Max J. Lahaye

Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial.

AIM OF THE STUDY In patients from the Dutch TME trial patterns of local recurrence (LR) in rectal cancer were studied. The purpose was to reconstruct the most likely mechanisms of LR and the effect of preoperative radiotherapy. METHODS 1417 patients were analyzed; 713 were randomized into preoperative radiotherapy and total mesorectal excision (RT + TME), 704 into TME alone. Of the 114 patients with LR, the subsites of LR were determined and related to tumor and treatment factors. RESULTS Overall 5-year LR-rate was 4.6% in the RT + TME group and 11.0% in the TME group. Presacral local recurrences occurred most in both groups. Radiotherapy reduced anastomotic LR significantly, except when after low anterior resection (LAR) distal margins were less than 5 mm. Abdominoperineal resection (APR) mainly resulted in presacral LR. Even after resection with a negative circumferential resection margin, LR-rates were high. Thirty percent of the patients had advanced tumors, which resulted in 58% of all LRs. Lateral LR comprised 20% of all LR. Presacral and lateral LR resulted in a poor prognosis, in contrast to anterior or anastomotic LRs with a relatively good prognosis. CONCLUSIONS RT reduces LR in all subsites and is especially effective in preventing anastomotic LR after LAR. APR-surgery mainly results in presacral LR, which may be prevented by a wider resection. In the TME trial many advanced tumors were included, rather requiring chemoradiotherapy instead of RT. Currently, with good imaging techniques, better selection can take place. Especially lateral LR might be a problem in the future.

USPIO-enhanced MR Imaging for Nodal Staging in Patients with Primary Rectal Cancer: Predictive Criteria

PURPOSE To prospectively determine diagnostic performance of predictive criteria for nodal staging with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging in primary rectal cancer patients, with histopathologic findings as reference standard. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Twenty-eight rectal cancer patients (18 men, 10 women; mean age, 68 years) underwent USPIO-enhanced MR. Two observers with different experience evaluated each node on three-dimensional T2*-weighted images for border irregularity, short- and long-axis diameter, and estimated percentage (<30%, 30%-50%, or >50%) of white region within the node. Ratio of measured surface area of white region within the node to measured surface area of total node (ratio(A)) was calculated. Signal intensity (SI) of gluteus muscle (SI(GM)), total node (SI(TN)), and white (SI(WR)) and dark (SI(DR)) regions within the node were used to calculate SI(TN)/SI(GM) and SI(WR)/SI(DR) ratios. Lesion-by-lesion, receiver operating characteristic curve, and interobserver agreement analyses were performed. The most accurate and practical criterion was evaluated by observer 3. RESULTS In 28 patients, 236 lymph nodes were examined. Area under the receiver operating characteristic curve (AUC) of estimated percentage of white region and ratio(A) were 0.96 and 0.99 (observer 1) and 0.95 and 0.97 (observer 2), respectively. AUC of estimated percentage criterion for observer 3 was 0.96. AUC of border, short- and long-axis diameter, and SI(TN)/SI(GM) and SI(WR)/SI(DR) ratios were 0.65, 0.75, 0.79, 0.85, and 0.75 (observer 1) and 0.58, 0.75, 0.79, 0.89, and 0.79 (observer 2), respectively. Interobserver agreement (kappa value) for estimated white region between observers 1 and 2, 1 and 3, and 2 and 3 were 0.77, 0.79, and 0.84, respectively. For observers 1 and 2, kappa value for border was 0.28. For observers 1 and 2, intraclass correlation coefficient for short- and long-axis diameters, ratio(A), and SI(TN)/SI(GM) and SI(WR)/SI(DR) ratios were 0.91, 0.96, 0.91, 0.72, and 0.92, respectively. CONCLUSION Estimated percentage of white region and measured ratio(A) are the most accurate criteria for predicting malignant nodes with USPIO-enhanced MR imaging; the first criterion is the most practical.

Locally advanced rectal cancer: MR imaging for restaging after neoadjuvant radiation therapy with concomitant chemotherapy. Part I. Are we able to predict tumor confined to the rectal wall?

PURPOSE To retrospectively assess accuracy of magnetic resonance (MR) imaging after radiation therapy with concomitant chemotherapy for downsizing of the primary lesion to ypT0-2 tumor confined to rectal wall in locally advanced rectal cancer, with histopathologic findings as reference standard, and to evaluate additional value of volumetric analysis. MATERIALS AND METHODS The institutional review board approved the study and waived informed consent. Sixty-seven patients met criteria of the study. T2-weighted MR images obtained before and after radiation therapy with concomitant chemotherapy were assessed for tumor stage by expert abdominal radiologist, colorectal surgeon, and general radiologist. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated; tumor volume was measured (compared with Mann-Whitney U test). Findings were correlated with histopathologic findings. RESULTS Sixty-seven patients (38 men, 29 women; mean age, 63 years) who underwent radiation therapy with concomitant chemotherapy and surgery (all but one) were evaluated. The PPV for prediction of tumor confined to rectal wall (ypT0-2) was 91% (10 of 11), 86% (six of seven), and 88% (seven of eight) for expert abdominal radiologist, surgeon, and general radiologist, respectively. In 24 patients, sensitivity was 42% (10), 25% (six), and 29% (seven). ypT0-2 tumors had significantly smaller volumes than did ypT3-4 tumors before radiation therapy with concomitant chemotherapy (55 vs 92 cm(3), P = .038). Volume reduction rates were significantly higher in ypT0-2 than in ypT3-4 tumors (89% vs 61%, P < .001). If volume before radiation therapy with concomitant chemotherapy was 50 cm(3) or smaller and volume reduction rate was 75% or higher, excised tumor was always confined to rectal wall (ypT0-2). By using these criteria, 43% (six of 14) of cases with overstaging could have been predicted to be ypT0-2 tumors correctly. CONCLUSION Downsizing to ypT0-2 tumors can be accurately predicted by combining morphologic tumor staging predictions with results from volumetric analyses. MR images obtained after radiation therapy with concomitant chemotherapy might be helpful in more individualized treatment planning.

Accuracy of Gadofosveset-enhanced MRI for Nodal Staging and Restaging in Rectal Cancer

Objective:To prospectively assess the accuracy of gadofosveset-enhanced magnetic resonance imaging (MRI) for nodal staging and restaging in rectal cancer. Background:Accurate preoperative assessment of nodal disease in rectal cancer impacts treatment management. Staging with modern imaging techniques (computed tomography, MRI and endorectal ultrasound) is insufficiently accurate for clinical decision making. This study aims to assess the accuracy of MRI using a novel lymph node magnetic resonance contrast, gadofosveset, for nodal staging and restaging in rectal cancer using a per node comparison with histology as the reference standard. Methods:Sixty-eight patients underwent gadofosveset-enhanced MRI at 1.5T. Twenty-six patients (primary staging group I) were treated with total mesorectal excision (with or without preoperative 5 × 5 Gy) and 42 (restaging group II) underwent a long course of chemoradiation followed by a restaging MRI and resection. Nodes were scored as benign or malignant by 2 radiologists (experienced and junior reader) first on standard MRI, then on gadofosveset-enhanced MRI. For group I the primary staging MRI was compared with histology. In group II the second, restaging MRI was compared with histology. Results:For the experienced reader, sensitivity, specificity, and area under the ROC-curve (AUC) improved from 76%, 82% and 0.84 on standard MRI to 80%, 97% and 0.96 on gadofosveset-MRI (P < 0.001). For the junior reader results improved from 69%, 85%, and 0.85 on standard MRI to 70%, 95%, and 0.93 on gadofosveset-MRI (P = 0.03). Interobserver agreement was good on both standard MRI (&kgr; 0.73) and gadofosveset-MRI (&kgr; 0.71). Conclusions:This study shows high reproducibility and significantly improved accuracy compared to standard MRI for gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer.

Locally advanced rectal cancer: MR imaging for restaging after neoadjuvant radiation therapy with concomitant chemotherapy. Part II. What are the criteria to predict involved lymph nodes?

PURPOSE To prospectively determine diagnostic performance of predictive criteria for nodal restaging after radiation therapy with concomitant chemotherapy by using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging in patients with rectal cancer. MATERIALS AND METHODS After institutional review board approval and informed consent were obtained, 39 patients (24 men, 15 women; mean age, 64 years) with rectal cancer underwent USPIO-enhanced two-dimensional (2D) T2-weighted fast spin-echo, three-dimensional (3D) T1-weighted gradient-echo, and 3D T2*-weighted MR for restaging. Two observers evaluated nodes for border irregularity, short- and long-axis diameters, and estimated percentage of white region (<30%, 30%-50%, or >50%) within the node (3D T2*-weighted images). Ratio of the measured surface area of the white region within the black node to the measured surface area of the total node (Ratio(A)) was calculated. Signal intensity (SI) in gluteus muscle (SI(GM)) and in total node (SI(TN)) were used to calculate SI(TN)/SI(GM) ratio. Histopathologic findings were reference standard. Receiver operating characteristic (ROC) curves were compared and interobserver agreement was determined. RESULTS Lesion-by-lesion analysis was feasible in 201 lymph nodes. Area under the ROC curve (AUC) of border and short- and long-axis diameters for observer 1 were 0.85, 0.87, and 0.88 and for observer 2 were 0.70, 0.89, and 0.87, respectively. AUC for estimated percentage of white region within the node, Ratio(A), and SI(TN)/SI(GM) ratio for observer 1 were 0.98, 0.99, and 0.62 and for observer 2 were 0.97, 0.98, and 0.65, respectively. AUC for USPIO-enhanced MR criteria was significantly better than AUC for conventional MR criteria (P < .01). All criteria except border irregularity and SI(TN)/SI(GM) ratio showed high interobserver agreement (kappa > 0.79). CONCLUSION The most reliable predictors for identifying benign nodes after radiation therapy with concomitant chemotherapy by using USPIO-enhanced MR imaging for restaging in patients with rectal cancer were estimated percentage of white region within the node and Ratio(A). Measurements on standard 2D T2-weighted fast spin-echo images versus primary staging results offer reasonably good accuracy to identify benign lymph nodes after therapy.

Mri After Chemoradiotherapy of Rectal Cancer: A Useful Tool to Select Patients for Local Excision

PURPOSE: If identification of good responders to neoadjuvant chemoradiotherapy in rectal cancer is possible, there might be opportunities for local excision in selected patients. The aim of this study was to determine whether postchemoradiation MRI in rectal cancer can accurately identify ypT0 to 2/ypN0, because both features are essential for identification of good responders. METHODS: Seventy-nine patients (4 hospitals) underwent postchemoradiation MRI, 62 received a lymph node-specific contrast agent (ultrasmall superparamagnetic iron oxide). An expert and general radiologist prospectively predicted whether the tumor penetrated the mesorectal fat and whether nodes were sterilized after chemoradiation. Histology was the reference standard. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: For prediction of whether a tumor penetrated the bowel wall, there was an negative predictive value of 0.90 and 0.76 for the expert and general radiologist, respectively. The negative predictive value for prediction of nodal status was 0.95 and 0.85 for expert and general radiologist, respectively. CONCLUSION: This prospective multicenter study demonstrates that MRI with a lymph node-specific contrast agent interpreted by an expert radiologist can select ypT0 to 2/ypN0 rectal cancer with low risk of undetected nodal metastases or invasion through the bowel wall. These patients could thus have been selected for local excision. However, future studies will have to prove equal outcome of such a modified surgical approach compared with current practice.

Mandatory imaging cuts costs and reduces the rate of unnecessary surgeries in the diagnostic work-up of patients suspected of having appendicitis

AbstractObjectiveTo evaluate whether mandatory imaging is an effective strategy in suspected appendicitis for reducing unnecessary surgery and costs.MethodsIn 2010, guidelines were implemented in The Netherlands recommending the mandatory use of preoperative imaging to confirm/refute clinically suspected appendicitis. This retrospective study included 1,556 consecutive patients with clinically suspected appendicitis in 2008–2009 (756 patients/group I) and 2011–2012 (800 patients/group II). Imaging use (none/US/CT and/or MRI) was recorded. Additional parameters were: complications, medical costs, surgical and histopathological findings. The primary study endpoint was the number of unnecessary surgeries before and after guideline implementation.ResultsAfter clinical examination by a surgeon, 509/756 patients in group I and 540/800 patients in group II were still suspected of having appendicitis. In group I, 58.5% received preoperative imaging (42% US/12.8% CT/3.7% both), compared with 98.7% after the guidelines (61.6% US/4.4% CT/ 32.6% both). The percentage of unnecessary surgeries before the guidelines was 22.9%. After implementation, it dropped significantly to 6.2% (p<0.001). The surgical complication rate dropped from 19.9% to 14.2%. The average cost-per-patient decreased by 594 € from 2,482 to 1,888 € (CL:−1081; −143).ConclusionIncreased use of imaging in the diagnostic work-up of patients with clinically suspected appendicitis reduced the rate of negative appendectomies, surgical complications and costs.Key Points• The 2010 Dutch guidelines recommend mandatory imaging in the work-up of appendicitis. • This led to a considerable increase in the use of preoperative imaging. • Mandatory imaging led to reduction in unnecessary surgeries and surgical complications. • Use of mandatory imaging seems to reduce health care costs.

Deep Learning for Fully-Automated Localization and Segmentation of Rectal Cancer on Multiparametric MR

Multiparametric Magnetic Resonance Imaging (MRI) can provide detailed information of the physical characteristics of rectum tumours. Several investigations suggest that volumetric analyses on anatomical and functional MRI contain clinically valuable information. However, manual delineation of tumours is a time consuming procedure, as it requires a high level of expertise. Here, we evaluate deep learning methods for automatic localization and segmentation of rectal cancers on multiparametric MR imaging. MRI scans (1.5T, T2-weighted, and DWI) of 140 patients with locally advanced rectal cancer were included in our analysis, equally divided between discovery and validation datasets. Two expert radiologists segmented each tumor. A convolutional neural network (CNN) was trained on the multiparametric MRIs of the discovery set to classify each voxel into tumour or non-tumour. On the independent validation dataset, the CNN showed high segmentation accuracy for reader1 (Dice Similarity Coefficient (DSC = 0.68) and reader2 (DSC = 0.70). The area under the curve (AUC) of the resulting probability maps was very high for both readers, AUC = 0.99 (SD = 0.05). Our results demonstrate that deep learning can perform accurate localization and segmentation of rectal cancer in MR imaging in the majority of patients. Deep learning technologies have the potential to improve the speed and accuracy of MRI-based rectum segmentations.

Diagnostic Accuracy of CT for Local Staging of Colon Cancer: A Systematic Review and Meta-Analysis

OBJECTIVE The purpose of this article is to determine the accuracy of CT in the detection of tumor invasion beyond the bowel wall and nodal involvement of colon carcinomas. A literature search was performed to identify studies describing the accuracy of CT in the staging of colon carcinomas. Studies including rectal carcinomas that were inseparable from colon carcinomas were excluded. Publication bias was explored by using a Deeks funnel plot asymmetry test. A hierarchic summary ROC model was used to construct a summary ROC curve and to calculate summary estimates of sensitivity, specificity, and diagnostic odds ratios (ORs). CONCLUSION On the basis of a total of 13 studies, pooled sensitivity, specificity, and diagnostic ORs for detection of tumor invasion beyond the bowel wall (T3-T4) were 90% (95% CI, 83-95%), 69% (95% CI, 62-75%), and 20.6 (95% CI, 10.2-41.5), respectively. For detection of tumor invasion depth of 5 mm or greater (T3cd-T4), estimates from four studies were 77% (95% CI, 66-85%), 70% (95% CI, 53-83%), and 7.8 (95% CI, 4.2-14.2), respectively. For nodal involvement (N+), 16 studies were included with values of 71% (95% CI, 59-81%), 67% (95% CI, 46-83%), and 4.8 (95% CI, 2.5-9.4), respectively. Two studies using CT colonography were included with sensitivity and specificity of 97% (95% CI, 90-99%) and 81% (95% CI, 65-91%), respectively, for detecting T3-T4 tumors. CT has good sensitivity for the detection of T3-T4 tumors, and evidence suggests that CT colonography increases its accuracy. Discriminating between T1-T3ab and T3cd-T4 cancer is challenging, but data were limited. CT has a low accuracy in detecting nodal involvement.

MRI for Local Staging of Colon Cancer : Can MRI Become the Optimal Staging Modality for Patients With Colon Cancer?

BACKGROUND: Colon cancer is currently staged with CT. However, MRI is superior in the detection of colorectal liver metastasis, and MRI is standard in local staging of rectal cancer. Optimal (local) staging of colon cancer could become crucial in selecting patients for neoadjuvant treatment in the near future (Fluoropyrimidine Oxaliplatin and Targeted Receptor Preoperative Therapy trial). OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of MRI for local staging of colon cancer. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at the Maastricht University Medical Centre. PATIENTS: In total, 55 patients with biopsy-proven colon carcinoma were included. MAIN OUTCOME MEASURES: All of the patients underwent an MRI (1.5-tesla; T2 and diffusion-weighted imaging) of the abdomen and were retrospectively analyzed by 2 blinded, independent readers. Histopathology after resection was the reference standard. Both readers evaluated tumor characteristics, including invasion through bowel wall (T3/T4 tumors), invasion beyond bowel wall of ≥5 mm and/or invasion of surrounding organs (T3cd/T4), serosal involvement, extramural vascular invasion, and malignant lymph nodes (N+). Interobserver agreement was compared using &kgr; statistics. RESULTS: MRI had a high sensitivity (72%–91%) and specificity (84%–89%) in detecting T3/T4 tumors (35/55) and a low sensitivity (43%–67%) and high specificity (75%–88%) in detecting T3cd/T4 tumors (15/55). For detecting serosal involvement and extramural vascular invasion, MRI had a high sensitivity and moderate specificity, as well as a moderate sensitivity and specificity in the detection of nodal involvement. Interobserver agreements were predominantly good; the more experienced reader achieved better results in the majority of these categories. LIMITATIONS: The study was limited by its retrospective nature and moderate number of inclusions. CONCLUSIONS: MRI has a good sensitivity for tumor invasion through the bowel wall, extramural vascular invasion, and serosal involvement. In addition, together with its superior liver imaging, MRI might become the optimal staging modality for colon cancer. However, more research is needed to confirm this. See Video Abstract at http://links.lww.com/DCR/A309.