BMC Cancer 2009, 9:421 http://www.biomedcentral.com/1471-2407/9/421 Ar ea under the cur ve BV1 BV2 BV3 0.552 0.805 0.895 icbRFnyeiggcfcoluderirsev3eeta(rh4Bs-eoVps3pte)raroragttrionefgsstchiohenarrabapycytpeclryaicsmtleicas1V((REBGOV1FC)l,)eccvyuecrllsveea2svaf(ioBlarVbp2ler),eadnicdt- Receiver-operating characteristics (ROC) curves for predicting disease progression by plasma VEGF lev- els available before the start of therapy cycle 1 (BV1), cycle 2 (BV2), and cycle 3 (BV3). During the estimation of therapy response, patients are generally grouped into responders (patients with remis- sion) and non-responders (patients with stable disease or progression). To increase the overall survival of the patients, it is of utmost importance to find the group of patients, at an early stage of their treatment, who are either (i) going to respond to the treatment or (ii) going to progress to a more advanced stage of disease. For both these groups, it would be necessary to focus on the mark- ers already being available before start of the second course of the treatment. This could be helpful in the better management of the cancer patients as an early prediction of response to therapy or disease progression can be used to either intensify treatment or change the treatment plan. Therefore, we conducted two different evaluations of plasma VEGF levels, available before cycle 2 of therapy (BV2), to address both clinical questions. For evaluation 1 (R+NC versus P), we selected a VEGF (BV2) cut-off levels of 312.6 pg/mL from the ROC curve (area under the curve = 0.805). At this cut-off, we were able to diagnose disease progression with a sensitivity and specificity of 71.4%. While for evaluation 2 (R versus NC+P), VEGF levels before cycle 2 (BV2) was able to pre- dict an insufficient therapy response with a sensitivity and specificity of 76.9% and 75.0%, respectively, when a cut- Area under the curve = 0.878 sRFmeeiangcrsuekitirevievreirti5ny-oapdnevdraasntpcineegcdicfinhcoiatnrya-socmtfeparlilasstcimeclsall(VuRnEOgGCcFa)lneccvueerrlvseatsoactaulcmuolarte Receiver-operating characteristics (ROC) curve to calculate sensitivity and specificity of plasma VEGF levels as a tumor marker in advanced non-small cell lung cancer. off of 232.1 pg/mL was applied. Interestingly, the kinetics of VEGF form cycle 1 to 2 (BV1-2) and cycle 1 to 3 (BV1- 3) also gave significant information for predicting disease progression as well as insufficient response to therapy. Although, our sample size was a limitation, the results show that monitoring the levels of circulating VEGF dur- ing the course of cytotoxic therapy can predict insufficient response to therapy and disease progression. Earlier stud- ies have not evaluated measurement of levels of VEGF at defined intervals during the initial treatment phase for predicting insufficient response to therapy and disease progression in NSCLC patients. So, a large-scale prospec- tive validation study is needed to confirm the relevance of the current findings presented here. Further, we compared plasma VEGF levels in 134 NSCLC patients and 100 controls. Also, correlation with various clinico-pathological factors and VEGF was looked at. This study highlights a few significant findings: (a) plasma VEGF levels were significantly higher in patients with NSCLC as compared to controls; (b) significant associa- tion was observed between plasma VEGF levels and tumor size. Also, there was some evidence to suggest a correla- tion between plasma VEGF levels and performance status, and nodal involvement. However, these associations did not reach the level of statistical significance. Page 10 of 12 (page number not for citation purposes)