuating lesion measuring 2 cm in size overlying the sternum. A new CT scan (Figures 1B–D) showed an increase in the size of the mediastinal mass, which now included air (Figures 1B–D, asterisk), air-fluid levels (Figures 1B, 1D arrow), dissection in the anterior chest wall with subcutaneous air (Figure 1C, double arrow) and a large left pleural effusion (Figures 1B–D). Sunitinib was discontinued and a thoracentesis was performed to remove a liter of straw colored fluid. Considering disease progression with tumor necrosis and superimposed infection with the possibility of bronchocutaneous fistula, antibiotic therapy was started. Subsequently, the patient’s clinical condition deteriorated rapidly with development of right ventricular heart failure and he died two weeks later. The autopsy revealed massive neoplastic infiltration of the heart, great vessels including the pulmonary artery and left lung with abundant tumor necrosis, most likely related to rapid progression of disease rather than anti-angiogenesis effects of sunitinib. This represents a very unusual finding in a patient with an aggressive thymic carcinoma.
Figure 1.
A) Bulky mediastinal mass on CT scan, without contrast, before sunitinib; B–D) Mediastinal mass containing air (asterisk), air-fluid levels (arrow), with dissection in the anterior chest wall and subcutaneous air (double arrow), and large left pleural effusion after three weeks of sunitinib.
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Disclosures: None
References
- A Phase 2 Study of Sunitinib in Patients with Advanced Relapsed or Refractory Thymoma or Thymic Carcinoma with at Least One Prior Line of Platinum-Based Systemic Chemotherapy. NCT01621568. www.clinicaltrials.gov.
- A Phase 1/2 Study of PXD101 (Belinostat) in Combination With Cisplatin, Doxorubicin and Cyclophosphamide in the First Line Treatment of Advanced or Recurrent Thymic, Malignancies. NCT01100944. www.clinicaltrials.gov.
- Pilot Trial of Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies. NCT01306045. www.clinicaltrials.gov.