RARE CASE OF PAZOPANIB-ASSOCIATED BILATERAL PNEUMOTHORACES IN A PATIENT WITH METASTATIC SYNOVIAL SARCOMA

Abstract

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Bilateral pneumothoraces are a rare occurrence, comprising 1.4% to 7.6% of cases [1]. Secondary causes of pneumothorax include bullous emphysema, cystic parenchymal lung disease and tuberculous lung disease [2]. Malignancy is a rare cause of pneumothorax, yet sarcomas have been associated with pneumothorax in 2% of patients [3]. Pazopanib, a tyrosine kinase inhibitor used in the treatment of metastasized sarcoma, has been shown to have a 3.3% risk of developing pneumothorax [4]. CASE PRESENTATION: A 24-year-old previously healthy Yemeni female initially presented with left-sided groin pain and swelling. Computed tomography of the pelvis showed a large heterogeneous mass in the proximal left thigh. Biopsy was consistent with synovial sarcoma. Staging via chest computed tomography showed multiple pulmonary nodules concerning for metastasis. Over the course of two years, she failed multiple lines of chemotherapy and had progression of disease with new and enlarging bilateral pulmonary nodules. She was started on fourth-line chemotherapy with pazopanib (Votrient) 400 mg daily. Two months later, she presented with shortness of breath, found to be tachypneic, tachycardic and hypoxemic. Chest x-ray revealed bilateral pneumothoraces with left mediastinal shift concerning for tension pneumothorax. Two tube thoracostomies were placed; however, course was complicated by persistent air leak bilaterally, requiring video-assisted thoracoscopic surgery with bullectomy and surgical talc pleurodesis. Patient had a slow resolution of pneumothorax and subsequently discharged home without recurrence. DISCUSSION: Bilateral pneumothoraces can be life-threatening and are associated with poor long term prognosis, especially in patients with poor underlying lung function [5]. Pneumothorax is seen in approximately 2% of sarcoma patients with pulmonary metastases. In patients with sarcoma and pulmonary metastases, 41.6% of pneumothoraces were bilateral, and typically associated with multiple lung nodules, cystic or cavitary lesions, or presence of pleural nodules or thickening [3]. Additionally, cytotoxic agents have been shown to induce cavitation in pulmonary lesions and increase the risk of pneumothorax development [6]. Per the PALETTE trial which led to the approval of pazopanib for use in sarcoma, there was a 3.3% risk for pneumothorax development [4], comparable to the baseline rate of pneumothorax development in patients with sarcoma. Nevertheless, bilateral pneumothoraces carry potentially fatal consequences. CONCLUSIONS: In patients with sarcoma undergoing treatment with pazopanib, a bilateral pneumothorax, though rare, may be life threatening and should be acutely suspected. REFERENCE #1: TG Rim, JS Bae, YS Yuk. Life-Threatening Simulatenous Bilateral Spontaneous Tension Pneumothorax - A case report. Korean J Thorac Cardiovasc Surg. 2011 Jun; 44(3): 253-256.2. Mason RJ, Braoddus VC, Murray JF, Nadel JA. Murray and Nadel's Textbook of Respiratory Medicine. 4th ed. Elsevier Saunders (2005); Vol 2, Chapter 81. Philadelphia, PA. REFERENCE #2: Hoag JB, Sherman M, Fasihuddin Q, Lund ME. A comprehensive review of spontaneous pneumothorax complicating sarcoma. CHEST. 2010 Sep; 138(3);510-8.4. Van der Graaf WT, Blay JY, Chawla SP, Kim DW, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19; 379(9829):1879-86. REFERENCE #3: Graf-Deuel E, Knoblauch, A. Simultaneous bilateral spontaneous pneumothorax. CHEST. 1994 Apr; 105(4):1142-6.6. Interiano RB, McCarville MB, Wu J, Davidoff AM, Sandoval J, Navid F. Pneumothorax as a complication of combination antiangiogenic therapy in children and young adults with refractory/recurrent solid tumors. J Pediatr Surg. 2015 Sep; 50(9):1484-9. DISCLOSURES: No relevant relationships by Sally Askar, source=Web Response No relevant relationships by Owais Nadeem, source=Web Response