PET-Derived Radiomics and Artificial Intelligence in Breast Cancer: A Systematic Review.

Breast cancer (BC) is a heterogeneous malignancy that still represents the second cause of cancer-related death among women worldwide. Due to the heterogeneity of BC, the correct identification of valuable biomarkers able to predict tumor biology and the best treatment approaches are still far from clear. Although molecular imaging with positron emission tomography/computed tomography (PET/CT) has improved the characterization of BC, these methods are not free from drawbacks. In recent years, radiomics and artificial intelligence (AI) have been playing an important role in the detection of several features normally unseen by the human eye in medical images. The present review provides a summary of the current status of radiomics and AI in different clinical settings of BC. A systematic search of PubMed, Web of Science and Scopus was conducted, including all articles published in English that explored radiomics and AI analyses of PET/CT images in BC. Several studies have demonstrated the potential role of such new features for the staging and prognosis as well as the assessment of biological characteristics. Radiomics and AI features appear to be promising in different clinical settings of BC, although larger prospective trials are needed to confirm and to standardize this evidence.

Radium-223 dichloride in clinical practice: a review.

The onset of skeletal metastases is typical of advanced-stage prostate cancer and requires a multidisciplinary approach to alleviate bone pain and try to delay disease progression. The current therapeutic armamentarium includes conventional analgesics, chemotherapeutic agents, immunotherapy, androgen-deprivation therapy, osteoclast inhibitors (bisphosphonates, denosumab), surgical interventions, external-beam radiotherapy and radionuclide metabolic therapy. Many studies in recent decades have demonstrated the efficacy of various radiopharmaceuticals, including strontium-89 and samarium-153, for palliation of pain from diffuse skeletal metastases, but no significant benefit in terms of disease progression and overall survival has been shown. The therapeutic landscape of metastatic skeletal cancer significantly changed after the introduction of radium-223, the first bone-homing radiopharmaceutical with disease-modifying properties. In this paper we extensively review the literature on the use of radium-223 dichloride in metastatic castration-resistant prostate cancer.

Does FDG PET-Based Radiomics Have an Added Value for Prediction of Overall Survival in Non-Small Cell Lung Cancer?

Objectives: Radiomics and machine learning are innovative approaches to improve the clinical management of NSCLC. However, there is less information about the additive value of FDG PET-based radiomics compared with clinical and imaging variables. Methods: This retrospective study included 320 NSCLC patients who underwent PET/CT with FDG at initial staging. VOIs were placed on primary tumors only. We included a total of 94 variables, including 87 textural features extracted from PET studies, SUVmax, MTV, TLG, TNM stage, histology, age, and gender. We used the least absolute shrinkage and selection operator (LASSO) regression to select variables with the highest predictive value. Although several radiomics variables are available, the added value of these predictors compared with clinical and imaging variables is still under evaluation. Three hundred and twenty NSCLC patients were included in this retrospective study and underwent 18F-FDG PET/CT at initial staging. In this study, we evaluated 94 variables, including 87 textural features, SUVmax, MTV, TLG, TNM stage, histology, age, and gender. Image-based predictors were extracted from a volume of interest (VOI) positioned on the primary tumor. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to reduce the number of variables and select only those with the highest predictive value. The predictive model implemented with the variables selected using the LASSO analysis was compared with a reference model using only a tumor stage and SUVmax. Results: NGTDM coarseness, SUVmax, and TNM stage survived the LASSO analysis and were used for the radiomic model. The AUCs obtained from the reference and radiomic models were 80.82 (95%CI, 69.01-92.63) and 81.02 (95%CI, 69.07-92.97), respectively (p = 0.98). The median OS in the reference model was 17.0 months in high-risk patients (95%CI, 11-21) and 113 months in low-risk patients (HR 7.47, p < 0.001). In the radiomic model, the median OS was 16.5 months (95%CI, 11-20) and 113 months in high- and low-risk groups, respectively (HR 9.64, p < 0.001). Conclusions: Our results indicate that a radiomic model composed using the tumor stage, SUVmax, and a selected radiomic feature (NGTDM_Coarseness) predicts survival in NSCLC patients similarly to a reference model composed only by the tumor stage and SUVmax. Replication of these preliminary results is necessary.

Brain 18 F-FET in a Case of Acute Myeloid Leukemia.

ABSTRACT: A 58-year-old woman, with a history of acute myeloid leukemia in complete response, was referred to the emergency department of our hospital for loss of consciousness. A brain MRI showed an intracranial mass suggestive for either primary brain tumor or brain metastasis. 18 F-FET PET/CT revealed increased uptake of the lesion. Metastasis from acute myeloid leukemia was diagnosed after brain biopsy. Whole-body 18 F-FDG PET/CT did not demonstrate other abnormal foci of 18 F-FDG accumulation, whereas brain lesion had an uptake slightly below the adjacent brain.

Positron Emission Tomography-Derived Radiomics and Artificial Intelligence in Multiple Myeloma: State-of-the-Art.

Multiple myeloma (MM) is a heterogeneous neoplasm accounting for the second most prevalent hematologic disorder. The identification of noninvasive, valuable biomarkers is of utmost importance for the best patient treatment selection, especially in heterogeneous diseases like MM. Despite molecular imaging with positron emission tomography (PET) has achieved a primary role in the characterization of MM, it is not free from shortcomings. In recent years, radiomics and artificial intelligence (AI), which includes machine learning (ML) and deep learning (DL) algorithms, have played an important role in mining additional information from medical images beyond human eyes' resolving power. Our review provides a summary of the current status of radiomics and AI in different clinical contexts of MM. A systematic search of PubMed, Web of Science, and Scopus was conducted, including all the articles published in English that explored radiomics and AI analyses of PET/CT images in MM. The initial results have highlighted the potential role of such new features in order to improve the clinical stratification of MM patients, as well as to increase their clinical benefits. However, more studies are warranted before these approaches can be implemented in clinical routines.

The Role of Molecular Imaging in Patients with Brain Metastases: A Literature Review.

Over the last several years, molecular imaging has gained a primary role in the evaluation of patients with brain metastases (BM). Therefore, the "Response Assessment in Neuro-Oncology" (RANO) group recommends amino acid radiotracers for the assessment of BM. Our review summarizes the current use of positron emission tomography (PET) radiotracers in patients with BM, ranging from present to future perspectives with new PET radiotracers, including the role of radiomics and potential theranostics approaches. A comprehensive search of PubMed results was conducted. All studies published in English up to and including December 2022 were reviewed. Current evidence confirms the important role of amino acid PET radiotracers for the delineation of BM extension, for the assessment of response to therapy, and particularly for the differentiation between tumor progression and radionecrosis. The newer radiotracers explore non-invasively different biological tumor processes, although more consistent findings in larger clinical trials are necessary to confirm preliminary results. Our review illustrates the role of molecular imaging in patients with BM. Along with magnetic resonance imaging (MRI), the gold standard for diagnosis of BM, PET is a useful complementary technique for processes that otherwise cannot be obtained from anatomical MRI alone.

PSMA PET/CT in Castration-Resistant Prostate Cancer: Myth or Reality?

BACKGROUND: prostate-specific membrane antigen (PSMA) ligand PET has been recently incorporated into international guidelines for several different indications in prostate cancer (PCa) patients. However, there are still some open questions regarding the role of PSMA ligand PET in castration-resistant prostate cancer (CRPC). The aim of this work is to assess the clinical value of PSMA ligand PET/CT in patients with CRPC. RESULTS: PSMA ligand PET has demonstrated higher detection rates in comparison to conventional imaging and allows for a significant reduction in the number of M0 CRPC patients. However, its real impact on patients' prognosis is still an open question. Moreover, in CRPC patients, PSMA ligand PET presents some sensitivity and specificity limitations. Due to its heterogeneity, CRPC may present a mosaic of neoplastic clones, some of which could be PSMA-/FDG+, or vice versa. Likewise, unspecific bone uptake (UBU) and second primary neoplasms (SNPs) overexpressing PSMA in the neoangiogenic vessels represent potential specificity issues. Integrated multi-tracer imaging (PSMA ligand and [18F]FDG PET) together with a multidisciplinary discussion could allow for reaching the most accurate evaluation of each patient from a precision medicine point of view.

Lutathera® Orphans: State of the Art and Future Application of Radioligand Therapy with 177Lu-DOTATATE.

Lutathera® is the first EMA- and FDA-approved radiopharmaceutical for radioligand therapy (RLT). Currently, on the legacy of the NETTER1 trial, only adult patients with progressive unresectable somatostatin receptor (SSTR) positive gastroenteropancreatic (GEP) neuroendocrine neoplasms (NET) can be treated with Lutathera®. Conversely, patients with SSTR-positive disease arising from outside the gastroenteric region do not currently have access to Lutathera® treatment despite several papers in the literature reporting the effectiveness and safety of RLT in these settings. Moreover, patients with well-differentiated G3 GEP-NET are also still "Lutathera orphans", and retreatment with RLT in patients with disease relapse is currently not approved. The aim of this critical review is to summarize current literature evidence assessing the role of Lutathera® outside the approved indications. Moreover, ongoing clinical trials evaluating new possible applications of Lutathera® will be considered and discussed to provide an updated picture of future investigations.

An Incidental Uptake of 18F-Choline in Paraganglioma.

ABSTRACT: We present a case of carotid glomus paraganglioma incidentally detected using 18F-choline PET/CT in a 63-year-old man with prostate cancer. 18F-choline PET/CT scan demonstrated a small area of 18F-choline uptake (SUVmax, 2.3) in the right parapharyngeal space of the neck, later diagnosed as paraganglioma with low proliferation index. 18F-choline PET/CT may represent a valid alternative for studying paraganglioma when either 18F-DOPA or 68Ga-SSA are not available.

The Role of Radiomics in the Era of Immune Checkpoint Inhibitors: A New Protagonist in the Jungle of Response Criteria.

Immune checkpoint inhibitors (ICI) have demonstrated encouraging results in terms of durable clinical benefit and survival in several malignancies. Nevertheless, the search to identify an "ideal" biomarker for predicting response to ICI is still far from over. Radiomics is a new translational field of study aiming to extract, by dedicated software, several features from a given medical image, ranging from intensity distribution and spatial heterogeneity to higher-order statistical parameters. Based on these premises, our review aims to summarize the current status of radiomics as a potential predictor of clinical response following immunotherapy treatment. A comprehensive search of PubMed results was conducted. All studies published in English up to and including December 2021 were selected, comprising those that explored computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) for radiomic analyses in the setting of ICI. Several studies have demonstrated the potential applicability of radiomic features in the monitoring of the therapeutic response beyond the traditional morphologic and metabolic criteria, as well as in the prediction of survival or non-invasive assessment of the tumor microenvironment. Nevertheless, important limitations emerge from our review in terms of standardization in feature selection, data sharing, and methods, as well as in external validation. Additionally, there is still need for prospective clinical trials to confirm the potential significant role of radiomics during immunotherapy.

Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives.

BACKGROUND: Renal masses detection is continually increasing worldwide, with Renal Cell Carcinoma (RCC) accounting for approximately 90% of all renal cancers and remaining one of the most aggressive urological malignancies. Despite improvements in cancer management, accurate diagnosis and treatment strategy of RCC by computed tomography (CT) and magnetic resonance imaging (MRI) are still challenging. Prostate-Specific Membrane Antigen (PSMA) is known to be highly expressed on the endothelial cells of the neovasculature of several solid tumors other than prostate cancer, including RCC. In this context, recent preliminary studies reported a promising role for positron emission tomography (PET)/CT with radiolabeled molecules targeting PSMA, in alternative to fluorodeoxyglucose (FDG) in RCC patients. PURPOSE: The aim of our review is to provide an updated overview of current evidences and major limitations regarding the use of PSMA PET/CT in RCC. METHODS: A literature search, up to 31 December 2021, was performed using the following electronic databases: PubMed, SCOPUS, Web of Science, and Google Scholar. RESULTS: The findings of this review suggest that PSMA PET/CT could represent a valid imaging option for diagnosis, staging, and therapy response evaluation in RCC, particularly in clear cell RCC. CONCLUSIONS: Further studies are needed for this "relatively" new imaging modality to consolidate its indications, timing, and practical procedures.

18F-FDG PET/CT in Labrune Syndrome.

A 69-year-old woman presented with cognitive impairment related to attentive, executive, and mnemonic functions; progressive worsening of walking, speaking, writing, and reading ability; and double sphincter incontinence. Leukoencephalopathy, cystic lesions, and calcifications, suspected for Labrune syndrome, were observed at MRI and CT brain images. Generalized wave abnormalities were also visible at electroencephalogram. Functional brain imaging performed with F-FDG PET/CT demonstrated a decreased glucose metabolism in impaired brain regions, in accordance with MRI findings. Genetic testing confirmed a mutation of SNORD118.

18F-FDG uptake in main arterial branches of patients with large vessel vasculitis: visual and semiquantitative analysis.

OBJECTIVE: Over the last decade, the contribution of (18)F-FDG (FDG) PET/CT imaging to the diagnosis of large vessel vasculitis has been widely investigated. The aim of this study was to evaluate a more extensive role for PET/CT in grading vascular inflammation in patients with different clinical stages of disease. METHODS: The images of 66 PET/CT studies of 34 patients, performed at diagnosis and/or during follow-up were reviewed. FDG uptake in different regions of aorta and in its major branches was visually (regional Score: rS) and semiquantitatively (regional SUVmean: rSUV) assessed. The global vascular uptake was also evaluated for each study by summing all rSs (summed Score; sS) and averaging rSUVs (averaged SUV; aSUV). FDG uptake in 15 PET/CT studies of control age-matched subjects without signs or symptoms of vasculitis was also analyzed. RESULTS: Higher levels of regional and global FDG uptake were found at diagnosis in comparison with follow-up studies of 12 patients with complete longitudinal observation (p value range 0.0552-0.0026). In the latter group high values were generally observed when disease relapse or incomplete response to therapy (active disease) occurred, whereas lower uptake was found in studies of remitted patients (p = <0.01), whose FDG levels were similar to those of control subjects. At ROC analysis performed on all image dataset, optimal cut-off levels of regional and global FDG vascular uptake provided a good discrimination between 25 patients at diagnosis and 15 control subjects (aSUV greater than 0.697; PPV = 92.3; NPV = 92.9). Major overlap was observed among FDG levels of 21 patients with active disease and in remission (aSUV greater than 0.653; PPV = 58.3; NPV = 94.1). Similar performances of visual and semiquantitative analyses were found when areas under curves (AUCs) were compared. CONCLUSIONS: (18)F-FDG PET/CT has a promising role in grading inflammation in patients with large arteries vasculitis. Nevertheless, a cut-off based analysis of FDG vascular uptake is not sufficient to separate patients with active and inactive disease during follow-up.

18F-Choline PET/CT-Positive Lytic Bone Lesions in Prostate Cancer and Accidental Myeloma Detection.

F-choline PET/CT was performed for suspected prostate cancer relapse in a 67-year-old man with hip pain and a rapid rise in prostate-specific antigen values (1.1 ng/mL). PET imaging showed an area of increased F-choline bone uptake in the right ischium. Coregistered CT images showed a lytic bone lesion. The infrequent CT appearance of a possible prostate carcinoma metastasis led to additional laboratory testing that showed a monoclonal γ-peak and to subsequent biopsy, which revealed a solitary plasmocytoma.

Tako-tsubo: a transitory impairment of microcirculation? A case report.

The tako-tsubo syndrome, or transient left ventricular apical ballooning, has been widely described in Japan as a cardiomyopathy which resembles acute myocardial infarction on presentation, but characterized by a normal coronary tree and a favorable outcome. Conversely few series have been described in Europe and etiology and mechanism are still unknown. We describe the case of a 74-year-old Italian woman with tako-tsubo cardiomyopathy, one of the first Italian cases reported to our knowledge. In the acute phase, echocardiography and ventriculography showed the typical mid-apical systolic left ventricular dysfunction, with an angiographically normal coronary tree. A few days after, technetium-99m single-photon emission computed tomography disclosed a large mid-apical perfusion defect and dobutamine stress echocardiography showed a typical "biphasic" response. Three months later, all of these tests normalized with normal left ventricular function. In conclusion, the results of functional tests, during the acute and subacute phases, suggest that, in the absence of evident coronary spasm, a transitory reduction of the coronary reserve played a role in the pathogenesis. In the absence of epicardial coronary obstruction this could be due to a transient microcircle dysfunction, and may be attributed to a spasm followed by impaired vasodilation capability.

Missing sentinel lymph node in cutaneous melanoma.

The American Society of Clinical Oncology guidelines recommend sentinel lymph node biopsy (SLNB) for all patients with melanoma tumors of intermediate thickness (between 1 and 4 mm). In case of patients with thick melanoma tumors (>4 mm), SLNB may be recommended as well, for staging purposes and to facilitate regional disease control. We report a case of an 82-year-old man, undergone excision of a cutaneous melanoma of the right thigh, which shows some limitation of SLNB in thick melanoma. Lymphoscintigraphy, performed as single-photon emission computed tomography/computed tomography (SPECT/CT), failed to identify the real sentinel lymph node, as tracer uptake was seen in A right inguinal node. Due to the presence on CT co-registered images of another suspicious node (with no radiopharmaceutical uptake) in the crural region, and considering the "high-risk" pathologic features of the removed primary lesion, a 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) staging scan was planned. PET/CT showed high metabolic activity in the suspected crural lymphadenopathy. Histopathology demonstrated massive invasion of the crural ("sentinel") node and no metastatic cells in the inguinal node. This report highlights both the higher accuracy of lymphoscintigraphy, when performed as SPECT/CT and the potential utility of 18F-FDG PET/CT in regional staging.

Prognostic value of exercise cardiac tomography performed late after percutaneous coronary intervention in symptomatic and symptom-free patients.

The long-term prognostic value of single-photon emission computed tomography (SPECT) performed late after percutaneous coronary intervention (PCI) has not been extensively evaluated. Moreover, the role of myocardial ischemia at SPECT in symptom-free patients after PCI is not clear. This study was designed to determine the long-term prognostic value of SPECT in predicting cardiac events after PCI in symptomatic and symptom-free patients. Exercise technetium-99m sestamibi SPECT was performed in 206 patients between 12 and 18 months after PCI. All patients were followed for a mean period of 37 +/- 16 months. Cardiac death, nonfatal myocardial infarction, and late revascularization procedures were considered to be events. Myocardial ischemia at SPECT was detectable in 44 patients. During follow-up, 24 patients experienced events (cardiac death in 4 patients, myocardial infarction in 10, and late revascularization in 10). At univariate analysis, the summed stress score (p <0.05) and summed difference score (p <0.001) were significant predictors of cardiac events. Event-free survival curves showed a higher event rate in patients with than without ischemia (p <0.001). The occurrence of cardiac events was higher in the presence of ischemia at SPECT in symptomatic and symptom-free patients (both p <0.001). The results of this study demonstrate that the extent and severity of myocardial ischemia at exercise SPECT performed between 12 and 18 months after PCI predicts cardiac events during long-term follow-up in symptomatic and symptom-free patients.

Current role of bone scan with phosphonates in the follow-up of breast cancer.

A number of studies have demonstrated that bone scintigraphy has high sensitivity and efficacy in the early detection of bone metastases from several tumours, including breast cancer. Bone scintigraphy is the most definitive tool for diagnosing and monitoring metastatic spread of breast cancer. However, in the past decade there has been a wide debate on its impact on survival time, morbidity and quality of life. Worldwide economic restrictions and these studies have led to the adoption of an almost minimalist policy for breast cancer follow-up using evidence-based guidelines. The recommended breast cancer surveillance testing includes only a few procedures (history, physical and breast self-examination, patient education on symptoms, pelvic examination). The routine use of additional tests, such as blood cell count, tumour markers, liver ultrasonography, bone scan and chest X-rays, is not recommended. Accordingly, scintigraphy should be reserved for a limited number of patients. On the other hand, early diagnosis of bone involvement may reduce the risk of skeletal related events, thus leading to a significant improvement in quality of life. Furthermore, new drugs (e.g. bisphosphonates) can now delay the onset of bone metastasis and reduce the number of patients who experience skeletal complications. In conclusion, the evidence of the clinical usefulness of bone scintigraphy (to allow early planning of new treatments in advanced disease) has to be re-evaluated, possibly by large randomised prospective trials.