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Purpose: This review aims to provide a comprehensive summary of DECT techniques, acquisition workflows, and post-processing methods. By doing so, we aim to elucidate the advantages and disadvantages of DECT compared to conventional single-energy CT imaging., Methods: A systematic search was conducted on MEDLINE/EMBASE for DECT studies in liver imaging published between 1980 and 2024. Information regarding study design and endpoints, patient characteristics, DECT technical parameters, radiation dose, iodinated contrast agent (ICA) administration and postprocessing methods were extracted. Technical parameters, including DECT phase, field of view, pitch, collimation, rotation time, arterial phase timing (from injection), and venous timing (from injection) from the included studies were reported, along with formal narrative synthesis of main DECT applications for liver imaging., Results: Out of the initially identified 234 articles, 153 met the inclusion criteria. Extensive variability in acquisition parameters was observed, except for tube voltage (80/140 kVp combination reported in 50% of articles) and ICA administration (1.5 mL/kg at 3-4 mL/s, reported in 91% of articles). Radiation dose information was provided in only 40% of articles (range: 6-80 mGy), and virtual non-contrast imaging (VNC) emerged as a common strategy to reduce the radiation dose. The primary application of DECT post-processed images was in detecting focal liver lesions (47% of articles), with predominance of study focusing on hepatocellular carcinoma (HCC) (27%). Furthermore, a significant proportion of the articles (16%) focused on enhancing DECT protocols, while 15% explored metastasis detection., Conclusion: Our review recommends using 80/140 kVp tube voltage with 1.5 mL/kg ICA at 3-4 mL/s flow rate. Post-processing should include low keV-VMI for enhanced lesion detection, IMs for tumor iodine content evaluation, and VNC for dose reduction. However, heterogeneous literature hinders protocol standardization., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The use of prone position (PP) has been widespread during the COVID-19 pandemic. Whereas it has demonstrated benefits, including improved oxygenation and lung aeration, the factors influencing the response in terms of gas exchange to PP remain unclear. In particular, the association between baseline quantitative computed tomography (CT) scan results and gas exchange response to PP in invasively ventilated subjects with COVID-19 ARDS is unknown. The present study aimed to compare baseline quantitative CT results between subjects responding to PP in terms of oxygenation or CO 2 clearance and those who did not., Methods: This was a single-center, retrospective observational study including critically ill, invasively ventilated subjects with COVID-19-related ARDS admitted to the ICUs of Niguarda Hospital between March 2020-November 2021. Blood gas samples were collected before and after PP. Subjects in whom the P aO 2 /F IO 2 increase was ≥ 20 mm Hg after PP were defined as oxygen responders. CO 2 responders were defined when the ventilatory ratio (VR) decreased during PP. Automated quantitative CT analyses were performed to obtain tissue mass and density of the lungs., Results: One hundred twenty-five subjects were enrolled, of which 116 (93%) were O 2 responders and 51 (41%) CO 2 responders. No difference in quantitative CT characteristics and oxygen were observed between responders and non-responders (tissue mass 1,532 ± 396 g vs 1,654 ± 304 g, P = .28; density -544 ± 109 HU vs -562 ± 58 HU P = .42). Similar findings were observed when dividing the population according to CO 2 response (tissue mass 1,551 ± 412 g vs 1,534 ± 377 g, P = .89; density -545 ± 123 HU vs -546 ± 94 HU, P = .99)., Conclusions: Most subjects with COVID-19-related ARDS improved their oxygenation at the first pronation cycle. The study suggests that baseline quantitative CT scan data were not associated with the response to PP in oxygenation or CO 2 in mechanically ventilated subjects with COVID-19-related ARDS., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Benign Prostatic Hyperplasia (BPH) is the most frequent cause of Lower Urinary Tract Symptoms (LUTSs) in elderly populations. Minimally invasive treatments of BPH are safe and effective and are gaining popularity among both professionals and patients. Prostate Artery Embolization (PAE) has proven to be effective in Trans-Urethral Resection of the Prostate (TURP) in terms of prostate volume reduction and LUTS relief. PAE entails the selective catheterization of the prostatic artery and later embolization of distal vessels with beads of various calibers. Universal consensus regarding the ideal particle size is yet to be defined. We retrospectively evaluated 24 consecutive patients (median age: 75 years; range: 59-86 years) treated with PAE at our institution from October 2015 to November 2022. Particles of different sizes were employed; 12 patients were treated with 40-120 µm particles, 5 with 100 µm, 5 with 100-300 µm and 2 with 250 µm. Technical success, defined as selective prostate artery catheterization and controlled release of embolizing beads, was achieved in all patients. Removal vs. retention of the urinary catheter at the first post-procedural urological visit was the main clinical objective. No major peri-procedural complications were recorded, with 56% of patients successfully removing the urinary catheter.

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management.

Objective: In liver transplantation, chronic rejection is still poorly studied. This study aimed to investigate the role of imaging in its recognition., Methods: This study is a retrospective observational case-control series. Patients with histologic diagnosis of chronic liver transplant rejection were selected; the last imaging examination (computed tomography or magnetic resonance imaging) before the diagnosis was evaluated. At least 3 controls were selected for each case; radiological signs indicative of altered liver function were analyzed. χ 2 Test with Yates correction was used to compare the rates of radiologic signs in the case and control groups, also considering whether patients suffered chronic rejection within or after 12 months. Statistical significance was set at P < 0.050., Results: A total of 118 patients were included in the study (27 in the case group and 91 in the control group). Periportal edema was appreciable in 19 of 27 cases (70%) and in 6 of 91 controls (4%) ( P < 0.001); ascites and hepatomegaly were present in 14 of 27 cases (52%) and 12 of 27 cases (44%), respectively, and in 1 of 91 controls (1%) ( P < 0.001); splenomegaly was present in 13 of 27 cases (48%) and in 8 of 91 controls (10%) ( P < 0.001); and biliary tract dilatation was present in 13 of 27 cases (48%) and in 11 of 91 patients controls (5%) ( P < 0.001). In the controls, periportal edema was significantly less frequent beyond 12 months after transplant (1% vs 11%; P = 0.020); the other signs after 12 months were not significant., Conclusions: The identification of periportal edema, biliary dilatation, ascites, and hepatosplenomegaly can serve as potential warning signs of ongoing chronic liver rejection. It is especially important to investigate periportal edema if it is present 1 year or more after orthotopic liver transplantation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic mesenteric ischemia (CMI) arises from the inability to achieve adequate intestinal blood flow after meals, leading to an imbalance between oxygen and metabolite supply and demand. The true incidence of CMI remains uncertain. However, the occurrence of mesenteric artery occlusive disease (MAOD) is relatively common among the elderly population. Delays in diagnosing CMI can often be attributed to several factors, including the variability in patient symptoms and the range of potential causes for chronic abdominal pain with weight loss. Mikkelson pioneered the introduction of a surgical treatment for occlusive lesions of the superior mesenteric artery (SMA) in 1957. The inaugural performance of endovascular revascularization (ER) for visceral vessels took place in 1980. The literature has documented two types of endovascular revascularization (ER) methods: percutaneous transluminal angioplasty (PTA) and primary stenting (PMAS). Despite the limited quality of available evidence, the consensus among experts is strongly in favor of PMAS over PTA alone for the treatment of atherosclerotic mesenteric artery stenosis. There are several key areas of focus for chronic mesenteric ischemia (CMI) treatment. Randomized controlled trials comparing different stent types, such as covered stents versus bare metal stents, are needed to evaluate efficacy, patency rates, and long-term outcomes in CMI patients.

Budd-Chiari syndrome (BCS) is a rare clinical entity characterized by hepatic venous outflow obstruction, resulting in liver congestion and subsequent chronic parenchymal damage. This condition often leads to the development of focal liver lesions, including benign focal nodular hyperplasia-like regenerative nodules, hepatocellular carcinoma, and perfusion-related pseudo-lesions. Computed tomography, ultrasound, and magnetic resonance are the commonly employed imaging modalities for the follow-up of BCS patients and for the detection and characterization of new-onset lesions. The accurate differentiation between benign and malignant nodules is crucial for optimal patient management and treatment planning. However, it can be challenging due to the variable and overlapping characteristics observed. This review aims to provide a comprehensive overview of the imaging features and differential diagnosis of focal liver lesions in BCS, emphasizing the key findings and discussing the challenges associated with their interpretation, with the purpose of facilitating the subsequent clinical decision-making.

Background: The role of computed tomography (CT) in the diagnosis and characterization of coronavirus disease 2019 (COVID-19) pneumonia has been widely recognized. We evaluated the performance of a software for quantitative analysis of chest CT, the LungQuant system, by comparing its results with independent visual evaluations by a group of 14 clinical experts. The aim of this work is to evaluate the ability of the automated tool to extract quantitative information from lung CT, relevant for the design of a diagnosis support model., Methods: LungQuant segments both the lungs and lesions associated with COVID-19 pneumonia (ground-glass opacities and consolidations) and computes derived quantities corresponding to qualitative characteristics used to clinically assess COVID-19 lesions. The comparison was carried out on 120 publicly available CT scans of patients affected by COVID-19 pneumonia. Scans were scored for four qualitative metrics: percentage of lung involvement, type of lesion, and two disease distribution scores. We evaluated the agreement between the LungQuant output and the visual assessments through receiver operating characteristics area under the curve (AUC) analysis and by fitting a nonlinear regression model., Results: Despite the rather large heterogeneity in the qualitative labels assigned by the clinical experts for each metric, we found good agreement on the metrics compared to the LungQuant output. The AUC values obtained for the four qualitative metrics were 0.98, 0.85, 0.90, and 0.81., Conclusions: Visual clinical evaluation could be complemented and supported by computer-aided quantification, whose values match the average evaluation of several independent clinical experts., Key Points: We conducted a multicenter evaluation of the deep learning-based LungQuant automated software. We translated qualitative assessments into quantifiable metrics to characterize coronavirus disease 2019 (COVID-19) pneumonia lesions. Comparing the software output to the clinical evaluations, results were satisfactory despite heterogeneity of the clinical evaluations. An automatic quantification tool may contribute to improve the clinical workflow of COVID-19 pneumonia., (© 2023. The Author(s).)

Background: The impact of spontaneous portosystemic shunts (SPSSs) on natural history of cirrhotic patients was recently evaluated through the measurement of total shunt area (TSA), a novel tool that allows a comprehensive assessment of SPSSs extension, identifying a direct correlation of higher TSA with lower patient survival. The role of SPSSs in liver transplant (LT) is still debated: we sought to investigate the clinical impact of TSA on the development of early allograft dysfunction (EAD), acute kidney injury (AKI), postoperative complications, and graft and patient survival following LT., Methods: Preoperative imaging of 346 cirrhotic patients undergoing primary LT between 2015 and 2020 were retrospectively revised, recording the size and anatomy of each SPSS to calculate TSA. The impact of TSA and selected patient and donor characteristics on the development of EAD, AKI, and clinically relevant complications was evaluated through univariate and multivariate logistic regression, whereas their effect on graft and patient survival was investigated through Cox regression analysis., Results: A TSA exceeding 78.54 mm 2 resulted as an independent risk factor for the development of EAD (odds ratio [OR]: 2.327; P = 0.003), grade 3 AKI (OR: 2.093; P = 0.041), and clinically relevant complications (OR: 1.962; P = 0.015). Moreover, higher TSA was significantly related to early graft and patient survivals, emerging as an independent risk factor for 12-mo graft loss (hazard ratio: 3.877; P = 0.007) and patient death (hazard ratio: 2.682; P = 0.018)., Conclusions: Higher TSA emerged as a significant risk factor for worse postoperative outcomes following LT, supporting the need for careful hemodynamic assessment and management of patients presenting multiple/larger shunts., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cancers of the Vater ampulla (ampullary cancers, ACs) account for less than 1% of all gastrointestinal tumors. ACs are usually diagnosed at advanced stage, with poor prognosis and limited therapeutic options. BRCA2 mutations are identified in up to 14% of ACs and, differently from other tumor types, therapeutic implications remain to be defined. Here, we report a clinical case of a metastatic AC patient in which the identification of a BRCA2 germline mutation drove a personalized multimodal approach with curative-intent., Case Presentation: A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy., Conclusions: Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent., (© 2023. The Author(s).)

Purpose: To identify differences in chest computed tomography (CT) of the symptomatic coronavirus disease 2019 (COVID-19) population according to the patients' severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination status (non-vaccinated, vaccinated with incomplete or complete vaccination cycle)., Material and Methods: CT examinations performed in the Emergency Department (ED) in May-November 2021 for suspected COVID-19 pneumonia with a positive SARS-CoV-2 test were retrospectively included. Personal data were compared for vaccination status. One 13-year experienced radiologist and two 4th-year radiology residents independently evaluated chest CT scans according to CO-RADS and ACR COVID classifications. In possible COVID-19 pneumonia cases, defined as CO-RADS 3 to 5 (ACR indeterminate and typical) by each reader, high involvement CT score (≥ 25%) and CT patterns (presence of ground glass opacities, consolidations, crazy paving areas) were compared for vaccination status., Results: 184 patients with known vaccination status were included in the analysis: 111 non-vaccinated (60%) for SARS-CoV-2 infection, 21 (11%) with an incomplete vaccination cycle, and 52 (28%) with a complete vaccination cycle (6 different vaccine types). Multivariate logistic regression showed that the only factor predicting the absence of pneumonia (CO-RADS 1 and ACR negative cases) for the 3 readers was a complete vaccination cycle (OR = 12.8-13.1compared to non-vaccinated patients, p ≤ 0.032). Neither CT score nor CT patterns of possible COVID-19 pneumonia showed any statistically significant correlation with vaccination status for the 3 readers., Conclusions: Symptomatic SARS-CoV-2-infected patients with a complete vaccination cycle had much higher odds of showing a negative CT chest examination in ED compared to non-vaccinated patients. Neither CT involvement nor CT patterns of interstitial pneumonia showed differences across different vaccination status., Competing Interests: The authors report no conflict of interest., (© Pol J Radiol 2023.)

Rationale and Objectives: To evaluate the impact of COVID-19 pandemic on diagnostic imaging workload in a tertiary referral hospital., Materials and Methods: Radiological examinations performed in pre-pandemic period (2015-2019) and in pandemic period (2020-2021) were retrospectively included. Based on epidemiological data and restriction measures, four pandemic waves were identified. For each of them, the relative change (RC) in workload was calculated and compared to the 5-year averaged workload in the corresponding pre-COVID-19 periods. Workload variations were also assessed according to technique (radiographs, CT, MRI, ultrasounds), body district (chest, abdomen, breast, musculoskeletal, head/neck, brain/spine, cardiovascular) and care setting (inpatient, outpatient, emergency imaging, pre-admission imaging)., Results: A total of 1384380 examinations were included. In 2020 imaging workload decreased (RC = -11%) compared to the average of the previous 5 years, while in 2021 only a minimal variation (RC = +1%) was observed. During first wave, workload was reduced for all modalities, body regions and types of care setting (RC from -86% to -10%), except for CT (RC = +3%). In subsequent waves, workload increased only for CT (mean RC = +18%) and, regarding body districts, for breast (mean RC = +23%) and cardiovascular imaging (mean RC = +23%). For all other categories, a workload comparable to pre-pandemic period was almost only restored in the fourth wave. In all pandemics periods workload decrease was mainly due to reduced outpatient activity (p < 0.001), while inpatient and emergency imaging was increased (p < 0.001)., Conclusion: Evaluating imaging workload changes throughout COVID-19 pandemic helps to understand the response dynamics of radiological services and to improve institutional preparedness to face extreme contingency., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: To develop a pipeline for automatic extraction of quantitative metrics and radiomic features from lung computed tomography (CT) and develop artificial intelligence (AI) models supporting differential diagnosis between coronavirus disease 2019 (COVID-19) and other viral pneumonia (non-COVID-19)., Methods: Chest CT of 1,031 patients (811 for model building; 220 as independent validation set (IVS) with positive swab for severe acute respiratory syndrome coronavirus-2 (647 COVID-19) or other respiratory viruses (384 non-COVID-19) were segmented automatically. A Gaussian model, based on the HU histogram distribution describing well-aerated and ill portions, was optimised to calculate quantitative metrics (QM, n = 20) in both lungs (2L) and four geometrical subdivisions (GS) (upper front, lower front, upper dorsal, lower dorsal; n = 80). Radiomic features (RF) of first (RF1, n = 18) and second (RF2, n = 120) order were extracted from 2L using PyRadiomics tool. Extracted metrics were used to develop four multilayer-perceptron classifiers, built with different combinations of QM and RF: Model1 (RF1-2L); Model2 (QM-2L, QM-GS); Model3 (RF1-2L, RF2-2L); Model4 (RF1-2L, QM-2L, GS-2L, RF2-2L)., Results: The classifiers showed accuracy from 0.71 to 0.80 and area under the receiving operating characteristic curve (AUC) from 0.77 to 0.87 in differentiating COVID-19 versus non-COVID-19 pneumonia. Best results were associated with Model3 (AUC 0.867 ± 0.008) and Model4 (AUC 0.870 ± 0.011. For the IVS, the AUC values were 0.834 ± 0.008 for Model3 and 0.828 ± 0.011 for Model4., Conclusions: Four AI-based models for classifying patients as COVID-19 or non-COVID-19 viral pneumonia showed good diagnostic performances that could support clinical decisions., (© 2023. The Author(s).)

Review efficacy and safety of minimally-invasive treatments for Low Urinary Tract Symptoms (LUTS) in patients affected by Benign Prostate Hyperplasia (BPH). We performed a systematic review of the literature from 1993 to 2022 leveraging original research articles, reviews, and case-studies published in peer-reviewed journals and stored in public repositories. Prostate artery embolization (PAE), transurethral needle ablation (TUNA), transurethral microwave thermotherapy (TUMT), high intensity focused ultrasound (HIFU), laser treatments and Cryoablation are valid and safe alternatives to the gold standard (surgery) in the treatment of LUTS in patients affected by BPH, with fewer undesired effects being reported.

Growing evidence suggests that artificial intelligence tools could help radiologists in differentiating COVID-19 pneumonia from other types of viral (non-COVID-19) pneumonia. To test this hypothesis, an R-AI classifier capable of discriminating between COVID-19 and non-COVID-19 pneumonia was developed using CT chest scans of 1031 patients with positive swab for SARS-CoV-2 ( n = 647) and other respiratory viruses ( n = 384). The model was trained with 811 CT scans, while 220 CT scans ( n = 151 COVID-19; n = 69 non-COVID-19) were used for independent validation. Four readers were enrolled to blindly evaluate the validation dataset using the CO-RADS score. A pandemic-like high suspicion scenario (CO-RADS 3 considered as COVID-19) and a low suspicion scenario (CO-RADS 3 considered as non-COVID-19) were simulated. Inter-reader agreement and performance metrics were calculated for human readers and R-AI classifier. The readers showed good agreement in assigning CO-RADS score (Gwet's AC2 = 0.71, p < 0.001). Considering human performance, accuracy = 78% and accuracy = 74% were obtained in the high and low suspicion scenarios, respectively, while the AI classifier achieved accuracy = 79% in distinguishing COVID-19 from non-COVID-19 pneumonia on the independent validation dataset. The R-AI classifier performance was equivalent or superior to human readers in all comparisons. Therefore, a R-AI classifier may support human readers in the difficult task of distinguishing COVID-19 from other types of viral pneumonia on CT imaging.

Purpose: The clinical impact of routine CT imaging after pancreaticoduodenectomy (PD) has not been properly investigated. The aim of this study was to investigate the role of routine CT scan after PD for the detection of postoperative complications., Methods: Prospectively collected data of consecutive patients undergoing PD and receiving routine postoperative CT imaging were retrospectively analyzed. The primary endpoint was accuracy of CT imaging in identifying major complications. The secondary endpoint was identification of preoperative and intraoperative factors associated with severe complications. A subgroup analysis of CT scan accuracy in identifying severe complications in patients stratified by fistula risk score (FRS) and presence of early clinical alterations was also performed., Results: A total of 145 patients were included. Routine CT scan had low specificity (Sp = 0.36) and high sensitivity (Sn = 0.98) for predicting major complications, with an accuracy of 0.57. At multivariate logistic regression analysis, only fistula moderate-high FRS (p = 0.029) was independently associated with severe complications. In patients with negligible-low FRS, CT scan showed a Sp of 0.63 and a Sn of 1.0 with an accuracy of 0.69. In patients with moderate-high FRS, CT scan had a Sp of 0.19, a Sn of 0.97 and an accuracy of 0.5. In the 20 (14%) patients with negligible-low FRS and no clinical alterations, no deaths or readmissions occurred regardless of CT findings, while one severe complication occurred in the positive CT scan group. In all other groups, no deaths or readmissions occurred in case of negative CT, with only one severe complication in the moderate-high FRS group with clinical alterations. In case of positive CT, the rate of severe complications was 47% in case of negligible-low FRS and clinical alterations, 40% in case of moderate-high FRS with no clinical alterations, and 45% in case of moderate-high FRS and clinical alterations., Conclusions: Routine postoperative CT scan after PD should not be performed in patients with negligible-low FRS and no clinical alterations. In all other patients, a negative CT scan appears to be highly accurate in identifying patients who will have an uneventful course and who could benefit from early discharge., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC), but the emergence of resistance mutations restricts their efficacy. We previously showed that RAS, BRAF and EGFR mutant alleles, which appear in circulating tumor DNA (ctDNA) during EGFR blockade, decline upon therapy withdrawal. We hypothesized that monitoring resistance mutations in blood could rationally guide subsequent therapy with anti-EGFR antibodies. We report here the results of CHRONOS, an open-label, single-arm phase 2 clinical trial exploiting blood-based identification of RAS/BRAF/EGFR mutations levels to tailor a chemotherapy-free anti-EGFR rechallenge with panitumumab (ClinicalTrials.gov: NCT03227926 ; EudraCT 2016-002597-12). The primary endpoint was objective response rate. Secondary endpoints were progression-free survival, overall survival, safety and tolerability of this strategy. In CHRONOS, patients with tissue-RAS WT tumors after a previous treatment with anti-EGFR-based regimens underwent an interventional ctDNA-based screening. Of 52 patients, 16 (31%) carried at least one mutation conferring resistance to anti-EGFR therapy and were excluded. The primary endpoint of the trial was met; and, of 27 enrolled patients, eight (30%) achieved partial response and 17 (63%) disease control, including two unconfirmed responses. These clinical results favorably compare with standard third-line treatments and show that interventional liquid biopsies can be effectively and safely exploited in a timely manner to guide anti-EGFR rechallenge therapy with panitumumab in patients with mCRC. Further larger and randomized trials are warranted to formally compare panitumumab rechallenge with standard-of-care therapies in this patient setting., (© 2022. The Author(s).)

We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodological item able to predict the frequency of complete pathological responses and, consequently, the outcome of patients with locally advanced rectal cancer addressed to neoadjuvant chemoradiotherapy (C-RT) and subsequently, to radical surgery. In particular, we carried out a retrospective analysis including 100 patients with locally advanced rectal adenocarcinoma who received C-RT and then radical surgery in three different oncological institutions between January 2013 and December 2019. Our experimental design was focused on the evaluation of the gross tumor volume (GTV) at baseline and after C-RT by means of MRI, which was contoured on T2, DWI, and ADC sequences. Multiple texture parameters were extracted by using a LifeX Software, while D-TA was calculated as percentage of variations in the two time points. Both univariate and multivariate analysis (logistic regression) were, therefore, carried out in order to correlate the above-mentioned TA parameters with the frequency of pathological responses in the examined patients' population focusing on the detection of complete pathological response (pCR, with no viable cancer cells: TRG 1) as main statistical endpoint. ROC curves were performed on three different datasets considering that on the 21 patients, only 21% achieved an actual pCR. In our training dataset series, pCR frequency significantly correlated with ADC GLCM-Entropy only, when univariate and binary logistic analysis were performed (AUC for pCR was 0.87). A confirmative binary logistic regression analysis was then repeated in the two remaining validation datasets (AUC for pCR was 0.92 and 0.88, respectively). Overall, these results support the hypothesis that D-TA may have a significant predictive value in detecting the occurrence of pCR in our patient series. If confirmed in prospective and multicenter trials, these results may have a critical role in the selection of patients with locally advanced rectal cancer who may benefit form radical surgery after neoadjuvant chemoradiotherapy.

Background: Drug-induced interstitial lung disease (DIILD) is a form of interstitial lung disease resulting from exposure to drugs causing inflammation and possibly interstitial fibrosis. Antineoplastic drugs are the primary cause of DIILD, accounting for 23%-51% of cases, with bleomycin, everolimus, erlotinib, trastuzumab-deruxtecan and immune checkpoint inhibitors being the most common causative agents. DIILD can be difficult to identify and manage, and there are currently no specific guidelines on the diagnosis and treatment of DIILD caused by anticancer drugs., Objective: To develop recommendations for the diagnosis and management of DIILD in cancer patients., Methods: Based on the published literature and their clinical expertise, a multidisciplinary group of experts in Italy developed recommendations stratified by DIILD severity, based on the Common Terminology Criteria for Adverse Events., Results: The recommendations highlight the importance of multidisciplinary interaction in the diagnosis and management of DIILD. Important components of the diagnostic process are physical examination and careful patient history-taking, measurement of vital signs (particularly respiratory rate and arterial oxygen saturation), relevant laboratory tests, respiratory function testing with spirometry and diffusing capacity of the lung for carbon monoxide and computed tomography/imaging. Because the clinical and radiological signs of DIILD are often similar to those of pneumonias or interstitial lung diseases, differential diagnosis is important, including microbial and serological testing to exclude or confirm infectious causes. In most cases, management of DIILD requires the discontinuation of the antineoplastic agent and the administration of short-term steroids. Steroid tapering must be undertaken slowly to prevent reactivation of DIILD. Patients with severe and very severe (grade 3 and 4) DIILD will require hospitalisation and often need oxygen and non-invasive ventilation. Decisions about invasive ventilation should take into account the patient's cancer prognosis., Conclusions: These recommendations provide a structured step-by-step diagnostic and therapeutic approach for each grade of suspected cancer-related DIILD., Competing Interests: Disclosure PC has received honoraria for consultation from Daiichi Sankyo. PAA has received grants and honoraria for consultation from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Idera Pharmaceuticals, Immunocore, Italfarmaco, iTeos Therapeutics, Lunaphore Technologies, Merck Serono, MSD, Nektar Therapeutics, Nouscom, Novartis, OncoSec, Pfizer, Pierre Fabre Pharma, 4SC, Regeneron Pharmaceuticals, Roche-Genentech, Sandoz, Sanofi, Seagen and Sun Pharma. RD has received grants and honoraria for consultation from AstraZeneca, Eli Lilly, Gilead Sciences, GlaxoSmithKline, Novartis and Pfizer. PT has received grants and honoraria for consultation from Daiichi Sankyo, Incyte, MedicAir and Vertex. AC has received honoraria for consultation from Angelini, Gilead Sciences and Janssen. MDL has received honoraria for consultation from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead Sciences, MSD, Novartis, Pfizer, Pierre Fabre Pharma, Roche-Genentech and Seagen. AF has received grants and honoraria for consultation from Amgen, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Incyte, Merck Serono, MSD, Pierre Fabre Pharma, Roche-Genentech and Servier. LR has received grants and honoraria for consultation from Biogen, Boehringer Ingelheim, Celgene Corporation, Cipla, CSL Behring, FibroGen, Nitto BioPharma, Pliant Therapeutics, Promedior, Respivant Sciences, Roche-Genentech, Sanofi Aventis and Zambon. SS has received grants and honoraria for consultation from Agenus, AstraZeneca, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, CheckMab, Daiichi Sankyo, Merck Serono and Seagen. The remaining authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: To evaluate the potential benefits of the Magnetic Resonance-guided high intensity Focused Ultrasound (MRgFUS) introduction in the clinical practice, for the treatment of uterine fibroids, in comparison with the standard "conservative" procedures, devoted to women who wish to preserve their uterus or enhance fertility: myomectomy and uterine artery embolization (UAE)., Methods: A Health Technology Assessment was conducted, assuming the payer's perspective (Italian National Healthcare Service). The nine EUnetHTA Core Model dimensions were deeply investigated, by means of i) a literature review; ii) the implementation of health economics tools (useful for uterine fibroids patients' clinical pathway economic evaluation, and budget impact analysis), to define MRgFUS economic and organizational sustainability, and iii) administration of specific questionnaires filled by uterine fibroids' experts, to gather their perceptions on the three possible conservative approaches (MRgFUS, UAE and myomectomy)., Results: Literature revealed that MRgFUS would generate several benefits, from a safety and an efficacy profile, with significant improvement in symptoms relief. Advantages emerged concerning the patients' perspective, thus leading to a decrease both in the length of hospital stay (p-value< 0.001), and in patients' productivity loss (p-value = 0.024). From an economic point of view, the Italian NHS would present an economic saving of - 6.42%. A positive organizational and equity impact emerged regarding the capability to treat a larger number of women, thus performing, on average, 131.852 additional DRGs., Conclusions: Results suggest that MRgFUS could be considered an advantageous technological alternative to adopt within the target population affected by uterine fibroids, demonstrating its economic and organisational feasibility and sustainability, with consequent social benefits., (© 2022. The Author(s).)

Background: Retzius-sparing (RS) robot-assisted radical prostatectomy represents a valid surgical treatment option for prostate cancer (PCa) patients. However, the available evidence on the role of RS in high-risk (HR) PCa setting is sparse., Objective: To describe our RS technique for HR-PCa patients and to evaluate intra-, peri-, and postoperative oncological and functional outcomes., Design Setting and Participants: A total of 340 D'Amico HR-PCa patients underwent RS at a single high-volume centre between 2011 and 2020., Surgical Procedure: Surgical procedures were performed by five experienced robotic surgeons., Measurements: Complications were collected according to the standardised methodology proposed by the European Association of Urology guidelines. Postoperative outcomes were evaluated in patients with complete follow-up data ( n  = 320). Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen values of ≥0.2 ng/ml. Urinary continence (UC) recovery was defined as the use of zero or one safety pad. Kaplan-Meier and multivariable logistic and Cox regression models were performed., Results and Limitations: Fourteen patients (4%) experienced intraoperative complications and 52 90-d complications occurred in 44 patients (14%), of whom 24 had Clavien-Dindo 3a/b. Final pathology reported 49% International Society of Urological Pathology (ISUP) grade 4-5, 55% ≥pT3a, and 28.8% positive surgical margins (PSMs; 9.4% focal and 19.4% extended PSMs). The median follow-up was 47 mo. Overall, 35.3% and 1.3% harboured BCR and died from PCa. At 4 yr of follow-up, BCR-free survival and additional treatment-free survival were 63.6% and 56.6%, respectively. ISUP 4-5 at biopsy (odds ratio [OR]: 2.6), prostate volume (OR: 1.03), partial or full nerve sparing (OR: 1.9), and full bladder neck preservation (OR: 2.2) were independent predictors of PSMs. Pathological ISUP 4-5 (hazard ratio [HR]: 1.5) and PSMs (HR: 2.3) were independent predictors of BCR. Pathological ISUP 4-5 (HR: 1.5), PSMs (HR: 2.4), pT ≥3b (HR: 1.8), and pN ≥1 (HR: 1.8) were independent predictors of additional treatment. Immediate UC recovery was recorded in 53% patients. The 1- and 2-yr UC recovery and erectile function recovery were, respectively, 84% and 85%, and 43% and 50%., Conclusions: RS in HR-PCa patients allows optimal intra-, peri-, and postoperative outcomes. The RS approach should be considered a valid surgical treatment option for HR-PCa patients in expert hands., Patient Summary: Relying on the largest cohort of high-risk prostate cancer patients treated with Retzius sparing (RS), we observed that the RS approach is safe and allows optimal cancer control, without significantly compromising functional outcomes., (© 2022 The Author(s).)

High energy blunt trauma patients with normal vital signs are usually investigated with a Contrast Enhanced Computed Tomography (CECT) for torso injuries. CECT involves high levels of radiations, often showing no injuries in patients over-triaged to the trauma center. The aim of our study was to suggest an alternative diagnostic protocol based on Emergency Room (ER) tests (physical exam, blood tests, extended FAST, Chest and Pelvis X-ray) to avoid CECT in selected patients. A prospective cohort study was conducted from September 2018 to September 2019. Five hundred patients fulfilled the inclusion criteria. Patients received torso-CECT scan only if they had at least one positive ER test. The validity of the single component of the protocol and the global validity of the ER tests to detect torso injuries was assessed through sensitivity, specificity, positive (PPV) and negative (NPV) predictive value, positive (+ LR) and negative (- LR) likelihood ratio. Multivariate analysis was performed to identify independent predictors of torso injuries. One hundred and seventy patients received a torso-CECT scan because of positive ER tests. ER tests showed a global sensitivity for torso injuries of 86.96% (95% CI 80.17-92.08) specificity of 83.98%(95% CI 79.79-87.60), PPV of 67.42% (95% CI 61.83-72.54), NPV of 94.41% (95% CI 91.63-96.30) + LR of 5.43 (95% CI 4.25-6.93), - LR of 0.16 (95% CI 0.10-0.24). ER tests in an experienced center seem to be able to identify more severe blunt trauma patients needing CECT. Further studies are advisable to confirm these results., (© 2021. Italian Society of Surgery (SIC).)

Background : The latest Liver Imaging Reporting and Data System (LI-RADS) classification by the American College of Radiology has been recently endorsed in the American Association for the Study of Liver Disease (AASLD) guidelines for Hepatocellular carcinoma (HCC) management. Although the LI-RADS protocol has been developed as a diagnostic algorithm, there is some evidence concerning a possible correlation between different LI-RADS classes and specific pathological features of HCC. We aimed to investigate such radiological/pathological correlation and the possible prognostic implication of LI-RADS on a retrospective cohort of HCC patients undergoing surgical resection. Methods : We performed a retrospective analysis of the pathological characteristics of resected HCC, exploring their distribution among different LI-RADS classes and analyzing the risk factors for recurrence-free, overall and cancer-specific survival Results : LI-RADS-5 (LR-5) nodules showed a higher prevalence of microvascular invasion (MVI), satellitosis and capsule infiltration, as well as higher median values of alpha-fetoprotein (αFP) compared to LI-RADS-3/4 (LR-3/4) nodules. MVI, αFP, satellitosis and margin-positive (R1) resection resulted as independent risk factors for recurrence-free survival, while LI-RADS class did not exert any significant impact. Focusing on overall survival, we identified patient age, Eastern Cooperative Oncology Group performance status (ECOG-PS), Model for End Stage Liver Disease (MELD) score, αFP, MVI, satellitosis and R1 resection as independent risk factors for survival, without any impact of LI-RADS classification. Last, MELD score, log10αFP, satellitosis and R1 resection resulted as independent risk factors for cancer-specific survival, while LI-RADS class did not exert any significant impact. Conclusions : Our results suggest an association of LR-5 class with unfavorable pathological characteristics of resected HCC; tumor histology and underlying patient characteristics such as age, ECOG-PS and liver disease severity exert a significant impact on postoperative oncological outcomes.

The purpose of this paper is to develop and validate a delta-radiomics score to predict the response of individual colorectal cancer liver metastases (lmCRC) to first-line FOLFOX chemotherapy. Three hundred one lmCRC were manually segmented on both CT performed at baseline and after the first cycle of first-line FOLFOX, and 107 radiomics features were computed by subtracting textural features of CT at baseline from those at timepoint 1 (TP1). LmCRC were classified as nonresponders (R-) if they showed progression of disease (PD), according to RECIST1.1, before 8 months, and as responders (R+), otherwise. After feature selection, we developed a decision tree statistical model trained using all lmCRC coming from one hospital. The final output was a delta-radiomics signature subsequently validated on an external dataset. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values in correctly classifying individual lesions were assessed on both datasets. Per-lesion sensitivity, specificity, PPV, and NPV were 99%, 94%, 95%, 99%, 85%, 92%, 90%, and 87%, respectively, in the training and validation datasets. The delta-radiomics signature was able to reliably predict R- lmCRC, which were wrongly classified by lesion RECIST as R+ at TP1, (93%, averaging training and validation set, versus 67% of RECIST). The delta-radiomics signature developed in this study can reliably predict the response of individual lmCRC to oxaliplatin-based chemotherapy. Lesions forecasted as poor or nonresponders by the signature could be further investigated, potentially paving the way to lesion-specific therapies.

Objective: To outline a practical method of performing prostate cancer radiotherapy in patients with bilateral metal hip prostheses with the standard resources available in a modern general hospital. The proposed workflow is based exclusively on magnetic resonance imaging (MRI) to avoid computed tomography (CT) artifacts., Case Description: This study concerns a 73-year-old man with bilateral hip prostheses with an elevated risk prostate cancer. Magnetic resonance images with assigned electron densities were used for planning purposes, generating a synthetic CT (sCT). Imaging acquisition was performed with an optimized Dixon sequence on a 1.5T MRI scanner. The images were contoured by autosegmentation software, based on an MRI database of 20 patients. The sCT was generated assigning averaged electron densities to each contour. Two volumetric modulated arc therapy plans, a complete arc and a partial one, where the beam entrances through the prostheses were avoided for about 50° on both sides, were compared. The feasibility of matching daily cone beam CT (CBCT) with MRI reference images was also tested by visual evaluations of different radiation oncologists., Conclusions: The use of magnetic resonance images improved accuracy in targets and organs at risk (OARs) contouring. The complete arc plan was chosen because of 10% lower mean and maximum doses to prostheses with the same planning target volume coverage and OAR sparing. The image quality of the match between performed CBCTs and MRI was considered acceptable. The proposed method seems promising to improve radiotherapy treatments for this complex category of patients.

Objectives: To evaluate the inter-observer reliability of modified Response Evaluation Criteria In Solid Tumours (mRECIST) of patients with hepatocellular carcinoma (HCC) undergoing neo-adjuvant treatments before liver transplant (LT). The agreement of tumor number, size, transplant criteria, and the radiological-pathological concordance were also assessed., Methods: A total of 180 radiological studies before/after neo-adjuvant therapies performed on 90 patients prior to LT were reviewed from three expert centers. Kappa-statistic and intraclass correlation (ICC) were evaluated on mRECIST and on tumoral features. Complete radiological response (CR) was compared with complete pathological response (CPR)., Results: Before neo-adjuvant therapies, the agreement on tumor number, size, and transplant criteria ranged from moderate (defined as ICC of 0.41-0.60) to almost perfect (ICC of 0.81-0.99), being higher with magnetic resonance imaging (MRI) than CT (0.657-0.899 and 0.422-0.776, respectively). After neo-adjuvant therapies, the agreement decreased, as ICCs ranged between 0.518 and 0.663 with MRI and between 0.508 and 0.677 with CT. Concordant mRECIST pairs were 201 of 270 reviews (76.3%) with a kappa of 0.648 indicating substantial agreement. When the three observers completely agreed on CR, the positive predictive value for CPR was 51.6%. The negative predictive value was 94.2% with a kappa of 0.512 indicating fair agreement between radiology and pathology., Conclusions: mRECIST agreement was substantial among the three observers involved. The agreement on tumor number, size, and transplant criteria ranged from moderate to almost perfect, with the highest ICCs obtained with MRI before neo-adjuvant therapies. Finally, the predictive value of mRECIST in the diagnosis of CPR was only fair., Key Points: • The review of 180 radiological exams of patients with hepatocellular carcinoma before and after neo-adjuvant therapies showed that the concordance among three different raters on mRECIST diagnosis was substantial. • The inter-observer reliability on fulfilment of transplant criteria slightly decreased when evaluated through CT and after loco-regional therapies. • The radiological diagnosis of complete response after neo-adjuvant therapies was predictive of complete pathological response in only 51.6% of cases., (© 2021. European Society of Radiology.)

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model., Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses., Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD., Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed., Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) has the second-highest tumor incidence and is a leading cause of death by cancer. Nearly 20% of patients with CRC will have metastases (mts) at the time of diagnosis, and more than 50% of patients with CRC develop metastases during their disease. Unfortunately, only 45% of patients after a chemotherapy will respond to treatment. The aim of this study is to develop and validate a machine learning algorithm to predict response of individual liver mts, using CT scans. Understanding which mts will respond or not will help clinicians in providing a more efficient per-lesion treatment based on patient specific response and not only following a standard treatment. A group of 92 patients was enrolled from two Italian institutions. CT scans were collected, and the portal venous phase was manually segmented by an expert radiologist. Then, 75 radiomics features were extracted both from 7x7 ROIs that moved across the image and from the whole 3D mts. Feature selection was performed using a genetic algorithm. Results are presented as a comparison of the two different approaches of features extraction and different classification algorithms. Accuracy (ACC), sensitivity (SE), specificity (SP), negative and positive predictive values (NPV and PPV) were evaluated for all lesions (per-lesion analysis) and patients (per-patient analysis) in the construction and validation sets. Best results were obtained in the per-lesion analysis from the 3D approach using a Support Vector Machine as classifier. We reached on the training set an ACC of 81%, while on test set, we obtained SE of 76%, SP of 67%, PPV of 69% and NPV of 75%. On the validation set a SE of 61%, SP of 60%, PPV of 57% and NPV of 64% were reached. The promising results obtained in the validation dataset should be extended to a larger cohort of patient to further validate our method.Clinical Relevance- to develop a radiomics signatures predicting single liver mts response to therapy. A personalized mts approach is important to avoid unnecessary toxicity offering more suitable treatments and a better quality of life to oncological patients.

Although the diagnostic value of Liver Imaging Reporting and Data System (LI-RADS) protocol is well recognized in clinical practice, its role in liver transplant (LT) setting is under-explored. We sought to evaluate the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in a single-centre retrospective cohort of transplanted hepatocellular carcinoma (HCC) patients, exploring which LI-RADS subclasses need to be considered in order to grant the best Metroticket 2.0 performance. The most recent pre-LT imaging of 245 patients undergoing LT for HCC between 2005 and 2015 was retrospectively and blindly reviewed, classifying all nodules according to LI-RADS protocol. Metroticket 2.0 accuracy was subsequently tested incorporating all vital nodules identified during multi-disciplinary team (MDT) meetings attended before LI-RADS reclassification of the latest pre-LT imaging, LR-5 and LR-treatment-viable (LR-TR-V), LR-4/5 and LR-TR-V, and LR-3/4/5 and LR-TR-V nodules respectively. Considering their extremely low probability for harbouring HCC, LR-1 and LR-2 nodules were not considered in this analysis. Incorporation of all HCCs identified during MDT meetings attended before LI-RADS reclassification of the latest pre-LT imaging resulted in a Metroticket 2.0 c-index of 0.72, [95% confidence interval (CI) 0.64-0.80]. Metroticket 2.0 c-index dropped to 0.60 [95% CI: 0.48-0.72] when LI-RADS-5 and LI-RADS-TR-V (P = 0.0089) or LI-RADS-5, LI-RADS-4 and LI-RADS-TR-V (P = 0.0068) nodules were entered in the calculator. Conversely, addition of LI-RADS-3 HCCs raised the Metroticket 2.0 c-index to 0.65 [95% CI: 0.54-0.86], resulting in a not statistically significant diversion from the original performance (0.72 vs. 0.65; P = 0.08). Exclusion of LR-3 and LR-4 nodules from Metroticket 2.0 calculator resulted in a significant drop in its accuracy. Every nodule with an intermediate-to-high probability of harbouring HCC according to LI-RADS protocol seems to contribute to tumour burden and should be entered in the Metroticket 2.0 calculator in order to grant appropriate performance., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background Lower muscle mass is a known predictor of unfavorable outcomes, but its prognostic impact on patients with COVID-19 is unknown. Purpose To investigate the contribution of CT-derived muscle status in predicting clinical outcomes in patients with COVID-19. Materials and Methods Clinical or laboratory data and outcomes (intensive care unit [ICU] admission and death) were retrospectively retrieved for patients with reverse transcriptase polymerase chain reaction-confirmed SARS-CoV-2 infection, who underwent chest CT on admission in four hospitals in Northern Italy from February 21 to April 30, 2020. The extent and type of pulmonary involvement, mediastinal lymphadenopathy, and pleural effusion were assessed. Cross-sectional areas and attenuation by paravertebral muscles were measured on axial CT images at the T5 and T12 vertebral level. Multivariable linear and binary logistic regression, including calculation of odds ratios (ORs) with 95% CIs, were used to build four models to predict ICU admission and death, which were tested and compared by using receiver operating characteristic curve analysis. Results A total of 552 patients (364 men and 188 women; median age, 65 years [interquartile range, 54-75 years]) were included. In a CT-based model, lower-than-median T5 paravertebral muscle areas showed the highest ORs for ICU admission (OR, 4.8; 95% CI: 2.7, 8.5; P < .001) and death (OR, 2.3; 95% CI: 1.0, 2.9; P = .03). When clinical variables were included in the model, lower-than-median T5 paravertebral muscle areas still showed the highest ORs for both ICU admission (OR, 4.3; 95%: CI: 2.5, 7.7; P < .001) and death (OR, 2.3; 95% CI: 1.3, 3.7; P = .001). At receiver operating characteristic analysis, the CT-based model and the model including clinical variables showed the same area under the receiver operating characteristic curve (AUC) for ICU admission prediction (AUC, 0.83; P = .38) and were not different in terms of predicting death (AUC, 0.86 vs AUC, 0.87, respectively; P = .28). Conclusion In hospitalized patients with COVID-19, lower muscle mass on CT images was independently associated with intensive care unit admission and in-hospital mortality. © RSNA, 2021 Online supplemental material is available for this article.

Purpose: To assess the impact of lung segmentation accuracy in an automatic pipeline for quantitative analysis of CT images., Methods: Four different platforms for automatic lung segmentation based on convolutional neural network (CNN), region-growing technique and atlas-based algorithm were considered. The platforms were tested using CT images of 55 COVID-19 patients with severe lung impairment. Four radiologists assessed the segmentations using a 5-point qualitative score (QS). For each CT series, a manually revised reference segmentation (RS) was obtained. Histogram-based quantitative metrics (QM) were calculated from CT histogram using lung segmentationsfrom all platforms and RS. Dice index (DI) and differences of QMs (ΔQMs) were calculated between RS and other segmentations., Results: Highest QS and lower ΔQMs values were associated to the CNN algorithm. However, only 45% CNN segmentations were judged to need no or only minimal corrections, and in only 17 cases (31%), automatic segmentations provided RS without manual corrections. Median values of the DI for the four algorithms ranged from 0.993 to 0.904. Significant differences for all QMs calculated between automatic segmentations and RS were found both when data were pooled together and stratified according to QS, indicating a relationship between qualitative and quantitative measurements. The most unstable QM was the histogram 90th percentile, with median ΔQMs values ranging from 10HU and 158HU between different algorithms., Conclusions: None of tested algorithms provided fully reliable segmentation. Segmentation accuracy impacts differently on different quantitative metrics, and each of them should be individually evaluated according to the purpose of subsequent analyses., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Pulmonary parenchymal and vascular damage are frequently reported in COVID-19 patients and can be assessed with unenhanced chest computed tomography (CT), widely used as a triaging exam. Integrating clinical data, chest CT features, and CT-derived vascular metrics, we aimed to build a predictive model of in-hospital mortality using univariate analysis (Mann-Whitney U test) and machine learning models (support vectors machines (SVM) and multilayer perceptrons (MLP)). Patients with RT-PCR-confirmed SARS-CoV-2 infection and unenhanced chest CT performed on emergency department admission were included after retrieving their outcome (discharge or death), with an 85/15% training/test dataset split. Out of 897 patients, the 229 (26%) patients who died during hospitalization had higher median pulmonary artery diameter (29.0 mm) than patients who survived (27.0 mm, p < 0.001) and higher median ascending aortic diameter (36.6 mm versus 34.0 mm, p < 0.001). SVM and MLP best models considered the same ten input features, yielding a 0.747 (precision 0.522, recall 0.800) and 0.844 (precision 0.680, recall 0.567) area under the curve, respectively. In this model integrating clinical and radiological data, pulmonary artery diameter was the third most important predictor after age and parenchymal involvement extent, contributing to reliable in-hospital mortality prediction, highlighting the value of vascular metrics in improving patient stratification.

Coronavirus disease 2019 (COVID-19) emerged in early December 2019 in China, as an acute lower respiratory tract infection and spread rapidly worldwide being declared a pandemic in March 2020. Chest-computed tomography (CT) has been utilized in different clinical settings of COVID-19 patients; however, COVID-19 imaging appearance is highly variable and nonspecific. Indeed, many pulmonary infections and non-infectious diseases can show similar CT findings and mimic COVID-19 pneumonia. In this review, we discuss clinical conditions that share a similar imaging appearance with COVID-19 pneumonia, in order to identify imaging and clinical characteristics useful in the differential diagnosis.

Purpose: The capability of lung ultrasound (LUS) to distinguish the different pulmonary patterns of COVID-19 and quantify the disease burden compared to chest CT is still unclear., Methods: PCR-confirmed COVID-19 patients who underwent both LUS and chest CT at the Emergency Department were retrospectively analysed. In both modalities, twelve peripheral lung zones were identified and given a Severity Score basing on main lesion pattern. On CT scans the well-aerated lung volume (%WALV) was visually estimated. Per-patient and per-zone assessments of LUS classification performance taking CT findings as reference were performed, further revisioning the images in case of discordant results. Correlations between number of disease-positive lung zones, Severity Score and %WALV on both LUS and CT were assessed. The area under receiver operating characteristic curve (AUC) was calculated to determine LUS performance in detecting %WALV ≤ 70 %., Results: The study included 219 COVID-19 patients with abnormal chest CT. LUS correctly identified as positive 217 (99 %) patients, but per-zone analysis showed sensitivity = 75 % and specificity = 66 %. The revision of the 121 (55 %) cases with positive LUS and negative CT revealed COVID-compatible lesions in 42 (38 %) CT scans. Number of disease-positive zones, Severity Score and %WALV between LUS and CT showed moderate correlations. The AUCs for LUS Severity Score and number of LUS-positive zones did not differ in detecting %WALV ≤ 70 %., Conclusion: LUS in COVID-19 is valuable for case identification but shows only moderate correlation with CT findings as for lesion patterns and severity quantification. The number of disease-positive lung zones in LUS alone was sufficient to discriminate relevant disease burden., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background : Single hepatocellular carcinoma (HCC) benefits from surgical resection (SR) or US-guided percutaneous ablation (PA), although the best approach is still debated. We evaluated the impact of Li-RADS classification on the oncological outcomes of SR vs. PA as single HCC first-line treatment. Methods : We retrospectively and blindly classified treatment-naïve single HCC that underwent SR or PA between 2010 and 2016 according to Li-RADS protocol. Overall survival (OS), recurrence free survival (RFS) and local recurrence after SR and PA were compared for each Li-RADS subclass before and after propensity-score matching (PS-M). Results : Considering the general population, SR showed better 5-year OS (68.3% vs. 52.2%; p = 0.049) and RFS (42.5% vs. 29.8%; p = 0.002), with lower incidence of local recurrence (8.2% vs. 44.4%; p < 0.001), despite a significantly higher frequency of clinically-relevant complications (12.8% vs. 1.9%; p = 0.002) and a higher Comprehensive Complication Index (12.1 vs. 2.2; p < 0.001). Focusing on different Li-RADS subclasses, we highlighted better 5-year OS (67.1% vs. 46.2%; p = 0.035), RFS (45.0% vs. 27.0% RFS; p < 0.001) and lower incidence of local recurrence (9.7% vs. 48.6%; p < 0.001) after SR for Li-RADS-5 HCCs, while these outcomes did not differ for Li-RADS-3/4 subclasses; such results were confirmed after PS-M. Conclusions : Our analysis suggests a potential prognostic role of Li-RADS classification, supporting SR over PA especially for Li-RADS-5 single HCC.

Purpose: Quantitative metrics in lung computed tomography (CT) images have been widely used, often without a clear connection with physiology. This work proposes a patient-independent model for the estimation of well-aerated volume of lungs in CT images (WAVE)., Methods: A Gaussian fit, with mean (Mu.f) and width (Sigma.f) values, was applied to the lower CT histogram data points of the lung to provide the estimation of the well-aerated lung volume (WAVE.f). Independence from CT reconstruction parameters and respiratory cycle was analysed using healthy lung CT images and 4DCT acquisitions. The Gaussian metrics and first order radiomic features calculated for a third cohort of COVID-19 patients were compared with those relative to healthy lungs. Each lung was further segmented in 24 subregions and a new biomarker derived from Gaussian fit parameter Mu.f was proposed to represent the local density changes., Results: WAVE.f resulted independent from the respiratory motion in 80% of the cases. Differences of 1%, 2% and up to 14% resulted comparing a moderate iterative strength and FBP algorithm, 1 and 3 mm of slice thickness and different reconstruction kernel. Healthy subjects were significantly different from COVID-19 patients for all the metrics calculated. Graphical representation of the local biomarker provides spatial and quantitative information in a single 2D picture., Conclusions: Unlike other metrics based on fixed histogram thresholds, this model is able to consider the inter- and intra-subject variability. In addition, it defines a local biomarker to quantify the severity of the disease, independently of the observer., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

In a kidney transplant recipient, bladder and graft ureter displacement into a groin hernia is a highly unusual cause of obstructive uropathy that may lead to graft dysfunction or graft loss. We report the case of a White man, 56 years old, who had previously, at the age of 19 years, undergone a kidney transplant from a deceased donor, to mitigate chronic glomerulonephritis. The patient presented to us with a reducible left inguinal hernia with worsening kidney function, and we used the Lichtenstein hernioplasty technique to surgically repair the hernia, which was followed by an uneventful postoperative course. Existing literature has identified few cases of kidney graft dysfunction due to inguinal hernias. Groin hernia repair of this type in this specific circumstance remains a subject of debate. However, in our opinion, with attention to appropriate reductions of immunosuppressive therapy, the Lichtenstein technique is safe for transplant recipients and the use of mesh greatly reduces the risk of hernia recurrence.

The aim of our study was to develop and validate a machine learning algorithm to predict response of individual HER2-amplified colorectal cancer liver metastases (lmCRC) undergoing dual HER2-targeted therapy. Twenty-four radiomics features were extracted after 3D manual segmentation of 141 lmCRC on pretreatment portal CT scans of a cohort including 38 HER2-amplified patients; feature selection was then performed using genetic algorithms. lmCRC were classified as nonresponders (R-), if their largest diameter increased more than 10% at a CT scan performed after 3 months of treatment, responders (R+) otherwise. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values in correctly classifying individual lesion and overall patient response were assessed on a training dataset and then validated on a second dataset using a Gaussian naïve Bayesian classifier. Per-lesion sensitivity, specificity, NPV and PPV were 89%, 85%, 93%, 78% and 90%, 42%, 73%, 71% respectively in the testing and validation datasets. Per-patient sensitivity and specificity were 92% and 86%. Heterogeneous response was observed in 9 of 38 patients (24%). Five of nine patients were carriers of nonresponder lesions correctly classified as such by our radiomics signature, including four of seven harboring only one nonresponder lesion. The developed method has been proven effective in predicting behavior of individual metastases to targeted treatment in a cohort of HER2 amplified patients. The model accurately detects responder lesions and identifies nonresponder lesions in patients with heterogeneous response, potentially paving the way to multimodal treatment in selected patients. Further validation will be needed to confirm our findings., (© 2020 Union for International Cancer Control.)

The purpose of this pictorial essay is to review the imaging findings of adrenal lesions. Adrenal lesions could be divided into functioning or non-functioning masses, primary or metastatic, and benign or malignant. Imaging techniques have undergone significant advances in recent years. The most significant objective of adrenal imaging is represented by the detection and, when possible, characterization of adrenal lesions in order to direct patient management correctly. The detection and management of adrenal lesions is based on cross-sectional imaging obtained with non-contrast CT (tumour density), contrast-enhanced CT including delayed washout (either absolute percentage washout or relative percentage one) and finally with MR chemical shift analysis (loss of signal intensity between in-phase and out-of-phase images including both qualitative and quantitative estimates of signal loss). The small incidental adrenal nodules are benign, in most of cases; some tumors such as lipid-rich adenoma and myelolipoma have characteristic features that can be diagnosed accurately in CT. On contrary, if the presenting contrast-enhanced CT shows an adrenal mass with uncertain or malignant morphologic features, particularly in patients with a known history of malignancy, further evaluations should be considered. The most significative implications for radiologists are represented by how to assess risk of malignancy on imaging and what follow-up to indicate if an adrenal incidentaloma is not surgically removed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-559). The series “Multimodality Advanced Imaging and Intervention in Gland Diseases” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

Background: ERBB2 amplification occurs in 5% of RAS wild-type metastatic colorectal cancer (mCRC) and it has been shown to be a target for treatment with 2 HER2-directed combinations of trastuzumab and lapatinib or trastuzumab and pertuzumab. We present long-term clinical results of trastuzumab and lapatinib (HERACLES-A trial) at 6.7 years (82 months) follow-up and focus on central nervous system (CNS) recurrences., Patients and Methods: Patients had histologically confirmed KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive mCRC. HER2 positivity was assessed by immunohistochemistry and in situ hybridization HERACLES diagnostic criteria. Patients were treated with intravenous trastuzumab 4 mg/kg loading dose, then 2 mg/kg once per week, and oral lapatinib 1000 mg per day until disease progression or toxicity. Patients who presented with symptoms or signs of CNS disease received brain computed tomography scan or magnetic resonance imaging., Results: A total of 35 patients received trastuzumab and lapatinib and 32 were evaluable for response. One patient (3%) achieved complete response (CR), 8 (25%) partial response, and 13 (41%) stable disease. Therefore, response rate was 28%. Median progression-free survival was 4.7 months (95% confidence interval [CI] 3.7-6.1). Median overall survival was 10.0 months (95% CI 7.9-15.8). One patient achieved sustained CR still maintained at 7 years of follow-up. Progression in the central nervous system (CNS) occurred in 6 (19%) of 32 patients., Conclusions: Long-term (6.7 years) follow-up analysis of HERACLES-A supports using of trastuzumab and lapatinib as treatment reference for KRAS wild-type, chemorefractory HER2-positive mCRC. In this subset of patients, prolongation of survival is accompanied by CNS recurrences that will require diagnostic and therapeutic attention in future studies. Clinicaltrials. Gov identifier: NCT 03225937., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Acute pancreatitis (AP) is a common disease that may involve pancreas and peripancreatic tissues with a prevalence of up to 50 per 100,000 individuals for year. The Atlanta classification was assessed for the first time in 1992 and modified in 2012 in order to describe morphological features of AP and its complications. AP can be morphologically distinguished in two main types: interstitial edematous pancreatitis (IEP) and necrotizing pancreatitis (NEP). This classification is very important because the presence of necrosis is directly linked to local or systemic complications, hospital stays and death. Magnetic resonance (MR) is very useful to characterize morphological features in AP and its abdominal complications. Particularly we would like to underline the diagnostic, staging and prognostic role of T1-weighted images with fat suppression that could be significant to assess many features of the AP inflammatory process and its complications (detection of the pancreatic contour, pancreatic necrosis, presence of haemorrhage). Signs of inflammatory and edema are instead observed by T1-weighted images. MR cholangiopancreatography (MRCP) is necessary to study the main pancreatic duct and the extrahepatic biliary tract and contrast-enhancement magnetic resonance imaging (MRI) allows to assess the extent of necrosis and vascular injuries., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-554). The series “Multimodality Advanced Imaging and Intervention in Gland Diseases” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

Background: Radiomics is expected to improve the management of metastatic colorectal cancer (CRC). We aimed at evaluating the impact of liver lesion contouring as a source of variability on radiomic features (RFs)., Methods: After Ethics Committee approval, 70 liver metastases in 17 CRC patients were segmented on contrast-enhanced computed tomography scans by two residents and checked by experienced radiologists. RFs from grey level co-occurrence and run length matrices were extracted from three-dimensional (3D) regions of interest (ROIs) and the largest two-dimensional (2D) ROIs. Inter-reader variability was evaluated with Dice coefficient and Hausdorff distance, whilst its impact on RFs was assessed using mean relative change (MRC) and intraclass correlation coefficient (ICC). For the main lesion of each patient, one reader also segmented a circular ROI on the same image used for the 2D ROI., Results: The best inter-reader contouring agreement was observed for 2D ROIs according to both Dice coefficient (median 0.85, interquartile range 0.78-0.89) and Hausdorff distance (0.21 mm, 0.14-0.31 mm). Comparing RF values, MRC ranged 0-752% for 2D and 0-1567% for 3D. For 24/32 RFs (75%), MRC was lower for 2D than for 3D. An ICC > 0.90 was observed for more RFs for 2D (53%) than for 3D (34%). Only 2/32 RFs (6%) showed a variability between 2D and circular ROIs higher than inter-reader variability., Conclusions: A 2D contouring approach may help mitigate overall inter-reader variability, albeit stable RFs can be extracted from both 3D and 2D segmentations of CRC liver metastases.

Objective: To describe a left epididymitis and para-aortical involvement caused by Mycobacterium tuberculosis hominis reactivation after bacillus Calmette-Guérin instillation for non-muscle-invasive bladder cancer., Patient and Methods: A Caucasian male, aged 76 years, exposed to bacillus Calmette-Guérin for a high-grade non-muscle-invasive bladder cancer in 2015, reported painful and progressive left scrotal swelling with purulent discharge from a cutaneous fistulous track that yielded, on liquid culture, a pan-susceptible Mycobacterium tuberculosis hominis strain. Moreover, after 6 months of anti-tuberculosis treatment, an abdominal peri-aortic mass, sized 4 cm, was found and a surgical biopsy showed necrotizing granulomas; however, although smear microscopy and Xpert MTB/Rif™ performed on fresh biopsy sample were positive, liquid cultures resulted negative, indicating treatment efficacy., Results: Numerous peculiar and multi-organ involvement due to BCGitis after intravesical immunotherapy have been previously described, including 17 scientific articles about epididymitis, however, no reports so far showed reactivation of Mycobacterium tuberculosis hominis after bacillus Calmette-Guérin treatment., Conclusion: Although BCGitis is more prevalent in patients undergoing bacillus Calmette-Guérin instillation for non-muscle-invasive bladder cancer, tuberculosis by other species of Mycobacterium tuberculosis should be always ruled out by molecular and conventional microbiology in patients with a history of Mycobacterium tuberculosis hominis exposure.

The aim of this multicentric study is an inter-center benchmarking, to assess how different set tools applied to the same radiomics workflow affected the radiomics features (RFs) values. This topic is of key importance to start collaboration between different centers and to bring radiomic studies from benchmark to bedside. A per-lesion analysis was performed on 56 metastases (mts) selected from 14 patients. A single radiologist performed the segmentation of all mts, and RFs were extracted from the same segmentation of each mts, using two different software and file formats. Potential sources of discrepancies were evaluated. The intraclass correlation coefficient was used to describe how strongly the same radiomic measurements calculated in the two different centers resemble each other. Moreover, means of the relative changes of each RF were calculated, compared and gradually reduced. We showed that, after matching all formulas, discrepancies in RFs calculation between two centers ranged from 1% to 277%. Therefore, we evaluated other sources of variability using a stepwise approach, which led us to reduce the inter-center discrepancies to 0% for 22/25 RFs and below 2% for 3 RFs out of 25. In this study we demonstrated that different radiomic applications and masks formats might strongly impact the computation of some RFs. Therefore, when dealing with multi-center studies it is mandatory to adopt all strategies that can help in limiting the differences, thus keeping in mind the feasibility of these strategies in large cohort studies.

Background: HER2 is a therapeutic target for metastatic colorectal cancer (mCRC), as demonstrated in the pivotal HERACLES-A (HER2 Amplification for Colo-rectaL cancer Enhanced Stratification) trial with trastuzumab and lapatinib. The aim of HERACLES-B trial is to assess the efficacy of the combination of pertuzumab and trastuzumab-emtansine (T-DM1) in this setting., Methods: HERACLES-B was a single-arm, phase II trial, in patients with histologically confirmed RAS/BRAF wild-type and HER2+ mCRC refractory to standard treatments. HER2 positivity was assessed by immunohistochemistry and in situ hybridisation according to HERACLES criteria. Patients were treated with pertuzumab (840 mg intravenous load followed by 420 mg intravenous every 3 weeks) and T-DM1 (3.6 mg/kg every 3 weeks) until disease progression or toxicity. Primary and secondary end points were objective response rate (ORR) and progression-free survival (PFS). With a Fleming/Hern design (H0=ORR 10%; α=0.05; power=0.85), 7/30 responses were required to demonstrate an ORR ≥30% (H1)., Results: Thirty-one patients, 48% with ≥4 lines of previous therapies, were treated and evaluable. ORR was 9.7% (95% CI: 0 to 28) and stable disease (SD) 67.7% (95% CI: 50 to 85). OR/SD ≥4 months was associated with higher HER2 immunohistochemistry score (3+ vs 2+) (p = 0.03). Median PFS was 4.1 months (95% CI: 3.6 to 5.9). Drug-related grade (G) 3 adverse events were observed in two patients (thrombocytopaenia); G≤2 AE in 84% of cycles (n = 296), mainly nausea and fatigue., Conclusions: HERACLES-B trial did not reach its primary end point of ORR; however, based on high disease control, PFS similar to other anti-HER2 regimens, and low toxicity, pertuzumab in combination with T-DM1 can be considered for HER2+mCRC as a potential therapeutic resource., Trial Registration Number: 2012-002128-33 and NCT03225937., Competing Interests: Competing interests: AS-B is advisory board member for Amgen, Bayer, Sanofi and Servier. SL reports consulting or advisory roles in Amgen, Bayer, Merck, Lilly and Servier; speakers’ bureau roles at Lilly, Roche and BMS, and research funding from Amgen and Merck. VZ is advisory board member for Bristol-Myers Squibb and Merck; speakers’ bureau for AstraZeneca and Lilly; reports personal fees from Bayer, Roche, Servier. FC reported recepit of honoraria or consultation fees for speaker, consultancy or advisory roles at Amgen, Bayer, Bristol-Myers Squibb, Celgene, Merck Serono, Pfizer, Roche, Servier; direct research funding as the principal investigator for institutional research projects from Amgen, Bayer, Merck Serono, Roche, Ipsen; institutional financial interests, financial support for clinical trials or contracted research from Merck Serono, Roche, Symphogen, Array; leadership Positions in Professional Societies (non-financial interests) including ESMO past president, and president of the Associazione Italiana Oncologia Toracica. AAr reports grants and personal fees from BMS, personal fees from MSD, personal fees from Eli-Lilly, personal fees from Boehringer, personal fees from Pfizer, grants from Celgene, grants and personal fees from Roche, outside the submitted work. AAm is advisory Board from Amgen, Roche, Bayer. LT reports grants from Symphogen, grants from Servier, grants from Merus, grants from Pfizer, grants from Menarini, personal fees from AstraZeneca, personal fees from Merck KGaA, personal fees from Eli Lilly, outside the submitted work. SS is advisory board member for Amgen, Bayer, BMS, CheckmAb, Clovis, Daiichi-Sankyo, Merck, Roche-Genentech, Seattle Genetics., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)