Value of intra-tumor heterogeneity evaluated by diffusion-weighted MRI for predicting pathological stages and therapeutic responses to chemoradiotherapy in lower rectal cancer

Aim: Diffusion-weighted MRI (DWI) has the potential to reveal intra-tumor structural heterogeneity consisting of stroma through an evaluation of uniformity on DWI. In present study, we examined the diagnostic value of intra-tumor heterogeneity evaluated by DWI in lower rectal cancer (LRC). Patients and Methods: A total of 172 LRC patients underwent radical surgery between 2009 and 2017. T1 tumors and cases without pre-operative MRI were excluded. Twenty-nine primary resection cases (PR) and 37 pre-operative chemoradiotherapy followed by radical surgery cases (pCRT) were targeted. Intra-tumor heterogeneity on DWI was quantified using a specific formula (HSD). Structural heterogeneity was objectively quantified by an image analysis of resected specimens using a digital microscope (HSP). The relationships between HSD and HSP, pathological factors, and tumor regression grades (TRG) of pCRT were evaluated. Results: The relationship between HSD and HSP was analyzed by a linear regression model in PR cases, revealing a positive correlation (R(2)=0.43). PR cases were divided into HSD-high and HSD-low according to the median. There were more pT3 or N(+) cases in HSD-high (p=0.038, 0.095). HSD before pCRT correlated with TRG (grade 1 versus 2/3) in pCRT cases (p=0.001). The diagnostic accuracy of HSD for predicting T and N stages and therapeutic grades was evaluated by cut-off values calculated using a ROC curve and revealed that each factor may be accurately diagnosed. Conclusion: Intra-tumor heterogeneity on DWI corresponded with stromal pathological heterogeneity. It is useful for predicting T3 or deeper tumor invasion, pathological N(+), and the therapeutic effects of pCRT.