Predicting response to chemoradiotherapy in rectal cancer via visual morphologic assessment and staging on baseline MRI: a multicenter and multireader study.

PURPOSE: Pre-treatment knowledge of the anticipated response of rectal tumors to neoadjuvant chemoradiotherapy (CRT) could help to further optimize the treatment. Van Griethuysen et al. proposed a visual 5-point confidence score to predict the likelihood of response on baseline MRI. Aim was to evaluate this score in a multicenter and multireader study setting and compare it to two simplified (4-point and 2-point) adaptations in terms of diagnostic performance, interobserver agreement (IOA), and reader preference. METHODS: Twenty-two radiologists from 14 countries (5 MRI-experts,17 general/abdominal radiologists) retrospectively reviewed 90 baseline MRIs to estimate if patients would likely achieve a (near-)complete response (nCR); first using the 5-point score by van Griethuysen (1=highly unlikely to 5=highly likely to achieve nCR), second using a 4-point adaptation (with 1-point each for high-risk T-stage, obvious mesorectal fascia invasion, nodal involvement, and extramural vascular invasion), and third using a 2-point score (unlikely/likely to achieve nCR). Diagnostic performance was calculated using ROC curves and IOA using Krippendorf's alpha (α). RESULTS: Areas under the ROC curve to predict the likelihood of a nCR were similar for the three methods (0.71-0.74). IOA was higher for the 5- and 4-point scores (α=0.55 and 0.57 versus 0.46 for the 2-point score) with best results for the MRI-experts (α=0.64-0.65). Most readers (55%) favored the 4-point score. CONCLUSIONS: Visual morphologic assessment and staging methods can predict neoadjuvant treatment response with moderate-good performance. Compared to a previously published confidence-based scoring system, study readers preferred a simplified 4-point risk score based on high-risk T-stage, MRF involvement, nodal involvement, and EMVI.

GEP-NET radiomics: a systematic review and radiomics quality score assessment.

OBJECTIVE: The number of radiomics studies in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is rapidly increasing. This systematic review aims to provide an overview of the available evidence of radiomics for clinical outcome measures in GEP-NETs, to understand which applications hold the most promise and which areas lack evidence. METHODS: PubMed, Embase, and Wiley/Cochrane Library databases were searched and a forward and backward reference check of the identified studies was executed. Inclusion criteria were (1) patients with GEP-NETs and (2) radiomics analysis on CT, MRI or PET. Two reviewers independently agreed on eligibility and assessed methodological quality with the radiomics quality score (RQS) and extracted outcome data. RESULTS: In total, 1364 unique studies were identified and 45 were included for analysis. Most studies focused on GEP-NET grade and differential diagnosis of GEP-NETs from other neoplasms, while only a minority analysed treatment response or long-term outcomes. Several studies were able to predict tumour grade or to differentiate GEP-NETs from other lesions with a good performance (AUCs 0.74-0.96 and AUCs 0.80-0.99, respectively). Only one study developed a model to predict recurrence in pancreas NETs (AUC 0.77). The included studies reached a mean RQS of 18%. CONCLUSION: Although radiomics for GEP-NETs is still a relatively new area, some promising models have been developed. Future research should focus on developing robust models for clinically relevant aims such as prediction of response or long-term outcome in GEP-NET, since evidence for these aims is still scarce. KEY POINTS: • The majority of radiomics studies in gastroenteropancreatic neuroendocrine tumours is of low quality. • Most evidence for radiomics is available for the identification of tumour grade or differentiation of gastroenteropancreatic neuroendocrine tumours from other neoplasms. • Radiomics for the prediction of response or long-term outcome in gastroenteropancreatic neuroendocrine tumours warrants further research.

Clinical response assessment on DW-MRI compared with FDG-PET/CT after neoadjuvant chemoradiotherapy in patients with oesophageal cancer.

PURPOSE: In about 30% of patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection for locally advanced oesophageal cancer no vital tumour is found in the resection specimen. Accurate clinical response assessment is critical if deferral from surgery is considered in complete responders. Our study aimed to compare the performance of MRI and of FDG-PET/CT for the detection of residual disease after nCRT. METHODS: Patients with oesophageal cancer eligible for nCRT and oesophagectomy were prospectively included. All patients underwent FDG-PET/CT and MRI before and between 6 and 8 weeks after nCRT. Two radiologists scored the MRI scans, and two nuclear medicine physicians scored the FDG-PET/CT scans using a 5-point score for residual disease. Histopathology after oesophagectomy represented the reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for detection of residual tumour (ypT+), residual nodal disease (ypN+), and any residual disease (ypT+Nx/ypT0N+). RESULTS: Seven out of 33 (21%) patients had a pathological complete response. The AUCs for individual readers to detect ypT+ were 0.71/0.70 on diffusion-weighted (DW)-MRI and 0.54/0.57 on FDG-PET/CT, and to detect ypN+ were 0.89/0.81 on DW-MRI and 0.75/0.71 on FDG-PET/CT. The AUCs/sensitivities/specificities for the individual readers to detect any residual disease were 0.74/92%/57% and 0.70/96%/43% on MRI; these were 0.49/69%/29% and 0.60/69%/43% on FDG-PET/CT, respectively. CONCLUSION: MRI reached higher diagnostic accuracies than FDG-PET/CT for the detection of residual tumour in oesophageal cancer patients at 6 to 8 weeks after nCRT.

Magnetic resonance assessment of sinusoidal obstruction syndrome after neoadjuvant chemotherapy for colorectal liver metastases is not reproducible.

BACKGROUND: Sinusoidal obstruction syndrome (SOS) due to chemotherapy can cause severe hepatotoxicity, leading to impaired outcome in patients with colorectal cancer. A previous study introduced gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to diagnose SOS. PURPOSE: To assess the reproducibility of Gd-EOB-MRI-based SOS diagnosis and its relationship with response to chemotherapy and long-term outcome. MATERIAL AND METHODS: Twenty-six Gd-EOB-MRI scans of patients undergoing chemotherapy for colorectal liver metastases (CRLM) were retrospectively analyzed. Three radiologists, blinded to clinical data, independently scored presence and severity of SOS on a 5-point scale (0, definitely not present to 4, definitely present). Patients with a score ≥3 were considered SOS+. Inter-observer agreement between readers was assessed with kappa statistics. Response (RECIST 1.1.), occurrence of new CRLM during follow-up (hepatic progression) and overall survival (OS) were compared between patients with and without SOS. RESULTS: The inter-observer agreement of SOS scores was poor, with quadratic kappas of 0.17-0.40. For the binary outcome of SOS+ (confidence level [CL] 3-4) vs. SOS- (CL 0-2) agreement was poor, with kappas of 0.03-0.37. Median follow-up was 24 months (range 4-44 months). Response and OS between patients with and without SOS did not differ significantly for any of the readers. CONCLUSION: Inter-observer agreement for the diagnosis of SOS on Gd-EOB-MRI is poor. No significant correlation with relevant outcomes was found for any of the readers. Therefore, MRI for SOS diagnosis might be less useful than previously reported. Other techniques should be explored to accurately diagnose SOS in absence of histological confirmation.

Response assessment after (chemo)radiotherapy for rectal cancer: Why are we missing complete responses with MRI and endoscopy?

PURPOSE: To evaluate what features on restaging MRI and endoscopy led to a false clinical diagnosis of residual tumour in patients with a pathological complete response after rectal cancer surgery. METHODS: Patients with an unrecognized complete response after (chemo)radiotherapy were selected in a tertiary referral centre for rectal cancer treatment. An unrecognized complete response was defined as a clinical incomplete response at MRI and/or endoscopy with a pathological complete response of the primary tumour after surgery. The morphology of the tumour bed and the lymph nodes were evaluated on post-CRT T2-weighted MRI (T2-MRI) and diffusion weighted imaging (DWI). Post-CRT endoscopy images were evaluated for residual mucosal abnormalities. MRI and endoscopy features were correlated with histopathology. RESULTS: Thirty-six patients with an unrecognized complete response were included. Mucosal abnormalities were present at restaging endoscopy in 84%, mixed signal intensity on T2-MRI in 53%, an irregular aspect of the former tumour location on T2-MRI in 69%, diffusion restriction on DWI in 51% and suspicious lymph nodes in 25%. CONCLUSIONS: Overstaging of residual tumour after (chemo)radiotherapy in rectal cancer is mainly due to residual mucosal abnormalities at endoscopy, mixed signal intensity or irregular fibrosis at T2-MRI, diffusion restriction at DWI and residual suspicious lymph nodes. Presence of these features is not definitely associated with residual tumour and in selected cases an extended waiting interval can be considered.

DWI for Assessment of Rectal Cancer Nodes After Chemoradiotherapy: Is the Absence of Nodes at DWI Proof of a Negative Nodal Status?

OBJECTIVE: When considering organ preservation in patients with rectal cancer with good tumor response, assessment of a node-negative status after chemoradiation therapy (CRT) is important. DWI is a very sensitive technique to detect nodes. The study aim was to test the hypothesis that the absence of nodes at DWI after CRT is concordant with a ypN0 status. MATERIALS AND METHODS: A retrospective study was performed of 90 patients with rectal cancer treated with CRT followed by restaging MRI at 1.5 T, including DWI (highest b value, 1000 s/mm2). Two independent readers counted the number of nodes visible in the mesorectal compartment on DW images obtained after CRT. The number of nodes on DWI (0 vs ≥ 1) was compared with the number of metastatic nodes at histopathology or long-term clinical follow-up (yN0 vs yN-positive status). RESULTS: Seventy-one patients had a yN0 status, and 19 had a yN-positive status. For 10 patients, no nodes were observed at DWI, which was concordant with a yN0 status in 100% of cases. In the other 61 patients with a yN0 status, the median number of nodes detected at DWI was three (range, 1-17 nodes). To differentiate between yN0 and yN-positive status, sensitivity was 100%, specificity was 14%, the positive predictive value was 24%, and the negative predictive value was 100%. CONCLUSION: Although the absence of nodes at DWI is not a frequent finding, it appears to be a reliable predictor of yN0 status after CRT in patients with rectal cancer. DWI may thus be a helpful adjunct in assessing response after CRT and may help select patients for organ-saving treatment.

Non-invasive MR assessment of macroscopic and microscopic vascular abnormalities in the rectal tumour-surrounding mesorectum.

OBJECTIVES: To evaluate the MRI macroscopic and microscopic parameters of mesorectal vasculature in rectal cancer patients. METHODS: Thirteen patients with rectal adenocarcinoma underwent a dynamic contrast-enhanced MRI at 1.5 T using a blood pool agent at the primary staging. Mesorectal macrovascular features, i.e., the number of vascular branches, average diameter and length, were assessed from baseline-subtracted post-contrast images by two independent readers. Mesorectal microvascular function was investigated by means of area under the enhancement-time curve (AUC). Histopathology served as reference standard of the tumour response to CRT. RESULTS: The average vessel branching in the mesorectum around the tumour and normal rectal wall was 8.2 ± 3.8 and 1.7 ± 1.3, respectively (reader1: p = 0.001, reader2: p = 0.002). Similarly, the tumour-surrounding mesorectum displayed circa tenfold elevated AUC (p = 0.01). Interestingly, patients with primary node involvement had a twofold higher number of macrovascular branches compared to those with healthy nodes (reader1: p = 0.005 and reader2: p = 0.03). A similar difference was observed between good and poor responders to CRT, whose tumour-surrounding mesorectum displayed 10.7 ± 3.4 and 5.6 ± 1.5 vessels, respectively (reader1/reader2: p = 0.02). CONCLUSIONS: We showed at baseline MRI of rectal tumours a significantly enhanced macrovascular structure and microvascular function in rectal tumour-surrounding mesorectum, and the association of primary mesorectal macrovascular parameters with node involvement and therapy response. KEY POINTS: • Vascular MRI reveals macrovascular and microvascular abnormalities in the rectal tumour-surrounding mesorectum. • Formation of highly vascular stroma precedes the actual tumour invasion. • High macrovascular parameters are associated with node involvement. • Mesorectal vascular network differs for good and poor responders.

Assessment of Clinical Complete Response After Chemoradiation for Rectal Cancer with Digital Rectal Examination, Endoscopy, and MRI: Selection for Organ-Saving Treatment.

BACKGROUND: The response to chemoradiotherapy (CRT) for rectal cancer can be assessed by clinical examination, consisting of digital rectal examination (DRE) and endoscopy, and by MRI. A high accuracy is required to select complete response (CR) for organ-preserving treatment. The aim of this study was to evaluate the value of clinical examination (endoscopy with or without biopsy and DRE), T2W-MRI, and diffusion-weighted MRI (DWI) for the detection of CR after CRT. METHODS: This prospective cohort study in a university hospital recruited 50 patients who underwent clinical assessment (DRE, endoscopy with or without biopsy), T2W-MRI, and DWI at 6-8 weeks after CRT. Confidence levels were used to score the likelihood of CR. The reference standard was histopathology or recurrence-free interval of >12 months in cases of wait-and-see approaches. Diagnostic performance was calculated by area under the receiver operator characteristics curve, with corresponding sensitivities and specificities. Strategies were assessed and compared by use of likelihood ratios. RESULTS: Seventeen (34 %) of 50 patients had a CR. Areas under the curve were 0.88 (0.78-1.00) for clinical assessment and 0.79 (0.66-0.92) for T2W-MRI and DWI. Combining the modalities led to a posttest probability for predicting a CR of 98 %. Conversely, when all modalities indicated residual tumor, 15 % of patients still experienced CR. CONCLUSIONS: Clinical assessment after CRT is the single most accurate modality for identification of CR after CRT. Addition of MRI with DWI further improves the diagnostic performance, and the combination can be recommended as the optimal strategy for a safe and accurate selection of CR after CRT.

Magnetization transfer ratio: a potential biomarker for the assessment of postradiation fibrosis in patients with rectal cancer.

OBJECTIVES: Magnetization transfer-magnetic resonance imaging (MT-MRI) uses differences in the magnetization interaction of the free "unbound" water protons and the macromolecular-bound protons. The aim of this study was to evaluate whether the magnetization transfer ratio (MTR) may be used to identify fibrosis in patients with rectal cancer treated with chemoradiotherapy. MATERIALS AND METHODS: This study was part of a rectal cancer imaging study, which was approved by the local institutional review board. Twenty-six patients, treated with neoadjuvant chemoradiotherapy, underwent a standard MRI including T2-weighted sequences and a diffusion-weighted sequence. An axially oriented MT sequence was performed at the center of the (former) tumor location. Regions of interest were manually drawn on the MT-MRI (with reference to the T2-weighted and diffusion-weighted images), covering areas of residual tumor, fibrosis, or the normal or edematous rectal wall. The results were compared with that of the histopathological examination. Differences in MTR between the 4 tissue types were analyzed, and a receiver operating characteristic (ROC) curve was generated to assess the diagnostic potential. RESULTS: Thirty-eight regions of interest were analyzed on the MT-MRI. The mean (SD) MTR of the fibrosis was 37.7% (2.7%), which was significantly higher than that of the residual tumor (29.6% [4.2%]; P < 0.001), the normal rectal wall (30.3% [4.7%]; P = 0.003), and the edematous rectal wall (18.2% [4.0%]; P < 0.001). The use of MTR resulted in an area under the ROC-curve of 0.96, a sensitivity of 88%, and a specificity of 90% for the diagnosis of fibrosis. CONCLUSIONS: Magnetization transfer ratio can be used to discriminate postradiation fibrosis from residual tumor and the normal rectal wall after chemoradiotherapy. Magnetization transfer imaging can thus be a promising tool for the unsolved dilemma of interpreting postradiation fibrosis in rectal cancer.

Gadofosveset-enhanced MRI for the assessment of rectal cancer lymph nodes: predictive criteria.

PURPOSE: To confirm the use of the nodal signal intensity (SI) and the 'chemical shift' artefact as diagnostic criteria for detecting nodal metastases from rectal cancer on gadofosveset contrast-enhanced MRI. METHODS: Thirty-three patients underwent a non-enhanced and gadofosveset-enhanced 3D-T1W GRE-MRI at 1.5T. For each lymph node, the SI of the middle part of the node (mSI) and white rim of the chemical shift artefact encircling the node (wSI) were measured on the non-enhanced and gadofosveset-enhanced images. Second, the aspect of the chemical shift artefact encircling the nodes was scored using a 4-point scale. Results were compared with histology on a node-by-node basis. RESULTS: 289 nodes (55 N+) were analysed. On gadofosveset-MRI, mSI and wSI were significantly higher for the benign than for the metastatic lymph nodes (p < 0.001). Areas under the ROC curve (AUC) for identification of metastases were 0.74 (mSI) and 0.73 (wSI). The chemical shift criterion rendered an AUC of 0.85. The combination of mSI and the chemical shift criterion resulted in an AUC of 0.88 and the rendered an AUC of 0.86-0.92 when subjectively (visually) assessed by two independent readers. CONCLUSIONS: Benign lymph nodes show significant contrast enhancement after gadofosveset injection, while metastatic nodes do not. The uptake of gadofosveset in the nodes also affects the chemical shift artefact encircling the nodes. Combined assessment of these two features on gadofosveset-enhanced MRI provides a high diagnostic performance for diagnosing metastatic lymph nodes in patients with rectal cancer.

Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy--conventional MR volumetry versus diffusion-weighted MR imaging.

PURPOSE: To determine diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of complete tumor response (CR) after combined radiation therapy with chemotherapy (CRT) in patients with locally advanced rectal cancer (LARC) by means of volumetric signal intensity measurements and apparent diffusion coefficient (ADC) measurements and to compare the performance of DW imaging with that of T2-weighted MR volumetry. MATERIALS AND METHODS: A retrospective analysis of 50 patients with LARC, for whom clinical and imaging data were retrieved from a previous imaging study approved by the local institutional ethical committee and for which all patients provided informed consent, was conducted. Patients underwent pre- and post-CRT standard T2-weighted MR and DW MR. Two independent readers placed free-hand regions of interest (ROIs) in each tumor-containing section on both data sets to determine pre- and post-CRT tumor volumes and tumor volume reduction rates (volume). ROIs were copied to an ADC map to calculate tumor ADCs. Histopathologic findings were the standard of reference. Receiver operating characteristic (ROC) curves were generated to compare performance of T2-weighted and DW MR volumetry and ADC. The intraclass correlation coefficient (ICC) was used to evaluate interobserver variability and the correlation between T2-weighted and DW MR volumetry. RESULTS: Areas under the ROC curve (AUCs) for identification of a CR that was based on pre-CRT volume, post-CRT volume, and volume, respectively, were 0.57, 0.70, and 0.84 for T2-weighted MR versus 0.63, 0.93, and 0.92 for DW MR volumetry (P = .15, .02, .42). Pre- and post-CRT ADC and ADC AUCs were 0.55, 0.54, and 0.51, respectively. Interobserver agreement was excellent for all pre-CRT measurements (ICC, 0.91-0.96) versus good (ICC, 0.61-0.79) for post-CRT measurements. ICC between T2-weighted and DW MR volumetry was excellent (0.97) for pre-CRT measurements versus fair (0.25) for post-CRT measurements. CONCLUSION: Post-CRT DW MR volumetry provided high diagnostic performance in assessing CR and was significantly more accurate than T2-weighted MR volumetry. Post-CRT DW MR was equally as accurate as volume measurements of both T2-weighted and DW MR. Pre-CRT volumetry and ADC were not reliable.

What is the most accurate whole-body imaging modality for assessment of local and distant recurrent disease in colorectal cancer? A meta-analysis : imaging for recurrent colorectal cancer.

PURPOSE: The objective of this study was to compare the diagnostic performance of positron emission tomography (PET), PET/CT, CT and MRI as whole-body imaging modalities for the detection of local and/or distant recurrent disease in colorectal cancer (CRC) patients who have a (high) suspicion of recurrent disease, based on clinical findings or rise in carcinoembryonic antigen (CEA). METHODS: A meta-analysis was undertaken. PubMed and Embase were searched for studies on the accuracy of whole-body imaging for patients with suspected local and/or distant recurrence of their CRC. Additionally, studies had to have included at least 20 patients with CRC and 2 × 2 contingency tables had to be provided or derivable. Articles evaluating only local recurrence or liver metastasis were excluded. Summary receiver-operating characteristic (ROC) curves were constructed from the data on sensitivity and specificity of individual studies and pooled estimates of diagnostic odds ratios (DORs) and areas under the ROC curve (AUCs) were calculated. To test for heterogeneity the Cochran Q test was used. RESULTS: Fourteen observational studies were included which evaluated PET, PET/CT, CT and/or MRI. Study results were available in 12 studies for PET, in 5 studies for CT, in 5 studies for PET/CT and in 1 study for MRI. AUCs for PET, PET/CT and CT were 0.94 (0.90-0.97), 0.94 (0.87-0.98) and 0.83 (0.72-0.90), respectively. In patient based analyses PET/CT had a higher diagnostic performance than PET with an AUC of 0.95 (0.89-0.97) for PET/CT vs 0.92 (0.86-0.96) for PET. CONCLUSION: Both whole-body PET and PET/CT are very accurate for the detection of local and/or distant recurrent disease in CRC patients with a (high) suspicion of recurrent disease. CT has the lowest diagnostic performance. This difference is probably mainly due to the lower accuracy of CT for detection of extrahepatic metastases (including local recurrence). For clinical practice PET/CT might be the modality of choice when evaluating patients with a (high) suspicion of recurrent disease, because of its best performance in patient based analyses and confident prediction of disease status.