Response reassessment

Reassessment tools of response were applied, including clinical examination and symptoms inquiry, DRE, endoscopy, endoscopic biopsy, MRI, PET-CT, and laboratory assays including AFP, CEA, CA199, CA72.4, CA242, CA125, NSE. The tools for evaluation were planned when the nCRT was ended based on multi-disciplinary treatment (MDT) discussion. At least three different reassessment tools were applied to reassess patient response to nCRT. In our practice, definition of rectum follows the international Delphi consensus, and it was considered as the upper rectal boundary when the point of the sigmoid take-off was visualized on imaging [22]. The dentate line was considered as the surgical definition of lower rectal boundary. All the patients were diagnosed using endoscopy and pathological confirmation from biopsy, and the distance from the to the lower edge of the tumor to anus was measured and used in our analysis.

Based on the reassessment results, specific therapeutic regimen was decided and developed in the MDT meeting. MRI with T2WI, DWI and DCE were performed with a 3.0 T scanner in our center. There were perspective reports with written records including endoscopy, pathology, MRI, examination, which were further verified by specialists and MDT discussions. cCR, near-cCR, or non-cCR had been assigned during the treatment period, and further quantified in this study. The quantified score was introduced to divide the reassessment reports level, based on previous studies by Maas [10, 12], Habr-Gama [23], MSKRS [24], and ESMO [25], in addition to being designed based on our practice and other research [26]. In addition, the ulcer, irregularity and other related abnormality in reassessment tools of endoscopy were considered potentially non-CR instead of near-cCR. “Normal,” “alleviated,” and “unalleviated” symptoms after nCRT were respectively assigned with 0, 1, 2. Similarly, in the reassessment results of the DRE, “the tumor negative,” “nodularity or abnormity,” and “nodularity with blood” were respectively assigned to 0, 1, 2. In general, a variety of intricate results were simplified into three level and quantified with “0,” “1,” “2,” representing “cCR,” “near-cCR or possible non-cCR,” “non-cCR” respectively. The score details are shown in Table ​Table2,2, and the definition of cCR or near-cCR was determined by following per under the score in Table ​Table3.3. Time interval to reassessment (TTR) after the end of nCRT was recorded, including time to clinical examination (TTC), time to DRE (TTD), time to endoscopy (TTE), time to biopsy (TTB), time to MRI (TTM), and time to laboratory biomarker assay (TTA). A time interval > 4 weeks was recommended, and the chosen time was mainly influenced by appointments in line. The schematic overview is shown in Fig. 2.

Reassessment results quantified assignment

DRE digital rectal examination, mriCR MRI predicted complete response, near-mriCR MRI predicted near complete response, non-mriCR MRI predicted not complete response

The performance of complete response prediction in reassessment tools combinations

Youden Index = Sensitivity + Specificity-1. The theoretical range of the Youden Index is from -1 to 1, and the practical range in use is often from 0 to 1. Index with negative values were reasonable and indicated it was unsuitable or even misleading for practice as reassessment tool

The schematic overview. The locally advanced rectal cancer patients received routine multimodal therapy consisting of assessment, nCRT, response reassessment, surgery or wait-and-watch. The patients with predictive cCR were recommended to accept wait-and-watch strategy. Reassessment tools of response includes MRI, endoscopy, biopsy, clinical symptom, DRE, assay of blood. Abbreviation: nCRT: neoadjuvant chemoradiation; TTM: time to MRI; TTE: time to endoscopy; TTB: time to biopsy; TTC: time to clinical symptom; TTD: time to digital rectal examination; TTA: time to assay of blood; TTS: time to surgery