Extramural Depth Research Articles

The importance of preoperative T3 stage substaging by 3D endorectal ultrasonography for the prognosis of middle and low rectal cancer.

The study aimed to validate the role of 3D-endorectal ultrasonography in prognosis and recurrence for patients with T3-stage rectal cancer by evaluating the preoperative extramural depth of tumor invasion. In this study, we investigated the medical records of rectal cancer patients who were admitted to Changhai Hospital's Colorectal Surgery Division. The sample group was categorized into three subgroups (T3a, T3b, and T3c) based on the extent of tumor progression (<5 mm, 5-10 mm, and >10 mm) to assess the endorectal ultrasonography diagnostic performance. The 5-year disease-free survival and overall survival were assessed using the Kaplan-Meier method and a log rank test. Cox regression analysis verified the tumor invasion depth's significance as a prognostic predictor, and it was also utilized to evaluate other independent risk variables for recurrence after surgery. The study included 72 individuals with low and middle rectal cancer from January 2014 to November 2019. Twenty-two individuals had stage T3a, 22 had stage T3b, and 28 had stage T3c based on preoperative endorectal ultrasonography. Endorectal ultrasonography had 88.0%, 86.8%, and 76.2% overall accuracy for stratifying subgroups, respectively. According to the Kaplan-Meier curve, 5-year OS was 100%, 83.5%, and 92.9% for T3a, T3b, and T3c (p = 0.172), and 5-year disease-free survival was 100%, 80.8%, and 72.9% for T3a, T3b, and T3c, respectively (p = 0.014). A distinct risk factor for 5-year disease-free survival was the degree of tumor infiltration (p = 0.039). Preoperative T3 stage subdivision allows for categorization of prognosis and survival. Endorectal ultrasonography reports should make explicit declarations of T3a, T3b, and T3c scales.

Predictive value of infiltrating tumor border configuration of rectal cancer on MRI

BackgroundInfiltrating tumor border configuration (iTBC) is assessed by postoperative pathological examination, thus, is not helpful for preoperative treatment strategies. The study aimed to detect iTBC by magnetic resonance imaging (MRI) and evaluate its predictive value.Materials and methodsA total of 153 patients with rectal cancer were retrospectively analyzed. Clinicopathological and MRI data mainly including tumor border configuration (TBC) on MRI, MRI-detected extramural vascular invasion (MEMVI), tumor length, tumor growth pattern, maximal extramural depth, pathology-proven lymph node metastasis (PLN) and pathology-proven extramural vascular invasion (PEMVI) were analyzed. The correlation of MRI factors with PEMVI and PLN was analyzed by univariate and multivariate logistic regression analyses. The nomograms were established based on multivariate logistic regression analysis and were confirmed by Bootstrap self-sampling. The receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to evaluate the diagnostic efficiency.ResultsFifty cases of PEMVI and 48 cases of PLN were found. Forty cases of PEMVI and 34 cases of PLN in 62 cases of iTBC were also found. iTBC, MEMVI and maximal extramural depth were significantly associated with PEMVI and PLN (P < 0.05). iTBC (odds ratio = 3.84 and 3.02) and MEMVI (odds ratio = 7.27 and 3.22) were independent risk factors for PEMVI and PLN. The C-indices of the two nomograms for predicting PEMVI and PLN were 0.863 and 0.752, respectively. The calibration curves and ROC curves of the two nomograms showed that the correlation between the predicted and the actual incidence of PEMVI and PLN was good. The AUCs of iTBC for predicting PEMVI and PLN were 0.793 (95% CI: 0.714–0.872) and 0.721 (95% CI: 0.632–0.810), respectively. The DeLong test showed that the predictive efficiency of the nomogram in predicting PEMVI was better than that of iTBC (P = 0.0009) and MEMVI (P = 0.0095).ConclusioniTBC and MEMVI are risk factors for PEMVI and pelvic lymph node metastasis. The nomograms based on iTBC show a good performance in predicting PEMVI and pelvic lymph node metastasis, possessing a certain clinical reference value.Trial registrationThis study was approved by the Ethics Committee of Beijing Friendship Hospital, and individual consent was waived for this retrospective analysis.

Predictive value of lesion morphology in rectal cancer based on MRI before surgery

ObjectiveTo explore the relationship of MRI morphology of primary rectal cancer with extramural vascular invasion (EMVI), metastasis and local recurrence.Materials and methodsThis retrospective study included 153 patients with rectal cancer. Imaging factors and histopathological index including nodular projection (NP), cord sign (CS) at primary tumor margin, irregular nodules (IN) of mesorectum, MRI-detected peritoneal reflection invasion (PRI), range of rectal wall invasion (RRWI), patterns and length of tumor growth, maximal extramural depth (EMD), histologically confirmed local node involvement (hLN), MRI T stage, MRI N stage, MRI-detected extramural vascular invasion (mEMVI) and histologically confirmed extramural vascular invasion (hEMVI) were evaluated. Determining the relationship between imaging factors and hEMVI, synchronous metastasis and local recurrence by univariate analysis and multivariable logistic regression, and a nomogram validated internally via Bootstrap self-sampling was constructed based on the latter.ResultsThirty-eight cases of hEMVI, fourteen cases of synchronous metastasis and ten cases of local recurrence were observed among 52 NP cases. There were 50 cases of mEMVI with moderate consistency with hEMVI (Kappa = 0.614). NP, CS, EMD and mEMVI showed statistically significant differences in the negative and positive groups of hEMVI, synchronous metastasis, and local recurrence. Compared to patients with local mass growth, the rectal tumor with circular infiltration had been found to be at higher risk of synchronous metastasis and local recurrence (P < 0.05). NP and IN remained as significant predictors for hEMVI, and mEMVI was a predictor for synchronous metastasis, while PRI and mEMVI were predictors for local recurrences. The nomogram for predicting hEMVI demonstrated a C-index of 0.868, sensitivity of 86.0%, specificity of 79.6%, and accuracy of 81.7%.ConclusionNP, CS, IN, large EMD, mEMVI, and circular infiltration are significantly associated with several adverse prognostic indicators. The nomogram based on NP has good predictive performance for preoperative EMVI. mEMVI is a risk factor for synchronous metastasis. PRI and mEMVI are risk factors for local recurrence.

Identifying Tumor Deposits in Patients with Locally Advanced Rectal Cancer: Using Multiplanar High-Resolution T2WI.

The prognosis of postoperative tumor deposits (TDs) is worse than positive lymph node metastases alone. To detect TDs by using multiplanar high-resolution T2-weighted imaging (HRT2WI). This retrospective study enrolled 130 patients with locally advanced rectal cancer (LARC). Using pathology-proven tumor deposits (pTDs) as the gold standard, all patients were divided into the pTDs-negative and pTDs-positive groups, the correlation of clinicopathological factors and image features [such as MRI-detected tumor deposits (mTDs), MRI-detected metastatic lymph node (mLN), MRI-detected extramural vascular invasion (mEMVI), maximal extramural depth (EMD), etc.] with pTDs were analyzed by univariate analysis and multivariate binary logistic regression analysis, and the nomogram was established based on the latter. The diagnostic efficiency was evaluated by the receiver operating characteristic curve (ROC) analysis and area under curve (AUC). mTDs, mLN, mEMVI, and EMD were significantly different between the pTDs-positive and pTDs-negative groups (P < 0.05), with the AUC of 0.767, 0.746, 0.664 and 0.644, respectively. mTDs and mLN were independent risk factors for pTDs (odds ratio: 5.74 and 3.90, P < 0.05). The AUC, sensitivity, specificity, negative predictive value, and accuracy of the nomogram were 0.814 (95% CI: 0.720 ~ 0.908), 73.9%, 79.4%, 93.4%, and 78.5%, respectively. Seventeen of 23 patients with pTDs were identified as mTDs, with a moderate agreement between pTDs and mTDs (Kappa=0.419). Multiplanar HRT2WI can be used as a preoperative diagnostic tool to identify TDs in LARC. The combined model constructed by mTDs and mLN shows a good diagnostic performance for TDs.

Predictive value of MRI-detected tumor deposits in locally advanced rectal cancer.

Although tumor deposits (TDs) are not the same as lymph nodes, the prognosis of patients with TDs is similar or worse than that of patients with metastatic lymph nodes. TDs are mostly assessed by the histology of samples after surgery, thus, not helpful for preoperative treatment strategies. The primary objective of this study was to detect TDs by MRI and evaluate its predictive value. A total of 114 patients with rectal cancer were retrospectively analyzed. Clinicopathological and MRI data mainly including MRI- detected TDs (mTDs), tumor border configuration (TBC) on MRI, MRI-detected extramural vascular invasion (mEMVI), MRI-detected lymph node metastasis (mLN), MRI T stage, MRI N stage, the range of rectal wall involved by the tumor, peritoneal reflection invasion, tumor length, tumor location, cord sign at the tumor edge, nodular protrusion at the tumor edge, maximal extramural depth and pathology-proven lymph node involvement (pLN) were evaluated. The correlation of MRI factors with postoperative distant metastasis (PDM) and pLN were analyzed by univariate analysis and multivariate logistic regression analysis, and nomograms were established based on the latter. The diagnostic efficiency was evaluated by the receiver operating characteristic curve (ROC) and area under the curve (AUC). A total of 38 cases of pLN, 13 of PDM and 17 of pathology-proven TDs (pTDs) were found. Ten cases of PDM and 22 cases of pLN in 30 mTDs cases were also found. Chi-square test showed that mTDs, mLN, TBC, mEMVI, MRI T stage, nodular protrusion, cord sign, maximal extramural depth and peritoneal reflection invasion were correlated with PDM and pLN (P<0.05). mTDs and peritoneal reflection invasion were independent risk factors for PDM (odds ratio: 10.15 and 8.77, P<0.05), mTDs and mLN were independent risk factors for pLN (odds ratio: 5.50 and 5.91, P<0.05), and Hosmer-Lemeshow test showed that the results of two models were not statistically significant, suggesting that the fit was good. On this basis, two nomograms for predicting PDM and pLN were confirmed by Bootstrap self-sampling, and the C-indices of the two nomograms were 0.837 and 0.817, respectively. The calibration curves and ROC curves of the two nomograms showed that the correlation between the predicted and the actual incidence of PDM and pLN was good. The DeLong test showed that the predictive efficiency of the nomogram in predicting pLN was better than that of mLN (P=0.0129). mTDs are a risk factor for PDM and lymph node metastasis. The two nomograms based on mTDs showed a good performance in predicting PDM and lymph node metastasis, possessing a certain clinical value.

Diagnostic Performance of Rectal CT for Staging Rectal Cancer: Comparison with Rectal MRI and Histopathology.

To compare the diagnostic performance of rectal CT with that of high-resolution rectal MRI and histopathology in assessing rectal cancer. Sixty-seven patients with rectal cancer who underwent rectal CT with rectal distension using sonographic gel and high-resolution MRI were enrolled in this study. The distance from the anal verge/anorectal junction, distance to the mesorectal fascia (MRF), extramural depth (EMD), extramesorectal lymph node (LN) involvement, extramural venous invasion (EMVI), and T/N stages in rectal CT/MRI were analyzed by two gastrointestinal radiologists. The CT findings of 20 patients who underwent radical surgery without concurrent chemoradiotherapy were compared using histopathology. Interclass correlations and kappa statistics were used. The distance from the anal verge/anorectal junction showed an excellent intraclass correlation between CT and MRI for both reviewers. For EMD, the distance to the MRF, presence of LNs, extramesorectal LN metastasis, EMVI, T stage, and intermodality kappa or weighted kappa values between CT and MRI showed excellent agreement. Among the 20 patients who underwent radical surgery, T staging, circumferential resection margin involvement, EMVI, and LN metastasis on rectal CT showed acceptable concordance rates with histopathology. Dedicated rectal CT may be on par with rectal MRI in providing critical information to patients with rectal cancer.

NEOPRISM-CRC: Neoadjuvant pembrolizumab stratified to tumor mutation burden for high-risk stage 2 or stage 3 deficient-MMR/MSI-high colorectal cancer.

TPS3645 Background: The prognostic advantage of early stage deficient-MMR/MSI-High CRC is lost after relapse, so there is a pressing clinical need to maximize the chance of cure in the early stages where prevalence of dMMR is higher comprising approximately 12% of Stage 3 and 20% of Stage 2 CRC. The efficacy of adjuvant checkpoint inhibition in this patient group has yet to be demonstrated in the context of micrometastatic disease without a supporting immune-competent microenvironment. Longitudinal studies especially in the neoadjuvant setting would optimally interrogate post-immunotherapy changes both in time and space. The NEOPRISM-CRC (NEOadjuvant PembRolizumab In Stratified Medicine – ColoReCtal) study is a Phase II Trial to determine whether neoadjuvant Pembrolizumab stratified to tumour mutation burden (TMB) is efficacious and safe. It will also be a platform to explore the relationships between possible predictive novel biomarkers and response to Pembrolizumab in blood, tumour tissue and microbiome. Methods: The study population consists of subjects with newly diagnosed operable dMMR/MSI-H CRC. Patients must be fit and eligible for planned curative surgery based on a) radiological node positive T1-4 CRC or b) high risk T3 defined as EITHER ≥ 5mm of extramural depth of invasion or unequivocal EMVI on imaging (regardless of depth), or T4 disease. They will receive one of two pre-operative regimens depending upon their TMB based on the FoundationOne®CDx test (FM1CDx). All patients will have one 21 day cycle of Pembrolizumab 200 mg IV. Prior to cycle 2 and with the result of the FM1CDx test, patients will continue their treatment as follows: A) TMB-high (defined as ≥20 mutations per Mb) or TMB-medium (defined as 6-19 mutations per Mb), or MSI-H on PCR if FM1CDx test is not evaluable: A further 2 cycles of Pembrolizumab 200 mg IV every 21 days. B) TMB-low (defined as ≤5 mutations per Mb), or if FM1CDx and PCR tests are not evaluable: No further Pembrolizumab given. Surgery to remove the CRC will be performed 4-6 weeks after the last dose of Pembrolizumab in both arms. Following resection patients may receive adjuvant chemotherapy in accordance with local institutional guidelines. The primary end point is pathological complete response rate (pCR). Secondary endpoints include 3 year RFS, OS, safety and health-related quality of life. Up to 32 patients will be registered over a 18-24 month period assuming that the pCR with 3 cycles of Pembrolizumab will be ≥ 33% for patients with high or medium TMB based on the FM1CDx profile, and intend to rule out a percentage ≤10%. To reach 80% power with 5% statistical significance, 19 patients are required in the high/medium TMB arm. The trial will be considered a success if at least 5/19 patients have a pCR after 3 cycles of Pembrolizumab. Enrolment will commence in March 2022. Clinical trial information: NCT05197322.

Percentage of Tumor Invasion at Pretreatment High-Resolution Magnetic Resonance Imaging: Associating With Aggressive and Tumor Response in Chinese T3 Rectal Cancer-Preliminary Results.

PurposeThe purpose of the study was to assess the ability of percentage of tumor invasion (PTI) of T3 rectal cancer on pretreatment MRI as an imaging biomarker to reflect aggressiveness and to predict tumor response after neoadjuvant chemoradiation (NCRT) in Chinese population.MethodsA total of 107 Chinese rectal cancer patients who underwent pretreatment MRI staging as T3 were included. The extramural depth of tumor invasion (EMD), the distance between outer border of muscularis propria (MP) and mesorectal fascia (MRF) we called “thickness of the mesorectum (TM)”) at the same slice and direction were measured at pretreatment MRI, and PTI was equal to EMD/TM, was calculated. The EMD and PTI of subgroups based on pretreatment CEA, CA19-9 levels; N category and pathological complete response (pCR) were compared. The parameters, which described tumor invasion, were compared between pCR and non-pCR group. Student t-tests and logistic analysis were applied.ResultsThe pretreatment PTI was higher in CEA ≥5.2 ng/ml patients (58.52% ± 27.68%) than in CEA <5.2 ng/ml patients (47.27% ± 24.15%) (p = 0.034). The pretreatment EMD in non-pCR group (7.21 ± 2.85 mm) was higher than in pCR group (6.14 ± 3.56 mm) (p = 0.049). The pretreatment PTI in non-pCR group (57.4% ± 26.4%) was higher than in pCR group (47.3% ± 29.1%) (p = 0.041). Compared with patients with PTI ≥50%, MRF (+), more patients with PTI <50%, MRF (−) showed pCR (OR = 8.44, p = 0.005; OR = 6.32, p = 0.024).ConclusionThe PTI obtained at pretreatment MRI may serve as an imaging biomarker to reflect tumor aggressiveness and predict which T3 rectal cancer patients may benefit from NCRT in Chinese population.

Study of Correlation between MRI Morphology of Primary Tumor and Extramural Vascular Invasion in Rectal Cancer

Introduction. In clinical settings, nodular projection (NP) and cord sign (CS) at the tumor edge and irregular nodules (IN) in the mesorectum often appeared together with extramural vascular invasion (EMVI). We aim to evaluate the diagnostic efficiency of the MRI morphology of primary tumor in predicting EMVI in patients with rectal cancer (RC). Methods. This retrospective study included 156 patients with RC. Clinical and imaging factors including NP at the primary tumor’s edge, CS at the primary tumor’s edge, maximal extramural depth (EMD), IN in the mesorectum, growth pattern, tumor length, range of rectal wall invaded (RRWI) by tumor, peritoneal reflex invasion by surgery, and pathology-proven local node involvement (PLN) were evaluated. Then, ROC curve was drawn to depict the meaningful indicators in multivariate analyses. Results. There were 53 (34%) patients with pathological extramural venous invasion (pEMVI). Among the clinical and imaging factors evaluated, NP, CS, IN, EMD, PLN, differentiation, and peritoneal reflex invasion were significantly associated with pEMVI. NP and PLN were independent predictors of EMVI. Areas under the ROC curve (AUC) of NP for prediction of EMVI was 0.82 (95% CI, 0.74–0.90), with a sensitivity of 73.58%, a specificity of 90.29%, a positive predictive value (PPV) of 75.59%, a negative predictive value (NPV) of 86.92%, and an accuracy of 84.62%, respectively. Conclusions. Patients with primary tumor with EMVI usually showed NP and CS. NP was an independent predictor of EMVI and helpful for the diagnosis of EMVI in RC patients.

Diagnosis of Nonperitonealized Colorectal Cancer with Computerized Tomography Image Features under Deep Learning.

This study aimed to explore the value of abdominal computerized tomography (CT) three-dimensional reconstruction using the dense residual single-axis super-resolution algorithm in the diagnosis of nonperitonealized colorectal cancer (CC). 103 patients with nonperitonealized CC (the lesion was located in the ascending colon or descending colon) were taken as the research subjects. The imagological tumor (T) staging, the extramural depth (EMD) of the cancer tissues, and the extramural vascular invasion (EMVI) grading were analyzed. A dense residual single-axis super-resolution network model was also constructed for enhancing CT images. It was found that the CT images processed using the algorithm were clear, and the peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) were 33.828 dB and 0.856, respectively. In the imagological T staging of CC patients, there were 17 cases in the T3 stage and 68 cases in the T4 stage. With the EMD increasing, the preoperative carcinoembryonic antigen (CEA) highly increased, and the difference was statistically significant (P < 0.05). The postoperative hospital stays of patients were also different with different grades of EMVI. The hospital stay of grade 1 patients (19.45 days) was much longer than that of grade 2 patients (13.19 days), grade 3 patients (15.36 days), and grade 4 patients (14.36 days); the differences were of statistical significance (P < 0.05). It was suggested that CT images under the deep learning algorithm had a high clinical value in the evaluation of T staging, EMD, and EMVI for the diagnosis of CC.

Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review and meta-analysis.

There is increasing evidence to support the use of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). However, its safety, efficacy and side effect profile is yet to be completely elucidated. This review aims to assess NAC regimens, duration, compare completion rates, intra-operative and post-operative complication profiles and oncological outcomes, in order to provide guidance for clinical practice and further research. PubMed, EMBASE and MEDLINE were searched for a systematic review of the literature from 2000 to 2020. Eight eligible studies were included, with a total of 1213 patients, 752 (62%) of whom received NAC. Of the eight studies analysed, two were randomised controlled trials comparing neoadjuvant chemotherapy followed by oncological resection to upfront surgery and adjuvant chemotherapy, three were prospective single-arm phase II trials analysing neoadjuvant chemotherapy followed by surgery only, one was a retrospective study comparing neoadjuvant chemotherapy followed by surgery versus surgery first followed by adjuvant chemotherapy and the remaining two were single-arm retrospective studies of neoadjuvant chemotherapy followed by surgery. All cases of LACC were determined and staged by computed tomography; majority of the studies defined LACC as T3 with extramural depth of 5 mm or more, T4 and/or nodal positivity. NAC administered was either folinic acid, fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) with the exception of one study which utilised 5-fluorouracil and mitomycin. Most studies had NAC completion rates of above 83% with two notable exceptions being Zhou et al. and The Colorectal Cancer Chemotherapy Study Group of Japan who both recorded a completion rate of 52%. Time to surgery from completion of NAC ranged on average from 16 to 31 days. The anastomotic leak rate in the NAC group ranged from 0 to 4.5%, with no cases of postoperative mortality. The R0 resection rate in the NAC group was 96.1%. Meta-analysis of both RCTs included in this study showed that neoadjuvant chemotherapy increased the likelihood of a negative resection margin T3/4 advanced colon cancer (pooled relative risk of 0.47 with a 95% confidence interval) with no increase in adverse consequence of anastomotic leak, wound infection or return to theatre. Our systematic review and meta-analysis show that NAC is safe with an acceptable side effect profile in the management of LACC. The current data supports an oncological benefit for tumour downstaging and increased in R0 resection rate.

Clinical Relevance and Practical Approach for Challenging Rectal Cancer MRI Findings

MRI is the standard of care for clinical staging of rectal cancer, but has limitations. The purpose of this review is to describe and simplify the clinical relevance of common challenging findings on rectal cancer MRI, and to outline a practical approach to these findings for radiologists. Recent literature regarding T2 versus T3 stages, extramural depth of invasion, circumferential resection margin/mesorectal fascia involvement, anal sphincter involvement, anterior peritoneal reflection involvement, extramural vascular invasion, and lymph node involvement are reviewed. These findings are structured by the surgical implications, oncological implications, and prognostic implications, with a practical approach summary for each finding. The clinical implications of common challenging rectal cancer MRI findings are summarized with up-to-date supporting evidence and useful suggestions for practicing radiologists.

Pharmacokinetically-guided preoperative FOLFOX chemotherapy for locally advanced colon cancer patients.

4104 Background: Preliminary results from ongoing randomised trials suggest that neoadjuvant chemotherapy (NAC) may be an alternative approach to conventional adjuvant therapy. We assessed the feasibility and activity of incorporating a pharmacokinetically (PK) guided dose adjustment of 5-FU within preoperative Folfox. Methods: Radiologically staged LACC pts, T4 or T3 with extramural depth &gt;5mm beyond the muscularis propia, were planned to receive 4-6 biweekly cycles of Oxalipatin (85mg/m²), Leucovorin (400 mg/m²), bolus 5-FU (400 mg/m2) and infusional 5-FU (initial dose of 2400mg/m² in 46h and subsequent cycles tailored according to PK monitoring in order to reach a target 5-FU area under the curve (AUC) between 20-30 mg∙h∙L-1). Dihidrouracil deshidrogenase was determined before the first cycle in order to detect pts with 5-Fu intolerance. Three serum samples were obtained during the 5-Fu infusion in the first two cycles. Pathological tumor regression was graded according to the MSKCC classification and toxicity to the NCI-CTCAE 4.0. Results: From June 2012 to August 2017, 45 pts (M/F: 35/10; median age 63) with LACC (T3: 66.7%; T4: 31.1%; T2: 2.2%; N+:66.6%) were evaluated. Median dose of 5-FU was 4500 mg. 48.9% of the pts required a 5-FU dose increase to reach the target AUC. Side effects profile included G3 neutropenia (3 pts), G2 diarrhea (2 pts) and G2 asthenia (9 pts). NAC was discontinued in 3 pts due to small bowell obstruction requiring surgery (no progressive disease during NAC). R0 resection rate was 100% (93.3% laparoscopy-assited). MSKCC score included grades 4, 3+ and 3 in 11.1%, 26.7% and 28.9% of pts, respectively. A complete pathological response was found in 5 pts (11.1%). Median number of harvested nodes was 16 (7-51), 80% ypN0. Those pts with AUC 25-30 had a 3-fold higher likelihood of achieving a MSKCC 3, 3+ and 4 responses. Median time to hospital discharge was 7 days (range 4-22). After a median follow-up of 60 months (44-66), 5-year actuarial PFS is 88.8%. Conclusions: Preoperative PK-adjusted FOLFOX in LACC pts is safe and well tolerated, achieving remarkable rates of major pathological responses and R0 resections.

Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With “Good Prognosis” Rectal Cancer Eligible for Primary Surgery

Chemoradiotherapy (CRT), followed by surgery, is the recommended approach for stage II and III rectal cancer. While CRT decreases the risk of local recurrence, it does not improve survival and leads to poorer functional outcomes than surgery alone. Therefore, new approaches to better select patients for CRT are important. To conduct a phase 2 study to evaluate the safety and feasibility of using magnetic resonance imaging (MRI) criteria to select patients with "good prognosis" rectal tumors for primary surgery. Prospective nonrandomized phase 2 study at 12 high-volume colorectal surgery centers across Canada. From September 30, 2014, to October 21, 2016, a total of 82 patients were recruited for the study. Participants were patients newly diagnosed as having rectal cancer with MRI-predicted good prognosis rectal cancer. The MRI criteria for good prognosis tumors included distance to the mesorectal fascia greater than 1 mm; definite T2, T2/early T3, or definite T3 with less than 5 mm of extramural depth of invasion; and absent or equivocal extramural venous invasion. Patients with rectal cancer with MRI-predicted good prognosis tumors underwent primary surgery. The primary outcome was the proportion of patients with a positive circumferential resection margin (CRM) rate. Assuming a 10% baseline probability of a positive CRM, a sample size of 75 was estimated to yield a 95% CI of ±6.7%. Eighty-two patients (74% male) participated in the study. The median age at the time of surgery was 66 years (range, 37-89 years). Based on MRI, most tumors were midrectal (65% [n = 53]), T2/early T3 (60% [n = 49]), with no suspicious lymph nodes (63% [n = 52]). On final pathology, 91% (n = 75) of tumors were T2 or greater, 29% (n = 24) were node positive, and 59% (n = 48) were stage II or III. The positive CRM rate was 4 of 82 (4.9%; 95% CI, 0.2%-9.6%). The use of MRI criteria to select patients with good prognosis rectal cancer for primary surgery results in a low rate of positive CRM and suggests that CRT may not be necessary for all patients with stage II and III rectal cancer. ISRCTN.com identifier: ISRCTN05107772.

Selection of Patients With Rectal Cancer for Preoperative Chemoradiotherapy: Are T Category and Nodal Status All That Matters?

Although the accuracy of preoperative MRI staging has been established on follow-up histopathologic examination, the reproducibility of MRI staging has been evaluated in studies with expert radiologists reading a large sample of MRI images and therefore is not generalizable to the real-world setting. The purpose of this study was to evaluate the interrater reliability of MRI for distance to the mesorectal fascia, T category, mesorectal lymph node status, and extramural depth of invasion for preoperative staging of primary rectal cancer. This was a prospective, cross-sectional survey. The study was conducted in Ontario, Canada. Participants included GI radiologists. Participants read 5 preselected staging MRIs using a synoptic report and participated in an educational Webinar. Distance to the mesorectal fascia, T category, extramural depth of invasion, and mesorectal lymph node status for each MRI were abstracted. Data were analyzed in aggregate using percentage of agreement, Fleiss κ, and interclass correlation coefficients to assess interrater reliability. Reliability was highest for distance to the mesorectal fascia with an intraclass correlation of 0.58 (95% CI, 0.27-0.80). Kappa scores for T category, mesorectal lymph node status, and extramural depth of invasion were 0.38 (95% CI, 0.23-0.46), 0.41 (95% CI, 0.32-0.49), and 0.37 (95% CI, 0.16-0.82). There was no difference when radiologists were stratified by experience or volume. Scores may have been affected by MRI selection, because they were chosen to demonstrate diagnostic challenges for the Webinar and did not reflect a representative sample. Interrater reliability was highest for distance to mesorectal fascia, and therefore, it may be a more reliable criterion than T category, extramural depth of invasion, or mesorectal lymph node status. Combined with the fact that an uninvolved mesorectal fascia is more consistent with the overall goal of rectal cancer surgery, it should be considered as an important MRI criterion for preoperative treatment decision making in the real-world setting. See Video Abstract at http://links.lww.com/DCR/A763.

Low- Versus High-Risk Rectal Cancer Based on MRI Features: Outcomes in Patients Treated Without Neoadjuvant Chemoradiotherapy

The objective of this study was to compare the prognoses of patients with low- and high-risk rectal cancer detected by MRI who were treated without neoadjuvant chemoradiotherapy (NCRT) and to determine independent risk factors. This retrospective study included 185 patients with pathologically proven rectal adenocarcinoma who were treated without NCRT. Cancer was defined as high risk if one or more of the following factors were present: extramural depth of tumor invasion greater than 5 mm or stage T4a or T4b for tumor in the mid or high rectum; involvement of intersphincteric space, levators, or adjacent organs for tumor in the low rectum; extramural venous invasion (EMVI); or circumferential resection margin (CRM) involvement. Patients without any of those risk factors were placed in the low-risk group. The Kaplan-Meier method and Cox proportional hazards regression model were used to compare the survival outcomes between the two groups and to investigate the univariate and multivariate influences of the risk factors. Cancer was deemed to be low risk in 65 (35.1%) patients and high risk in 120 (64.9%) patients. The two patient groups had statistically significant differences in 3-year actuarial overall survival (OS; 100% vs 88.3%, p = 0.0044), disease-free survival (DFS; 92.3% vs 60.0%, p < 0.0001), and local recurrence (LR; 1.5% vs 10.0%, p = 0.0297). CRM involvement was identified as an independent risk factor for OS (hazard ratio [HR], 4.78; 95% CI, 1.24-18.45), DFS (HR, 2.44; 95% CI, 1.24-4.81), and LR (HR, 3.92; 95% CI, 1.07-14.41). Moreover, EMVI was identified as an independent risk factor for DFS (HR, 2.46; 95% CI, 1.28-4.74). The LR and long-term survival of patients in the low-risk group were more favorable than those of patients in the high-risk group. EMVI and CRM status were independent risk factors.

Prognostic Value of Diffusion MR Imaging and Clinical-Pathologic Factors in Patients with Rectal Cancer

Background: Apparent diffusion coefficient (ADC) value measured from diffusion-weighted magnetic resonance (MR) images are highly correlated with pathological T or N stage, tumor differentiation grade, and extramural depth of tumor in patients with rectal cancer. Objectives: To assess the prognostic value of diffusion MR imaging and clinical-pathologic risk factors in patients with rectal cancer. Patients and Methods: This retrospective study was approved by our institutional review board and written informed consent was waived. Sixty-one consecutive patients with rectal cancer (41 men and 20 women; mean age, 64.5 ± 12.1 years; range, 32 - 86 years) underwent pelvic MR imaging. Tumor ADC value and clinical-pathologic risk factors were tested as possible risk factors for postoperative local recurrence or distant metastasis (LRDM) as well as disease-free survival outcome. Results: Of 62 tumors, 12 (19.4%) had postoperative LRDM (median follow-up 38.5 months). Plasmatic CA19-9 level (P = 0.0027), pathological N stage (P = 0.0018), lymphatic invasion (P < 0.0001), and tumor ADC value (P = 0.0076) were independently associated with postoperative LDRM. High plasmatic CA19-9 level (≥ 37 U/mL) (P = 0.010), ly2 (P = 0.020), ly3 (P < 0.0001), pathological N2 (P = 0.006), and low tumor ADC value (< 0.996 × 10-3 mm2/sec) (P = 0.0026) were associated with reduced disease-free survival. Conclusion: Preoperative tumor ADC and plasmatic CA19-9 were significantly associated with postoperative LRDM and disease-free survival in rectal cancer.

T3 subclassification using the EMD/mesorectum ratio predicts neoadjuvant chemoradiation outcome in T3 rectal cancer patients.

To evaluate the feasibility of the EMD (extramural depth)/mesorectum ratio as a marker for T3 rectal cancer and its ability to predict tumour response to neoadjuvant chemoradiation and survival. From 2010 to 2016, 284 T3 rectal cancer patients who underwent high resolution MRI before neoadjuvant chemoradiation were enrolled. The EMD was defined as the distance from the outer edge of the muscularis propria to the outermost edge of the tumour. The measurement of the tumour EMD and mesorectum was in the same layer and their ratio was calculated. Receiver operating characteristic analysis and relative area under the curve statistics were used to choose the cut-off value. The association of the EMD/mesorectum ratio and other MRI or clinical factors with the tumour regression grade (TRG) was analysed. Cox regression analysis was used to estimate independent risk factors for disease-free survival (DFS) and overall survival (OS). The mean EMD/mesorectum ratio was 0.47 ± 0.3. We chose an EMD/mesorectum ratio of 0.5 in further analyses after receiver operating characteristic analysis. Of 284 patients, 177 (62.3%) had an EMD/mesorectum ratio≤0.5. Patients with an EMD/mesorectum ratio≤0.5 had a higher TRG 0-1 rate than patients with a ratio>0.5 (53.1% vs 36.4%, p = 0.006). A multivariate analysis identified that an EMD/mesorectum ratio>0.5 [hazardratio(HR) 2.020; p = 0.028] and ypTNM II-III (HR 3.550; p = 0.017) were independent prognostic factors to indicate decreased DFS. For OS, only patients with TRG 2-3 had decreased OS compared with patients with TRG 0-1 (HR 2.959; p = 0.035). When the EMD/mesorectum ratio was applied to categorize T3 rectal cancer patients, the ratio of 0.5 can be used as a cut-off value for T3 rectal cancer. Patients with a ratio≤0.5 had a higher response rate and better DFS. However, further validation is needed in a larger sample of patients. Advances in knowledge: The EMD/mesorectum ratio may serve to predict tumour response to neoadjuvant chemoradiation and survival in T3 rectal cancer patients.

JOURNAL CLUB: Preoperative MRI Evaluation of Primary Rectal Cancer: Intrasubject Comparison With and Without Rectal Distention.

The aim of this study was to determine whether rectal distention influences the accuracy of MRI for tumor staging and for measuring of maximal extramural depth of tumor spread and distance between tumor and mesorectal fascia (MRF). Fifty patients with rectal carcinoma underwent MRI before and after rectal distention. Both sets of MR images were reviewed by two radiologists. The scores for depiction of the mass (1-4 scale), T and N category, distance from normal rectal wall to MRF, maximal extramural depth of tumor spread, and distance between tumor and MRF were evaluated. The visualization scores on MR images obtained with the rectum distended were significantly higher than those on images obtained without distention (90% vs 58% for score 4, p < 0.001). The accuracy of T category assessed on distended images was slightly higher than the accuracy on nondistended images (88.6% vs 84.1% for observer 1, 84.1% vs 81.8% for observer 2), but the accuracy of N category was stable. The distance between normal rectal wall and MRF was significantly less on distended images than on nondistended images (p < 0.05). However, there was no significant difference between nondistended and distended images for maximal extramural depth and distance between tumor and MRF (p > 0.05). Rectal distention significantly improved visualization of tumors on MR images. It also improved T category assessment to some extent. Although the distance between normal rectal wall and MRF was significantly less with rectal distention than without rectal distention, maximal extramural depth and the distance between tumor and MRF did not vary significantly with or without rectal distention.

Diagnostic performance of MRI for prediction of candidates for local excision of rectal cancer (ypT0-1N0) after neoadjuvant chemoradiation therapy.

To evaluate the diagnostic performance of rectal MRI in predicting candidates for local excision (LE; ypT0-1N0) after neoadjuvant chemoradiation therapy (CRT) in patients with rectal cancer. The institutional review board approved our retrospective study and waived informed consent. Inclusion criteria were as follows: patients with pathologically confirmed mid to lower rectal cancer (cT3NxM0 before neoadjuvant CRT) who underwent neoadjuvant CRT and had MRI performed at 3T before and after neoadjuvant CRT. A total of 168 patients met the study criteria between 2011 and 2012. Two observers independently assessed tumor and nodal stages on MR images obtained after neoadjuvant CRT. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying a candidate for LE (ypT0-1N0) were calculated. Interobserver agreement was assessed with kappa value. Predictive factors for ypT0-1N0 were evaluated by logistic regression models. MRI had relatively high accuracy, specificity, and NPV (85.9%, 93.8%, and 88.9% for observer 1 and 85.3%, 96.1%, and 86.6% for observer 2), moderate PPV (71.4% and 76.2%), and relatively low sensitivity (57.1% and 45.7%) for predicting ypT0-1N0. The interobserver agreement was fair (kappa value = 0.593). Carcinoembryonic antigen levels after neoadjuvant CRT and the maximal extramural depth of tumor spread were significant predictors of ypT0-1N0 (P = 0.037 and 0.017, respectively). MRI after neoadjuvant CRT can predict a candidate for LE (ypT0-1N0) after neoadjuvant CRT with moderate PPV and relatively high NPV. J. Magn. Reson. Imaging 2016;44:471-477.