Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery

• Published in: British journal of cancer Vol. 102; no. 1; pp. 73 - 79
• Main Authors: Byrne, M, Reynolds, J V, O'Donnell, J S, Keogan, M, White, B, Murphy, S, Maher, S G, Pidgeon, G P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.01.2010; Nature Publishing Group
• Subjects: Abdomen; Adenocarcinoma - blood; Adenocarcinoma - drug therapy; Adenocarcinoma - immunology; Adenocarcinoma - radiotherapy; Adenocarcinoma - surgery; Adult; Aged; Anticoagulants - therapeutic use; Biological and medical sciences; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer surgery; Cancer therapies; Carcinoma, Squamous Cell - blood; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - radiotherapy; Carcinoma, Squamous Cell - surgery; Chemotherapy; Clinical Study; Combined Modality Therapy; Cytokines; Cytokines - blood; Disease prevention; Drug Resistance; Enoxaparin - therapeutic use; Epidemiology; Esophageal cancer; Esophageal Neoplasms - blood; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - immunology; Esophageal Neoplasms - radiotherapy; Esophageal Neoplasms - surgery; Esophagectomy; Esophagus; Factor VIII - metabolism; Female; Fibrin Fibrinogen Degradation Products - analysis; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Hospitals; Humans; Intercellular Signaling Peptides and Proteins - blood; Male; Medical research; Medical sciences; Middle Aged; Molecular Medicine; Neoadjuvant Therapy; Neoplasm Proteins - metabolism; NF-kappa B - metabolism; Oncology; Ostomy; Patients; Postoperative Complications - blood; Postoperative Complications - chemically induced; Postoperative Complications - etiology; Proteins; Pulmonary Embolism - diagnostic imaging; Pulmonary Embolism - etiology; Radiation therapy; Review boards; Thromboembolism; Thrombophilia - blood; Thrombophilia - chemically induced; Thrombophilia - etiology; Tomography, X-Ray Computed; Tumors; Venous Thromboembolism - etiology; Ireland; multimodal; pro-coagulant; oesophageal cancer; immunoinflammation; Esophageal disease; Malignant tumor; Radiotherapy; Long term; Esophagus cancer; Neoadjuvant treatment; Coagulant; Chemotherapy; Treatment; Cancerology; Surgery; Digestive diseases; Combined treatment; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605463

Background: The association between cancer, major surgery and venous thromboembolism (VTE) is well established. Multimodal therapy is increasingly being used as standard treatment for localised gastrointestinal cancer. The aim of this study was to examine the markers of pro-coagulation response and VTE risk in an exemplar multimodal model of pre-operative combination chemotherapy and radiation therapy, followed by complex cancer surgery. Methods: Consecutive patients ( n =36) with localised oesophageal cancer were studied at baseline after the first and second cycles of chemoradiation, and on post-operative days 1–28, and at 3, 6 and 9 months. Factors regulating the pro- and anti-coagulant response, as well as pro-inflammatory markers including NF κ B activation in peripheral blood mononuclear cells, were examined. All patients received enoxaparin 40 mg s.c. postoperatively up to discharge, and underwent pulmonary CT-pulmonary angiography and venography on day 10 postoperatively. Results: Four (11%) non-fatal thromboembolic events were documented, all after hospital discharge. Neoadjuvant therapy before surgery activated factor VIII (FVIII) and pro-inflammatory NF κ B, and increased D-dimers, pro-thrombin fragment 1+2 (F1+2) and the thrombin-anti-thrombin complex (TAT). Surgery significantly ( P <0.05) increased pro-thrombin time (PT), activated partial thromboplastin time, fibrinogen, D-dimers, TAT, F1+2 and FVIII up to 6 months. Conclusion: These data highlight the linked pro-coagulant and immunoinflammatory pathways in the multimodal management of oesophageal cancer, and suggest that the duration of current standard thromboprophylaxis regimens warrants further study.