1046: Expression, Prognostic Value, and Impact of Chemotherapy on Plasma Angiogenic Factors VEGF, IL-8, and Basic FGF for Lung Cancer Patients Receiving Radiotherapy

Abstract

Angiogenesis is associated with tumor invasion and metastasis. We investigate the prognostic value of circulating angiogenic cytokines and impact of chemotherapy schedule on the expression of circulating VEGF, IL-8, and bFGF in lung cancer pts receiving concurrent radiation (RT). 70 pts enrolled in a clinical protocol with prospective serial blood sampling before, weekly during RT and after RT. VEGF, IL-8 and bFGF levels were measured in 687, 699 and 384 blood specimens, respectively, using Enzyme Linked Immunosorbent Assay. Prognostic value was analyzed by univariate and multivariate analyses. Cytokine changes over time were analyzed by three therapy groups: (1) pts receiving thoracic RT without chemotherapy; (2) pts receiving thoracic RT with full-dose chemotherapy (standard-dose CDDP/VP-16 or CDDP/Velban); and (3) pts receiving thoracic RT with low-dose chemotherapy (CDDP or paclitaxel). Cytokine value at each time point was compared with pre-treatment baseline for each pt. The proportion of pts with decreasing cytokine value (relative to baseline) at each time point was calculated. If treatment schedule had no effect on cytokine levels, these proportions should fluctuate around 50% and show no trend over time. The sign-test was applied to check whether the calculated proportions were significantly different from 50%. A Student t-test was also implemented to corroborate the findings obtained with the sign test. For the latter test, a signed squared root transformation was preliminary applied to correct for skewness. Univariate and multivariate analysis showed a lack of prognostic value of these angiogenic cytokines while treatment modality was a significant factor for survival. A high proportion of pts experienced a decrease in plasma VEGF (around 70%) and IL-8 (around 60%) during the concurrent low-dose chemoRT treatment period (week 1 to week 7) but not with RT alone or with high-dose chemoRT. The decrease in VEGF was found statistically significant from week 1 through week 6. A decrease of VEGF from week 7 to week 9 was observed but did not reach significance, likely due to a lack of power with fewer observations at later time points. The decrease of VEGF extended to week 15 (6 weeks post-RT) with significance at week 11 (4 weeks post RT) and week 15 by the t-test. There was no significant decrease after week 19 (12 weeks post RT). No significant decrease in VEGF was found among pts of Group 1 (no concurrent chemotherapy) and 2 (concurrent full-dose chemoRT). The decrease in IL-8 with low-dose chemoRT did not reach statistical significance. There were no significant changes in bFGF in any of the three treatment groups using either the t- or the sign tests. In this cohort of pts, the pre-treatment and last values of VEGF, IL-8 and bFGF did not provide prognostic significance. Pts undergoing low-dose chemotherapy with concurrent RT had a statistically significant decrease of plasma VEGF. A similar pattern of decrease was observed for IL-8 but not reaching statistical significance, and there was no decrease of bFGF. The decrease of VEGF was seen not only during chemoRT period but also extended up to 6-12 weeks post RT. Such finding was not observed in radiation only group or with full-dose concurrent chemoRT group.