Radiolabelled somatostatin analogues detect neuroendocrine tumours (NETs), but may reveal other tumour types. We examined the prevalence of possible meningioma in patients with known or suspected NETs imaged with 68Ga-DOTATATE PET-computed tomography (CT) on the basis of central nervous system uptake and compared with findings on magnetic resonance and contrast-enhanced CT imaging. Retrospective imaging reports from 313 patients who had undergone 68Ga-DOTATATE PET imaging for primary or repeat NET staging were searched to identify suspected meningiomas on PET. Images were then compared with findings on subsequent complementary MRI or contrast-enhanced CT scanning (performed within mean±112 days of PET-CT) if available. Of 313 patients, 22 had regions of uptake suggestive of meningioma. MRI was available for 12 patients and contrast-enhanced CT was available for one patient. Of these, one patient with known von Hippel-Lindau syndrome had probable cerebellar NET metastasis. Six patient scans indicated lesions consistent with PET. Two of these reported initially did not comment on meningioma. No obvious lesion was found in the remaining six patients; however, five showed a possible correlation to venous structures. The mean maximum standardized uptake value±SEM for lesions in all 21 probable meningioma patients was 4.90±0.45. 68Ga-DOTATATE is a sensitive marker of probable meningioma and may identify small lesions not reported on subsequent MRI. Lesions clearly observed on PET were identified on review in half of patients where complementary MR or CT imaging was available. Haemangioblastoma and metastatic NETs may have focal peripheral uptake similar to meningioma on 68Ga-DOTATATE PET and should be considered in the differential.

Identification of ARID1A/ATR synthetic lethality led to ATR inhibitor phase II trials in ovarian clear cell carcinoma (OCCC), a cancer of unmet need. Using multiple CRISPR-Cas9 mutagenesis and interference screens, we show that inactivation of protein phosphatase 2A (PP2A) subunits, including PPP2R1A, enhance ATRi sensitivity in ARID1A mutant OCCC. Analysis of a new OCCC cohort indicates that 52% possess oncogenic PPP2R1A p.R183 mutations and of these, one half possessed both ARID1A as well as PPP2R1A mutations. Using CRISPR-prime editing to generate new isogenic models of PPP2R1A mutant OCCC, we found that PPP2R1A p.R183W and p.R183P mutations cause ATRi-induced S phase stress, premature mitotic entry, genomic instability and ATRi sensitivity in OCCC tumour cells. p.R183 mutation also enhanced both in vitro and in vivo ATRi sensitivity in preclinical models of ARID1A mutant OCCC. These results argue for the assessment of PPP2R1A mutations as a biomarker of ATRi sensitivity.

MRI, CT, and US helped detect occult sites of thrombosis in a large majority of patients presenting with vaccine-induced thrombocytopaenia and thrombosis after receiving their first dose of the ChA... This case series reports 40 patients (median age, 41 years [interquartile range (IQR) 32- 52, 22 men) with confirmed vaccine-induced immune thrombotic thrombocytopaenia after administration of thei...

Background: Evaluate equilibrium contrast-enhanced CT (EQ-CT) texture analysis (EQ-CTTA) against histologically-quantified fibrosis, serum-based enhanced liver fibrosis panel (ELF) and imaging-based extracellular volume fraction (ECV) in chronic hepatitis. Methods: This study was a re-analysis of image data from a previous prospective study. Pre- and equilibrium-phase post-IV contrast CT datasets were collected from patients with chronic hepatitis with contemporaneous liver biopsy and serum ELF measurement between April 2011 and July 2013. Biopsy samples were analysed to derive collagen proportionate area (CPA). EQ-CTTA was performed with a filtration histogram technique using texture analysis software, with texture quantification using statistical and histogram-based metrics (mean, skewness, standard deviation, entropy, etc.). Association between pre-contrast and EQ-CTTA against CPA, ECV and ELF was evaluated using Spearman’s rank correlation coefficient (r_s). Results: Complete datasets collected in 29 patients (16 male; 13 female), mean age (range): 49 (22–66 years). Liver ECV, CPA and ELF had a median (interquartile range) of 0.26 (0.24–0.29); 5.0 (3.0–13.7) and 9.71 (8.39–10.92). Difference in segment VII hepatic CTTA (medium texture scale) between EQ-CT and pre-contrast images was significantly and positively associated with ELF score (mean: r_s = 0.69, p < 0.001; skewness: r_s = 0.57, p = 0.007). Significant negative associations were observed between pre-contrast and EQ-CT whole hepatic CTTA (coarse texture scale) with CPA (pre-contrast, SD: r_s = −0.66, p < 0.001) and ECV (EQ-CT, entropy: r_s = −0.58, p = 0.006). Conclusions: Hepatic EQ-CTTA demonstrates significant association with validated markers of liver fibrosis, suggesting a role in non-invasive quantification of severity in diffuse fibrosis.