Context Pheochromocytomas and paragangliomas (PPGLs) are believed to harbor malignant potential; about 10% to 15% of pheochromocytomas and up to 50% of abdominal paragangliomas will exhibit metastatic behavior. Evidence Acquisition Extensive searches in the PubMed database with various combinations of the key words pheochromocytoma, paraganglioma, metastatic, malignant, diagnosis, pathology, genetic, and treatment were the basis for the present review. Data Synthesis To pinpoint metastatic potential in PPGLs is difficult, but nevertheless crucial for the individual patient to receive tailor-made follow-up and adjuvant treatment following primary surgery. A combination of histological workup and molecular predictive markers can possibly aid the clinicians in this aspect. Most patients with PPGLs have localized disease and may be cured by surgery. Plasma metanephrines are the main biochemical tests. Genetic testing is important, both for counseling and prognostic estimation. Apart from computed tomography and magnetic resonance imaging, molecular imaging using ⁶⁸Ga-DOTATOC/DOTATATE should be performed. ¹²³I-MIBG scintigraphy may be performed to determine whether ¹³¹I-MIBG therapy is a possible option. As first-line treatment in patients with metastatic disease, ¹⁷⁷Lu-DOTATATE or ¹³¹I-MIBG is recommended, depending on which shows best expression. In patients with very low proliferative activity, watch-and-wait or primary treatment with long-acting somatostatin analogues may be considered. As second-line treatment, or first-line in patients with high proliferative rate, chemotherapy with temozolomide or cyclophosphamide + vincristine + dacarbazine is the therapy of choice. Other therapies, including sunitinib, cabozantinib, everolimus, and PD-1/PDL-1 inhibitors, have shown modest effect. Conclusions Metastatic PPGLs need individualized management and should always be discussed in specialized and interdisciplinary tumor boards. Further studies and newer treatment modalities are urgently needed.

Lung carcinoids are neuroendocrine tumors, categorized as typical or atypical carcinoids based on their histological appearance. While most of these tumors are slow-growing neoplasms, they still possess malignant potential. Many patients are diagnosed incidentally on chest X-rays or CT scans. Presenting symptoms include cough, hemoptysis, wheezing, dyspnea, and recurrent pneumonia. Endocrine symptoms, such as carcinoid syndrome or ectopic Cushing’s syndrome, are rare. Surgery is the primary treatment and should be considered in all patients with localized disease, even when thoracic lymph node metastases are present. Patients with distant metastases may be treated with somatostatin analogues, chemotherapy, preferably temozolomide-based, mTOR inhibitors, or peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE. Most patients have an excellent prognosis. Poor prognostic factors include atypical histology and lymph node metastases at diagnosis. Long-term follow-up is mandatory since metastases may occur late.

This study of nonverbal bias in political campaign coverage is the first longitudinal study to produce the same results in different elections: Ordinary TV viewers can and do perceive bias in the facial expressions of television news anchors, specifically NBC's Tom Brokaw, CBS's Dan Rather, and ABC's Peter Jennings. Two of the three anchors exhibited significantly more positive facial expressions when they mentioned one presidential candidate than the other in the 1996 election, whereas all three exhibited bias for one candidate in both 2000 and 2004. Viewers who continue to perceive media bias when content analyses find none may be picking up on the more subtle, nonverbal elements of media coverage that are captured only in visual studies.

A comparison was made of how Swedish adults evaluated political parties and the party leaders under three different survey methods: in-person interviews, telephone interviews, and mailed questionnaires. Both the party leaders and the parties were evaluated more negatively by people responding on the mailed questionnaires. Telephone and in-person interviewees did not differ significantly. The evidence did not indicate that the mailed questionnaire respondents answered more carelessly or in a less coherent manner. The level of evaluation was affected by the method, but the structure of the answers was not. The results imply that most estimates of popular support for political leaders underestimate the level of disapproval.

Background: Patients with advanced malignant adrenal tumors face poor prognoses with limited treatment options. Emerging data suggest that these rare tumors exhibit immunogenicity, potentially benefiting from intensified immunotherapy. Methods: The SPENCER trial (NCT04187404) evaluates EO2401, an off-the-shelf in vivo peptide immunotherapy containing three synthetic HLA-A*02 restricted-peptides called OncoMimic and derived from human gut commensals that exhibit molecular mimicry to tumor-associated antigens (BIRC5, FOXM1, IL13RA2) combined with nivolumab in patients with locally advanced or metastatic adrenocortical carcinoma (ACC) or malignant pheochromocytoma/ paraganglioma (PPGL). We performed T cell receptor (TCR) repertoire sequencing to profile the TCR architecture in ACC and characterize vaccination imprints. Results: Here we show that ACC patients are characterized by a restricted peripheral T cell richness. EO2401 does not expand highly shared TCR clones across patients but diversifies pre-existing T cell clusters. These clusters are not converging on known neoantigen-specific TCRs but exhibit generation probabilities characteristic of public clones some of which being shared across patients. Conclusions: These findings suggest that EO2401-based peptide immunotherapy combined with checkpoint inhibition can broaden and activate public, pre-existing T cell clusters, potentially enhancing tumor-specific immune responses.

Background: This study aimed to evaluate whether early renal and bone marrow effects – previously identified through laboratory tests – can be detected using MRI and 18F-FLT PET-MR in neuroendocrine tumor patients treated with 177Lu-DOTATATE. Despite known early changes, precise clinical tools to monitor these effects remain limited. Methods: Ten patients with metastatic NETs, scheduled to initiate at least four treatment cycles of 177Lu-DOTATATE, were included. MRI was performed at all designated treatment time points, whereas F-FLT PET was acquired only at baseline and on day 2 following treatment initiation. Bone marrow (BM) fat conversion, proliferative activity, and renal effects were studied with MRI and 18F-FLT PET-MR. Laboratory tests for hematology and kidney and liver function were taken. Results: Six patients completed the full imaging protocol with MRI, of whom 18F-FLT PET-MR examinations were performed in two patients. All subjects demonstrated increased BM fat content during the study interval, with a mean of +12.8%. The magnitude of the increase varied substantially, from +3.8% to +23.5%. There was a strong correlation between increased BM fat content and reduced peripheral blood cell counts. Decreased FLT uptake was found on day 2 after treatment. An increase in renal arterial flow and parenchymal volume was detected during the first week after treatment. No sustained renal effects were observed. Conclusions: The hematological effects observed with laboratory tests after 177Lu-DOTATATE treatment in neuroendocrine tumor patients can be detected by MRI as an increase in bone marrow fat content. This finding was supported by decreased FLT uptake on 18F-FLT PET-MR, indicating decreased bone marrow cell proliferation. MRI can also identify renal effects associated with this therapy.