Early conformational changes at tumour bed and long term response after neoadjuvant therapy in locally-advanced rectal cancer

Objectives To evaluate how changes in tumour scar depth angle and thickness in the post-neoadjuvant period relate to long-term response in locally-advanced rectal cancer patients. Methods Informed consent was obtained from all patients and institutional review board approved this retrospective study. Sixty-nine consecutive locally-advanced rectal cancer patients who underwent neoadjuvant therapy and were selected for “Watch-and-Wait” were enrolled. Two radiologists, O1 and O2, blindly and independently reviewed the 1st and 2nd post-neoadjuvant therapy pelvic MRI T2-weighted images and recorded depth angle and thickness of the tumour scar. Value changes were calculated by simple subtraction (2nd-1st). Mann-Whitney U test was employed to assess for significant differences between sustained clinical complete responders (SCR), defined as patients with pathologic complete response or clinical complete response with a minimum follow-up of 1 year; and non-sustained complete responders (non-SCR). Interobserver agreement was estimated using intraclass correlation coefficient (ICC). Data on mrTRG, DWI and endoscopy at 1st and 2nd timepoints were retrieved for comparison. Results In SCR, depth angle change between 1st (med = 10 weeks after end of radiotherapy) and 2nd (med = 23 weeks after end of radiotherapy) timepoints was significantly different (O1:p = 0.004; O2:p = 0.010): the SCR group showed a depth angle reduction (O1:med=-4.45; O2:med=-2.35), whereas non-SCRs showed a depth angle increase (O1:med=+2.60; O2:med=+7.40). Also, at 2nd timepoint, SCR scars were significantly thinner both for O1 (p = 0.003; SCR:med = 7.05 mm; non-SCR:med = 9.4 mm) and O2 (p = 0.006; SCR:med = 6.45 mm; non-SCR:med = 8.2 mm). A depth angle increase >21o between 1st and 2nd timepoints and a scar thickness >10 mm at 2nd timepoint were not sensitive but were highly specific for a non-SCR (91/94 %) for both observers. Interobserver agreement was good for scar depth angle change (ICC = 0.65) and excellent for scar thickness at 2nd timepoint (ICC = 0.84). Of the retrieved data, only DWI at 2nd timepoint was discriminative (p = 0.043) providing a similar sensitivity (33 %) and a slightly lower specificity (87.5 %). Conclusion Tumour scar expansion >21° between 1st and 2nd post-neoadjuvancy MRI and a scar thickness >10 mm at 2nd post-neoadjuvancy MRI may consistently indicate a non-SCR with high specificity in locally-advanced rectal cancer patients.