Prediction of Kirsten rat sarcoma (KRAS) mutation in rectal cancer with amide proton transfer-weighted magnetic resonance imaging.

Background: Kirsten rat sarcoma (KRAS) mutation drives resistance to anti-epidermal growth factor receptor (anti-EGFR)-targeted therapies in rectal cancer. Amide proton transfer-weighted magnetic resonance imaging (APTw MRI) might be a supplement to the evaluation of KRAS mutation because the APTw value can reflect mobile cellular protein content in vivo. This study aimed to determine whether APTw MRI could predict KRAS mutation in rectal cancer and compare this technique with diffusion-weighted imaging (DWI).

Methods: This retrospective study reviewed 153 consecutive patients with rectal cancer from April 2019 to June 2021 in our hospital. Among them, a total of 55 patients who did not undergo neoadjuvant chemoradiotherapy and underwent preoperative APTw MRI, DWI, and postoperative KRAS tests were included in this study. In two-dimensional APTw images, two radiologists manually delineated three regions of interest (ROIs) along tumor contour in the largest slice and the adjacent two slices of tumor respectively. The mean APTw value within a ROI was calculated, and the values of three ROIs were averaged for each patient. In consecutive DWI images, two radiologists depicted the ROIs of the whole lesion, and the mean apparent diffusion coefficient (ADC) was generated. The intraclass correlation coefficient (ICC), Shapiro-Wilk test and Student's t-test were used for statistical analyses. Receiver operating characteristic (ROC) curves were constructed for APTw and ADC values respectively, and the area under the curve (AUC) was used to evaluate the diagnostic performance for the prediction of KRAS mutation.

Results: Among these 55 patients, KRAS mutation occurred in 21 patients. The ICCs of two independent raters for APTw and ADC values were 0.937 [95% confidence interval (CI), 0.914-0.953] and 0.976 (95% CI, 0.959-0.986), respectively. ADC values did not show a statistically significant difference between the KRAS-mutant group and the wild type (WT) group (P=0.733). KRAS-mutant tumors exhibited a higher APTw value than WT tumors in patients with rectal non-mucinous adenocarcinoma (3.324%±0.685% vs. 2.230%±0.833%, P<0.001). The AUC of the APTw value was 0.827 (95% CI, 0.701-0.916), with a cutoff value of 2.4% (sensitivity, 95.2%; specificity, 55.9%).

Conclusions: DWI cannot differentiate mutant KRAS genes from WT genes in patients with rectal cancer, but APTw MRI has potential for evaluating KRAS mutation in rectal cancer. The APTw value had moderate diagnostic performance in the prediction of KRAS mutation with a high sensitivity but a low specificity. APTw MRI might be a promising supplement to KRAS genomic analysis in rectal cancer patients.