Imaging-guided precision medicine in non-resectable gastro-entero-pancreatic neuroendocrine tumors: A step-by-step approach.

The majority of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are diagnosed at a non-resectable stage due to non-specific clinical syndromes, late manifestations from mass effects, or incidental detection of a clinically silent disease. Management strategies include curative or cytoreduction surgery, imaging-guided intervention, chemotherapy, immunotherapy, and radionuclide therapies. In this step-by-step review, we provide a structured approach for standardized reading and reporting of medical imaging studies covering content and terminology. This review explains which imaging studies should be used for different NETs and what should be reported when interpreting these studies. This standardized data collection guide should enable precision medicine for the management of patients with GEP-NETs of neuroectodermal origin: gastrointestinal-NETs (giNETs) and pancreatic NETs (pNETs). To improve outcomes from GEP-NETs, it contains a comprehensive evaluation of imaging aids for determining surgical non-resectability, and serves as a surrogate measure for tumor differentiation and proliferation, assessing the spatial and temporal heterogeneity of the tumor sites with prognostic and therapeutic implications.

A 22-Year-Old Woman With Fever, Palpitations, and a Cardiac Mass.

CASE PRESENTATION: A 22-year-old woman was admitted to our department for fever of unknown origin. The patient reported intermittent fever and nonspecific abdominal pain for several years. Six months before admission she started complaining of palpitations and exertional dyspnea. She had no weight loss, chest pain, headache, or joint complaints. Medical history was unremarkable. She did not consume tobacco, alcohol, or illicit drugs. The patient was from Malia. She had lived in France for 4 years and did not report recent travel.

Imaging-guided precision medicine in glioblastoma patients treated with immune checkpoint modulators: research trend and future directions in the field of imaging biomarkers and artificial intelligence.

Immunotherapies that employ immune checkpoint modulators (ICMs) have emerged as an effective treatment for a variety of solid cancers, as well as a paradigm shift in the treatment of cancers. Despite this breakthrough, the median survival time of glioblastoma patients has remained at about 2 years. Therefore, the safety and anti-cancer efficacy of combination therapies that include ICMs are being actively investigated. Because of the distinct mechanisms of ICMs, which restore the immune system's anti-tumor capacity, unconventional immune-related phenomena are increasingly being reported in terms of tumor response and progression, as well as adverse events. Indeed, immunotherapy response assessments for neuro-oncology (iRANO) play a central role in guiding cancer patient management and define a "wait and see strategy" for patients treated with ICMs in monotherapy with progressive disease on MRI. This article deciphers emerging research trends to ameliorate four challenges unaddressed by the iRANO criteria: (1) patient selection, (2) identification of immune-related phenomena other than pseudoprogression (i.e., hyperprogression, the abscopal effect, immune-related adverse events), (3) response assessment in combination therapies including ICM, and (4) alternatives to MRI. To this end, our article provides a structured approach for standardized selection and reporting of imaging modalities to enable the use of precision medicine by deciphering the characteristics of the tumor and its immune environment. Emerging preclinical or clinical innovations are also discussed as future directions such as immune-specific targeting and implementation of artificial intelligence algorithms.

Diagnostic and Therapeutic Uptake of Intrathyroid Metastasis of Midgut Neuroendocrine Tumor on 68Ga-DOTANOC PET/CT and 177Lu-DOTATATE Imaging.

A 58-year-old woman with 5-year history of grade 1 progressive metastatic intestinal neuroendocrine tumor with metachronous liver metastases initially treated by surgery and liver embolization underwent Ga-DOTANOC PET/CT before Lu-DOTATATE therapy. Ga-DOTANOC PET/CT revealed increased uptake in several liver metastases and right iliac lymph nodes, consistent with radiopeptide therapy, including a hypodense isthmic thyroid nodule. Fine needle ultrasound-guided biopsy of the thyroid nodule was realized. Immunohistochemistry was positive for CD56, chromogranin, and synaptophysin and negative for calcitonin, confirming neuroendocrine tumor intrathyroid metastasis. Lu-DOTATATE SPECT/CT showed therapeutic uptake on the thyroid metastasis.

The role of multimodal imaging in guiding resectability and cytoreduction in pancreatic neuroendocrine tumors: focus on PET and MRI.

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms that secrete peptides and neuro-amines. pNETs can be sporadic or hereditary, syndromic or non-syndromic with different clinical presentations and prognoses. The role of medical imaging includes locating the tumor, assessing its extent, and evaluating the feasibility of curative surgery or cytoreduction. Pancreatic NETs have very distinctive phenotypes on CT, MRI, and PET. PET have been demonstrated to be very sensitive to detect either well-differentiated pNETs using 68Gallium somatostatin receptor (SSTR) radiotracers, or more aggressive undifferentiated pNETS using 18F-FDG. A comprehensive interpretation of multimodal imaging guides resectability and cytoreduction in pNETs. The imaging phenotype provides information on the differentiation and proliferation of pNETs, as well as the spatial and temporal heterogeneity of tumors with prognostic and therapeutic implications. This review provides a structured approach for standardized reading and reporting of medical imaging studies with a focus on PET and MR techniques. It explains which imaging approach should be used for different subtypes of pNET and what a radiologist should be looking for and reporting when interpreting these studies.

FDG atrial uptake is associated with an increased prevalence of stroke in patients with atrial fibrillation.

PURPOSE: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with an increased risk of stroke. Indeed, silent AF is frequently identified in unexplained ischemic stroke. 18F-FDG-PET/CT is a powerful tool for assessing myocardial metabolic shift and inflammation, both potentially at stake in AF. This case-control study investigated whether AF could promote FDG uptake in atria after physiological myocardial glucose uptake suppression, and the potential relationship between FDG atrial uptake and prevalence of stroke. METHODS: We retrospectively enrolled 128 patients (64 consecutive patients with AF and 64 without AF as the control group, matched for age and sex) who underwent 18F-FDG-PET/CT after a high-fat low-carbohydrate diet. We analyzed visual and quantitative FDG uptake parameters of the right and left atria (RA/LA) and the right and left appendages (RAA/LAA), and selected clinical features including history of stroke. RESULTS: Diffuse right atrial uptake was present in a third of patients with AF and only two patients in the control group. FDG uptake intensity of both atria was significantly associated with the underlying heart rhythm. The occurrence of stroke was strongly associated with detectable atrial uptake in multivariate analysis, with an odds ratio superior to that of other known risk factors. CONCLUSIONS: This study shows a significant correlation between FDG atrial uptake and AF. While inconsistent, this pattern seems to be associated with an increased prevalence of cardioembolic stroke.

Could FDG-PET imaging play a role in the detection of progressing atherosclerosis in HIV-infected patients?

Important progresses in the management of patients with human immunodeficiency virus, in particular the advent of new anti-retroviral therapies (ART), have turned this rapidly fatal condition into a controllable chronic disease with a life expectancy that approaches the one from the general population. Cardiovascular diseases have now become one of the leading causes of non-HIV-related mortality in this population. Several factors including the presence of HIV in the vascular wall and the development of dyslipidemia and alteration in body fat distribution under ART might play a role the progression of atherosclerosis in HIV-infected patients. The use of imaging biomarkers may help to identify the factors associated with an increased risk of cardiovascular events and select high-risk patients who will benefit the most from the early implementation of preventive treatments.

Spleno-hepatic index to predict portal hypertension by equilibrium radionuclide ventriculography.

BACKGROUND: Structural and morphological changes accompanying liver cirrhosis lead to portal hypertension (PHT), which is the first step of most of the complications in patients with liver cirrhosis. Therefore, the development of noninvasive techniques to detect PHT is crucial for prognosis and treatment. AIM: The aim of our study was to assess the diagnostic performance of a new spleno-hepatic index (SHI) measured from equilibrium radionuclide ventriculography (ERV) images in detecting patients with cirrhotic PHT. METHODS AND RESULTS: A total of 38 patients with PHT were compared with 30 controls without liver disease. The SHI was measured on the sum of the tomographic images from the ERV and calculated according to the following formula: SHI=(mean splenic count×longest hepatic length)/mean hepatic count. Mean SHI was 54±14 and 36±8 (P<0.001) among patients with PHT and controls, respectively. A cutoff value of 40 for the SHI allowed a sensitivity of 90% and specificity of 77% to detect PHT. SHI greater than 51 was 100% specific. In a subset of 25 patients, SHI was not correlated with hepatic venous pressure gradient measured invasively in the right hepatic vein (R=-0.08, P=0.70). CONCLUSION: Quantification of SHI derived from ERV could be used to detect liver cirrhosis with PHT although it is not linearly correlated with the hepatic venous pressure gradient. SHI should be considered as a useful index for the identification of PHT in patients referred for the detection/exploration of cirrhotic cardiomyopathy by ERV.

Fluorine-18-fluorocholine PET/CT parameters predictive for hematological toxicity to radium-223 therapy in castrate-resistant prostate cancer patients with bone metastases: a pilot study.

PURPOSE: This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy. PATIENTS AND METHODS: F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra. Bone metastatic disease was quantified on the basis of the maximum standardized uptake value (SUV), total lesion activity (TLA=MBTV×SUVmean), or MBTV/height (MBTV/H) and TLA/H. F-FCH PET/CT bone tumor burden and activity were analyzed to identify which parameters could predict hematological toxicity [on hemoglobin (Hb), platelets (PLTs), and lymphocytes] while on Ra therapy. Pearson's correlation was used to identify the correlations between age, prostate-specific antigen, and F-FCH PET parameters. RESULTS: MBTV ranged from 75 to 1259 cm (median: 392 cm). TLA ranged from 342 to 7198 cm (median: 1853 cm). Patients benefited from two to six cycles of Ra (n=56 cycles in total). At the end of Ra therapy, five of the 15 (33%) patients presented grade 2/3 toxicity on Hb and lymphocytes, whereas three of the 15 (20%) patients presented grade 2/3 PLT toxicity.Age was correlated negatively with both MBTV (r=-0.612, P=0.015) and TLA (r=-0.596, P=0.018). TLA, TLA/H, and MBTV/H predicted hematological toxicity on Hb, whereas TLA/H and MBTV/H predicted toxicity on PLTs at the end of Ra cycles. Receiver operating characteristic curve analysis allowed to define the cutoffs for MBTV (915 cm) and TLA (4198 cm) predictive for PLT toxicity, with an accuracy of 0.92 and 0.99. CONCLUSION: Tumor bone burden calculation is feasible with F-FCH PET/CT with freely available open-source software. In this pilot study, baseline F-FCH PET/CT markers (TLA, MBTV) have shown abilities to predict Hb and PLT toxicity after Ra therapy and could be explored for patient selection and treatment optimization.