The Incidence and Outcome of Venous Thrombo-Embolism (VTE) In Non-Small Cell Lung Cancer Patients with Adenocarcinoma Histology In Comparison with Squamous Histology
Authors: Bhat Ashwini , Surapaneni Rakesh , Hageboutros Alexandre , Milcarek Barry , Hunter Krystal , Coakley Susan , Ferber Andres 
Published: October 2019

Abstract
Abstract 4221

Background:
There have been only limited studies on the incidence and outcome of venous thrombosis in non-small cell lung cancer patients by histology. Patients with adenocarcinoma are believed to have the highest risk of developing venous thrombosis.

Objectives:
1. To study the incidence and outcome of thrombosis in patients with non- small cell lung cancer. 2. To determine the differences in the venous thrombotic risk between adenocarcinoma and squamous cell carcinoma subtypes.

Patients/Methods:
we conducted a retrospective chart review analysis of all the non-small cell lung cancer patients diagnosed in 2008 and 2009 at our institution. Patient and tumor characteristics as well as all venous thrombotic events (VTE) in the course of the disease were recorded. Incidence rates of VTE were calculated as both cumulative incidence and as person-time events (events per 1000 patient years of follow-up). We counted person-years of follow-up for each subject from the date of initial lung cancer diagnosis until the date of a thrombotic event, the date of death, or the end of the study period (30 June 2010), whichever occurred first. Analysis of the difference between squamous cell carcinoma and adenocarcinoma histological subgroups was done using Cox proportional Hazards model. For survival and outcome analysis of patients who develop VTE after diagnosis of lung cancer, we again used a Cox proportional Hazards model with the thrombotic event as a time -dependent variable.

Results:
Among133 patients with non-small cell lung cancer, 86 had adenocarcinoma, 42 had squamous cell histology and 5 were large cell carcinomas (the latter were excluded from the analysis). The mean age of the patients was 66.2 years and their median survival was 377 days (1.04 years).We observed 25 events of VTE over 82.89 years of follow-up for an overall incidence of VTE of 301.6 per 1000 person-years. Among 86 patients with adenocarcinoma histology, we found 21 VTEs (24.4%) Among 42 patients with squamous cell carcinoma, 4 VTE s occurred (9.5 %). The incidence of VTE for patients with adenocarcinoma was 422 per 1000 person-years (95% CI: 282 – 568) and for patients with squamous cell carcinoma 125.97 per 1000 person-years (95 % CI: 36 – 298) resulting in a trend towards higher VTE incidence in patients with adenocarcinoma as compared to patients with squamous cell carcinoma. When the rate ratio between the adenocarcinoma (21/49.7) and squamous cell cancer (4/31.8) are compared, the rate ratio is 3.359 (1.207 – 9.352). The risk of developing a VTE was 2 fold increased for patients with adenocarcinoma vs. squamous cell carcinoma (crude hazard ratio 2.375 [95%CI: 0.664–8.491]) There was a trend towards lower survival time in patients who develop a VTE during the course of their disease compared to patients who did not develop a VTE. (HR 0.992, 95% CI:.449 – 2.193). 5 of the 21 patients in the adenocarcinoma group who had VTE had a second VTE despite anticoagulation.

Discussion:
Only few studies have described the absolute risk as incidence rates of VTE in lung cancer patients. One study in 2004 reported the incidence of VTE is 20-fold increased in lung cancer patients compared to general population; with 3-fold increase in patients with adenocarcinoma histology. Our study confirms the trend towards increased risk of VTE in adenocarcinoma histology, along with a worse outcome. Also, of interest, is the unusually high incidence of VTE noted in our study cohort compared to the reference studies (20.9% vs. 7.2%). This finding might be due to the enhanced awareness and high clinical suspicion leading to increased testing for VTE in the cancer patients. Based on these findings, prophylactic anticoagulation in these patients may be warranted to prevent development of venous thrombosis. This needs to be studied in a prospective clinical trial in the future.

Disclosures:
No relevant conflicts of interest to declare.