Introduction

Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) has become a standard treatment in patients with locally advanced rectal cancer (LARC) [1], which could decrease loco-regional recurrence rate and even increase overall survival. After nCRT, approximately 15%-27% of LARC patients would achieve a complete pathologic response (pCR) [2, 3]. These patients will have a favourable long-term outcome with excellent local control and disease-free survival. Moreover, Maas and Intven M found that patients with a pCR had an excellent long-term outcome regardless of surgical resection.Accordingly, with the introduction of organ-sparing treatments in rectal cancer there is an increasing need for reliable selection methods to select pCR and non-pCR to after CRT. Therefore, the purpose of the present study was to evaluate the utility of IVIM-DWI in discriminating the pathological response to nCRT for LARC patients.

Methods

This prospective single-center study was approved by the Medical Ethics Committee in our institution. Firty-two patients with LARC underwent preoperative IVIM-DWI examination at baseline (pre-nCRT) and 8 weeks after the end of nCRT (post-nCRT). A total of 12 b values (0, 10, 20, 30, 50, 80,100, 150, 200, 400, 600 and 800 s/mm2) were applied with a single-shot diffusion weighted spin-echo echo-planar (ssSE-DW-EPI) sequence. After surgery, the patients were divided into the complete response (pCR) (TRG 4) and non-complete response (non-pCR) (TRG 0,1,2 or 3) groups, and into the good response (GR) (TRG 3 or 4) and the poor response (PR) (TRG 0,1 and 2) groups, according to the Dworak tumor regression grade (TRG) system. The pre-nCRT and post-nCRT IVIM-derived metrics (ADC,D,D* and f), together with their changes (∆metrics) induced by nCRT, were compared between the pCR and non-pCR groups and between the GR and PR groups. The diagnostic efficacy of the IVIM-DWI parameters was determined by using receiver-operating characteristic curve (ROC) analysis. Correlations between TRG score and the IVIM-DWI parametric values were also analyzed.

Results

After nCRT, the ADC and D values for LARC increased significantly (all P<0.05). TRG score revelled positive correlation with pref (r=0.357, P=0.020), postD (r=0.551, P=0.000) and ∆%D (r =0.605, P=0.000). The IVIM-DWI parametric values for the pCR (n=10), non-pCR (n=32), GR (n=15) and PR (n=27) groups are summarized in Table 1. The preD*, pref, postD, ∆%ADC and ∆%D values demonstrated significant differences between the pCR and non-pCR groups, whereas the postD, ∆%ADC and ∆%D values showed obvious differences between the GR and PR groups (Figures 1) .Figures 4 and Figures 5 show representative images of LARC from different pathological response groups.Based on ROC curve analysis, the diagnostic performance of the IVIM-DWI parameters in identifying pathological response are showed in Figures 2 and Figures 3. For discriminating pCR from non-pCR, ∆%D had the highest area under the curve (AUC) (0.881), sensitivity (90.0%) and positive predictive value (95.9%) among the five IVIM-DWI parameters. The AUC value of ∆%D was significantly higher than that of ∆%ADC in discriminating the pCR from non-pCR groups (P=0.009). Among the three IVIM-DWI parameters which were helpful in distinguishing the good from poor responders, postD had the highest specificity (100%) and positive predictive value (100%) with an AUC of 0.790, whereas ∆%D had the highest sensitivity (93.3%) and negative predictive value (94.1%) with an AUC of 0.807.

Discussion and Conclusion

The present study found that CRT causes obvious changes in the diffusion-related parameters (ADC and D) values in LARC. The increase of diffusion-related parametric values may reflect the reduction of cellularity due to necrosis and apoptosis as treatment effect of CRT[4]. TRG score demonstrated obviously positive correlations with the post-CRT diffusion-related parametric value (postD and ∆%D), suggesting that the diffusion- related microenvironment in LARC after CRT has significant relevance to the status of tumor residual. This suggestion was also supported by our observation that there were obviously higher postD and ∆%D values for the pCR（versus non-pCR）and GR（versus PR）.The preD* and pref for the pCR group were significantly higher than those for the non-pCR group. Additionally, TRG score reveled positive correlation with pref in this study. These findings indicate higher baseline perfusion might result in better sensitivity to nCRT for LARC. Higher preD* and pref values represent higher vascularization, perfusion and oxygenation level in tissues, which would lead to better therapeutic response to nCRT. Moreover, higher vascularization and perfusion can result in better delivery of chemotherapeutics into tumor tissue [5].In conclusion, the present study demonstrates that IVIM-DWI is potentially useful in discriminating pathological response to nCRT for LARC patients.

Acknowledgements

No acknowledgement found.

References

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