Early Changes in Apparent Diffusion Coefficient Predict the Quantitative Antitumoral Activity of Capecitabine, Oxaliplatin, and Irradiation in HT29 Xenografts in Athymic Nude Mice

Abstract

PURPOSE: The purpose of this study was to evaluate the possible use of changes in apparent diffusion coefficient (ADC) measured by magnetic resonance imaging for pretreatment prediction and early detection of tumor response in a mouse model during fractionated chemoradiotherapy. MATERIALS AND METHODS: Athymic mice with bilateral HT29 xenografts on rear flanks were allocated into three groups: control, capecitabine, and capecitabine and oxaliplatin. The left flanks of the mice Received daily irradiation. T2 and diffusion images were acquired before therapy and weekly for the following 9 weeks. Pretreatment and changes in ADC were calculated and compared with tumor doubling growth delay. RESULTS: No correlations between pretreatment ADC and changes in tumor volumes after therapy were seen. All treated tumors, except those receiving capecitabine (P = .06), showed increased mean tumor ADC values 11 days after initialization of therapy (P < .05) before returning to pretreatment values within 5 days posttherapy (day 18 after onset of therapy). This increase in mean tumor ADC showed a strong positive correlation (r = 0.92, P < .01) with mean tumor doubling growth delay. CONCLUSIONS: Pretreatment ADC values did not predict the effectiveness of therapy, whereas early changes in mean ADC quantitatively correlated with treatment outcome.

Keywords

• Apparent diffusion coefficient
• HT29
• oxaliplatin
• capecitabine
• prediction of therapy response