Original article Significance of thromboembolic phenomena occurring before and during chemoradiotherapy for localized carcinoma of the esophagus and gastroesophageal junction E. D. Tetzlaff, 1 A. M. Correa, 2 R. Komaki, 3 S. G. Swisher, 2 D. Maru, 4 W. A. Ross, 5 J. A. Ajani 1 1 Departments of Gastrointestinal Medical Oncology and 2 Thoracic and Cardiovascular Surgery, 3 Radiation Oncology, 4 Pathology, and 5 GI Medicine and Nutrition at the University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA SUMMARY. Thromboembolic event (TEE) is the most common complication and a second cause of mortality in cancer patients. Multiple hypotheses for occurrence of TEE have been proposed. There are no reports on the frequency/impact of TEE in localized gastroesophageal cancer patients. We hypothesized that TEE at baseline and during chemoradiotherapy (CTRT) in gastroesophageal cancer patients would have an impact on overall survival (OS) of these patients. All consecutive patients with gastroesophageal cancer undergoing CTRT from 2001 to 2004 were eligible for this analysis. Baseline and subsequent TEEs were documented and correlated with patient characteristics and OS. One hundred ninety-eight patients were analyzed. TEEs were documented in 9.6% of the patients. At baseline, TEEs were documented in 4.0% of the patients. During CTRT, TEEs were documented in 6.1% of the patients. Pulmonary embolism (43.5%) and lower extremity venous thromboses (39%) were the most frequent TEEs. Median OS for patients with a TEE occurring at anytime was 17.7 versus 32.0 months for patients who never developed a TEE (P = 0.014). TEEs at baseline correlated with poor median survival: 13.1 versus 30.7 months for those without a TEE (P = 0.029). In a multivariable analysis, TEE at baseline and/or during CTRT was an independent predictor of OS (hazard ratio, 1.818; P = 0.040). Our data are the first to document the frequency of TEE in gastroesophageal cancer patients undergoing CTRT, and that TEE is an independent prognosticator of OS. Active research to prevent and treat TEEs is needed to improve survival of patients with localized gastro- esophageal cancer. KEY WORDS: gastroesophageal cancer chemotherapy, prognosis, radiotherapy, survival, thrombosis. INTRODUCTION The association between thrombosis and malignancy is well established in the medical literature. 1–3 When cancer and a thromboembolic event (TEE) are diag- nosed simultaneously or close together, patients often have a more advanced stage of the cancer at diagnosis and a poor prognosis. 3 A number of hypotheses have been proposed for the occurrence of TEEs in cancer patients. 4 These include: (i) expression of tissue factor by tumor cells; (ii) chemotherapy and tumor lysis as an inducing cause; (iii) cancer procoagulant, a cys- teine protease initiating the thrombosis cascade; (iv) tissue factor and angiogenesis; and (v) participation by microparticles or “platelet dust.” Whatever might be the initiating factors, the morbidity and mortality caused by TEE is undeniable and not well docu- mented in patients with localized gastroesophageal cancer. Our previous review of 191 patients with advanced gastric and gastroesophageal junction adenocarcinoma suggests that TEEs at baseline and/or during palliative chemotherapy are frequent and are associated with poor overall survival (OS). 5 However, there are no established guidelines for therapy of TEE in advanced upper gastrointestinal cancers. Patients with gastrointestinal cancer that develop a TEE may experience unique circumstances for which specific guidelines may be needed. For example, gastroesophageal cancer patients with their Address correspondence to: Dr Jaffer A. Ajani, MD, Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77005-4341, USA. Email: Jajani@mdanderson.org Diseases of the Esophagus (2008) 21, 575–581 DOI: 10.1111/j.1442-2050.2008.00829.x © 2008 Copyright the Authors Journal compilation © 2008, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus 575