Magnetic resonance imaging for the clinical management of rectal cancer patients: recommendations from the 2012

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1 Eur Radiol (2013) 23: DOI /s GASTROINTESTINAL Magnetic resonance imaging for the clinical management of rectal cancer patients: recommendations from the 2012 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting Regina G. H. Beets-Tan & Doenja M. J. Lambregts & Monique Maas & Shandra Bipat & Brunella Barbaro & Filipe Caseiro-Alves & Luís Curvo-Semedo & Helen M. Fenlon & Marc J. Gollub & Sofia Gourtsoyianni & Steve Halligan & Christine Hoeffel & Seung Ho Kim & Andrea Laghi & Andrea Maier & Søren R. Rafaelsen & Jaap Stoker & Stuart A. Taylor & Michael R. Torkzad & Lennart Blomqvist Received: 23 January 2013 /Revised: 12 March 2013 /Accepted: 30 March 2013 /Published online: 7 June 2013 # European Society of Radiology 2013 Abstract Objectives To develop guidelines describing a standardised approach regarding the acquisition, interpretation and reporting of magnetic resonance imaging (MRI) for clinical staging and restaging of rectal cancer. Methods A consensus meeting of 14 abdominal imaging experts from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) was conducted following the RAND-UCLA Appropriateness Method. Two independent (non-voting) chairs facilitated the meeting. Two hundred and Electronic supplementary material The online version of this article (doi: /s ) contains supplementary material, which is available to authorized users. R. G. H. Beets-Tan : D. M. J. Lambregts : M. Maas Maastricht University Medical Centre+, Maastricht, The Netherlands S. Bipat : J. Stoker Academic Medical Centre, Amsterdam, The Netherlands B. Barbaro Catholic University School of Medicine, Rome, Italy F. Caseiro-Alves : L. Curvo-Semedo Coimbra University Hospitals, Coimbra, Portugal H. M. Fenlon Mater Misericordiae University Hospital, Dublin, Ireland M. J. Gollub Memorial Sloan-Kettering Cancer Center, New York, USA S. Gourtsoyianni University Hospital of Heraklion, Crete, Greece S. Gourtsoyianni Guy s & St. Thomas NHS FT, London, UK S. Halligan : S. A. Taylor Centre for Medical Imaging, University College London, London, United Kingdom C. Hoeffel Reims University Hospital, Reims, France S. H. Kim Inje University Haeundae Paik Hospital, Busan, South-Korea A. Laghi Sapienza - University of Rome, Rome, Italy A. Maier Medical University of Vienna, Vienna, Austria S. R. Rafaelsen Vejle Hospital, Vejle, Denmark M. R. Torkzad Uppsala University, Uppsala, Sweden L. Blomqvist Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden R. G. H. Beets-Tan (*) Department of Radiology, Maastricht University Medical Centre+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands r.beets.tan@mumc.nl

2 Eur Radiol (2013) 23: thirty-six items were scored by participants for appropriateness and classified subsequently as appropriate or inappropriate (defined by 80 % consensus) or uncertain (defined by < 80 % consensus). Items not reaching 80 % consensus were noted. Results Consensus was reached for 88 % of items: recommendations regarding hardware, patient preparation, imaging sequences, angulation, criteria for MRI assessment and MRI reporting were constructed from these. Conclusions These expert consensus recommendations can be used as clinical guidelines for primary staging and restaging of rectal cancer using MRI. Key Points These guidelines recommend standardised imaging for staging and restaging of rectal cancer. The guidelines were constructed through consensus amongst 14 abdominal imaging experts. Consensus was reached by in 88 % of 236 items discussed. Keywords Rectal cancer. Consensus. Guideline. Magnetic resonance imaging. Tumour staging Introduction In many countries magnetic resonance imaging (MRI) is now central to the investigation and management of rectal cancer. International guidelines for the management of rectal cancer recommend MRI as pivotal for staging the primary tumour [1, 2]. MRI accurately identifies prognostic markers for risk of local recurrence and helps to stratify patients into those needing preoperative chemoradiotherapy [3, 4]. Recently the role of MRI has expanded to encompass assessment of response to preoperative (chemoradiotherapy) treatment. For example, patients exhibiting a good response can be directed towards less extensive surgery or minimally invasive alternatives [5, 6]. In order to best achieve all these objectives, MRI should be performed according to state-ofthe-art principles and reported in a structured fashion so that important findings impacting directly on therapeutic decision making are not omitted. Although experts in the field generally regard MRI as invaluable, there is some professional disagreement relating to its accuracy and the generalisability of results obtained from specialist centres. These concerns relate partly to the wide range of different available MR protocols and a lack of standardisation that serves to increase variation between different centres. In particular, the minimal requirements for an optimal MR protocol are unclear. There is, therefore, a need for recommendations from an expert panel regarding the performance and interpretation of state-of-the-art rectal MRI. This paper reports the recommendations of a panel of expert radiologists from leading colorectal cancer centres an initiative of the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). These experts participated in a formal consensus process aimed at defining a state-of-the-art MR protocol for rectal cancer, how it should be performed, and how the imaging findings should be interpreted and reported. Materials and methods The consensus method The RAND-UCLA Appropriateness Method (RAM) was chosen as it combines all available evidence (unlike Cochrane Reviews, which summarise the best available evidence following application of inclusion and exclusion criteria) with the collective judgement of experts to yield a statement regarding the appropriateness of a specific question [7]. The RAM is a modified Delphi method that, unlike the original Delphi, provides panellists with the opportunity to discuss their judgements during a face-to-face meeting, which appears to additionally motivate panellists to participate. In summary, RAM combines postal and face-to-face rounds, and panellists rate each question twice, in a two-round modified Delphi process. The basic steps for applying the RAM are shown in Fig. 1. Step 1 Step 2 Literature review Two of the organising members (D.M.J.L., M.M.) in consensus performed a literature review to synthesise the available scientific evidence regarding the imaging of rectal cancer. They searched the PubMed and Medline databases for all relevant English language original articles, systematic reviews and meta-analyses published between 1990 and October 2011 using the following search terms: imaging, magnetic resonance imaging or MRI, rectal neoplasms, staging, restaging, response evaluation and chemoradiation, chemoradiotherapy, chemotherapy and/or radiotherapy. Additional studies were traced by tracking the reference lists of the retrieved studies. The collected evidence was primarily used to extract the relevant topics which should be addressed by the panel in order to construct the questionnaire. Construct of the questionnaire A questionnaire consisting of 229 items was constructed in November The first draft was produced by three of the organising members (R.G.H.B.T., D.M.J.L., M.M.). Refinements were made in consultation with two separate advising organising members (L.B., S.B.). The questionnaire was designed to address: 1. The role of MRI in relation to alternative techniques for primary staging and restaging of rectal cancer (i.e. non-mucinous type adenocarcinoma) after neoadjuvant treatment.

3 2524 Eur Radiol (2013) 23: Step 1: Literature review - Search: relevant papers on staging and restaging of rectal cancer - Selection and classification of articles - Synthesi sing the evidence Step 2: Creating list of questions - Topics: imaging techniques, MR imaging requirements, imaging criteria, MRI reporting - Answer options: binomial (YES/NO), ordinal (not recommended/ recommended/mandatory) numerical (e.g. mm) Step 3: Panel selection Panel composition (ESGAR members): - 14 abdominal radiologists with known expertise in rectal cancer imaging - academic, tertiary, general centres Step 4: 1 st round (postal) - Primary questionnaire questions - No interaction Step 5 a: Data analysing - Modifying questions - Creating summary ratings - (Prepare for face to face panel meeting) Step 6: 2 nd round (postal) - 7 additional questions - No interaction Step 5b: Data analy sing - Creating new summary ratings - (Prepare for face to face panel meeting) Step 7 panel meeting - 46 items discussed - 13 panellists present - 2 chairs, 3 observers Step 5c: Data analy sing - Creating final summary ratings final items Step 8: Data -reporting - Appropriate with 80% agreement - Inappropriate with 80% agreement - Uncertain (< 80% agreement) Fig. 1 The basic steps in applying the RAND-UCLA Appropriateness Method (RAM) 2. The minimum and optimal imaging requirements (hardware, patient preparation, imaging sequences). 3. Criteria for the primary MRI staging and restaging after neoadjuvant treatment. 4. MRI reporting. Each item was scored using a binomial (YES/NO), ordinal (e.g. not recommended, recommended, mandatory) or numerical (e.g. millimetre) scale. For the ordinal scale, mandatory was defined as definitely required for the routine staging of rectal cancer ; recommended was defined as advised, but not absolutely required to be included in the routine staging of rectal cancer ; not recommended was defined as not required for the routine staging of rectal cancer. Step 3 Panel selection The panel consisted of 14 leading abdominal radiologists with known expertise within the field of rectal cancer imaging. The panellists were all members of the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). The chairs were Regina Beets-Tan from Maastricht University Medical Centre, The Netherlands and Lennart Blomqvist from Karolinska University Hospital, Sweden. Step 4 Questionnaire completion before the meeting The initial questionnaire was sent to panellists by mail, March Panellists rated individually; there was no interaction among panellists at this stage. Step 5 Data acquisition and data analyses As stated above, answers were obtained in binomial, ordinal or numerical scales (unlike the standard appropriateness score ranging from 1 to 9), according to the individual item in question. Each item was classified as: (1) Appropriate with 80 % agreement, (2) Inappropriate with 80 % agreement or Step 6 Step 7 (3) Uncertain when no consensus could be reached (defined as < 80 % agreement). Additional (second) questionnaire completion before the meeting Based on responses to the initial questionnaire by panellists, seven additional questions were constructed and subsequently sent to the panel members. These additional questions were aimed at clarifying potentially conflicting answers as a result of certain questions deemed ambiguous by panellists initially. Panel meeting The panel meeting took place during the annual ESGAR meeting, Edinburgh, June 13, Thirteen of the 14 panellists attended. The meeting was moderated by two independent (non-voting) chairs, R.G.H.B.T. and L.B. Three non-contributing (nonvoting) observers (D.M.J.L., M.M., SB) documented key points of discussion and outcomes from the voting rounds. Two weeks before the meeting, panellists received the results of the first and second questionnaire rounds, which formed the basis for discussion during the face-to-face meeting. In addition, panellists received a list of the relevant literature identified during Step 1 above and were asked to compare the questionnaire results with the available evidence. The panel discussion focused on items for which no consensus had been achieved during the first two questionnaire rounds. After discussion of these items, the panellists were asked to vote. Decisions were made in line with the original scales used, i.e. binomial, ordinal, numerical. During the discussion, panellists found some items to be either inadequately or ambiguously phrased, in which case the items were either rephrased and voted on, or deleted.

4 Eur Radiol (2013) 23: Step 8 Results Data-reporting Data from the initial questionnaire, second round, and face-to-face meeting were collected and descriptive metrics calculated by D.M.J.L. and M.M. Each item was ultimately classified as: (1) appropriate with 80 % agreement, (2) Inappropriate with 80 % agreement or (3) Uncertain (no consensus, i.e. < 80 % agreement). Demographic data of panellists base hospitals are summarised in Table 1. The initial pre-meeting questionnaire comprised 229 items. The second questionnaire round added a further seven, for a total of 236. During the face-to-face meeting the items on which no consensus had been reached during the first two rounds were discussed. Two additional items were added, two items were deleted, and wording was rephrased in three items. Hence, the final number of items was 236. The final results from the consensus procedure for these 236 items are given in electronic supplementary material Appendix 1. Areas of consensus In the pre-meeting questionnaires, consensus was reached in 190/236 of items (81 %). This number increased to 208/236 (88 %) after the panel meeting. The main recommendations based on the items on which 80 % consensus was reached are listed in Table 2. Areas lacking consensus After the panel meeting, lack of consensus remained in 28 of the items (12 %). The main issues on which no consensus was reached are summarised in Table 3. Discussion Using the RAM method, we ultimately achieved consensus for 88 % of the individual items. Although a consensus of 80 % or more was not achieved for 12 % of items, reasonable agreement (60 79 %) was obtained in 7 % out of these 12 %. Imaging techniques The panel reached consensus that MRI is the imaging technique of first choice for primary staging of rectal cancer. There was a 100 % agreement that endorectal ultrasound (EUS) remains the imaging method of first choice to differentiate between T1 and T2 tumours if local resection is being considered [3]. Discussion regarding the best imaging technique to differentiate between T2 and T3 tumours reached 67 % agreement that either EUS or MRI can be used. Panellists could not agree which technique is best for primary staging in the absence of access to MRI. Both computed tomography (CT) and EUS were voted for equally. Positron emission tomography (PET) or PET/CT was not an option for most (92 %) of the panellists. For restaging after a long course of chemoradiotherapy (CRT), it was agreed that MRI should be performed routinely. Three quarters (75 %) agreed that the combination of endoscopy with MRI is the best approach to confirming a complete response Table 1 Demographic data from the hospitals of the panellists Median (range) number of patients diagnosed with rectal cancer per year 50 (20 250) MRI used as a standard staging tecnique for rectal cancer 100 % Restaging after chemoradiation performed routinely 77 % MRI used since MR vendors Siemens 42 % Philips 17 % GE 25 % Multiple 17 % Field strength 1.5 T 77 % 3.0 T 8 % 1.5 T and 3.0 T 15 % Use of a surface coil 100 % Use of an endorectal coil 0 % Use of spasmolytics (buscopan or glucagon) 38 % Use of endorectal filling 23 % Use of intravenous contrast material 15 %

5 2526 Eur Radiol (2013) 23: Table 2 Summary of recommendations (items reaching 80 % consensus) I II III IV IMAGING TECHNIQUES MRI is recommended as the technique of first choice for the overall primary staging of rectal cancer. For the specific differentiation between T1 and T2 tumours, endorectal ultrasound is recommended It is recommended to routinely perform restaging of rectal cancer after neoadjuvant chemoradiation. The recommended technique of first choice is MRI MR IMAGING REQUIREMENTS AND SEQUENCES Hardware and patient preparation The minimal recommended field strength for adequate (re)staging of rectal cancer is 1.0 T MRI, but ideally higher fieldstrengths should be used. There is no consensus on whether this should be 1.5 T or 3.0 T MRI. The use of an external coil is recommended and the use of an endorectal coil is not recommended. The routine use of endorectal filling or an enema is not recommended Sequences and sequence angulation It is recommended to routinely include 2D T2-weighted sequences in a standard clinical MR protocol for the (re)staging of rectal cancer. Use of DWI is not obligatory for primary staging but is recommended for restaging (specifically for assessment of the T-stage) after CRT. 3D T2-weighted and fatsuppressed sequences are inappropriate and not recommended. The use of contrast enhanced dynamic or steady state T1-weighted sequence is inappropriate and not recommended. Use of a sagittal and axial 2D T2-weighted sequence is mandatory for the assessment of tumour height, T-N-stage, MRF involvement and the presence of EMVI both before and after neoadjuvant treatment. The use of a coronal 2D T2-weighted sequence is recommended. The recommended optimal slice thickness for staging and restaging MRI is uncertain and ranges between 1 and 3 mm (maximum 4 mm). The axial and coronal T2-weighted sequence should be angulated perpendicular and parallel to the tumour axis for tumours in the middle and upper part of the rectum. For low rectal tumours, angulation depends on the extent of the tumour and may be performed perpendicular and parallel to either the tumour axis or the anal canal. Performance of MRI At primary staging, MRI can differentiate between (1) T2 and T3 tumours, (2) T3 and T4 tumours, (3) N0 and N+ status (4) free and involved mesorectal fascia using 2D T2W sequences only. Differentiation between T1 and T2 tumours is not possible with MR imaging. After neoadjuvant treatment, MRI can differentiate between (1) yt1-2 and yt3-4 tumours, (2) yn0 and yn+ status and (3) tumour-free and persistent mesorectal fascia involvement using 2D T2-weighted sequences only. It is unclear whether diffusion-weighted imaging is helpful for nodal restaging and assessment of mesorectal fascia involvement after CRT. It is unclear whether it is possible to reliably differentiate between a complete response (yt0) or residual tumour using either 2D T2-weighted sequences or diffusion-weighted MRI Extramural venous invasion can be reliably assessed on a 2D T2-weighted sequence and a contrast enhanced sequence is not helpful. CRITERIA FOR MR IMAGING ASSESSMENT Primary staging Stranding into the mesorectal fat is an equivocal sign that may indicate either a T2 tumour with desmoplasia or a T3 tumour with tumoural strands. Criteria for lymph node staging on T2-weighted sequences are signal intensity, border contour and shape. Size is also a predictor, but there is no optimal cut-off threshold for involved nodes. The mesorectal fascia (MRF) should be considered involved if the distance between tumour and MRF is 1 mm and threatened if the distance between tumour and MRF is 2 mm If on primary staging MRI stranding extends from the tumour into the mesorectal fascia, it should be considered involved. The assessment of extramural venous invasion is recommended but not obligatory. Restaging after neoadjuvant treatment A normalised, two-layered rectal wall after CRT should be considered a sign of a clinically complete tumour response (yt0). A hypointense, fibrotic residue is an equivocal feature that may indicate either residual tumour or a complete response. Size is more reliable as a criterion for lymph node staging after neoadjuvant treatment. A reduction in size and homogeneity of the nodal signal intensity is indicative of a sterilised node. It is not clear whether normalisation of the shape (oval) or border (regular) is an indicator of sterilised nodes. When a fat pad reappears between the tumour and mesorectal fascia after chemoradiation, this indicates regression from the mesorectal fascia. The presence of stranding into the mesorectal fascia after chemoradiation should be considered an equivocal sign that may or may not indicate persistent mesorectal fascia involvement. There is no consensus as to whether the assessment of extramurai venous invasion at restaging MRI is recommended MRI REPORTING a. Primary staging Full agreement was reached that the following items should be included: - The distance from the anal verge or anorectal junction to the lower pole of the tumour

6 Eur Radiol (2013) 23: Table 2 (continued) - The tumour length - The T-stage and any tumour deposits within the mesorectum - The N-stage - The presence/absence of suspicious extramesorectal lymph nodes - Involvement of the mesorectal fascia - The smallest distance (mm) between the tumour and the mesorectal fascia and its location Although non-unanimously agreed, it is recommended to also include the following items: - The circumferential location of the tumour within the wall (e.g. lateral, anterior, posterior) - In the case of a T3 tumour, the extent (mm) of extramural growth - The number of suspicious lymph nodes - The presence/absence of extramural vascular invasion (EMVI) - The morphological pattern of tumour growth (e.g. annular, polypoid, mucinous, ulcerated, perforated) b. Restaging after neoadjuvant treatment Full agreement was reached that the following items should be included: - The distance from the anal verge or anorectal junction to the lower pole of the tumour - The tumour length - The presence / absence of a residual tumour - The presence / absence of fibrosis - The yt-stage and any remaining tumour deposits within the mesorectum - The yn-stage and number of remaining suspicious lymph nodes - The presence of any remaining suspicious extramesorectal lymph nodes - Persistent involvement / regression from the mesorectal fascia - The smallest distance (mm) between the remaining tumour and the mesorectal fascia and its location Although non-unanimously agreed, it is also recommended to include the following items: - The circumferential location of the tumour within the wall (e.g. lateral, anterior, posterior) - In the case of a yt3 tumour, the extent (mm) of extramural growth - The morphological pattern of tumour growth (e.g. annular, polypoid, mucinous, ulcerated, perforated) Although it is recommended to report extramural venous invasion at primary staging MRI, it is not clear whether it should also be reported at restaging MRI. after CRT. There was no agreement on the optimal field strength, although most believed that 1.5 T is preferable to 3 T (75 % vs 33 %). The panel agreed that 1.0-T MRI should only be used if there is no access to a 1.5-T or 3.0- T system. Hypothetically, it is also feasible to perform staging at 1.0 Tesla, although the panel believes that it is important to assess whether the diagnostic performance is at a sufficient level which depends on factors such as equipment (e.g. outdated versus modern magnet, closed versus open MR system). MR imaging requirements No consensus was reached regarding the use of spasmolytic agents (e.g. Buscopan or Glucagon). Routine administration was advised by 50 % of the panel. Arguments for their use were the presence of bowel movement artefacts on the (sagittal) planning scan. Furthermore, spasmolytics may be advised when imaging is performed at 3 T, because movement artefacts tend to be more significant. Panellists agreed that routine rectal filling (e.g. with ultrasonography gel) is not recommended. The main argument against routine endorectal filling was that the primary goal of staging with MRI is not to assess the endoluminal part of the tumour as this is achieved at endoscopy; rather, the aim of MRI is to assess the extent of transmural tumour growth and its relationship to the mesorectal structures. Distension of the rectum by endoluminal contrast agents can compress the mesorectal fat, which may overestimate fascial involvement and hamper evaluation of mesorectal nodes [8]. Some, however, suggested that filling might be helpful in specific cases; for example, to facilitate tumour detection for readers with limited experience in reading rectal MRI or to reduce susceptibility artefacts on diffusion-weighted acquisitions.

7 2528 Eur Radiol (2013) 23: Table 3 Items lacking consensus I MR IMAGING REQUIREMENTS It is unclear what the technique of second choice for rectal cancer staging is. The most frequently suggested techniques of second choice are CT (46 %) and endorectal ultrasound (31 %). There is no consensus on the optimal field strength for adequate rectal cancer staging. It should be at least 1.0 T, but 75 % indicate that 1.5 T and 33 % indicate that 3 T is the optimal field strength. There is no consensus on the benefit of using a 3D T2-weighted sequence. It may be used as an alternative to 2D T2-weighted sequences in three directions. There is agreement that dynamic or steady state contrast enhanced T1-weighted imaging is not helpful, but there is no consensus on the benefit of using unenhanced T1-weighted imaging. There is no consensus on the routine use of spasmolytics. Although axial and coronal images are recommended for low rectal tumours, it is unclear how its angulation should ideally be performed. There was only 54 % agreement that the anal canal should be taken as an anatomical landmark for angulation. A diffusion-weighted sequence is only recommended at restaging MRI after CRT and is beneficial for the evaluation of yt stage. Currently, there is insufficient evidence for the use of DWI at primary staging, nor is there sufficient evidence for its use in lymph nodes and mesorectal fascia (MRF) assessment. II CRITERIA FOR MR IMAGING ASSESSMENT There is no consensus on whether normalisation in shape and border contour are appropriate criteria for sterilisation of lymph nodes after chemoradiation. III MR IMAGING REPORTING There is no consensus on whether after CRT the tumour volume, the circumferential growth and the presence/absence of EMVI should be routinely reported. MR imaging sequences A consensus was reached that the minimum requirement for a standard MR rectal protocol is 2D T2-weighted sequences in sagittal, axial and oblique coronal planes. The sagittal sequence should be used to determine the longitudinal tumour axis in order to angle the axial and coronal planes as perpendicular and parallel to the tumour axis as possible, respectively. For low tumours, coronal planes should be angled parallel to the anal canal so that the relation of the tumour s lower pole to the anal sphincter muscles and its relationship to the adjacent pelvic floor can be evaluated, as this will determine the surgical approach. Armed with this knowledge, surgeons would opt to perform a total mesorectal excision (TME) with low anastomosis or modified TME with wider excision margins [9]. Because the mesorectum and its fascia taper caudally as they funnel towards the pelvis floor, this region (including the anterior pelvic organs, such as the prostate/seminal vesicles in male patients and uterus/vagina in female patients) is at increased risk of involvement by low tumours and angulation of axial planes here is crucial. Despite the higher performance of MRI compared with CT for assessment of anterior invasion into the prostate/seminal vesicles or vagina/uterus this remains very difficult to assess on MRI [10]. Radiographic technicians should be thoroughly trained to perform angulation properly. While use of a 3D T2-weighted sequence could theoretically avoid these difficulties, available evidence is lacking and the panel did not recommend this approach as a replacement for multiplanar 2D T2-weighted sequences. In addition to T2-weighted sequences, the panel recommends that a diffusion-weighted sequence should be included in the restaging MR protocol. There is no evident benefit for diffusion-weighted imaging (DWI) at primary staging but there is growing evidence that DWI improves the diagnostic performance of MRI when evaluating response (the yt-stage) after CRT. DWI is of additional value to T2-weighted fast-spin echo (FSE) sequences to differentiate between the patients whose response is good versus poor [11 13]. The panel did not reach consensus regarding whether DWI is valuable for assessment of a complete response after CRT, although three quarters (75 %) recommended it in this specific setting. There was no consensus regarding any benefit of DWI at restaging for assessment of yn-stage and/or mesorectal fascia involvement after CRT. So far, only a limited number of studies support the use of DWI to evaluate lymph node [14 16] and mesorectal fascia status [17], but no clear evidence is available regarding these specific applications. Around 70 % agreement was reached for the use of DWI for nodal (re)staging. DWI, although probably

8 Eur Radiol (2013) 23: not accurate for nodal characterisation, may be useful for locating nodes, which is supported by the literature [15, 18]. Fat-suppressed sequences were considered inappropriate because the mesorectal fascia is not well visualised. The use of contrast-enhanced dynamic or steady state T1-weighted sequences is not recommended either. While some studies have investigated dynamic contrast-enhanced MRI for tumour response evaluation [19] or lymph-node-specific contrast agents [20, 21] for nodal staging, the available evidence is limited and consensus was reached that at present there is no role for contrast-enhanced MR sequences in either the primary MR staging or restaging of rectal cancer. The use of additional unenhanced T1-weighted sequences to T2- weighted FSE was supported by 25 % of the panelists, mainly to characterise coincidental findings in other pelvic organs. Criteria for MRI assessment A clear consensus was reached for most of the imaging criteria. The main discussion items for which no agreement was achieved were related to size criteria for diagnosis of involved lymph nodes and the evaluation of extramural venous invasion (EMVI). Regarding nodal assessment, panellists all recommend that size should remain the prime criterion for malignancy. The panel was aware that in clinical practice size thresholds in the range of 5 8 mm are often advocated. Available evidence, however, indicates that no single diameter threshold is sufficiently accurate to differentiate benign from malignant nodes, and that the choice of a threshold is contingent upon the desired balance between sensitivity and specificity, which varies per clinical setting. Accordingly, panellists chose not to recommend a single threshold and possible cut-off points ranging between 1 mm (i.e. any visible node) and 6 mm were suggested. Other criteria such as margin irregularity, heterogeneity of nodal texture and shape, are also occasionally beneficial for differentiation [22], although only around % consensus was reached regarding the use of these criteria as predictive markers for nodal metastases on restaging MRI. Regarding the assessment of EMVI as a routine component of MR evaluation, 25 % of the panellists consider it mandatory for primary staging, while 67 % considered it not obligatory but useful. Evidence exists that EMVI assessed by MRI correlates with the presence of EMVI at histology, and that its presence is associated with subsequent relapse and poor survival [23]. For restaging following CRT, there was no agreement as to whether evaluation of EMVI remains beneficial. This lack of consensus probably reflects a paucity of evidence for the benefit of EMVI assessment after preoperative CRT. In currently available publications, EMVI was mainly assessed in patients undergoing immediate surgery (without preoperative treatment). In studies where the whole cohort was investigated, no subset analyses were performed comparing patients undergoing immediate surgery with those undergoing preoperative CRT [23, 24]. MRI reporting Overall, panellists reached excellent consensus regarding those items that should be included routinely in clinical reports, for both primary staging and restaging after CRT (see Table 2). The only items without agreement were whether or not tumour volume and specifically in the restaging setting the extent of circumferential tumour growth and the presence or absence of EMVI should be included in the report. Methodological limitations Our study has a few limitations. A single panellist was absent during the face-to-face meeting. For the items that were discussed and voted upon during the panel meeting, we therefore calculated the percentage of agreement based on the forms for those panellists who were present. Second, most of the panel members were experts mainly working in the field of MRI, which may have introduced some bias into the imaging techniques advised. Third, the recommendations in this paper mainly concern the staging of nonmucinous type adenocarcinoma. No specific recommendations regarding the assessment of mucinous tumours are provided. Also, the paper does not include any recommendations regarding the assessment of rectal tumours with relation to peritoneal reflection. Although in many European centres peritoneal reflection is not routinely used for treatment stratification, in the USA it is often an important landmark that influences the treatment decision whether (if tumour is below the peritoneal reflection) or not (if the tumour is above it) patients should receive neoadjuvant treatment. In these cases there is evidence that radiologists can accurately determine the level of the peritoneal reflection using MRI [25, 26]. A final limitation, inherent to a face-to-face methodology, is that bias might be introduced by the undue influence of any panellists whose personality was prone to dominate during discussions. Nevertheless, we feel that this potential drawback does not outweigh the benefits of the face-to-face design, which provides an opportunity to identify and clarify questions that had been obscure during previous rounds. Moreover, two nonvoting chairs presided over the meeting to ensure that discussions were structured and well-balanced.

9 2530 Eur Radiol (2013) 23: SYNOPSIS AND KEY RECOMMENDATIONS I. RECOMMENDATIONS FOR RECTAL CANCER (MR) IMAGING: Imaging techniques: o MRI is the technique of first choice both for primary staging and restaging after neoadjuvant chemoradiation treatment (CRT). o Endorectal ultrasound is the technique of first choice for the differentiation and staging of T1 tumours. Optimal MR protocol: o Should include 2D T2-weighted sequences in sagittal, axial and coronal planes with a recommended slice thickness ranging between 1 and 3 mm (maximum 4 mm). o The axial and coronal sequences should be angulated perpendicular and parallel to the longest tumour axis as identified on the sagittal images. In low tumours, coronal planes should be angled parallel to the anal canal to evaluate the relationship between the lower pole of the tumour and the anal sphincter complex. o A diffusion-weighted (DWI) sequence is only recommended for restaging after CRT and is beneficial for the evaluation of yt stage. Currently, there is insufficient evidence for the use of DWI for primary T-staging and for assessment of lymph nodes and the mesorectal fascia (MRF). o Use of fat-suppressed and contrast-enhanced sequences is not recommended. o Routine endorectal filling is not recommended. o Spasmolytics may be used in cases where significant bowel movement artefacts are visible on the planning images. Primary staging: o Should comprise an assessment of TN-stage, MRF involvement and extramural vascular invasion (EMVI). o Stranding into mesorectal fat is an equivocal sign that may indicate either a T2 or T3 tumour o Predictive criteria for lymph node involvement are round shape, irregular border contour and heterogeneous signal intensity. Size is a predictor, but there is no optimal cut-off threshold for involved nodes. o The MRF is involved if the distance between it and the tumour is 1 mm. A tumour to MRF distance of 1 to 2 mm indicates a threatened MRF. Restaging after CRT: o Should comprise an MR assessment of ytn-stage and MRF involvement. There is no consensus on whether EMVI should be reassessed after CRT. o A normal, two-layered rectal wall after CRT is suggestive of a complete response, whereas any fibrotic residue is an equivocal feature that may indicate either residual tumour or complete response. o Nodal size (short axis diameter) after CRT is more reliable. A reduction in size and homogeneity of nodal signal intensity are predictive of a sterilized node. It is unclear whether normalization of the shape or border is an indicator of sterilized nodes. o If a fat pad reappears between the tumour and MRF after CRT, the MRF should be considered uninvolved. Persistent stranding into the MRF should be considered an equivocal sign that may or may not indicate persistent MRF involvement. II. RECOMMENDATIONS FOR MRI REPORTING IN RECTAL CANCER: Primary staging: A primary MRI staging report should include: o The distance from the anorectal junction to the lower pole of the tumour o Tumour length, T-stage and any tumour deposits within the mesorectum o N-stage including any suspicious extramesorectal lymph nodes o Involvement of the MRF including the shortest distance (mm) between the tumour and MRF and its location ( o clock) The following items are not obligatory but recommended: o The circumferential location of the tumour (lateral, anterior, posterior) o In case of a T3 tumour, the extent (mm) of extramural growth o The number of suspicious lymph nodes o Extramural vascular invasion (EMVI) o The morphological pattern of tumour growth (annular, polypoid, mucinous, ulcerated, perforated) Restaging after CRT: A restaging MRI report should include: o The presence of residual tumour and/or fibrosis o The distance from the anorectal junction to the lower pole of the tumour o Tumour length, yt-stage and any remaining tumour deposits within the mesorectum o yn-stage and number of remaining suspicious lymph nodes within and outside the mesorectum o Persistent MRF involvement including the shortest distance (mm) between the tumour and MRF and its location ( o clock) The following items are not obligatory but recommended: o The circumferential location of the tumour (lateral, anterior, posterior) o In case of a T3 tumour, the extent (mm) of extramural growth o The morphological pattern of tumour growth (annular, polypoid, mucinous, ulcerated, perforated)

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