Hyperprogressive Disease (HPD) in Solid Tumours Receiving Immune Checkpoint Inhibitors in a Real-World Setting.

Introduction: Hyperprogressive disease (HPD) is a state of accelerated tumor growth from cancer immunotherapy, associated with poor outcome. The reported incidence is 6% to 29% among studies using varying definitions of HPD, with no predictive biomarkers. Tumor infiltrating lymphocytes (TILs) are prognostic and predictive for immunotherapy benefit in various tumor types, but have only been tested for correlation with HPD in one study. Objectives: The objective of the study was to determine the prevalence of HPD in solid tumor patients treated with immune checkpoint inhibitor therapy in a real-world setting, and to assess clinicopathological features as potential biomarkers for HPD. Methods: We conducted a retrospective analysis of solid tumor patients treated with immune checkpoint inhibitors at a single institution. Imaging pre-immunotherapy and postimmunotherapy were assessed for HPD, and correlated against clinicopathological factors, including TILs and programmed death-ligand 1 (PD-L1) status through archival tumor assessment. HPD was defined per Matos et al as response evaluation criteria in solid tumors (RECIST) progressive disease, minimum increase in measurable lesions of 10 mm, plus increase of ≥40% in sum of target lesions compared with baseline and/or increase of ≥20% in sum of target lesions compared with baseline plus new lesions in at least 2 different organs. Results: HPD occurred in 11 of 87 patients (13%), and associated with inferior overall survival (median 5.5 months vs 18.3 months, P = .002). However, on multivariate analysis, only liver metastases (hazard ratio [HR] 4.66, 95% confidence interval [CI] 2.27-9.56, P < .001) and PD-L1 status (HR 0.53, 95% CI 0.30-0.95, P = .03) were significantly associated with survival. Presence of liver metastases correlated with occurence of HPD (P = .01). Age, sex, and monotherapy versus combination immunotherapy were not predictive for HPD. PD-L1 status and TILs were not associated with HPD. Conclusions: We found 13% HPD among solid tumor patients treated with immunotherapy, consistent with the range reported in prior series. Assessment for HPD is feasible outside of a clinical trials setting, using modified criteria that require comparison of 2 imaging studies. Liver metastases were associated with risk of HPD, while TILs and PD-L1 status were not predictive for HPD.

Translocator protein localises to CD11b+ macrophages in atherosclerosis.

BACKGROUND AND AIMS: Atherosclerosis is characterized by lipid deposition, monocyte infiltration and foam cell formation in the artery wall. Translocator protein (TSPO) is abundantly expressed in lipid rich tissues. Recently, TSPO has been identified as a potential diagnostic tool in cardiovascular disease. The purpose of this study was to determine if the TSPO ligand, 18F-PBR111, can identify early atherosclerotic lesions and if TSPO expression can be used to identify distinct macrophage populations during lesion progression. METHODS: ApoE-/- mice were maintained on a high-fat diet for 3 or 12 weeks. C57BL/6J mice maintained on chow diet served as controls. Mice were administered 18F-PBR111 intravenously and PET/CT imaged. After euthanasia, aortas were isolated, fixed and optically cleared. Cleared aortas were immunostained with DAPI, and fluorescently labelled with antibodies to TSPO, the tissue resident macrophage marker F4/80 and the monocyte-derived macrophage marker CD11b. TSPO expression and the macrophage markers were visualised in fatty streaks and established plaques by light sheet microscopy. RESULTS: While tissue resident F4/80 + macrophages were evident in the arteries of animals without atherosclerosis, no CD11b + macrophages were observed in these animals. In contrast, established plaques had high CD11b and low F4/80 expression. A ∼3-fold increase in the uptake of 18F-PBR111 was observed in the aortas of atherosclerotic mice relative to controls. CONCLUSIONS: Imaging of TSPO expression is a new approach for studying atherosclerotic lesion progression and inflammatory cell infiltration. The TSPO ligand, 18F-PBR111, is a potential clinical diagnostic tool for the detection and quantification of atherosclerotic lesion progression in humans.

Ventriculopleural Shunt Dysfunction Due to a Loculated Pleural Collection Demonstrated on SPECT/CT Imaging.

A 35-year-old woman presented with increasing drowsiness on a background of childhood meningitis and hydrocephalus managed with a ventriculopleural shunt. Her cerebral CT and chest radiograph were unchanged from previous imaging and did not identify significant pathology. Because of clinical suspicion of cerebrospinal fluid shunt dysfunction, she was referred for a cerebrospinal fluid shunt study, which demonstrated tracer accumulation within a loculated pleural collection in the left costophrenic recess.

A comparison of 4D flow MRI-derived wall shear stress with computational fluid dynamics methods for intracranial aneurysms and carotid bifurcations - A review.

BACKGROUND: 4D flow MRI is a relatively quick method for obtaining wall shear stress (WSS) in vivo, a hemodynamic parameter which has shown promise in risk stratification for rupture of cerebrovascular diseases such as intracranial aneurysms and atherosclerotic plaques. The accuracy of such measurements is still largely unknown. OBJECTIVE: To quantify the accuracy of 4D flow MRI-derived wall shear stress values for intracranial aneurysms and carotid bifurcations. METHOD: We performed a review of all original research articles which compared the magnitudes of WSS derived from 4D flow MRI with corresponding values derived from computational fluid dynamics (CFD) within both intracranial aneurysms and carotid bifurcations. RESULT: For intracranial aneurysms and carotid bifurcations, 4D flow MRI-derived WSS estimations are generally lower in magnitude compared to WSS derived by CFD methods. These differences are more pronounced in regions of higher WSS. However, the relative distributions of WSS derived from both methods are reasonably similar. CONCLUSION: Pooled analysis suggests that WSS magnitudes obtained by 4D flow MRI are underestimated, while the relative distribution is reasonably accurate, the latter being an important factor for determining the natural history of intracranial aneurysms and other cerebrovascular diseases. 4D flow MRI shows enormous potential in providing new risk stratification parameters which could have significant impact on individualized treatment decisions and improved patient outcomes.

Adrenocorticotropic Hormone-Secreting Neuroendocrine Tumor of the Rectum Demonstrated on 68Ga-DOTATATE and 18F-FDG PET Imaging.

An 81-year-old man with Cushing syndrome was referred for a Ga-DOTATATE PET/CT study to investigate for an ectopic source of adrenocorticotropic hormone. The scan demonstrated mildly increased octreopeptide uptake at a rectal mass and focal uptake at multiple regions throughout the bone marrow of the axial skeleton, consistent with metastases. A subsequent F-FDG PET/CT study was performed for further evaluation and demonstrated markedly increased metabolism at the previously identified rectal mass, in addition to the liver and multiple regions throughout the skeleton. Histopathology from biopsy of the rectal mass confirmed a small cell neuroendocrine carcinoma.