Predicting response to treatment in human cancers of the uterine cervix: Sequential biopsies during external beam radiotherapy

Purpose: To quantify cervix tumor response via weekly biopsies during therapy. Methods and Materials: Pretreatment and subsequent weekly biopsies (when feasible) were obtained during radical external beam radiotherapy, reduced to single-cell suspensions, and assessed for DNA content by flow cytometry. Results: Data for 41 patients ranging from FIGO Stage Ib to IIIb and with follow-up >100 days are presented. No clinically significant complications due to the weekly biopsies were noted. The actuarial progression-free survival at 2 years was 68%, with initial pelvic progression observed in 3 patients. The biopsies showed (1) Increased tumor cell proliferation was evident even for the earliest on-treatment samples; (2) Sustained cell yields, coupled with high proliferation 2 or more weeks into treatment, were associated with early failure; and (3) Therapy often "selected" for cell subpopulations that were only minor components of the pretreatment biopsy. Conclusions: "Accelerated repopulation" began surprisingly rapidly in cervix tumors after the initiation of chemoradiotherapy, and patients with a sustained cell yield and S-phase fraction 2 or more weeks into therapy were at increased risk for tumor progression. Although clearly implicating tumor (re)growth kinetics as a factor in outcome, the sequential biopsy data also suggested interplay between growth potential and in situ sensitivity to treatment. (C) 2004 Elsevier Inc.