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 >21^º 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.