ASTRO RESEARCH FELLOWSHIP - APOPTOSIS AS A PREDICTOR OF TUMOR RESPONSE TO RADIATION IN STAGE IB CERVICAL-CARCINOMA

Purpose: Levels of apoptosis predict for tumor responsiveness to radia tion in various animal systems. To investigate the potential role of a poptosis as a predictor of response in human tumors, a retrospective r eview was undertaken of patients with adenocarcinoma of the cervix who se primary lesion at presentation measured at least 4 cm and who under went definitive radiation therapy. A previous report had indicated tha t roughly half this group of patients should have a long-term relapse free survival. Methods and Materials: Pretreatment biopsy specimens of 44 patients with Stage IB adenocarcinoma of the cervix, whose primary lesion at presentation measured at least 4 cm in greatest dimension, were scored for apoptosis by two independent investigators without kno wledge of the treatment outcome, and the results were averaged, Actuar ial methods were used to assess overall survival, disease-free surviva l, determinate survival, and local control as a function of the baseli ne level of apoptosis. Patients ranged in age from 21 to 87 years and were treated with definitive radiotherapy between 1964 and 1989. Follo w-up for the surviving patients ranged from 1 to 278 months, with a me an of 101 months.. Results: Patients whose tumors had a baseline level of apoptosis above the median value (2%) had a better overall surviva l than those with lower levels of apoptosis (p = 0.056). A similar tre nd for disease-free survival (p = 0.32) and determinate survival (p = 0.27) did not reach statistical significance, perhaps because of the s mall number of patients. Because only 6 of the 44 patients (13%) had a local tumor failure, it was not possible to establish a correlation b etween the pretreatment level of apoptosis and the Local tumor control by radiation. Conclusion: The baseline level of apoptosis predicted f or survival in patients with Stage IB cervical adenocarcinoma, Further investigation of the measurement of apoptosis as a potential predicti ve assay is warranted in other human tumor systems.