BMC Cancer 2009, 9:421 http://www.biomedcentral.com/1471-2407/9/421 Background Lung cancer is one of the commonest neoplasms all over the world with approximately 1.35 million new cases worldwide in 2002 [1]. It is the most devastating cause of cancer-related deaths with more than 1.18 million deaths in 2002 [1]. Survival at 5 years measured by the SEER pro- gram in the United States is 15%, the best recorded at the population level. The average 5 year survival in Europe is 10%, not much better than the 8.9% observed in develop- ing countries [1]. The poor outcome is attributable to the fact that almost two-third of cases are diagnosed when loco-regional and/or metastatic extension has already occurred [2]. The only treatment available at this stage is chemotherapy and/or radiotherapy. Although response rates for chemotherapy and radiotherapy are low, several studies have demonstrated moderate beneficial effects concerning survival, time to disease progression, and quality of life when compared with best supportive care [3]. The current staging investigations after cytotoxic ther- apies, like chemotherapy and/or radiotherapy, involve imaging procedures, like computed tomography (CT) and positron-emission tomography (PET)-CT. However, these procedures can monitor only macroscopic alteration of tumor mass, that too after several cycles of chemotherapy (2-3 cycles of chemotherapy and/or radiotherapy). In addition, they also have a risk of exposure to harmful radi- ation to the patient. Thus, there is a growing need for a simple tool that can help in evaluating the prognosis, monitor the effect of treatment and most importantly pre- dict response to therapy at an early stage. One potential approach could be the quantification of tumor markers as they take into account the heterogeneity of the tumor mass which contain active, silent, apoptotic and necrotic part and they also represent the activity of the residual tumor disease. Therefore, any change in their levels should reflect the change in the tumor mass due to cyto- toxic therapies, which mean that they can potentially pro- vide a sensitive and cost-effective method for the prediction of prognosis of cancer patients. Further, serial assessment of tumor markers during cytotoxic therapies may help in predicting response to therapy at an early stage. This would help in optimizing disease management on an individual basis. In non-small cell lung cancer patients, several tumor markers, like CEA, CYFRA 21-1, and nucleosomes have shown considerable potential for predicting diagnosis, prognosis and therapy monitoring [4-9]. However, their potential in a clinical set-up is yet to be realized. There is now an increasing recognition of the importance of targeted therapies, especially anti-angiogenesis thera- pies, in solid tumors to improve the overall survival or progression free survival. The two most common approaches currently being explored are i) antibodies to vascular endothelial growth factor (VEGF) or soluble receptors that inhibit the binding of VEGF to its receptor and ii) tyrosine kinase inhibitors blocking downstream signaling from membrane bound tyrosine kinase recep- tors. It is therefore becoming essential to study the profile of circulating VEGF during cytotoxic therapies in an effort to evaluate its potential in predicting prognosis, response to therapy, and disease progression. We hypothesized that monitoring VEGF levels during the course of cytotoxic therapy may have the potential to predict the clinical ben- efits in terms of prognosis and response to therapy in advanced NSCLC patients. In the present study, we investigated the plasma levels of VEGF in a homogeneous group of patients with newly diagnosed and advanced NSCLC during first-line plati- num-based chemotherapy to analyze the utility of VEGF for the prediction of insufficient response to therapy and disease progression. In addition, we looked for any corre- lation between pre-treatment plasma levels of VEGF with various clinico-pathological parameters in patients with non-small cell lung cancer. Methods Subjects We evaluated 134 newly diagnosed and primarily untreated advanced stage lung cancer patients and 100 age-matched controls (patients without malignancy). All subjects were enrolled from Out Patient Department of Medicine, All India Institute of Medical Sciences, New Delhi, India between years 2006-2009. For all patients, a diagnosis of lung cancer was confirmed by the histologic examinations of biopsy and/or cytology specimens obtained during fiberoptic bronchoscopy or with a CT- guided procedure. Pre-treatment evaluation also included evaluation of Eastern Cooperative Oncology Group per- formance status (ECOG), X-ray and computed tomogra- phy (CT) scan of the chest and upper abdomen. If necessary, a CT or magnetic resonance imaging (MRI) scan of the brain, and radionuclide bone scan was per- formed. All the patients were staged according to the American Thoracic Society TNM classification [10]. Epide- miological data including demographics, family history, risk factors, occupational exposure, and histopathological data was recorded. Forty two (42) of these patients received platinum-based chemotherapy for a minimum of 3 cycles. In these patients, response to therapy was classi- fied according to the WHO guidelines defining "partial remission" (R) as tumor reduction ≥ 50%, "progression" (P) as tumor increase ≥ 25% or appearance of new tumor manifestations, and "no change" (NC; stable disease) as tumor reduction <50% or increase <25% [11]. Measurement of circulating plasma VEGF Venous blood was collected in sterile EDTA-coated vials from all subjects at baseline (BV1). Blood was also col- Page 2 of 12 (page number not for citation purposes)