A new schedule of one week on/one week off temozolomide as second-line treatment of advanced neuroendocrine carcinomas (TENEC-TRIAL): a multicenter, open-label, single-arm, phase II trial.

BACKGROUND: There is no consensus on the second-line treatment of patients with progressive high-grade neuroendocrine neoplasms (NENs G3) and large-cell lung neuroendocrine carcinoma. These patients generally have poor performance status and low tolerance to combination therapy. In this trial, we aim to evaluate the efficacy and safety of temozolomide given every other week in patients with advanced platinum-pretreated NENs G3. PATIENTS AND METHODS: This trial is an open-label, non-randomized, phase II trial. Patients with platinum-pretreated metastatic neuroendocrine carcinoma were treated with 75 mg/m2/day of temozolomide for 7 days, followed by 7 days of no treatment (regimen one week on/one week off). The primary endpoint was the overall response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and tolerability. This study is registered with ClinicalTrials.gov, NCT04122911. RESULTS: From 2017 to 2020, 38 patients were enrolled. Among the patients with determined Ki67, 12 out of 36 (33.3%) had a Ki67 index <55% and the remaining 24 out of 36 (66.6%) had an index ≥55%. Overall response rate was 18% (7/38), including one complete response and six partial responses. The median PFS was 5.86 months [95% confidence interval (CI) 4.8 months-not applicable) and the median OS was 12.1 months (95% CI 5.6-20.4 months). The 1-year PFS rate was 37%. No statistically significant difference in median PFS [hazard ratio 1.3 (95% CI 0.6-2.8); P = 0.44] and median OS [hazard ratio 1.1 (95% CI 0.5-2.4); P = 0.77] was observed among patients with Ki67 <55% versus ≥55%. Only G1-G2 adverse events were registered, the most common being G1 nausea, diarrhea and abdominal pain. CONCLUSION: One week on/one week off temozolomide shows promising activity in patients with poorly differentiated NEN. The good safety profile confirmed the possibility of using this scheme in patients with poor performance status.

Functional assessment in endometrial and cervical cancer: diffusion and perfusion, two captivating tools for radiologists.

Uterine cervical and endometrial cancers are two major gynecological malignancies, affecting women's health worldwide. Magnetic resonance imaging (MRI) is appropriate for evaluating malignant disease, thanks to the excellent soft tissue contrast and multiplanar imaging ability. Recently, functional MR techniques, namely diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE), have proved to be a precious support not only in cancer diagnosis but also in disease staging, in the therapy planning, in monitoring response to treatment and during long-term recurrence surveillance. In the field of gynecologic oncology, the European Society of Urogenital Radiology (ESUR) recommends DWI and dynamic contrast-enhanced imaging (DCE-MRI) for local staging of endometrial and cervical cancer, but the potential application of functional imaging in all different aspects of patient management seems very promising. The aim of this article is to summarize the existing literature, providing a comprehensive update on the role of functional MRI in endometrial and cervical cancer.

Diagnostic approach to focal liver lesions at cross-sectional imaging: a primer for beginners.

Liver imaging encompasses a broad spectrum of diseases in different clinical backgrounds. The available literature is vast and reported data often lacks standardization. Because of all these issues, the differential diagnosis and the characterization of liver lesions can be challenging for the beginner. The aim of this narrative review is to provide the basics for an algorithm approach to liver lesions on cross-sectional imaging. First, some tips for the optimization of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) protocols will be provided. Liver Imaging Reporting and Data System (LI-RADS, version 2018) working group is proposing the adoption of their standardized lexicon beyond the original target population of LI-RADS (i.e., liver cirrhosis). Thus, the main imaging findings will be defined following the LI-RADS lexicon. Since the contrast study is the most important for lesion characterization, this narrative review separates the lesions into avascular, hypovascular, and hypervascular, with a focus on chronic liver disease (CLD) and hepatocellular carcinoma (HCC).

Coronary calcifications as a new prognostic marker in COVID-19 patients: role of CT.

OBJECTIVE: COVID-19 pneumonia, caused by the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic by the WHO on 11th March 2020. While Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) represents the diagnostic gold standard of infection, computed tomography (CT) has been shown to have an important role in supporting the diagnosis, quantifying the severity, and assessing the efficacy of treatment and its response. Coronary artery calcification (CAC) is a CT finding that estimates atherosclerosis and can be quantified using the coronary artery calcium score (CACS). The purpose of this study is to demonstrate the correlation between coronary artery calcification and mortality rate in COVID-19 patients. PATIENTS AND METHODS: Three hundred seventeen (317) hospitalized patients with SARS-CoV-2 infection were ruled in this retrospective study. All patients underwent a non-ECG-gated chest CT to evaluate lung parenchymal involvement. In the same cohort, we observed the two main coronary arteries (common trunk, circumflex, anterior interventricular and right coronary heart) using a visual score, so patients were divided into four groups based on Ordinal CAC Score (OCS) levels. RESULTS: The multivariate analysis proved that the OCS value was statistically correlated with the mortality rate (p < 0.001). In fact, in the group of patients with an OCS value of 0, the mortality rate was 10.1% (10/99 patients), in the group with OCS between 1 and 4 was 18.9% (21/111), in the OCS group of patients ranged from 5 to 8 was 30.4% (24/79) and in the OCS group between 9 and 12 was 46.4% (13/28). CONCLUSIONS: We suggest that calcific atheromasia of the coronary arteries in patients with COVID-19 can be considered a prognostic marker of clinical outcome.

Regorafenib monotherapy as second-line treatment of patients with RAS-mutant advanced colorectal cancer (STREAM): an academic, multicenter, single-arm, two-stage, phase II study.

BACKGROUND: Maintaining angiogenesis inhibition and switching the chemotherapy backbone represent the current second-line therapy in patients with RAS-mutant metastatic colorectal cancer (mCRC). Regorafenib, an oral multikinase inhibitor, prolonged overall survival (OS) in the chemorefractory setting. MATERIALS AND METHODS: STREAM was an academic, multicenter, single-arm phase II trial, evaluating the activity of regorafenib in RAS-mutant mCRC, in terms of the rate of patients who were progression-free after 6 months from study entry (6mo-PF). Patients were pretreated with fluoropyrimidine, oxaliplatin, and bevacizumab. According to Simon's two-stage design, ≥18 patients 6mo-PF were needed in the overall population (N = 46). Secondary endpoints were safety, objective response rate (ORR), progression-free survival (PFS), and OS. Early metabolic response by [18F]2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography ([18F]-FDG PET/CT) scan was an exploratory endpoint. EudraCT Number: 2015-001105-13. RESULTS: The number of patients 6mo-PF was 8/22 at the first stage and 14/46 in the overall population. The ORR was 10.9%, disease control rate was 54.6%, median (m)PFS was 3.6 months [95% confidence interval (CI) 1.9-6.7 months], mOS was 18.9 months (95% CI 10.3-35.3 months), and mPFS2 (from study entry to subsequent-line progression) was 13.3 months (95% CI 8.4-19.7 months). Long benefiter patients (>6mo-PF) significantly more often had a single metastatic site and lung-limited disease. No unexpected toxicity was reported. Grade ≥3 events occurred in 39.1% of patients, with hand-foot syndrome (13%), fatigue, and hyperbilirubinemia (6.5%) occurring mostly. Baseline metabolic assessment was associated with OS in the multivariate analysis, while early metabolic response was not associated with clinical outcomes. CONCLUSIONS: The study did not meet its primary endpoint. However, regorafenib was well tolerated and did not preclude subsequent treatments. Patients with good prognostic features (single metastatic site and lung-limited disease) reported clinical benefit with regorafenib. The exploratory metabolic analysis suggests that baseline [18F]-FDG PET/CT might be useful to select patients with a favorable outcome. A chemotherapy-free interval with regorafenib was associated with durable disease control in a selected group of patients with favorable clinical characteristics.

Technological advances in body CT: a primer for beginners.

Many technological advances have entered the clinical routine of Computed Tomography (CT) imaging. The new CT scanners have specific solutions in gantry design to bear the mechanical solicitations. The X-ray tubes have been improved for faster acquisitions at low radiation exposure, while the innovations in CT detectors provide a better image quality. The optimization of image quality and contrast, and the reduction of radiation dose, cannot be achieved without the implementation of adequate reconstruction software, such as Iterative Reconstructions (IR) and Artificial Intelligence (AI). In recent years, dual-energy (DECT) technology has expanded the indications of CT. In this narrative review, a panoramic overview of the technological novelties in CT imaging will be provided for optimal utilization of CT technology.

Degenerative and inflammatory musculoskeletal disorders: updates and hot topics in diagnostic and interventional imaging.

OBJECTIVE: The purpose of this review is to present the latest innovations and current topics in musculoskeletal diagnosis and interventional imaging, with a focus on degenerative and inflammatory diseases. MATERIALS AND METHODS: In this study, the search was conducted through the online databases PubMed and Google Scholar, including articles published in English in the past 15 years, in order to find existing studies, clinical cases, and reviews on the latest innovations and current topics in degenerative and inflammatory musculoskeletal pathologies. RESULTS: Imaging plays a pivotal role in the diagnosis and treatment of MSK degenerative and inflammatory disease. In the last few years continuous innovations and technological advances have allowed new clinical applications in the management of MSK disorder. Advanced magnetic resonance techniques, the introduction of fusion imaging techniques and new approaches to infiltrative medicine are revolutionizing the clinical and therapeutic approach to degenerative and inflammatory pathologies. Artificial intelligence also increasingly seeks to be applied in all fields of medicine and radiology with increasingly promising results. CONCLUSIONS: Imaging modalities undergo continuous innovations and revolutions due to technological advances, with direct repercussions on clinical applications and new therapeutic potential through interventional radiology techniques. In recent years, there have been particular innovations in the context of musculoskeletal imaging of degenerative and inflammatory diseases, both for diagnosis and intervention.

Prevalence and clinical impact of incidental findings on the unenhanced CT images of PET/CT scan in patients with multiple myeloma: the value of radiological reporting in the multimodal hybrid imaging.

OBJECTIVE: In the hybrid Positron Emission Tomography/Computed Tomography (PET/CT) method, the functional evaluation is integrated with the morphological information provided by co-registered CT, still performed for attenuation correction and lesion localization. However, co-registered CT images could provide additional diagnostic information that PET alone could underestimate. To optimize the diagnostic potential of this hybrid examination, we evaluated the prevalence and the clinical significance of incidental findings detected on co-registered CT images in a cohort of multiple myeloma (MM) patients. PATIENTS AND METHODS: We evaluated 112 MM patients (mean age 65.8 y), who underwent [18F]FDG-PET/CT during their regular workup. All co-registered CT images were retrospectively reviewed by two expert radiologists and each non-myelomatous incidental finding (nM-IF) was collected and clinically graded according to a nM-IF Reporting and Data System (nM-RADS). In addition, nM-IFs were classified according to anatomic localization (skull, lung, mediastinum, abdomen, breast, gastrointestinal, genitourinary and cardiovascular system and muscle/soft tissue). RESULTS: 163 nM-IFs were detected in 94/112 patients (83.9%) (mean value: 1.5 IFs per patient). The most interested anatomic districts were the lung (n=33; 20.2%), genitourinary (n=33; 20.2%) and gastrointestinal (n=30; 18.4%) systems. Focusing on the clinically significant findings (nM3+nM4), 92/163 (56.4%) IFs could have been required further investigations, of which 38/163 (23.3%) were potentially important and detected in 33/112 (29.5%) patients. CONCLUSIONS: The high percentage of potentially clinically significant IFs detected in MM patients emphasizes that co-registered CT images hold precious information often missed. Giving more relevance to co-registered CT with tailored acquisition and reconstruction protocols and dedicated reporting could optimize the potentiality of this multimodality imaging method with impact on clinical management.

Thoracic non-traumatic cardiovascular diseases: current perspective and multi-detectors Computed Tomography protocols optimization in the emergency setting.

Cardiovascular diseases (CVDs) are among the most common causes of access to the Emergency Department and among the leading causes of death worldwide. Accurate diagnostic algorithms are mandatory to ensure a rapid life-saving treatment. However, non-specific clinical presentation and unnecessary referrals to other subspecialties may lead to misinterpretation of the diagnosis and delays. In recent years, the development of imaging technologies has allowed Computed Tomography (CT) to play a prominent role in the concepts of CVD rule-in and rule-out. An optimization strategy for CT protocols is needed to reduce variability and improve image quality. A correct diagnostic suspicion is crucial, as different districts (i.e., heart, aorta and pulmonary circulation) may require different investigation techniques. Additionally, the CVD pre-test probability assessment is highly correlated with CT accuracy. The purpose of this narrative review is to analyze the current role of CT in the approach to the CVDs in the ED, and to analyze the main strategies of CT optimization.

Guiding antiferromagnetic transitions in Ca[Formula: see text]RuO[Formula: see text].

Understanding and controlling the transition between antiferromagnetic states having different symmetry content with respect to time-inversion and space-group operations are fundamental challenges for the design of magnetic phases with topologically nontrivial character. Here, we consider a paradigmatic antiferromagnetic oxide insulator, Ca[Formula: see text]RuO[Formula: see text], with symmetrically distinct magnetic ground states and unveil a novel path to guide the transition between them. The magnetic changeover results from structural and orbital reconstruction at the transition metal site that in turn arise as a consequence of substitutional doping. By means of resonant X-ray diffraction we track the evolution of the structural, magnetic, and orbital degrees of freedom for Mn doped Ca[Formula: see text]RuO[Formula: see text] to demonstrate the mechanisms which drive the antiferromagnetic transition. While our analysis focuses on a specific case of substitution, we show that any perturbation that can impact in a similar way on the crystal structure, by reconstructing the induced spin-orbital exchange, is able to drive the antiferromagnetic reorganization.

Radiological assessment of peritoneal carcinomatosis: a primer for resident.

The imaging has critical responsibility in the assessment of peritoneal lesions along with estimating the overall extent. Valuing disease burden is crucial for selection of combining cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (HIPEC) treatment. An approach that combines the strength of several imaging tools and increases diagnostic accuracy, should be chosen, even if the preferred imaging tool in patients with suspected Peritoneal Carcinomatosis (PC) is CT. The outcomes of PC are mainly correlated to tumor spread, localization, and lesion size. Accurate assessment of these features is critical for prognosis and treatment planning. These data can be evaluated by Peritoneal Cancer Index (PCI), a quantitative index suggested by Harman and Sugarbaker. Additionally, precise predictive biomarkers should be established to predict PC in patients at risk. The radiomics analysis could predict PC throughout the evaluation of cancers heterogeneity.

Non-traumatic non-cardiovascular thoracic emergencies: role of imaging.

Patients presenting to the emergency with thoracic symptoms could have a wide variety of causes, even if the traumatic and vascular causes are excluded. Therefore, the diagnosis is often a challenge for emergency physicians. Anamnesis, physical examination and laboratory testing need to be integrated with imaging to get a rapid diagnosis and to distinguish among the potential causes. This review discusses the role of diagnostic imaging studies in the emergency setting in patients with non-traumatic non-cardiovascular thoracic symptoms. The use of chest x-ray, bedside lung Ultrasound and Computed Tomography in the diagnosis and care of these patients have been reviewed as well as the common findings on imaging.

Optimization of CT protocol in polytrauma patients: an update.

Radiologists play a key role in the management of trauma patients. With the improvement of computed tomography (CT), radiologist makes an important contribution to the timely diagnosis of trauma-related findings and the choice of the most suitable treatment, improving patient outcomes. It is important to select the most appropriate imaging technique, which in the trauma patient is CT, and especially the most appropriate CT protocol, to correctly characterize trauma injuries. Currently, there is no agreement on what the optimal protocol is, acquisition times and number of contrast enhanced phases are not standardized. This is a review of the most recent literature on optimizing the CT protocol in polytrauma, with the intent of giving a useful tool for radiologists in the management of trauma patients.

CT study protocol optimization in acute non-traumatic abdominal settings.

Abdominal acute pain is a manifestation of heterogeneous medical conditions, with difficult clinical-laboratory assessment. Multi-detector CT (MDCT) is the gold standard imaging technique for evaluating adult patients with acute abdominal pain. Due to its fast execution and the high spatial resolution, CT is fundamental in the diagnostic and therapeutic work-up of patients with time-dependent pathology that could require surgical treatment, reducing mortality and morbidity. However, the radiological risk connected to the ionizing radiation use should not be underestimated, especially in young patients. The aim of this study is to identify optimized CT protocols to apply in the management of non-traumatic acute abdomen. In particular, this review is focused on the main emergency settings: acute pancreatitis, small bowel obstruction, acute appendicitis and acute diverticulitis. This survey would not be complete without mentioning Dual-Energy CT (DECT) technique, one of the last frontiers in CT, achieving encouraging results also in acute abdominal conditions.

Diagnostic performance of LI-RADS in adult patients with rare hepatic tumors.

OBJECTIVE: The rare hepatic tumor can have a wide spectrum of radiologic features, representing a diagnostic challenge. Our purpose is to report the experience of a National Cancer Center, emphasizing the radiological features encountered and assessing the LR-M categories in the diagnostic performances for these lesions. PATIENTS AND METHODS: We assessed 113 patients who underwent surgical resection or biopsy for rare liver lesions from May 2010 to December 2020. For these patients a computerized search of radiological records was performed to identify which had been studied with MRI and CT. For each lesion, the radiologists recorded the attenuation on CT studies and signal intensity (SI) in T1 weighted (W), in T2-W, DWI and in the related map of the apparent diffusion coefficient (ADC). We assessed the presence and the type of contrast enhancement (CE) during contrast study on CT and MRI and the enhancement was categorized according to LI-RADS 2018. We also assessed the presence of other features in LR-M categories (ancillary LR-M features) in order to classify different subgroups. The lesions were classified according to LR categories, and the gold standard was histological analysis. RESULTS: The final study population included 95 patients (46 females and 49 males), with a mean age of 51 years (range 38-83 years). 83 patients had solid lesions, 12 patients had cystic lesions (simple or complex). According to histological analysis, we categorized 79 patients with malignant lesions and 16 patients with benign lesions. According to radiological features we assessed as malignant 82 patients (79 true malignant and 3 false malignant), as benign 13 patients (all true benign). Therefore, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of radiological features to identify benign and malignant lesions were 100.0%, 81.3%, 96.3%, 100.0% and 96.8%, respectively. We found no significant difference in signal and contrast enhancement appearance among all LR-M categories (p-value =0.34 at Chi square test). However, among LR-M categories the presence of satellite nodules was a feature typical of cHCC-CC (p-value < 0.05 at Chi square test). The presence of intra lesion necrosis and haemorrhage was suggestive of sarcoma (p-value < 0.05 at Chi square test). CONCLUSIONS: High diagnostic accuracy was obtained by LI-RADS classification between malignant and benign lesion. The presence of ancillary features could help the radiologist towards a correct diagnosis.

Effect of the substrate on the electrical transport and fluctuation processes in NbRe and NbReN ultrathin films for superconducting electronics applications.

NbRe-based superconducting thin films recently received relevant interest in the field of low-temperature electronics. However, for these materials the electrical conduction mechanisms, in particular in the normal state, still need to be investigated in more detail. Here, NbRe and NbReN films of different thicknesses have been deposited on two different substrates, namely monocrystalline Si and [Formula: see text] buffered Si. The films were characterized by DC electrical transport measurements. Moreover, a connection with the charge carriers fluctuation processes has been made by analyzing the electrical noise generated in the normal state region. Despite the films morphology seems not to be affected by the substrate used, a lower noise level has been found for the ones grown on [Formula: see text], in particular for NbReN. From this study it emerges that both NbRe and NbReN ultrathin films are of very good quality, as far as the low-temperature electrical noise and conduction are concerned, with noise levels competitive with NbN. These results may further support the proposal of using these materials in a nanowire form in the field of superconducting electronics.

Diagnostic protocols in oncology: workup and treatment planning. Part 1: the optimitation of CT protocol.

The increase in oncology knowledge and the possibility of creating personalized medicine by selecting a more suitable therapy related to tumor subtypes, as well as the patient's management with cancer within a multidisciplinary team has improved the clinical outcomes. Early detection of cancer through screening-based imaging is probably the major contributor to a reduction in mortality for certain cancers. Nowadays, imaging can also characterize several lesions and predict their histopathological features and can predict tumor behaviour and prognosis. CT is the main diagnostic tool in oncologic imaging and is widely used for the tumors detection, staging, and follow-up. Moreover, since CT accounts for 49-66% of overall patient radiation exposure, the constant reduction, optimization, dose inter- and intraindividual consistency are major goals in radiological field. In the recent years, numerous dose reduction techniques have been established and created voltage modulation keeping a satisfactory image quality. The introduction of CT dual-layer detector technology enabled the acquisition of spectral data without additional CT x-ray tube or additional acquisitions. In addition, since MRI does not expose the body to radiation, it has become a mainstay of non-invasive diagnostic radiology modality since the 1980s.

Diagnostic protocols in oncology: workup and treatment planning. Part 2: Abbreviated MR protocol.

Magnetic resonance imaging (MRI) is a non-invasive imaging technique (non-ionizing radiation) with superior soft tissue contrasts and potential morphological and functional applications. However, long examination and interpretation times, as well as higher costs, still represent barriers to MRI use in clinical routine. Abbreviated MRI protocols have emerged as an alternative to standard MRI protocols. Abbreviated MRI protocols eliminate redundant sequences that negatively affect cost, acquisition time, patient comfort. However, the diagnostic information is generally not compromised. Abbreviated MRI protocols have already been utilized for hepatocellular carcinoma, for prostate cancer detection, and for nonalcoholic fatty liver disease screening.

Unveiling unconventional magnetism at the surface of Sr2RuO4.

Materials with strongly correlated electrons often exhibit interesting physical properties. An example of these materials is the layered oxide perovskite Sr2RuO4, which has been intensively investigated due to its unusual properties. Whilst the debate on the symmetry of the superconducting state in Sr2RuO4 is still ongoing, a deeper understanding of the Sr2RuO4 normal state appears crucial as this is the background in which electron pairing occurs. Here, by using low-energy muon spin spectroscopy we discover the existence of surface magnetism in Sr2RuO4 in its normal state. We detect static weak dipolar fields yet manifesting at an onset temperature higher than 50 K. We ascribe this unconventional magnetism to orbital loop currents forming at the reconstructed Sr2RuO4 surface. Our observations set a reference for the discovery of the same magnetic phase in other materials and unveil an electronic ordering mechanism that can influence electron pairing with broken time reversal symmetry.

Pancreatic cancer detection and characterization: state of the art and radiomics.

Pancreatic ductal adenocarcinoma (PDAC) represents a challenge for a multidisciplinary oncology team. Diagnosis of PDAC remains challenging due to overlapping imaging features with benign lesions, notwithstanding great advances with computed tomography (CT) and magnetic resonance imaging (MRI). The term "Radiomics" has recently been introduced to define a mathematical process to extract countless quantitative features from medical images (including each diagnostic technique) with high throughput computing for diagnosis and prediction. This article is an updated overview of the imaging techniques to be employed during detection and characterization of pancreatic cancer diagnostic workup. Particularly, the limitations and advantages of the different imaging techniques are discussed, with a particular focus on functional imaging. This overview is the result of a self-study without protocol and registration number. Articles published in the English language from January 2000 to January 2021 were included. We analyzed 15 papers on radiomics. The possibility of functional imaging, such as CT, MRI, and radiomics has revolutionized pancreatic imaging, improving the detection and characterization of the lesions and allowing a prognosis related to radiological features, favoring the process of personalized medicine.