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Background: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumor burden. Response Evaluation Criteria in Solid Tumors (RECIST) provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardized imaging protocol tailored to mCRC patients. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging endpoints and is an obstacle for research on novel imaging endpoints. Patients and methods: Acknowledging the recently highlighted potential of radiomics and artificial intelligence (AI) tools as decision support for patient care in mCRC, a multidisciplinary, international, and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method. Results: Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified. Conclusion: This consensus protocol attempts to promote standardization and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardization will increase reproducibility of radiomics and AI studies and serve as a catalyst for future research on imaging endpoints. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centers., peer-reviewed

Additional file 1. Supplementary tables and figure

Response evaluation criteria in solid tumours (RECIST) v1.1 are currently the reference standard for evaluating efficacy of therapies in patients with solid tumours who are included in clinical trials, and they are widely used and accepted by regulatory agencies. This expert statement discusses the principles underlying RECIST, as well as their reproducibility and limitations. While the RECIST framework may not be perfect, the scientific bases for the anticancer drugs that have been approved using a RECIST-based surrogate endpoint remain valid. Importantly, changes in measurement have to meet thresholds defined by RECIST for response classification within thus partly circumventing the problems of measurement variability. The RECIST framework also applies to clinical patients in individual settings even though the relationship between tumour size changes and outcome from cohort studies is not necessarily translatable to individual cases. As reproducibility of RECIST measurements is impacted by reader experience, choice of target lesions and detection/interpretation of new lesions, it can result in patients changing response categories when measurements are near threshold values or if new lesions are missed or incorrectly interpreted. There are several situations where RECIST will fail to evaluate treatment-induced changes correctly; knowledge and understanding of these is crucial for correct interpretation. Also, some patterns of response/progression cannot be correctly documented by RECIST, particularly in relation to organ-site (e.g. bone without associated soft-tissue lesion) and treatment type (e.g. focal therapies). These require specialist reader experience and communication with oncologists to determine the actual impact of the therapy and best evaluation strategy. In such situations, alternative imaging markers for tumour response may be used but the sources of variability of individual imaging techniques need to be known and accounted for. Communication between imaging experts and oncologists regarding the level of confidence in a biomarker is essential for the correct interpretation of a biomarker and its application to clinical decision-making. Though measurement automation is desirable and potentially reduces the variability of results, associated technical difficulties must be overcome, and human adjudications may be required.

Introduction Colorectal cancer (CRC), the 2nd cause of cancer death worldwide, is an indolent disease with 50% of patients eventually developing liver metastases (mCRC). Repeated cycles of different chemotherapies, combined with surgery in oligo-metastatic cases, are the therapeutic standard in mCRC. However, this strategy is resolutive in less than 15% of cases. Differentiating non- and short-term responders from potentially “cured” patients will spare patients needless toxicity and allow alternative treatments earlier, with conceivable cost and life savings. In this study we aimed to use CT texture analysis (CTTA) to identify specific imaging biomarkers of hepatic metastases, able to predict patient’s response to therapy and overall survival. Methods We exploited the imaging data-set of the HERACLES trial (NCT03225937): 23 patients with amplified Human Epidermal growth factor Receptor 2 (HER2) mCRC were included in the study. All had received anti HER2 treatment, and underwent CT examination every 8 weeks, until disease progression. CT scans were semi-automatically segmented to extract for each patient all liver metastases. Texture analysis was performed on each segmented area, computing for each lesion 34 quantitative parameters. Both mono-parametric and multi-parametric analysis were assessed to identify features most correlated to therapy response. We also performed a correlative survival (OS) analysis, considering subjects with good survival those with OS > 9 months. Results In 23 patients we found 124 metastases, 55 of which were classified as responding and 69 as non-responding. Nine parameters reached statistical significance in the mono-parametric analysis (best AUC=0.67, p=0.001), while in the multivariate regression ten parameters were used in the model, achieving and AUC equal to 0.82, with sensitivity of 82% and specificity 72%. For OS analysis, 12 patients were “good” and 11 “poor” survivors. In the mono-parametric analysis “cluster prominence” and “sum entropy” predicted OS with AUC equal to 0.78 and 0.83, respectively. The regression model with two variables (“cluster prominence” and “dissimilarity”) reached a sensitivity of 83% and a specificity of 82%. Conclusions Our study demonstrated CTTA as a potential biomarker to predict response of hepatic metastases to chemotherapy treatment, possibly saving patients predicted as non-responder from toxicity. Moreover, CTTA could give indications on patients OS, without the need for additional tests.

Electronic cleansing (EC) is used for computational removal of residual feces and fluid tagged with an orally administered contrast agent on CT colonographic images to improve the visibility of polyps during virtual endoscopic "fly-through" reading. A recent trend in CT colonography is to perform a low-dose CT scanning protocol with the patient having undergone reduced- or noncathartic bowel preparation. Although several EC schemes exist, they have been developed for use with cathartic bowel preparation and high-radiation-dose CT, and thus, at a low dose with noncathartic bowel preparation, they tend to generate cleansing artifacts that distract and mislead readers. Deep learning can be used for improvement of the image quality with EC at CT colonography. Deep learning EC can produce substantially fewer cleansing artifacts at dual-energy than at single-energy CT colonography, because the dual-energy information can be used to identify relevant material in the colon more precisely than is possible with the single x-ray attenuation value. Because the number of annotated training images is limited at CT colonography, transfer learning can be used for appropriate training of deep learning algorithms. The purposes of this article are to review the causes of cleansing artifacts that distract and mislead readers in conventional EC schemes, to describe the applications of deep learning and dual-energy CT colonography to EC of the colon, and to demonstrate the improvements in image quality with EC and deep learning at single-energy and dual-energy CT colonography with noncathartic bowel preparation. RSNA, 2018.

Supplemental material for Cost-effectiveness of colorectal cancer screening programmes using sigmoidoscopy and immunochemical faecal occult blood test by Carlo Senore, Cesare Hassan, Daniele Regge, Eva Pagano, Gabriella Iussich, Loredana Correale and Nereo Segnan in Journal of Medical Screening

To assess the effect of computer-aided detection (CAD) as a second reader on the sensitivity and specificity of computed tomographic (CT) colonography in detecting 6-9-mm colorectal cancer (CRC) lesions.Individuals with clinical indications for colonoscopy--either for symptoms or as part of participating in a surveillance program or CRC screening--were prospectively enrolled at one of 10 academic centers between July 2007 and May 2009. Institutional review board approval was obtained at each clinical site, and all participants provided written informed consent. All participants underwent CT colonography and colonoscopy on the same day. Experienced readers interpreted the CT colonography images unassisted and then reviewed all colorectal lesion-like structures pinpointed by the CAD algorithm. Segmental unblinding of CT colonoscopy findings at colonoscopy was utilized. The sensitivity and specificity of unassisted and CAD-assisted reading in identifying individuals with 6-9-mm lesions were calculated and compared by means of pairwise analysis.A total of 618 participants (mean age, 57.9 years; 54.5% male) were included in the final analysis. Of these participants, 464 (75.1%) had no lesions 6 mm or larger, and 52 (8.4%) had 6-9-mm lesions. The sensitivity of CT colonography with unassisted reading and that with CAD-assisted reading in identifying individuals with 6-9-mm lesions was 65.4% (95% confidence interval [CI]: 50.9%, 78.0%) and 76.9% (95% CI: 63.2%, 87.5%; P = .016), respectively. No significant change in specificity was observed: The specificity of CT colonography with unassisted and that with CAD-assisted reading was 91.8% (95% CI: 88.9%, 94.1%) and 90.9% (95% CI: 88.0%, 93.4%; P = .063), respectively. Evaluation of CAD candidates required an additional 1.6 minutes (25th-75th percentile: 1.0 minute to 3.4 minutes).The addition of CAD to reading performed by experienced readers resulted in a significant benefit in the detection of 6-9-mm polyps at CT colonography in this cohort.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120376/-/DC1.

Purpose: To prospectively compare clinical breast examination (CBE), mammography, ultrasonography (US), and contrast material-enhanced magnetic resonance (MR) imaging for screening women at genetic-familial high risk for breast cancer and report interim results, with pathologic finding as standard. Materials and Methods: Institutional review board of each center approved the research; informed written consent was obtained. CBE, mammography, US, and MR imaging were performed for yearly screening of BRCA1 or BRCA2 mutation carriers, first-degree relatives of BRCA1 or BRCA2 mutation carriers, or women enrolled because of a strong family history of breast or ovarian cancer (three or more events in first-or second-degree relatives in either maternal or paternal line; these included breast cancer in women younger than 60 years, ovarian cancer at any age, and male breast cancer at any age). Results: Two hundred seventy-eight women (mean age, 46 years ± 12 [standard deviation]) were enrolled. Breast cancer was found in 11 of 278 women at first round and seven of 99 at second round (14 invasive, four intraductal; eight were ≤10 mm in diameter). Detection rate per year was 4.8% (18 of 377) overall; 4.3% (11 of 258) in BHCA1 or BRCA2 mutation carriers and first-degree relatives of BRCA1 or BRCA2 mutation carriers versus 5.9% (seven of 119) in women enrolled because of strong family history; and 5.3% (nine of 169) in women with previous personal breast and/or ovarian cancer versus 4.3% (nine of 208) in those without. In six (33%) of 18 patients, cancer was detected only with MR imaging. Sensitivity was as follows: CBE, 50% (95% confidence interval [CI]: 29%, 71%); mammography, 59% (95% CI: 36%, 78%); US, 65% (95% CI: 41%, 83%); and MR imaging, 94% (95% CI: 82%, 99%). Positive predictive value was as follows: CBE, 82% (95% CI: 52%, 93%); mammography, 77% (95% CI: 50%, 92%); US, 65% (95% CI: 41%, 83%); and MR imaging, 63% (95% CI: 43%, 79%). Conclusion: Addition of MR imaging to the screening regimen for high-risk women may enable detection of otherwise unsuspected breast cancers. © RSNA, 2007.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a radiological tool for the detection and discrimination of breast lesions. The aim of this study is to evaluate a computer-aided diagnosis (CAD) system for discriminating malignant from benign breast lesions at DCE-MRI by the combined use of morphological, kinetic, and spatiotemporal lesion features.Fifty-four malignant and 19 benign breast lesions in 51 patients were retrospectively evaluated. Images were acquired at two centers at 1.5 T. Mass-like lesions were automatically segmented after image normalization and elastic coregistration of contrast-enhanced frames. For each lesion, a set of 28 3D features were extracted: ten morphological (related to shape, margins, and internal enhancement distribution); nine kinetic (computed from signal-to-time curves); and nine spatiotemporal (related to the variation of the signal between adjacent frames). A support vector machine (SVM) was trained with feature subsets selected by a genetic search. Best subsets were composed of the most frequent features selected by majority rule. The performance was measured by receiver operator characteristics analysis with a stratified tenfold cross-validation and bootstrap method for confidence intervals.SVM training by the three separated classes of features resulted in an area under the curve (AUC) of 0.90 ± 0.04 (mean ± standard deviation), 0.87 ± 0.06, and 0.86 ± 0.06 for morphological, kinetic, and spatiotemporal feature, respectively. Combined training with all 28 features resulted in AUC of 0.96 ± 0.02 obtained with a selected feature subset composed by two morphological, one kinetic, and two spatiotemporal features.Quantitative combination of morphological, kinetic, and spatiotemporal features is feasible and provides a higher discriminating power than using the three different classes of features separately.

Purpose Methods and Materials Results Conclusion References Personal Information, Purpose: To determine ADC values of healthy peripheral zone, tumoral peripheral zone, healthy central gland and tumoral central gland and identify an ADC diagnostic threshold for the clinical...

Daniele Regge,1 Stefano Cirillo,1 Annalisa Macera,1 Giovanni Galatola21Radiology Unit, 2Gastroenterology Unit, Institute for Cancer Research and Treatment, Candiolo, Turin, ItalyAbstract: Mangafodipir trisodium is a hepatobiliary contrast agent, taken up by the hepatocytes and largely excreted via the bile ducts. The agent increases the signal intensity of the normal liver, and to a lesser extent of the pancreas, adrenal glands, kidneys and myocardium, on T1-weighted imaging. The increase of the signal intensity on the T1 images allows better visualization of focal lesions, especially of those that are of non-hepatocitary origin such as metastases. For this reason the most important indication for the use of mangafodipir trisodium is in detecting liver metastases, especially when the information may influence therapeutic planning, which in many cases is surgical resection. New data show that this liver-specific contrast agent is accurate in detecting small lesions and in assessing the liver status following neoadjuvant chemotherapy, where other imaging techniques, such as CT and PET, fail. Other lesser indications for studies with mangafodipir trisodium are: in characterizing liver and pancreatic lesions; in identifying biliary leakage following bile duct and/or liver surgery; and possibly in the future in the assessment of the extent of myocardial damage.Keywords: mangafodipir trisodium, magnetic resonance imaging, contrast agent

To assess the diagnostic accuracy and predictive value of Lipiodol CT for hepatocellular carcinoma (HCC) before liver transplantation (OLT).Seventy-eight cirrhotic patients awaiting OLT underwent Lipiodol CT to demonstrate the presence and extent of possible HCC. Radiologically, focal uptake areas with dense, homogeneous or "mosaic" iodized oil uptake were considered to be neoplastic nodules. All patients underwent OLT within 4 months of Lipiodol CT. Pathologic examination of the explanted livers was performed using the standard technique and, if necessary, with additional slices. Pathologic findings were compared with radiologic results to calculate the diagnostic accuracy and predictive value of Lipiodol CT in relation to both patients and lesions.Lipiodol CT depicted 61 focal areas of iodized oil uptake in 48 patients; pathologic examinations detected 57 HCC lesions in 42 patients (diameter .8 cm, mean 2.2 cm); agreement with radiologic diagnosis was found in 35 patients only. Patient by patient, Lipiodol CT had 83.3% sensitivity, 63.8% specificity, 74.3% diagnostic accuracy, 72.9% positive predictive value (PPV), and 76.6% negative predictive value. Lesion by lesion, Lipiodol CT showed overall sensitivity and PPV of 75.4-70.5%, 74-69.8% for "small" HCCs (diameteror = 3 cm), and 72.9-71.1% for nodulesor = 2 cm in size. Eighteen uptake areas in 13 patients were diagnosed as HCC by Lipiodol CT but the finding was not confirmed at histology: 4 were hemangiomas and 14 corresponded to cirrhotic tissue without neoplastic foci.Our study, as the few others comparing radiologic results and pathologic findings of whole explanted liver, demonstrates that Lipiodol CT has relatively low diagnostic accuracy; particularly, specificity and PPV were limited by possible false positives, with HCC overstaging and mistakes in the indications/contraindications for OLT.

The correct selection of patients for liver transplantation, which is essential for surgical success, requires thorough radiological evaluation. The authors present their experience on 94 pretransplant adult patients that underwent a total of 251 diagnostic exams (Doppler US, CT, angiography and cholangiography) and interventional radiology maneuvers (biopsy, chemoembolization, biliary drainage). Three sclerosing cholangitis, 3 Budd-Chiari syndromes and 20 hepatocellular carcinomas in cirrhotic patients were identified; venous collaterals were present in 62.7% of the cases, 12.8%, of which had important spontaneous porto-systemic shunts; 6 patients had portal thrombosis; 20 arterial variations were found. Interventional maneuvers were useful and free of complications. US, CT and angiographic findings of each patient were compared. Integrating informations from different exams allowed a significant increase in the accuracy of diagnostic conclusions. Thanks to interventional maneuvers 5 patients could be selected for transplantation (hepatic arterial lipiodolization stopped the growth of 4 hepatic neoplasms; 2 infected fluid collections were sterilized by percutaneous US-guided drainage and topic therapy.

Some complications of liver transplantation appear as aspecific clinical and blood test abnormalities; others--e.g., hepatic artery thrombosis in the immediate postoperative period and stenosis of the biliary anastomosis before T-tube removal--require early diagnosis. These considerations justify the need of frequent radiologic examination in both the complicated course and the follow-up. The authors report their experience in 59 adult patients submitted to liver transplantation for irreversible liver disease in advanced stage (49 with cirrhosis, 10 with HCC; 5 with cholestatic hepatopathy; 3 with fulminant hepatitis; 1 with Budd-Chiari syndrome; 1 with metastatic APUDoma). Two hundred and sixty-three radiological examinations were performed (Doppler US, CT, angiography and cholangiography) which showed numerous early and delayed complications: 13 of them were treated with interventional radiology maneuvers (US-or CT-guided percutaneous drainage of fluid collections, biliary drainage, bilioplasty, arterial transcatheter embolization). Our results demonstrate that diagnostic and operative radiology are essential for the success of liver transplantation; integrated imaging is particularly important in the diagnosis of complications, while interventional radiology techniques can be usefully employed in their treatment.

Both traditional exams (rectal exploration, rectoscopy, barium enema, CEA) and advanced imaging (31 US, 40 CT and 11 MR) were performed for preoperative evaluation of rectal carcinoma in order to assess the accuracy of radiological imaging in the T and N staging. The results obtained have not been considered satisfactory and it is felt that US, CT and MR should not be employed routinely for rectal staging. Indeed accuracy of US, CT and MR is respectively 64%, 75% and 81% in the T evaluation and 64%, 70% and 64% in the N staging. In order to evaluate the effective usefulness of these three latter imaging techniques a double therapeutical choice was proposed. The first treatment option was suggested on the basis of traditional staging while a second choice was given considering US, TC and MR data also. Operatory findings subsequently allowed a definitive judgement on the influence of the different techniques on treatment selection. US has furnished useful data that could have allowed us to modify treatment in one case while in 5 other cases diagnostic error would have influenced treatment negatively. CT was useful in 5 cases while in 7 cases it would have influenced treatment choice negatively. MR would have been useful in one case and harmful in another. It is concluded that only patients with large neoplasms (stages T3 and T4) benefit from CT and MR staging with the exception of those cases that have tumors above the peritoneal fold or in strict relation with the sphincter structures. US was useful only in evaluating relations of neoplasms of the anterior rectal wall with nearby pelvic structures.

The results are reported of percutaneous transhepatic treatment with an electrohydraulic lithotripter in 4 cases of bile duct lithiasis. An electric discharge, generated by a bipolar electrode, gives origin to high-amplitude and low-frequency shock waves in the fluid medium which cause the stone to fragment. Complete resolution of lithiasis was obtained in 2 patients with intrahepatic calculosis. In the other 2 cases of massive lithiasis of intra and extrahepatic bile ducts the treatment, however incomplete, proved to be useful, as the biliary flux was rehabilitated and clinical symptoms disappeared. No relevant immediate side-effects were observed, except for well-tolerated pain during the discharges, and transitory hemobilia which solved spontaneously. No complications were observed in this series of patients. Electrohydraulic lithotripsy proves thus to be useful for supporting standard interventional radiology techniques in very complex cases of intra- and extrahepatic bile duct stones.

CT can be considered the most reliable technique in detecting nodal metastases of the cervical district. The Authors have studied 170 patients with laryngeal cancer (104 N0, 21 N1, 21 N2 and 24 N3 clinically) with CT of the cervical region during infusion of contrast material. All patients underwent radical neck dissection with pathological examination of the nodes. CT diagnosis and pathological findings were correlated. Our findings show that CT has an overall accuracy of 91.8% (100% in groups N2 and N3) and fed false positives and false negatives.

The purpose of this study is to describe our experience with cases of false negative findings at conventional colonoscopy (CC) that were identified by CT colonography (CTC). Conventional colonoscopy (CC) is the universally accepted gold-standard technique for the diagnosis of colonic polyps and cancers, however occasionally this method can generate false negative findings. We present examples of false negatives at CC, correctly identified by CT colonography (CTC), and later confirmed at a second endoscopy, describing the reasons of false negative, when possible. © 2013 Springer Science+Business Media New York.