J Cancer 2020; 11(1):168-176. doi:10.7150/jca.38354 This issue

Research Paper

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

Michihiro Kudou1, Masayoshi Nakanishi1✉, Yoshiaki Kuriu1, Yasutoshi Murayama1, Tomohiro Arita1, Mitsuo Kishimoto2, Eiichi Konishi2, Mariko Goto3, Kei Yamada3, Eigo Otsuji1

1. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan;
2. Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan;
3. Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

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Citation:
Kudou M, Nakanishi M, Kuriu Y, Murayama Y, Arita T, Kishimoto M, Konishi E, Goto M, Yamada K, Otsuji E. Value of intra-tumor heterogeneity evaluated by diffusion-weighted MRI for predicting pathological stages and therapeutic responses to chemoradiotherapy in lower rectal cancer. J Cancer 2020; 11(1):168-176. doi:10.7150/jca.38354. Available from https://www.jcancer.org/v11p0168.htm

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Abstract

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 (R2=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.

Keywords: rectal cancer, chemoradiotherapy, magnetic resonance imaging, diffusion-weighted image, radiomics.