Histogram analysis of diffusion-weighted magnetic resonance imaging as a biomarker to predict LNM in T3 stage rectal carcinoma

Background Preoperative identification of rectal cancer lymph node status is crucial for patient prognosis and treatment decisions. Rectal magnetic resonance imaging (MRI) plays an essential role in the preoperative staging of rectal cancer, but its ability to predict lymph node metastasis (LNM) is insufficient. This study explored the value of histogram features of primary lesions on multi-parametric MRI for predicting LNM of stage T3 rectal carcinoma. Methods We retrospectively analyzed 175 patients with stage T3 rectal cancer who underwent preoperative MRI, including diffusion-weighted imaging (DWI) before surgery. 62 patients were included in the LNM group, and 113 patients were included in the non-LNM group. Texture features were calculated from histograms derived from T2 weighted imaging (T2WI), DWI, ADC, and T2 maps. Stepwise logistic regression analysis was used to screen independent predictors of LNM from clinical features, imaging features, and histogram features. Predictive performance was evaluated by receiver operating characteristic (ROC) curve analysis. Finally, a nomogram was established for predicting the risk of LNM. Results The clinical, imaging and histogram features were analyzed by stepwise logistic regression. Preoperative carbohydrate antigen 199 level (p = 0.009), MRN stage (p < 0.001), T2WIKurtosis (p = 0.010), DWIMode (p = 0.038), DWICV (p = 0.038), and T2-mapP5 (p = 0.007) were independent predictors of LNM. These factors were combined to form the best predictive model. The model reached an area under the ROC curve (AUC) of 0.860, with a sensitivity of 72.8% and a specificity of 85.5%. Conclusion The histogram features on multi-parametric MRI of the primary tumor in rectal cancer were related to LN status, which is helpful for improving the ability to predict LNM of stage T3 rectal cancer.

Phase II trial of neoadjuvant mFOLFOX 6 with panitumumab (P) in T3 rectal cancer with clear mesorectal fascia (MRF) and KRAS, NRAS, BRAF, PI3KCA wild type (4WT). GEMCAD 1601 PIER trial.

3512 Background: Patients with advanced colorectal cancer with 4WT tumors achieve increased response rates with chemotherapy and anti-EGFR therapy as compared with chemotherapy alone. In clinically staged (c) T3 rectal cancer neoadjuvant oxaliplatin/fluoropyrimidine combination has shown to induce encouraging pathological complete response (pCR). We hypothesize that combining FOLFOX and P could improve outcomes in 4WT tumors. Methods: PIER was an investigator-initiated phase II, single-arm, multicentre clinical trial to evaluate the safety and efficacy of neoadjuvant mFOLFOX6 with P in pts < 75-y, with 4WT rectal cancer of the middle third staged as T3 by centrally-reviewed magnetic resonance imaging (MRI) and clear MRF, who were candidate for a R0 resection with sphincter preservation surgery. Pts received 6 cycles and underwent re-staging with MRI and sigmoidoscopy. Pts without progression underwent total mesorectal excision 4 weeks after the last cycle. Patients with progression were treated with pre-op chemoradiotherapy. The primary endpoint was pCR. The study followed a 2-Stage Simon’s MiniMax design (P0 of 16%, P1 of 35%, alpha and beta of 0.1). The target sample size was 35 patients and if 9 or more achieved a pCR, the results would be compatible with efficacy. We present primary and early secondary endpoints. Results: Between 9/2017 and 6/2020, 90 patients were screened (56 excluded; 42 were excluded due to mutations, 12 were excluded due to discrepancies with central review of radiology) of whom 34 were enrolled. In the ITT population a pCR was observed in 11 pts (32.3%; [95% CI 17.39-50.53]) and a near-complete pathological response (Mandard 1+2) was observed 17 pts (52.9%). Clinical complete or near complete response was achieved in 50% and there were no progressions. R0 resection rate and pathological circumferential resection margin neg- were 100%. Full compliance with induction was 88%. Neoadjuvant G3/4 toxicity occurred in 54% and was consistent with FOLFOX/P safety profile. G3/4 postoperative related toxicity was 19% with one reoperation. Conclusions: The study met the threshold for efficacy. mFOLFOX6 with P as neoadjuvant therapy can be effective and safe without unexpected toxicities in mrT3, clear MRF and 4WT rectal cancer and resulted in a higher rate of pCR compared with our previous series (GEMCAD 0801; The Oncologist 2014) in a similar molecular-unselected population. This study was funded by Amgen S.A. Clinical trial information: NCT03000374.

Diagnostic Value of Multi-Parameter MRI in Sub-Stage of T3 Rectal Cancer

The paper aims to explore the diagnostic value of multi-parameter MRI in sub-stage of T3 rectal cancer. According to the results of clear pathological evaluation, 52 patients were divided into T3I and T3II groups according to the maximum mesorectum depth of tumor infiltration. The χ2 test was used to compare the differences of the overall morphology index, morphological index of the extramural strips, type of time-signal intensity curve (TIC), and the location index of DWI diffusion-limited distribution between the two groups. The independent sample t was used to test and compare the differences in semi-quantitative parameters of DCE between the two lesion groups. The pathological results were used as the dependent variables, the indicators mentioned above with statistical differences were used as the independent variables, and a Logistic regression model was established to construct joint parameters and evaluate its diagnostic efficacy. The differences in the circumferential diameter of lesions and morphological index of extramural strips (p < 0.01), and DWI diffusion restricted distribution index (p < 0.01) of the two groups were statistically significant. The difference in the DCE semiquantitative parameter early enhancement ratio (EER) (p < 0.01) between the two groups. The maximum Youden index of a newly-constructed parameter diagnosis combination: circumferential diameter of lesions + extramural strips + distribution locations of limited diffusion on DWI + EER was 0.73, the area under receiver operating characteristic curve(ROC) was 0.887 and the diagnostic sensitivity and specificity were 85.24% and 87.34%. By making full use of multi-parameter information, combined with morphological index of extramural strips, circumferential diameter of lesions, EER and distribution locations of the diffusion-limited of DWI as evaluation indexes, it can provide a high diagnostic efficiency for the sub-stage of T3 rectal cancer.

Clinicopathologic Analysis of Lateral Margin Measured by Whole-Mount Section in T3 Rectal Cancer

Purpose: Total mesorectal excision is a standard technique for rectal cancer. The whole-mount section can encompass the entire specimen, so it is a more appropriate for measuring circumferential margin than conventional section. We analyzed the clinical characteristics and prognosis based on lateral margins (LMs) measured by whole-mount sections.Methods: Medical records of patients who were operated on for T3 rectal cancer from 2005 to 2015 were reviewed retrospectively. A total of 154 patients were included. The slides of the whole-mount sections were re-reviewed by a single pathologist.Results: We divided the groups according to the length of the LM (1 mm, 1.5 mm, and 2 mm). There was significantly frequent lymphovascular invasion and N state was higher when LM was short in all groups. There were more micrometastasis in group LM ≤1 mm (53.3% ≤1 mm vs. 26.6% >1 mm, P=0.039), but not in other groups. When looking at local recurrence alone, there was no significant difference between groups, but the 5-year local recurrence-free survival was significantly worse when LM ≤2 mm (P=0.050). In each analysis based on 1 mm and 1.5 mm, overall survival was worse when LM was short. In all groups, disease-specific survival was worse when LM was short.Conclusion: As previously known, securing a margin less than 1 mm negatively affects the prognosis. When LM was divided by 1.5 mm, there was a significant difference in overall survival. There was a significant difference in disease-specific survival when divided by 2 mm in T3 rectal cancer. However, further studies with more patients are necessary to secure the result.

Additional value of MRI-detected EMVI scoring system in rectal cancer: applicability in predicting synchronous metastasis

Introduction: Extramural vascular invasion (EMVI) has been recommended as an independent prognostic factor for poor overall survival rate in rectal cancer and can be used as a potential biomarker. Early prediction of prevalence of synchronous metastasis can elevate the disease-free survival rate. We aimed to evaluate the magnetic resonance imaging (MRI)–detected EMVI (mrEMVI) scoring system in predicting distant metastasis in T3 rectal cancer. Methods: Patients with postoperative histopathologically confirmed T3 rectal cancer without previous treatment from July 2014 to December 2015 were enrolled in this study. Two blinded radiologists evaluated mrEMVI status. mrEMVI was categorized as EMVI-positive or EMVI-negative in T2-weighted images using an mrEMVI scoring system. The results, along with other clinical characteristics (age, sex, tumor location, MRI-detected distance of mesorectal extension, lymphatic invasion, perineural invasion, mrEMVI score, and carcinoembryonic antigen [CEA]), were then correlated with synchronous metastases to determine the risk factors using univariate and multivariate analysis. Results: Of 180 patients, 38 were confirmed to be mrEMVI-positive, 142 mrEMVI-negative. There were 34 patients with synchronous metastasis, of whom 25 were mrEMVI-positive and 9 were mrEMVI-negative. Three factors were significantly associated with synchronous metastasis: mrEMVI ( p = 0.001; odds ratio = 8.665), histopathologic lymphatic invasion ( p = 0.001; odds ratio = 12.940), and preoperative CEA ( p = 0.026; odds ratio = 4.124). mrEMVI score 4 was more likely for synchronous metastasis ( p = 0.044; odds ratio = 9.429) than mrEMVI score 3 in rectal cancer. Conclusions: mrEMVI positivity is an independent risk factor for synchronous distant metastasis in rectal cancer. mrEMVI score 4 is a stronger risk factor for synchronous metastasis than mrEMVI score 3 in rectal cancer.