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

Abstract

To quantify cervix tumor response via weekly biopsies during therapy. 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. 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. "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.