Treatment response following combined capecitabine, oxaliplatin and radiation therapy monitored by diffusion weighted magnetic resonance imaging (DW-MRI) in a xenograft model

Background: Individualized cancer treatment requires prediction and early monitoring of response to therapy, and advanced MR techniques have evolved to promising tools for non-invasive response monitoring. Diffusion weighted magnetic resonance imaging (DW-MRI) provides in particular information about the microenvironment in tumour tissues and may thus be used in early monitoring of treatment response. Treatment induced necrosis and microvasculature damage will affect the apparent diffusion coefficient (ADC) measured DW-MRI. Several studies indicate that combined capecitabine, oxaliplatin and radiation therapy is an effective treatment of locally advanced rectal cancers. It has also been demonstrated that capecitabine and oxaliplatin both possess radiosensitizing properties. The aim of this study is to investigate whether the changes in ADC can predict tumor response following fractionated chemo-irradiation. Materials and Methods: Bilateral HT29 xenografts on the rear flank of athymic mice were treated with capecitabine (359 mg/kg/day) alone and fractionated irradiation (2 Gy x) or combined capecitabine and oxaliplatin (10 mg/kg) and fractionated irradiation. One group was kept as control. DWMR images were acquired prior to therapy and weekly for the 9 following weeks, and ADC values were calculated. Pre-treatment and changes in ADC were compared with tumour regrowth delay. Results: Increased ADC values were seen in all treated tumours, except those receiving capecitabine alone (p = 0.06), 11 days after onset of therapy (p