Massive Thrombosis of Brachiocephalic Veins and Superior Vena Cava Syndrome in a Patient with Non-Small Cell Lung Cancer Treated with the Epidermal Growth Factor Receptor Inhibitor Erlotinib

Abstract

The superior vena cava (SVC) syndrome occurs when obstruction of this vessel interrupts venous return of blood from the head, upper extremities and thorax to the right atrium. Most cases of SVC syndrome result from neoplasia, especially from lung cancer, but other non-cancer-associated causes may include fibrosis caused by radiotherapy, collagen-vascular diseases, arteriovenous shunts or thrombosis as a complication of use of central venous catheters or devices. We report here the case of a 60-year-old woman with non-small cell lung cancer who was treated, after three lines of chemotherapy, with the epidermal growth factor receptor inhibitor erlotinib and subsequently presented to the hospital with abrupt onset of syncope, shortness of breath and cyanosis (face, neck and trunk). A CT scan of the chest demonstrated a massive thrombosis of both brachiocephalic veins and the SVC. The patient was treated with the systemic thrombolytic agent urokinase, with resolution of the clinical picture and no bleeding complications. The possible pathogenetic causes of thrombosis of the brachiocephalic veins and SVC syndrome in this case are discussed. It is possible that acute thrombosis may be associated with erlotinib use, even if it is likely that cancer may be the main cause of the thrombotic complication.

Malignant thrombosis of the superior vena cava caused by non-small-cell lung cancer treated with radiation and erlotinib: a case with complete and prolonged response over 3 years

“…It is unfortunate that we did not obtain information about the presence or lack of somatic mutation in the EGFR gene of the tumor, just as in a previously reported case,8 as this has been associated with a higher responsiveness to erlotinib 11. We were limited by the biopsy sample volume and by the need to treat the SVC obstruction, as EGFR gene sequencing usually takes 1 to 2 weeks.…”

“…Erlotinib has been used to treat NSCLC patients with SVC syndrome in the past,7,8 and the tumors in these cases completely responded to the erlotinib. In one of these cases,7 erlotinib was used concurrently with stereotactic body radiation therapy.…”

Massive SVC Thrombus in a Woman With Heterozygous Methyl-Tetrahydrofolate Reductase A1298C Genetic Mutation

“…Indeed, Cadman et al showed that proximally-placed CVC (proximal third SVC or thoracic inlet veins) are 16 times more likely to thrombose than the ones placed distally(distal third of the SVC or right atrium) [3]. In case of malignancy, the pathogenesis of thrombus formation in the SVC can be complex related to many factors such as humoral ones, mechanic obstruction, or even fibrosis caused by radiotherapy [4]. Collagen vascular diseases and Behçet's disease are among rare risk factors for SVC thrombosis [5].…”

“…The treatment mainstay is made of low molecular weight heparin or vitamin K antagonists such as warfarin. In life-threatening situations however, thrombolytic therapy is used to dissolve massive clots obstructing the superior vena cava and its tributaries [4]. Placing SVC filters is very controversial and carries the risk of severe complications such as cardiac tamponade, pneumothorax, SVC perforation, or filter migration [16].…”

Rare serious complications of erlotinib therapy

“…For instance, superior vena cava syndrome has been reported following initiation of erlotinib therapy [5]. Patients may present with cyanosis and dyspnea.…”