Tuncer TUĞ, Bahar KURT, Fahrettin TALAY, Özlem KURT KAR, Defne KALAYCI

Plazma D-dimer düzeyleri akciğer kanserinde prognoz için bir belirteç olabilir mi?

Giriş: Tümör büyümesi ve yayılmasıyla ilişkili olabilen hemostatik aktivasyonun dolaşımdaki belirteçlerinin plazma konsantrasyonları malignitede prognozu tahmin ettiği gösterilmiştir. Bu çalışma akciğer kanserinde plazma D-dimer düzeyinin prognostik değerini araştırmak için tasarlanmıştır.Materyal ve Metod: Akciğer kanserli 138 hastada [98 küçük hücreli dışı akciğer kanseri (KHDAK), 40 küçük hücreli akciğer kanseri (KHAK)] plazma D-dimer düzeyleri herhangi bir tedavi başlamadan önce ve her kemoterapi öncesi ölçüldü.Bulgular: Çalışmada 124 (%89.9) erkek ve 14 (%10.1) kadın vardı. Ortalama yaşı 62.8 yıl (aralığı 38-84) idi. KHDAK hastaları için histopatolojik tipler arasında istatistiksel olarak anlamlı bir fark yoktu. Evre IIIA KHDAK grubu, evre I-II ve IV'e göre istatistiksel olarak anlamlı derecede yüksek D-dimer düzeyine sahipti. Progresif hasta grubunda 4. kür sonrasında D-dimer düzeyinin anlamlı şekilde arttığı görüldü. KHDAK hastalarında ortanca sağkalım süresi, düşük D-dimer düzeyi (≤ 1.2 ng/L) olan hastalarda 26.6 ay (%95 GA 17.6-35.6) ve yüksek D-dimer (> 1.2 ng/L) olanlarda ise 15.9 ay (%95 GA, 4.2-27.7; p= 0.037) idi. Cox-regresyon analizinde, D-dimer plazma seviyesi ve tümör evresi sağkalımın bağımsız prediktif faktörleri olarak tespit edilmiştir.Sonuç: Bu sonuçlar plazma D-dimer düzeyinin akciğer kanserinde azalmış sağkalım ve tedaviye kötü yanıtın bir belirteci olarak kullanılabileceğini düşündürmüştür.

Could plasma D-dimer levels be a predictive marker for prognosis in lung cancer?

Introduction: Plasma concentrations of circulatory markers of hemostatic activation which may be associated with tumor growth and dissemination have been shown to predict prognosis in malignancy. The present study was designed to investigate the prognostic value of plasma D-dimer level in lung cancer.Materials and Methods: Plasma levels of the D-dimer in 138 lung cancer patients [98 non-small cell lung cancer (NSCLC), 40 small cell lung cancer (SCLC)] were measured before the initiation of any therapy and each chemotherapy.Results: There were 124 (89.9%) men and 14 (10.1%) women with a mean age of 62.8 years (range 38-84). There were no statistically significant differences among the histopathologic types for NSCLC patients. Stage IIIA NSCLC group had statistically significant higher D-dimer level than stages I-II and IV. D-dimer levels were increased significantly after 4 cycles of chemotherapy in progressive disease. The median survival times in NSCLC patients were 26.6 months (95% CI, 17.6-35.6) and 15.9 months (95% CI, 4.2-27.7; p= 0.037) respectively, for patients with a low D-dimer level (≤ 1.2 ng/L) and a high D-dimer level (> 1.2 ng/L).With the cox-regression analysis, the plasma level of D-dimer and tumour stage were identified as independent predictive factors of the survival.Conclusion: These results suggest that plasmalevel of D-dimer can act as a predictive factor of decreased survival and a poor response to the treatment in lung cancer.

PDF

___

Edwards RL, Rickles FR, Moritz TE, Henderson WG, Zacharski LR, Forman WB, et al. Abnormalities of blood coagulation tests in patients with cancer. Am J Clin Pathol 1987; 88: 596-602.
Falanga A, Panova-Noeva M, Russo L. Procoagulant mechanisms in tumour cells. Best practice and research. Clin Hematol 2009; 22: 49-60.
Malik G, Knowles LM, Dhir R, Xu S, Yang S, Ruoslahti E, et al. Plasma fibronectin promotes lung metastasis by contributions to fibrin clots and tumor cell invasion. Cancer Research 2010; 70: 4327-34.
Thompson WD, Smith EB, Stirk CM, Marshall FI, Stout AJ, Kocchar A. Angiogenic activity of fibrin degradation products is located in fibrin fragment E. J Pathol 1992; 168: 47-53.
Lippi G, Franchini M, Targher G, Favaloro EJ. Help me, Doctor! My D-dimer is raised. Annals Med 2008; 40: 594-605.
Ay C, Dunkler D, Pirker R, Thaler J, Quehenberger P, Wagner O, et al. High D-dimer levels are associated with poor prognosis in cancer patients. Haematologica 2012; 97: 1158-64.
Falanga A, Rickles FR. Pathophysiology of the thrombophilic state in the cancer patient. Seminars in thrombosis and hemostasis. 1999; 25: 173-82.
Kwaan HC, Keer HN. Fibrinolysis and cancer. Seminars in thrombosis and hemostasis. 1990; 16: 230-5.
Bick RL. Coagulation abnormalities in malignancy: a review. Seminars in thrombosis and hemostasis 1992; 18: 353-72.
Buccheri G, Torchio P, Ferrigno D. Plasma levels of D-dimer in lung carcinoma: clinical and prognostic significance. Cancer 2003; 97: 3044-52.
Altiay G, Ciftci A, Demir M, Kocak Z, Sut N, Tabakoglu E, et al. High plasma D-dimer level is associated with decreased survival in patients with lung cancer. Clin Oncol (R Coll Radiol) 2007; 19: 494-8.
Unsal E, Atalay F, Atikcan S, Yilmaz A. Prognostic significance of hemostatic parameters in patients with lung cancer. Respir Med 2004; 98: 93-8.
Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166: 458-64.
Noble S. Low-molecular-weight heparin and survival in lung cancer. Thrombosis research 2012; 129(Suppl 1): S114-8.
Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol: Official Journal of the American Society of Clinical Oncology 2013; 31: 2189-204.
Komurcuoglu B, Ulusoy S, Gayaf M, Guler A, Ozden E. Prognostic value of plasma D-dimer levels in lung carcinoma. Tumori 2011; 97: 743-8.
Seitz R, Rappe N, Kraus M, Immel A, Wolf M, Maasberg M, et al. Activation of coagulation and fibrinolysis in patients with lung cancer: relation to tumour stage and prognosis. Blood Coagul Fibrinolysis 1993; 4: 249-54.
Antoniou D, Pavlakou G, Stathopoulos GP, Karydis I, Chondrou E, Papageorgiou C, et al. Predictive value of D-dimer plasma levels in response and progressive disease in patients with lung cancer. Lung Cancer 2006; 53: 205-10.
Taguchi O, Gabazza EC, Yasui H, Kobayashi T, Yoshida M, Kobayashi H. Prognostic significance of plasma D-dimer levels in patients with lung cancer. Thorax 1997; 52: 563-5.
Ferrigno D, Buccheri G, Ricca I. Prognostic significance of blood coagulation tests in lung cancer. Eur Respir J: Official Journal of the European Society for Clinical Respiratory Physiology 2001; 17: 667-73.