Synopsis

DCE-MRI can noninvasively reveal the presence and the permeability of micro-capillaries by the kinetic analysis of the contrast concentration¹. It has been used in the studies for diagnosis, characterization of predictive prognostic factors, monitoring of treatment response, and evaluation of the efficacy of novel treatment developments^2-3. KRAS mutation has been well known as predictive markers of resistance to epidermal growth factor receptor-targeted antibodies, may be useful as molecular markers for the clinical prognosis of CRCs⁴. However, There a are few data about whether the DCE-MRI parameters would behave different characteristics in rectal cancers with different KRAS status.

Purpose

To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters (including semi-quantitative and quantitative parameters) characteristics and potential differences in rectal cancers with different KRAS status.

Methods

Sixty-three patients with histological diagnosis of rectal cancer were included in this study. All pelvis magnetic resonance imaging was performed in a 3.0T MR unit (Philips 3.0T Ingenia, Philips Medical System, The Netherlands) including DCE-MRI (40 dynamic phases) with two different flip angles (5 and 10 degrees, respectively) T1-FFE (fast field echo) sequences as a reference. Semi-quantitative DCE-MRI parameters were relative enhancement (RE), maximum enhancement (ME), maximum relative enhancement (MRE), time to peak (TTP), wash in rate (WIR), wash out rate (WOR) and BE (brevity of enhancement), whereas quantitative parameters were Ktrans [transfer constant between blood plasma and extravascular extracellular space (EES)], Kep (rate between EES and blood plasma), Ve (extravascular Volume fraction), Vp (plasma volume fraction). DCE-MRI parameters were automatically calculated after region of interest (ROI) being selected along the outline of tumor maximal dimension (axial view), meanwhile, relevant signal intensity (SI) time curves were obtained. Patients were stratified into two groups: KRAS wild-type and mutant by amplification refractory mutation system (ARMS) method[5]. The DCE-MRI parameters between KRAS wild-type and mutant groups were compared by using independent samples t test or Mann-Whitney U test; Receiver operating characteristic(ROC) curve analysis was performed to evaluate the potential of DCE-MRI parameters for discriminating rectal cancer with different KRAS status. Interobserver agreements were evaluated using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. P＜0.05 was considered to indicate a statistically significant difference.

Results

There were 48 males and 15 females with a median age of 59.9 years (range, 26-85 years). According to pathological results, 63 patients were divided into 33 KRAS wild-type and 30 KRAS mutant patients. Interobserver reproducibility for DCE-MRI semi-quantitative and quantitative parameters was good to excellent (ICC=0.7695-0.9905, ICC=0.7826-0.9488, respectively; narrow with of 95% limits of agreement). Semi-quantitative parameters (Table 1): ME and WIR values were significantly higher in KRAS mutant group than those in wild-type group (P = 0.001, P = 0.009, respectively), whereas TTP values showed the different trend between two groups (p<0.001). However, no statistic differences were observed for other semi-quantitative parameters (including RE, MRE, WOR and BE) in different KRAS status. Quantitative parameters (Table 1): Ktrans and Vp both demonstrated higher values in KRAS mutant group than in wild-type group (p<0.001, p<0.001, respectively). Meanwhile, Kep and Ve values also showed a similar trend in patients with different KRAS status, however, no significantly statistic differences were found. According to ROC curve, ME, WIR, TTP, Ktrans and Vp values showed diagnostic significance with the AUC values(Table 2) of 0.743, 0.707, 0.822, 0.816 and 0.773, respectively. The cutoff values for TTP and Ktrans were 88.9 ( ≤88.9; sensitivity 90%, specificity 69.70% ), 1.11 ( >1.11; sensitivity 90%, specificity 60.61% ), respectively.

Conclusion

DCE-MRI parameters (including semi-quantitative and quantitative parameters) especially TTP and Ktrans, demonstrated different characteristics in rectal cancers with different KRAS status, potentially reflecting the possible KRAS status of rectal cancer.

Acknowledgements

No acknowledgement found.