Baseline metabolic tumor burden on FDG PET/CT scans predicts outcome in advanced NSCLC patients treated with immune checkpoint inhibitors.

PURPOSE: We aimed to evaluate if imaging biomarkers on FDG PET are associated with clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). METHODS: In this retrospective monocentric study, we included 109 patients with advanced NSCLC who underwent baseline FDG PET/CT before ICI initiation between July 2013 and September 2018. Clinical, biological (including dNLR = neutrophils/[leukocytes minus neutrophils]), pathological and PET parameters (tumor SUVmax, total metabolic tumor volume [TMTV]) were evaluated. A multivariate prediction model was developed using Cox models for progression-free survival (PFS) and overall survival (OS). The association between biomarkers on FDG PET/CT and disease clinical benefit (DCB) was tested using logistic regression. RESULTS: Eighty patients were eligible. Median follow-up was 11.6 months (95%CI 7.7-15.5). Sixty-four and 52 patients experienced progression and death, respectively. DCB was 40%. In multivariate analyses, TMTV > 75 cm3 and dNLR > 3 were associated with shorter OS (HR 2.5, 95%CI 1.3-4.7 and HR 3.3, 95%CI 1.6-6.4) and absence of DCB (OR 0.3, 95%CI 0.1-0.9 and OR 0.4, 95%CI 0.2-0.9). Unlike TMTV, dNLR was a significant prognostic factor for PFS (HR 1.9, 95%CI 1.1-3.3) along with anemia (HR 1.9, 95%CI 1.2-3.8). No association was observed between tumor SUVmax and PFS or OS. CONCLUSION: Baseline tumor burden (TMTV) on FDG PET/CT scans and inflammatory status (dNLR) were associated with poor OS and absence of DCB for ICI treatment in advanced NSCLC patients, unlike tumor SUVmax, and may be used together to improve the selection of appropriate candidates.

FDG-PET-CT/MRI in head and neck squamous cell carcinoma: Impact on pretherapeutic N classification, detection of distant metastases, and second primary tumors.

BACKGROUND: To assess the effect of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the pretherapeutic staging of N classification, detection rate of distant metastases, and second primaries. METHODS: Retrospective study on patients with head and neck carcinoma. We compared pretherapeutic N classification by ultrasound, computed tomography (CT)/magnetic resonance imaging (MRI), and FDG-PET-CT/MRI. RESULTS: A change in the N classification due to FDG-PET-CT/MRI was observed in 116 patients (39.5%) compared to N classification by ultrasound and fine-needle aspiration cytology. Patients with advanced nodal classification (>N2a) were more likely to be reclassified. Distant metastases were detected in 19 patients and a total of 36 second primaries were diagnosed by FDG-PET-CT/MRI. Detection of distant metastases was more likely in regional advanced disease (>N2a). Smokers (>10 py) had a significantly higher risk of second primary. CONCLUSION: FDG-PET-CT/MRI leads to a significant change in pretherapeutic N classification. The cumulative incidence of distant metastases and second primaries was 18.7%.

Partial Inhibition of Mitochondrial Complex I Reduces Tau Pathology and Improves Energy Homeostasis and Synaptic Function in 3xTg-AD Mice.

BACKGROUND: Accumulation of hyperphosphorylated tau (pTau) protein is associated with synaptic dysfunction in Alzheimer's disease (AD). We previously demonstrated that neuroprotection in familial mouse models of AD could be achieved by targeting mitochondria complex I (MCI) and activating the adaptive stress response. Efficacy of this strategy on pTau-related pathology remained unknown. OBJECTIVE: To investigate the effect of specific MCI inhibitor tricyclic pyrone compound CP2 on levels of human pTau, memory function, long term potentiation (LTP), and energy homeostasis in 18-month-old 3xTg-AD mice and explore the potential mechanisms. METHODS: CP2 was administered to male and female 3xTg-AD mice from 3.5-18 months of age. Cognitive function was assessed using the Morris water maze. Glucose metabolism was measured in periphery using a glucose tolerance test and in the brain using fluorodeoxyglucose F18 positron-emission tomography (FDG-PET). LTP was evaluated using electrophysiology in the hippocampus. The expression of key proteins associated with neuroprotective mechanisms were assessed by western blotting. RESULTS: Chronic CP2 treatment restored synaptic activity in female 3xTg-AD mice; cognitive function, levels of synaptic proteins, glucose metabolism, and energy homeostasis were improved in male and female 3xTg-AD mice. Significant reduction of human pTau in the brain was associated with increased activity of protein phosphatase of type 2A (PP2A), and reduced activity of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3ß (GSK3ß). CONCLUSION: CP2 treatment protected against synaptic dysfunction and memory impairment in symptomatic 3xTg-AD mice, and reduced levels of human pTau, indicating that targeting mitochondria with small molecule specific MCI inhibitors represents a promising strategy for treating AD.

Organizing Hematoma of the Maxillary Sinus Mimicking Malignancy Diagnosed by Fluorodeoxyglucose Positron-Emission Tomography (FDG PET/CT): A Case Report.

Organizing hematoma of the paranasal sinuses is a diagnostic dilemma clinically and radiographically, mimicking benign or malignant neoplastic processes. Although the diagnostic rate of this disease has increased as characteristic imaging findings are somewhat elucidated, endoscopic examination, preoperative biopsy, and computed tomography (CT) imaging do not give helpful information in differentiating these lesions from malignant neoplastic processes. A 55-year-old man presented with a 4-month history of recurrent nasal bleeding. He also complained of a left-sided nasal obstruction. CT findings were highly suggestive of a malignant tumor of the maxillary sinus. However, based on fluorodeoxyglucose F(18) positron-emission tomography (PET/CT) and magnetic resonance imaging (MRI), the provisional diagnosis of benign tumor rather than malignancy was made. Complete resection of the mass was achieved by simple transnasal endoscopic surgery using the Caldwell-Luc approach. Organizing hematoma of the maxillary sinus was diagnosed by histopathologic evaluation. The clinical, radiological, and histopathologic findings of the patient are presented. In this report, we have presented (18)FDG-PET findings of organized hematoma of the maxillary sinus (OHMS) that showed an increased FDG uptake in the peripheral rim of the mass with central photopenia. To our knowledge, this is the first case report in the literature reporting FDG-PET/CT findings of OHMS. Careful interpretation of metabolic (FDG-PET/CT) and anatomic (CT and MRI) images should be performed to accurately characterize the expansile lesion of the maxillary sinus in order to increase specificity and reduce equivocal findings significantly.

Relationship of serum inflammatory biomarkers with plaque inflammation assessed by FDG PET/CT: the dal-PLAQUE study.

OBJECTIVES: This study sought to longitudinally investigate the relationship between a broad spectrum of serum inflammatory biomarkers and plaque inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). BACKGROUND: Both plaque inflammation and serum biomarkers of inflammation are associated with atherothrombotic events; however, the relationship between them is unclear. METHODS: We conducted a post hoc analysis of the dal-PLAQUE (A Randomized Placebo-Controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors), a randomized, placebo-controlled study of dalcetrapib, a cholesteryl ester transfer protein inhibitor, in 130 patients with coronary heart disease, or coronary heart disease risk equivalents on stable lipid-lowering therapy. Baseline and change after 3-month follow-up in inflammatory biomarker levels and baseline and change after 3-month follow-up in aorta and carotid (18)F-FDG PET/CT (mean maximum target-to-background ratio of the most diseased segment [TBRmds]) were analyzed. RESULTS: Baseline myeloperoxidase positively correlated with baseline carotid TBRmds (rho = 0.25, p = 0.02). This correlation remained at the 3-month follow-up and was independent of traditional cardiovascular disease risk factors. Baseline lipoprotein-associated phospholipase A2 mass correlated with aorta TBRmds (rho = 0.21, p = 0.03). However, this correlation disappeared at the 3-month follow-up and was not independent of cardiovascular disease risk factors. There was no association between change from baseline in myeloperoxidase or lipoprotein-associated phospholipase A2 mass and change from baseline in aorta and carotid TBRmds. Baseline and change from baseline in high sensitivity C-reactive protein, interleukin 6, soluble P-selectin, soluble E-selectin, soluble intracellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and matrix-metalloproteinase 3 and 9 did not correlate with baseline or change from baseline in carotid or aorta TBRmds. CONCLUSIONS: Our data show that, in patients with coronary heart disease or at high risk of coronary heart disease on stable lipid-lowering therapy, circulating myeloperoxidase levels are associated with carotid plaque inflammation. (A Randomized, Placebo-controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors [dal-PLAQUE]; NCT00655473).

A case of chronic expanding hematoma resulting in fatal hemoptysis.

An 80-year-old woman presented with a huge intrathoracic mass which had increased in size over 4 years. Computed tomography showed a thick calcified capsule and early-enhanced streaks inside the mass. Needle biopsy aspirated pure blood and fibrous connective tissue. F-18 fluorodeoxyglucose positron-emission tomography showed moderate FDG uptake at the periphery with central photon defects. Gallium-67 scintigraphy showed no abnormal uptake. On suspicion of chronic expanding hematoma, we recommended surgical resection, but the patient requested only follow-up. One year later, she was hospitalized with cardiac tamponade and subsequent massive hemoptysis. Repeated embolization was ineffective, and the patient soon succumbed.

The Diagnostic Role of FDG PET/CT in Patients with Fever of Unknown Origin.

OBJECTIVE: Fever of unknown origin (FUO) is a challenge for the physician and needs use of clinical, laboratory, and imaging studies and also invasive and/or non-invasive interventions to detect the etiology. The aim of present study was to assess the role of FDG PET/CT in determining the etiology in patients with FUO. MATERIAL AND METHODS: Twenty-four patients (median age 52, range 5-77 years, 6 female, 18 male) who were diagnosed with FUO were retrospectively analyzed in this study. Before the FDG PET/CT studies, none of them had a definitive reason for their diseases investigated by conventional radiological or scintigraphic methods, clinical and laboratory observations. RESULTS: The positive result was achieved in 19 (79.2%) of 24 patients as findings of the FDG PET/CT. However, FDG PET/CT was useful for definitive diagnosis in 12 (63.2%) of 19 positive patients. Malignant diseases were determined to be the underlying cause of FUO in 5 (41.6%) of 12 patients. Noninfectious inflammatory causes were detected in 2 (16.7%) patients, infections were exhibited in 3 (25%) patients, and miscellaneous diseases demonstrated in 2 (16.7%) patients. In 7 patients the detected pathological uptakes on FDG PET/CT were not helpful for the definitive diagnosis. In remaining 5 patients who showed no pathological uptake in the FDG PET/CT, diagnosis could not be established by other methods, as well. The sensitivity, specificity, and positive and negative predictive values for the determination of FUO etiology were 92.3%, 45.4%, 63.1%, and 100% for FDG PET/CT. CONCLUSION: Our results demonstrate that FDG PET/CT seems to have considerable contribution to reveal the reason of undiagnosed patients with FUO investigated by conventional diagnostic methods, clinical and laboratory observations. CONFLICT OF INTEREST: None declared.