Usefulness of FDG-PET/CT-Based Radiomics for the Characterization and Genetic Orientation of Pheochromocytomas Before Surgery

International audienceSimple Summary: Around 40% of patients with pheochromocytomas (PHEO) carry a germline mutation. Early germline mutation identification is important for accurate treatment and follow-up in affected patients. The aim of our retrospective study was to assess the potential added value of FDG-PET/CT radiomics for the characterization of PHEO and their genetic orientation prior to surgery and genetic testing. We confirmed in an homogeneous population of 52 PHEO (49 patients) the usual avidity of these tumors for FDG (92%) and the impact of germline mutation on their phenotypic presentations with higher SUVmax observed in Cluster-1-related genes. Radiomics biomarkers provided valuable additional and independent information for discriminating genetically determined PHEO (Cluster-1 or Cluster-2-related genes) as well as sporadic forms. FDG-PET/CT is then useful for preoperative detection of PHEO, and when combined with texture features, provides evidences for a genetic predisposition. Abstract: Purpose: To assess the potential added value of FDG-PET/CT radiomics for the characterization of pheochromocytomas (PHEO) and their genetic orientation prior to surgery and genetic testing. Methods: This retrospective monocentric study, included 49 patients (52 tumors) that underwent both FDG-PET/CT and MIBG scan before surgery. A germline mutation was secondarily identified in 13 patients in one of the genes related to Cluster 1 (n = 4) or Cluster 2 (n = 9). No mutation was identified in 32 patients and 4 did not have genetic testing. Correlation between several PET-based biomarkers, including SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and textural features, and biochemical and genetic features were analyzed. Results: Sensitivity of FDG-PET/CT alone was 92%, and 98% when combined to MIBG. The SUVmax was significantly higher for mutated tumors classified in Cluster 1 than in Cluster 2 (p = 0.002) or for Cancers 2020, 12, 2424 2 of 15 tumors with no identified mutations (p = 0.04). MTV and TLG of the tumors with the most intense uptake discriminated mutated Cluster 2 from sporadic tumors, but not from Cluster 1 tumors. Textural features combined with MTV led to better differentiation between sporadic and mutated tumors (p < 0.05). Conclusion: FDG-PET/CT is useful for preoperative characterization of PHEO, and when combined with radiomics biomarkers, provides evidences for a genetic predisposition

Anti-CEA Pretargeted Immuno-PET Shows Higher Sensitivity Than DOPA PET/CT in Detecting Relapsing Metastatic Medullary Thyroid Carcinoma: Post Hoc Analysis of the iPET-MTC Study

International audiencePretargeting parameters for the use of anti-carcinoembryonic antigen (CEA) bispecific monoclonal antibody TF2 and the 68Ga-labeled IMP288 peptide for immuno-PET have been optimized in a first-in-humans study performed on medullary thyroid carcinoma (MTC) patients (the iPET-MTC study). The aim of this post hoc analysis was to determine the sensitivity of immuno-PET in relapsing MTC patients, in comparison with conventional imaging and 18F-l-dihydroxyphenylalanine (18F-DOPA) PET/CT. Methods: Twenty-five studies were analyzed in 22 patients. All patients underwent immuno-PET 1 and 2 h after 68Ga-IMP288 injection pretargeted by TF2, in addition to neck, thoracic, abdominal, and pelvic CT; bone and liver MRI; and 18F-DOPA PET/CT. The gold standard was histology or confirmation by one other imaging method or by imaging follow-up. Results: In total, 190 lesions were confirmed by the gold standard: 89 in lymph nodes, 14 in lungs, 46 in liver, 37 in bone, and 4 in other sites (subcutaneous tissue, heart, brain, and pancreas). The number of abnormal foci detected by immuno-PET was 210. Among these, 174 (83%) were confirmed as true-positive by the gold standard. Immuno-PET showed a higher overall sensitivity (92%) than 18F-DOPA PET/CT (65%). Regarding metastatic sites, immuno-PET had a higher sensitivity than CT, 18F-DOPA PET/CT, or MRI for lymph nodes (98% vs. 83% for CT and 70% for 18F-DOPA PET/CT), liver (98% vs. 87% for CT, 65% for 18F-DOPA PET/CT, and 89% for MRI), and bone (92% vs. 64% for 18F-DOPA PET/CT and 86% for MRI), whereas sensitivity was lower for lung metastases (29% vs. 100% for CT and 14% for 18F-DOPA PET/CT). Tumor SUVmax at 60 min ranged from 1.2 to 59.0, with intra- and interpatient variability. Conclusion: This post hoc study demonstrates that anti-carcinoembryonic antigen immuno-PET is an effective procedure for detecting metastatic MTC lesions. Immuno-PET showed a higher overall sensitivity than 18F-DOPA PET/CT for disclosing metastases, except for the lung, where CT remains the most effective examination

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p&lt;0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons