ANGIOGENESIS - AN INDICATOR OF METASTASIS IN NONSMALL CELL LUNG-CANCER INVADING THE THORACIC INLET

We have attempted to identify a biologic rationale for the local aggre ssiveness and late treatment failure of resected non-small cell lung c ancer involving the thoracic inlet. Tumor specimens from 28 patients w ho underwent a new transcervical approach were analyzed for the expres sion of tumor proliferative activity, suppressor-gene p53, intratumora l and peritumoral blood vessel invasion by tumor cells, the presence a nd degree of angiogenesis (induction of new capillaries and venules), and other biologic variables. Eighty-nine percent of the neoplasms wer e moderately or poorly differentiated, 89% expressed either an interme diate or high proliferative activity, 39% showed p53 aberrations, 71% exhibited induction of angiogenesis, and 39% had tumors that were posi tive for blood vessel invasion. With a median follow-up time of 3.5 ye ars (range, 8 to 145+ months), the overall projected 5-year survival w as 29% and the median disease-free interval was 23 months. Results of univariate and multivariate analysis of survival and the disease-free interval identified the degree of angiogenesis (density less than 1 ve rsus more than 1 and number of neovessels less than 6 versus more than 6) as the only independent and significant predictors of the disease- free interval. Patients whose tumor showed a density of angiogenesis o f 1 or greater and a number of neovessels of 6 or greater faced a sign ificantly (p = 0.0001) higher relative risk of suffering systemic recu rrence of their primary tumor than did their low-risk counterparts. Re sults demonstrate that angiogenesis significantly correlates with late treatment failure (metastasis), and this is acquired at a critical de nsity and number of vessels.