Malignant Pleural Mesothelioma: Staging and Radiological Response Criteria in Patients Treated with Immune Checkpoint Inhibitors.

Malignant pleural mesothelioma (MPM) is a rare and challenging cancer associated with asbestos fiber exposure, which offers limited treatment options. Historically, platinum-based chemotherapy has been the primary approach, but recent developments have introduced immunotherapy as a promising alternative for the treatment of this disease. Nevertheless, the unique growth patterns and occasionally ambiguous progressive characteristics of MPM make the interpretation of radiological assessments complex. Immunotherapy further complicates matters by introducing unconventional treatment response patterns such as hyperprogression and pseudoprogression. Consequently, there is a growing imperative to integrate the standard RECIST criteria with the mesothelioma-specific mRECIST criteria (version 1.1), as outlined in iRECIST. This comprehensive review is driven by the intent to provide a valuable resource for radiologists and clinicians engaged in the diagnosis, treatment, and monitoring of MPM in the era of immunotherapy. Specifically, the current imaging methods employed for staging and follow-up will be exposed and discussed, with a focus on the technical specificities and the mRECIST 1.1 methodology. Furthermore, we will provide a discussion about major clinical trials related to the use of immunotherapy in MPM patients. Finally, the latest advancements in radiomics, the applications of artificial intelligence in MPM, and their potential impact on clinical practice for prognosis and therapy, are discussed.

Primary adrenal insufficiency induced by immune checkpoint inhibitors: biological, clinical, and radiological aspects.

Immune checkpoint inhibitors (ICI) have become a cornerstone in medical oncology, with evolving therapeutic strategies and applications. These monoclonal antibodies, designed to enhance immune responses, have revealed a spectrum of immune-related adverse events (irAEs). While many irAEs exhibit favorable responses to corticosteroid or immunosuppressive therapy, most ICI-related endocrinopathies necessitate lifelong replacement therapy and pose significant clinical challenges. Adrenal insufficiency (AI), a noteworthy endocrine irAE, can manifest as primary AI (PAI) or secondary AI (SAI), resulting from adrenal or pituitary gland dysfunction, respectively. ICI-induced AI, albeit relatively infrequent, occurs in 1-2% of patients receiving single-agent anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) or Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) therapies and in a higher range of 4-9% when ICIs are used in combinations. Recognizing and addressing ICI-induced PAI is crucial, as it often presents with acute and potentially life-threatening symptoms, especially considering the expanding use of ICI therapy. This review provides an updated overview of ICI-induced PAI, exploring its clinical, diagnostic, and radiological aspects.

Breast MRI: Clinical Indications, Recommendations, and Future Applications in Breast Cancer Diagnosis.

PURPOSE OF REVIEW: This article aims to provide an updated overview of the indications for diagnostic breast magnetic resonance imaging (MRI), discusses the available and novel imaging exams proposed for breast cancer detection, and discusses considerations when performing breast MRI in the clinical setting. RECENT FINDINGS: Breast MRI is superior in identifying lesions in women with a very high risk of breast cancer or average risk with dense breasts. Moreover, the application of breast MRI has benefits in numerous other clinical cases as well; e.g., the assessment of the extent of disease, evaluation of response to neoadjuvant therapy (NAT), evaluation of lymph nodes and primary occult tumor, evaluation of lesions suspicious of Paget's disease, and suspicious discharge and breast implants. Breast cancer is the most frequently detected tumor among women around the globe and is often diagnosed as a result of abnormal findings on mammography. Although effective multimodal therapies significantly decline mortality rates, breast cancer remains one of the leading causes of cancer death. A proactive approach to identifying suspicious breast lesions at early stages can enhance the efficacy of anti-cancer treatments, improve patient recovery, and significantly improve long-term survival. However, the currently applied mammography to detect breast cancer has its limitations. High false-positive and false-negative rates are observed in women with dense breasts. Since approximately half of the screening population comprises women with dense breasts, mammography is often incorrectly used. The application of breast MRI should significantly impact the correct cases of breast abnormality detection in women. Radiomics provides valuable data obtained from breast MRI, further improving breast cancer diagnosis. Introducing these constantly evolving algorithms in clinical practice will lead to the right breast detection tool, optimized surveillance program, and individualized breast cancer treatment.

Assessment of clinical studies evaluating combinations of immune checkpoint inhibitors with locoregional treatments in solid tumors.

In the last decade, immunotherapy with immune checkpoint inhibitors (ICIs) has changed the therapeutic algorithm of cancer patients. ICIs combined with other therapeutic options, such as chemo- and targeted therapies, generate impressive results in cancer patients. Locoregional treatments (LRTs) play an important role in the management of various solid tumors (e.g., hepatocellular carcinoma (HCC), neuroendocrine tumors, etc.), and this therapeutic approach may enhance the activity of the immune response to tumor cells destroying primary tumors and leading to the release of several soluble molecules. This systematic review was performed to identify studies reporting objective response rate (ORR) and survival information in patients with solid tumors treated with ICIs plus LRTs. In the present work, fourteen studies were included, and the majority of them (five studies) enrolled patients with hepatocellular carcinoma (HCC), whereas the others included patients with different diseases. The highest ORRs were seen in HCC (67%, Y-90 RE plus ipilimumab and nivolumab) and melanoma (38%, dendritic cells with mRNA plus ipilimumab) patients. ORRs were not observed in liver metastases from melanoma and colorectal cancer. These data suggest that combination of ICIs and LRTs is feasible and more active in primary tumors (particularly HCC) than metastases with a synergistic effect on antitumor immunity. However, further studies are needed to better select patients, schedules, and setting of treatments.

Role of cardiac MRI in the diagnosis of immune checkpoint inhibitor-associated myocarditis.

Immune checkpoint inhibitor (ICI)-induced cardiotoxicity is a rare immune-related adverse event (irAE) characterized by a high mortality rate. From a pathological point of view, this condition can result from a series of causes, including binding of ICIs to target molecules on nonlymphocytic cells, cross-reaction of T lymphocytes against tumor antigens with off-target tissues, generation of autoantibodies and production of proinflammatory cytokines. The diagnosis of ICI-induced cardiotoxicity can be challenging, and cardiac magnetic resonance (CMR) represents the diagnostic tool of choice in clinically stable patients with suspected myocarditis. CMR is gaining a central role in diagnosis and monitoring of cardiovascular damage in cancer patients, and it is entering international cardiology and oncology guidelines. In this narrative review, we summarized the clinical aspects of ICI-associated myocarditis, highlighting its radiological aspects and proposing a novel algorithm for the use of CMR.

The restoring of interhemispheric brain connectivity following carotid endarterectomy: an exploratory observational study.

This study aimed to evaluate the differences of brain connectivity between healthy subjects (HS) and patients with extracranial internal carotid artery (eICA) stenosis before and after carotid endarterectomy (CEA). An exploratory prospective study was designed. The study population consisted of a patient group (PG) of 20 patients with eICA stenosis eligible for CEA, and a control group (CG) of 20 HS, matched for age and sex. The subjects of the PG group underwent Magnetic Resonance Imaging (MRI) for resting-state functional connectivity MRI (rs-fc MRI) analysis within one week from the CEA (pre-CEA) and 12 months following CEA (post-CEA). The CG underwent a single MRI with the same protocol utilized for the PG. Three region-of-interest to region-of-interest (ROI-to-ROI) rs-fc MRI analyses were conducted: analysis 1 to compare pre-CEA PG and CG; analysis 2 to compare pre-CEA PG and post-CEA PG; analysis 3 to compare post-CEA PG and CG. The Functional Network Connectivity multivariate parametric technique was used for statistical analysis, adopting a p-uncorrected (p-unc) < 0.05 as connection threshold, and a cluster level False Discovery Rate corrected p (p-FDR) < 0.05 as cluster threshold. The clusters were defined by using a data-driven hierarchical clustering procedure. Analysis 1 revealed two clusters of reduced interhemispheric connectivity of pre-CEA PG when compared to CG. Analysis 2 and 3 showed no statistically significant differences. Our exploratory analysis suggests that patients with eICA stenosis have reduced interhemispheric connectivity when compared to a matched control group, and this difference was not evident anymore following endarterectomy.

Radiomics and "radi- omics" in cancer immunotherapy: a guide for clinicians.

In recent years the concept of precision medicine has become a popular topic particularly in medical oncology. Besides the identification of new molecular prognostic and predictive biomarkers and the development of new targeted and immunotherapeutic drugs, imaging has started to play a central role in this new era. Terms such as "radiomics", "radiogenomics" or "radi…-omics" are becoming increasingly common in the literature and soon they will represent an integral part of clinical practice. The use of artificial intelligence, imaging and "-omics" data can be used to develop models able to predict, for example, the features of the tumor immune microenvironment through imaging, and to monitor the therapeutic response beyond the standard radiological criteria. The aims of this narrative review are to provide a simplified guide for clinicians to these concepts, and to summarize the existing evidence on radiomics and "radi…-omics" in cancer immunotherapy.

Early diagnosis of chemotherapy-induced cardiotoxicity by cardiac MRI.

Survival rate in cancer patients has improved over the course of the years. In cancer survivors, cardiovascular disease is the second leading cause of mortality and early detection and serial monitoring of cardiotoxicity are key factors towards the improvement of patients' outcomes. This review article will provide an overview of the existing literature regarding the tools that MRI can offer in the early diagnosis of myocardial damage.

Immune Checkpoint Inhibitor-Induced Pancreatic Injury: Imaging Findings and Literature Review.

The immunotherapy revolution in cancer treatment involves a variety of specialists, not only oncologists, but also internal medicine physicians, endocrinologists, dermatologists, gastroenterologists, rheumatologists, and radiologists, introducing new scenarios and novel challenges in the diagnosis and management of a number of novel immune-related adverse events. Among these, immune checkpoint inhibitor-induced pancreatic injury has been described (occurring in up to 4% of patients) and has been reported to be responsible for visits to the emergency departments in up to 1.9% of patients treated with immune checkpoint inhibitors. This side effect can be symptomatic or non-symptomatic, and can be associated with the development of long-term damage to the pancreas, requiring the involvement of different specialists, including radiologists and gastroenterologists in the multidisciplinary team that manages these patients. The aim of this narrative review is to provide a summary of the available literature related to immune checkpoint inhibitor-induced pancreatic injury including the epidemiology, the clinical findings, and the management algorithm for diagnosis with a detailed analysis of the differential diagnosis at imaging, and treatment. A more in-depth focus is dedicated to symptomatic acute pancreatitis with its peculiar findings at imaging (ultrasound, computed tomography, and magnetic resonance imaging).

Immunotherapy Associated Pulmonary Toxicity: Biology Behind Clinical and Radiological Features.

The broader use of immune checkpoint blockade in clinical routine challenges clinicians in the diagnosis and management of side effects which are caused by inflammation generated by the activation of the immune response. Nearly all organs can be affected by immune-related toxicities. However, the most frequently reported are: fatigue, rash, pruritus, diarrhea, nausea/vomiting, arthralgia, decreased appetite and abdominal pain. Although these adverse events are usually mild, reversible and not frequent, an early diagnosis is crucial. Immune-related pulmonary toxicity was most frequently observed in trials of lung cancer and of melanoma patients treated with the combination of the anti-cytotoxic T lymphocyte antigen (CTLA)-4 and the anti-programmed cell death-1 (PD-1) antibodies. The most frequent immune-related adverse event in the lung is represented by pneumonitis due to the development of infiltrates in the interstitium and in the alveoli. Clinical symptoms and radiological patterns are the key elements to be considered for an early diagnosis, rendering the differential diagnosis crucial. Diagnosis of immune-related pneumonitis may imply the temporary or definitive suspension of immunotherapy, along with the start of immuno-suppressive treatments. The aim of this work is to summarize the biological bases, clinical and radiological findings of lung toxicity under immune checkpoint blockade, underlining the importance of multidisciplinary teams for an optimal early diagnosis of this side effect, with the aim to reach an improved patient care.

Reorganization of brain networks following carotid endarterectomy: an exploratory study using resting state functional connectivity with a focus on the changes in Default Mode Network connectivity.

OBJECTIVES: To assess whether there is mid-term reorganization in brain networks connectivity after Carotid Endarterectomy (CEA) using resting state functional connectivity Magnetic Resonance (fc-rsMR), with a special focus on the Default Mode Network (DMN). MATERIALS AND METHODS: In this prospective exploratory study, 14 asymptomatic consecutive patients (10 males and 4 females, mean age 73.5) with unilateral, significant ICA stenosis eligible for CEA according to European Society for Vascular Surgery guidelines were prospectively recruited. The week before CEA procedure, each patient underwent both neurocognitive and rs-fcMR evaluations on the same day; the neurocognitive test consisted on a Mini Mental State Examination (MMSE). The same neurocognitive test and rs-fcMR examination were repeated on follow-up between 3-6 months after CEA. MMSE scores were compared using paired T-Student Test. Rs-fcMR Region Of Interest (ROI-to-ROI) and Seed-to-voxel group analysis were conducted using the CONN toolbox v18 and the SPM 12 software. RESULTS: Patients showed improvements in MMSE scores from before to after CEA (p-value = 0.0001). ROI-to-ROI analysis revealed several statistically significant connectivity changes following CEA, both in terms of positive and negative correlations; Seed-to-Voxel focusing on DMN revealed increased connectivity between medial prefrontal cortex (mPFC) and three different clusters of voxels. CONCLUSIONS: CEA procedure is associated with an improvement in neurocognitive performance (according to MMSE testing) and reorganization of functional connectivity, including the DMN. These results represent a starting point in order to design further studies for a better understanding of the reorganization of brain networks following CEA, and to investigate the potential role of CEA as a therapeutic procedure for cognitive impairments in selected patients with critical ICA stenosis.

Cancer immunotherapy-associated hypophysitis.

Side effects of immune checkpoint blockade are often said to be infrequent and usually mild. The uniqueness of endocrine immune-related adverse events is their non-reversibility, with incidence and prevalence destined to increase in the coming years, particularly if immunotherapy is used at earlier stages of neoplastic disease. Immune-related hypophysitis is one of these observed endocrine adverse events. It is often difficult to diagnose, sometimes occurring without specific symptoms. It can lead to irreversibly altered functioning of diverse endocrine glands. Radiographically, the differential diagnosis of hypophysitis includes pituitary apoplexy and primary and secondary neoplastic lesions. Immune-related hypophysitis is most common with single-agent anti-CTLA-4, followed by the combination of anti-CTLA-4 and anti-PD-1, while occurs infrequently when anti-PD-1 or anti-PD-L1 agents are administered alone. Hypophysitis with immune checkpoint blockade requires early recognition, diagnosis, and treatment. Patients can present with headache, visual disturbances or other endocrine-related syndromes or they can be asymptomatic. The manifestation of symptoms should prompt blood analysis and magnetic resonance imaging of the brain. Imaging is important to exclude secondary meningeal or parenchymal lesions. Management should include discontinuation of the immune checkpoint blockade, initiation of corticosteroid therapy and eventually hormone replacement therapy. Hypophysitis impacts treatment of the disease and usually requires long-term management of this irreversible side effect. A multidisciplinary team approach is merited to insure the correct diagnosis and management of immune-related hypophysitis.

The Abscopal Effect in the Era of Cancer Immunotherapy: a Spontaneous Synergism Boosting Anti-tumor Immunity?

Radiotherapy is one of the main treatment strategies used in cancer. Aside from the local control of the disease, which is mediated by a direct cytotoxic effect on tumor cells, radiotherapy has also been shown to exert immune-mediated local and systemic effects. Radiotherapy can elicit anti-tumor responses in distant sites from the radiation field; this phenomenon is known as the abscopal effect and has been described in patients previously treated with immune checkpoint blockade (ICB). Considering that the efficacy of immunotherapy has been demonstrated only in a subset of patients-who often benefit with lasting responses-efforts are ongoing to potentiate its activity with the development of new combination strategies. Radiotherapy might represent a potential candidate for a synergistic combination with immunotherapy, by improving the immunogenicity of tumors and by enhancing local and systemic immune effects. This review aims to summarize the current pre-clinical and clinical data on the immune effects of radiotherapy and their potential implications for cancer immunotherapy.

Radiation dose and image quality of computed tomography of the supra-aortic arteries: A comparison between single-source and dual-source CT Scanners.

PURPOSE: The purpose of this work was to compare the image quality and radiation dose delivered to patients during computed tomography (CT) angiography (CTA) of the supra-aortic arteries using two single-source (SS) and two dual-energy (DE) CT scanners. MATERIAL AND METHODS: In this retrospective study, 120 patients who underwent CTA of supra-aortic arteries were studied using four different types of CT scanners: a sixteen and forty-detector-row SS and two DE CT scanners. Seventy milliters of contrast medium were injected at a flow rate of 4mL/s using a power injector. For each patient the dose-length product (DLP), the volume computed tomography dose index (CDTIvol), the length of the scan and the effective dose (ED) were calculated. Qualitative and quantitative [image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)] image quality assessment was performed. RESULTS: A statistically significant lower value of the DE compared to the SS technology (P<0.0001) for the CDTI, DLP and ED was found, whereas we did not find any statistically significant difference between the four scanners for the measurements of the image noise, SNR and CNR. CONCLUSION: DS CT scanners allow performing CTAs with a reduced dose compared to SS CT scanner with comparable image quality.

Critical features and challenges associated with imaging in patients undergoing cancer immunotherapy.

Manipulating an individual's immune system through immune checkpoint blockade is revolutionizing the paradigms of cancer treatment. Peculiar patterns and kinetics of response have been observed with these new drugs, rendering the assessment of tumor burden particularly challenging in cancer immunotherapy. The mechanisms of action for immune checkpoint blockade, based upon engagement of the adaptive immune system, can generate unusual response patterns, including pseudoprogression, hyperprogression, atypical and delayed responses. In patients treated with immune checkpoint blockade and radiotherapy, a reduction in tumor burden at metastatic sites distant from the irradiation field (abscopal effect) has been observed, with synergistic systemic immune effects provoked by this combination. New toxicities have also been observed, due to excessive immune activity in several organs, including lung, colon, liver and endocrine glands. Efforts to standardize assessment of cancer immunotherapy responses include novel consensus guidelines derived by modifying World Health Organization (WHO) and Response Evaluation Criteria In Solid Tumors (RECIST) criteria. The aim of this review is to evaluate imaging techniques currently used routinely in the clinic and those being used as investigational tools in immunotherapy clinical trials.

Lung disease stratification using amalgamation of Riesz and Gabor transforms in machine learning framework.

Lung disease risk stratification is important for both diagnosis and treatment planning, particularly in biopsies and radiation therapy. Manual lung disease risk stratification is challenging because of: (a) large lung data sizes, (b) inter- and intra-observer variability of the lung delineation and (c) lack of feature amalgamation during machine learning paradigm. This paper presents a two stage CADx cascaded system consisting of: (a) semi-automated lung delineation subsystem (LDS) for lung region extraction in CT slices followed by (b) morphology-based lung tissue characterization, thereby addressing the above shortcomings. LDS primarily uses entropy-based region extraction while ML-based lung characterization is mainly based on an amalgamation of directional transforms such as Riesz and Gabor along with texture-based features comprising of 100 greyscale features using the K-fold cross-validation protocol (K = 2, 3, 5 and 10). The lung database consisted of 96 patients: 15 normal and 81 diseased. We use five high resolution Computed Tomography (HRCT) levels representing different anatomy landmarks where disease is commonly seen. We demonstrate the amalgamated ML stratification accuracy of 99.53%, an increase of 2% against the conventional non-amalgamation ML system that uses alone Riesz-based feature embedded with feature selection based on feature strength. The robustness of the system was determined based on the reliability and stability that showed a reliability index of 0.99 and the deviation in risk stratification accuracies less than 5%. Our CADx system shows 10% better performance when compared against the mean of five other prominent studies available in the current literature covering over one decade.