Management of rectal cancer in the era of total neoadjuvant therapy and watch and wait: A multidisciplinary team discussion at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting 2022.

Rectal cancer is a common malignancy. The management of rectal cancer has recently evolved and has undergone a paradigm shift with the advent of treatment approaches such as total neoadjuvant therapy and the watch-and-wait approach. However, despite the recently available evidence, there is no consensus on the optimal management approach in the setting of locally advanced rectal cancer. To address some of the controversies, a joint multidisciplinary panel discussion was conducted at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting in November 2022. Members from different subspecialties formed two panels and discussed three clinical cases in a debate format. Each case represented some of the complex issues faced by clinicians in this setting. The discussion is now presented in this manuscript, which depicts the different available management approaches and reiterates the importance of a multidisciplinary approach.

MRI restaging of rectal cancer: The RAC (Response-Anal canal-CRM) analysis joint consensus guidelines of the GRERCAR and GRECCAR groups.

PURPOSE: To develop guidelines by international experts to standardize data acquisition, image interpretation, and reporting in rectal cancer restaging with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Evidence-based data and experts' opinions were combined using the RAND-UCLA Appropriateness Method to attain consensus guidelines. Experts provided recommendations for reporting template and protocol for data acquisition were collected; responses were analysed and classified as "RECOMMENDED" versus "NOT RECOMMENDED" (if ≥ 80% consensus among experts) or uncertain (if < 80% consensus among experts). RESULTS: Consensus regarding patient preparation, MRI sequences, staging and reporting was attained using the RAND-UCLA Appropriateness Method. A consensus was reached for each reporting template item among the experts. Tailored MRI protocol and standardized report were proposed. CONCLUSION: These consensus recommendations should be used as a guide for rectal cancer restaging with MRI.

Assessment of a single-pass venous phase CT chest, abdomen and pelvis and dual-energy CT in general oncology outpatients.

INTRODUCTION: This study assessed replacing traditional protocol CT-arterial chest and venous abdomen and pelvis, with a single-pass, single-bolus, venous phase CT chest, abdomen and pelvis (CAP) protocol in general oncology outpatients at a single centre. METHODS: A traditional protocol is an arterial phase chest followed by venous phase abdomen and pelvis. A venous CAP (vCAP) protocol is a single acquisition 60 s after contrast injection, with optional arterial phase upper abdomen based on the primary tumour. Consecutive eligible patients were assessed, using each patient's prior study as a comparator. Attenuation for various structures, lesion conspicuity and dose were compared. Subset analysis of dual-energy (DE) CT scans in the vCAP protocol performed for lesion conspicuity on 50 keV virtual monoenergetic (VME) images. RESULTS: One hundred and eleven patients were assessed with both protocols. Forty-six patients had their vCAP scans using DECT. The vCAP protocol had no significant difference in the attenuation of abdominal structures, with reduced attenuation of mediastinal structures. There was a significant improvement in the visibility of pleural lesions (p < 0.001), a trend for improved mediastinal nodes assessment, and no significant difference for abdominal lesions. A significant increase in liver lesion conspicuity on 50 keV VME reconstructions was noted for both readers (p < 0.001). There were significant dose reductions with the vCAP protocol. CONCLUSION: A single-pass vCAP protocol offered an improved thoracic assessment with no loss of abdominal diagnostic confidence and significant dose reductions compared to traditional protocol. Improved liver lesion conspicuity on 50 keV VME images across a range of cancers is promising.

A longitudinal cohort study of watch and wait in complete clinical responders after chemo-radiotherapy for localised rectal cancer: study protocol.

BACKGROUND: Rectal Cancer is a common malignancy. The current treatment approach for patients with locally advanced rectal cancer involves neoadjuvant chemoradiotherapy followed by surgical resection of the rectum. The resection can lead to complications and long-term consequences. A clinical complete response is observed in some patients after chemoradiotherapy. A number of recent studies have shown that patients can be observed safely after completing chemoradiotherapy (without surgery), provided clinical complete response has been achieved. In this approach, resection is reserved for cases of regrowth. This is called the watch and wait approach. This approach potentially avoids unnecessary surgical resection of the rectum and the resulting complications. In this study, we will prospectively investigate this approach. METHODS: Adult patients with a diagnosis of rectal cancer planned to receive neoadjuvant long course chemoradiotherapy (± subsequent combination chemotherapy) will be consented into the study prior to commencing treatment. After completing the chemoradiotherapy (± subsequent combination chemotherapy), based on the clinical response, subjects will be allocated to one of the following arms: subjects who achieved a clinical complete response will be allocated to the watch and wait arm and others to the standard management arm (which includes resection). The aim of the study is to determine the rate of local failure and other safety and efficacy outcomes in the watch and wait arm. Patient reported outcome measures and the use of biomarkers as part of the clinical monitoring will be studied in both arms of the study. DISCUSSION: This study will prospectively investigate the safety of the watch and wait approach. We will investigate predictive biomarkers (molecular biomarkers and imaging biomarkers) and patient reported outcome measures in the study population and the cost effectiveness of the watch and wait approach. This study will also help evaluate a defined monitoring schedule for patients managed with the watch and wait approach. This protocol covers the first two years of follow up, we are planning a subsequent study which covers year 3-5 follow up for the study population. TRIAL REGISTRATION: Name of the registry: Australia and New Zealand Clinical Trials Registry (ANZCTR). TRIAL REGISTRATION NUMBER: Trial ID: ACTRN12619000207112 Registered 13 February 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376810.

Structured and shared MRI staging lexicon and report of rectal cancer: A consensus proposal by the French Radiology Group (GRERCAR) and Surgical Group (GRECCAR) for rectal cancer.

PURPOSE: To develop French guidelines by experts to standardize data acquisition, image interpretation, and reporting in rectal cancer staging with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Evidence-based data and opinions of experts of GRERCAR (Groupe de REcherche en Radiologie sur le CAncer du Rectum [i.e., Rectal Cancer Imaging Research Group]) and GRECCAR (Groupe de REcherche en Chirurgie sur le CAncer du Rectum [i.e., Rectal Cancer Surgery Research Group]) were combined using the RAND-UCLA Appropriateness Method to attain consensus guidelines. Experts scoring of reporting template and protocol for data acquisition were collected; responses were analyzed and classified as "Recommended" versus "Not recommended" (when ≥ 80% consensus among experts) or uncertain (when < 80% consensus among experts). RESULTS: Consensus regarding patient preparation, MRI sequences, staging and reporting was attained using the RAND-UCLA Appropriateness Method. A consensus was reached for each reporting template item among the experts. Tailored MRI protocol and standardized report were proposed. CONCLUSION: These consensus recommendations should be used as a guide for rectal cancer staging with MRI.

Optimising CT-chest protocols and the added value of venous-phase contrast timing; Observational case-control.

INTRODUCTION: To optimize CT chest protocol by comparing venous contrast timing with arterial timing for contrast opacification in vessels, qualitative image quality and radiologists' satisfaction and diagnostic confidence in assessing for potential nodal, pleural and pulmonary disease in general oncology outpatients. METHOD: Matched case-control study performed following CT protocol update. 92 patients with a range of primary malignancies with 2 CT chests in a 2-year period, one with an arterial phase protocol and the second in the 60 second venous phase, were included. Contrast attenuation in aorta, pulmonary artery and liver were measured. Subjective measurements assessed perivenous artefact, confidence in nodal pleural and pulmonary assessment and presence of pulmonary emboli. Statistical analysis was performed using paired and unpaired t-tests. RESULTS: Venous-phase CT demonstrated more consistent enhancement of the vessels, with higher attenuation of the nodes, pulmonary and pleural lesions. There was a significant reduction in perivenous beam hardening artefact on venous-phase CT (P < 0.001). Diagnostic confidence was significantly higher for nodal assessment and pleural abnormality visibility (P < 0.001) and pleural assessment (P < 0.05). There was no significant difference in pulmonary mass visibility. There was adequate enhancement to diagnose significant pulmonary emboli (PE) with 4 incidental PEs detected on the venous phase, extending to segmental vessels. CONCLUSION: Venous-phase CT chest performs better than arterial-phase on all fronts, without compromising assessment of incidental pulmonary emboli. When intravenous contrast is indicated in a routine chest CT (excluding a CT-angiogram), the default timing should be a venous or 60s phase.

Rectal MRI: the importance of high resolution T2 technique.

The cornerstone of the MRI rectal examination is the high resolution (HR) T2 sequence. There is varied definition of this term in national guidelines with a resultant wide variation in the spatial resolution of sequences termed 'high resolution'. This article comments on the importance of the original three dimensional HR T2 definition of 0.6 × 0.6 in plane resolution × 3 mm slice thickness with 4 NEX and demonstrates the effect reduced spatial resolution can have on image appearance and interpretation.

SPAR - a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: an AGITG clinical trial.

BACKGROUND: Retrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy (pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG). METHODS: A double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia. Patients will receive simvastatin 40 mg or placebo daily for 90 days starting 1 week prior to standard pCRT. Pelvic MRI 6 weeks after pCRT will assess mrTRG grading prior to surgery. The primary objective is rates of favourable (grades 1-2) mrTRG following pCRT with simvastatin compared to placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4-5). Secondary objectives include comparison of: rates of favourable pathTRG in resected tumours; incidence of toxicity; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection; cancer outcomes and pathological scores for radiation colitis. Tertiary objectives include: association between mrTRG and pathTRG grouping; inter-observer agreement on mrTRG scoring and pathTRG scoring; studies of T-cell infiltrates in diagnostic biopsies and irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Trial recruitment commenced April 2018. DISCUSSION: When completed this study will be able to observe meaningful differences in measurable tumour outcome parameters and/or toxicity from simvastatin. A positive result will require a larger RCT to confirm and validate the merit of statins in the preoperative management of rectal cancer. Such a finding could also lead to studies of statins in conjunction with chemoradiation in a range of other malignancies, as well as further exploration of possible mechanisms of action and interaction of statins with both radiation and chemotherapy. The translational substudies undertaken with this trial will provisionally explore some of these possible mechanisms, and the tissue and data can be made available for further investigations. TRIAL REGISTRATION: ANZ Clinical Trials Register ACTRN12617001087347. (www.anzctr.org.au, registered 26/7/2017) Protocol Version: 1.1 (June 2017).

Prostate MRI evolution in clinical practice: Audit of tumour detection and staging versus prostatectomy with staged introduction of multiparametric MRI and Prostate Imaging Reporting and Data System v2 reporting.

INTRODUCTION: We conducted a retrospective audit to compare dominant nodule detection and local staging before and after the introduction of functional sequences and PI-RADS v2 reporting to MRI prostate scans in routine private practice. METHODS: A retrospective audit was performed of 245 patients in four separate groups undergoing robotic prostatectomy for prostate cancer by a single urologist between 2009 and 2017. The initial 100 consecutive patients had T2 imaging only. The next 43 patients had T2 and DWI. 52 subsequent patients had T2, DWI and DCE sequences (mpMRI). A final 50 consecutive patients had mpMRI using PI-RADS v2 reporting. Preoperative MRI reports were compared with prostatectomy histopathology to determine the sensitivity of MRI in detecting dominant tumour nodule and T3 extension. RESULTS: The addition of DWI and DCE sequences improved sensitivity for detection of dominant tumour nodule, with a significant further increase using PI-RADS v2 reporting (38% for T2 vs. 62% for T2/DWI vs. 67% for mpMRI vs 91% for PI-RADS v2). The accuracy of detecting T3 disease was initially very low. The use of additional imaging techniques did not significantly influence this, but the use of a three category likelihood of extraprostatic extension in the PI-RADS v2 group had a significant increase in detection of T3 disease (sensitivity 27% vs. 23% vs. 38% vs 63%). CONCLUSION: This audit tracks the significant improvements in MRI detection of prostate cancer dominant tumour nodule and T3 extension in patients undergoing prostatectomy with changing techniques and reporting standards in routine clinical practice.

Does the Prostate Imaging-Reporting and Data System (PI-RADS) version 2 improve accuracy in reporting anterior lesions on multiparametric magnetic resonance imaging (mpMRI)?

INTRODUCTION: Multiparametric MRI (mpMRI) is useful in detecting anterior prostate tumours. Due to the location of anterior tumours, they are often diagnosed with a large size and may be suspicious for extra-prostatic extension (EPE). We aim to evaluate whether PI-RADS v2 is more accurate in assessing anterior prostate lesions identified on mpMRI compared to PI-RADS v1. METHODS: Patients with anterior prostate lesions diagnosed on mpMRI who proceeded to a cognitive fusion transperineal prostate biopsy were identified. Each mpMRI was blinded and read by two experienced prostate MRI radiologists and assigned a PI-RADS v1 and PI-RADS v2 score, and the presence of EPE was estimated. Correlation was made with transperineal histopathology and, where relevant, radical prostatectomy histopathology. Concordance measures between PI-RADS v1 and PI-RADS v2, and between examiners of the same PI-RADS score were calculated using a weighted kappa. RESULTS: Fifty-eight consecutive men were identified. Concordance between the examiners for PI-RADS v1 and for v2 showed substantial agreement (version 1: weighted kappa 0.71; version 2: weighted kappa 0.69). There was no difference in accuracy when using PI-RADS v1 or PI-RADS v2 to predict clinically significant cancer. There was poor correlation between EPE measured on mpMRI compared with EPE in radical prostatectomy histopathology. CONCLUSION: PI-RADS v2 is reproducible between radiologists but does not have improved accuracy for diagnosing anterior tumours of the prostate when compared to PI-RADS v1. Multiparametric MRI is accurate at detecting anterior tumours with a sensitivity of 86-88%.

Uncommon Anal Neoplasms.

Uncommon neoplasms of the anal canal are associated with significant diagnostic dilemma in clinical practice and a high index of suspicion and pathologic expertise is needed. The incidence is likely to increase, particularly of small, incidental lesions found because of use of more frequent colonoscopy and high-definition MRI. Generally treatment follows that of the same histologic subtype in other anatomic location. Surgical intervention is the cornerstone for cure in early/localized disease; however, removal of the anal canal is associated with significant morbidities and quality of life issues. A centralized global registry/database established under the auspices of the International Rare Care Initiative collaboration would be useful.

MRI rectal cancer in Australia and New Zealand: An audit from the PETACC-6 trial.

INTRODUCTION: An MRI audit substudy was conducted in patients who underwent an MRI prior to treatment in Australia and New Zealand as part of the PETACC-6 trial in locally advanced rectal cancer. METHODS: A total of 82 patients from 15 centres had rectal MRI scans reviewed for technique, data included in reports and comparison of reports with blinded central reporting by two experienced radiologists. RESULTS: In total, 82% performed minimum T2 sagittal and T2 axial oblique sequences. The high-resolution T2 sequence parameters varied significantly with only 33% obtaining a voxel size of <1.3 mm3 . The rate of inclusion of relevant findings in the reports was T3 distance in mm 21%, N stage 84%, circumferential resection margin (CRM) status 72%, extramural venous invasion (EMVI) status 29% and distance from the puborectalis sling 17%. In total, 31% reports included all of T stage with T3 substage, N stage and CRM involvement. In total, 17% reports included these 3 findings and EMVI. Eleven reports used a template with 82% of these including the first 3 findings. The agreement with central reporters was T stage 76%, N stage 70%, CRM status 57% and EMVI 16%. CONCLUSION: There is significant variation in scan quality and low rates of including all relevant findings in rectal MRI reports in the audit. The authors recommend adoption of routine sequences and template reports in both trial settings and routine practice to improve scan technique and adequacy of reports in rectal cancer MRI staging scans across Australia and New Zealand.

Primary pericardial mesothelioma presenting as multiple pericardial masses on CT.

We present the case of a 67-year-old male who was found to have multiple enhancing pericardial masses on CT imaging for investigation of weight loss and was subsequently diagnosed with primary pericardial mesothelioma. Although rare, pericardial mesothelioma is the most common primary malignancy of the pericardium and should be considered in the differential diagnosis of pericardial effusion, pericardial thickening or discreet pericardial mass. It is important for radiologists to be aware of pericardial mesothelioma as its clinical presentation is non-specific and it may be incidentally noted on radiological studies for investigation of apparently non-related symptoms. The prognosis of primary pericardial mesothelioma is universally poor.

Calcified nodal metastasis from squamous cell carcinoma of the head and neck.

Calcification within cervical lymph nodes is relatively rare, and most commonly ascribed to benign inflammatory or infectious processes. We present a case of a calcified submandibular nodal metastasis from squamous cell carcinoma of the lip and review the current published literature on nodal calcifications in the neck. To the authors' knowledge, calcification resulting from metastatic squamous cell carcinoma of the head and neck has been described only once previously.