Lung Cancer as a Leading Cause among Paraneoplastic Non-Bacterial Thrombotic Endocarditis: A Meta-Analysis of Individual Patients’ Data

Abstract

Hypercoagulability is strongly associated with cancer and may result in non-bacterial thrombotic endocarditis (NBTE). The aim of our meta-analysis was to explore the demographics and characteristics of this condition in cancer. Databases were systematically searched. The outcomes were to identify the annual trend in premortem diagnosis among the entire cohort and different subgroups and to identify differences in characteristics and survival in the considered population. A total of 121 studies with 144 patients were included. The proportion of marantic endocarditis associated with lung cancer was 0.29 (95% CI, 0.21–0.37; p < 0.001), that associated with pancreatic cancer was 0.19 (95% CI, 0.13–0.27; p < 0.001), that associated with advanced cancer stage (metastasis) was 0.69 (95% CI, 0.61–0.76; p < 0.001), and that associated with adenocarcinoma was 0.65 (95% CI, 0.56–0.72; p < 0.001). Median and 6-month overall survival (OS) were 1.3 months and 32.3%, respectively, with 6-month OS of 20.8% vs. 37.0% in lung vs. other cancers, respectively (p = 0.06) and 42.9% vs. 31.1% among those who underwent intervention vs. those who did not (p = 0.07). Cases discovered in recent years had better survival (HR = 0.98 (95% CI, 0.96–0.99; p = 0.003). While cancer-associated NBTE is a rare entity, lung cancers were the most common tumor site and are frequently associated with more advanced and metastatic cancer stages. The prognosis is dismal, especially among lung cancers.

Non-bacterial thrombotic endocarditis in ROS1-rearranged lung cancer: a report of two cases

“…This report highlights the importance of initial clinical suspicion of NBTE to make a prompt diagnosis, in order to obtain good clinical outcomes from directed oncological treatment. Despite that, one of our patients presented initial neurological worsening even receiving optimal treatment, due to the aggressiveness of this disease, as seen in some reports 79% of patients can have an embolic event 1 month after the NBTE diagnosis ( 7 ) and being the 3-month estimated overall survival of 26% of patients diagnosed of lung cancer induced NBTE ( 3 ). The main limitation of our report is the possible selection bias of our patients as we are reporting two cases with great improvement after treatment.…”

“…One severe form of TE is non-bacterial thrombotic endocarditis (NBTE), defined as the presence of sterile vegetations on cardiac valves that can cause organ damage by cardioembolic mechanism. It is very infrequent though with an estimated overall incidence between 0.9% and 1.6% in autopsy populations ( 3 ). Malignancy is the most frequent cause of NBTE, causing up to 75% of cases, and being lung cancer the most prevailing malignant cause (28% of malignant-related NBTE), while the remaining 25% correspond to non-malignant causes (i.e., systemic lupus erythematosus) ( 3 ).…”

“…It is very infrequent though with an estimated overall incidence between 0.9% and 1.6% in autopsy populations ( 3 ). Malignancy is the most frequent cause of NBTE, causing up to 75% of cases, and being lung cancer the most prevailing malignant cause (28% of malignant-related NBTE), while the remaining 25% correspond to non-malignant causes (i.e., systemic lupus erythematosus) ( 3 ). Medical treatment includes anticancer treatment, anticoagulation with heparin, direct oral anticoagulation (DOAC) or vitamin k antagonists ( 4 ).…”

Systemic embolization due to non-bacterial thrombotic endocarditis: An autopsy case report and mini review of the literature

“… 2 – 4 Common malignancies associated with NBTE include lung, pancreas, ovary, breast carcinomas, and malignant melanoma. 7 , 11 The disease was first described by Ziegler in 1888 in cadavers and refers to the formation of sterile, friable, thrombotic vegetations on normal or degenerated cardiac valves. 12…”

“…Moreover, factors associated with a patient’s characteristics and treatment (e.g., immobility, operative procedures, hospitalization, radiation therapy, central venous catheters, and chemotherapy-associated endothelial toxicity) participate further in its pathophysiology. 11 Endothelial injury is postulated to play a cardinal role in the pathogenesis of marantic endocarditis, leading to platelet deposition and activation and migration of inflammatory mononuclear cells to generate thrombi consisting of platelets, fibrin, and immune complexes. 13 Accumulating data show that malignant cells express cytokines, such as tumor necrosis factor-a, interleukin (IL)-1, and IL-6, which, apart from their relation to inflammation, are procoagulant factors, causing sloughing of vascular endothelial cells as well as increased blood sludging.…”