The effect of preoperative radiation therapy on glucose utilization and cell kinetics in patients with primary rectal carcinoma.

Abstract

Proliferating cells in neoplasms usually show rapid cell cycle times and high rates of glycolysis. Tumor glucose utilization (TuGluc), potential cell doubling time (Tpot), and the effect of radiotherapy (RT) were evaluated in patients with primary rectal carcinoma. 2-[18F]-fluoro-2-deoxy-glucose (18F-FDG) was administered and dynamic positron emission tomography (PET) performed to determine TuGluc. Cell kinetics were measured with flow cytometry after labeling with iodo-deoxy-uridine. Two groups of patients were investigated prospectively: 1) those patients undergoing surgery only and 2) those patients undergoing surgery after receiving 30 gray of RT. Twenty consecutive patients with a cT3-NX-M0 tumor and age > 50 years were selected and randomized. One patient was excluded because of unexpected liver metastases and another had incomplete data. At baseline, the TuGluc for Group 1 was 222+/-104 nmol/mL/minute (mean +/- 1 standard deviation), and was 215+/-126 nmol/mL/minute for Group 2 (P > 0.8). After RT TuGluc decreased to 77+/-39 nmol/mL/minute (P = 0.008). Tpot was 3.4+/-1.2 days for Group 1 and 2.6+/-2.0 days for Group 2 at baseline (P > 0.2). Two weeks after RT, Tpot slowed to 5.7+/-3.6 days (P = 0.04). A weak negative correlation (correlation coefficient = -0.36) was found between TuGluc and Tpot. After RT, the proportion of labeled cells had not changed from baseline levels (P > 0.2), suggesting undisturbed proliferation, but the DNA synthesis time had increased. The significant decrease of TuGluc indicated cell loss. Tumor FDG uptake and cell kinetics are not correlated strongly in rectal carcinoma. Preoperative RT results in an overall loss of tumor cells (tumor reduction) and an increase in Tpot, although proliferation of the viable cell fraction is maintained.