[18F]FDG PET/CT for therapeutic assessment of Abatacept in early-onset polymyalgia rheumatica.

PURPOSE: Evaluate the benefit of 2-deoxy-2-[18F]-fluoro-D-glucose ([18F] FDG) positron emission tomography/computed tomography (PET/CT) for the therapeutic assessment of Abatacept (ABA) as first-line therapy in early-onset polymyalgia rheumatica (PMR) patients. METHODS: This was an ancillary study of ALORS trial (Abatacept in earLy Onset polymyalgia Rheumatica Study) assessing the ability of ABA versus placebo to achieve low disease activity (C-Reactive Protein PMR activity score (CRP PMR-AS) ≤ to 10) without glucocorticoid (GC) at week 12 in patients with early-onset PMR. The patients underwent [18F] FDG PET/CT at baseline and after 12 weeks of treatment. Responses to treatments were evaluated according to CRP PMR-AS, Erythrocyte Sedimentation Rate (ESR) PMR-AS, Clin PMR-AS, and CRP-Imputed (Imput-CRP) PMR-AS. Quantitative score by maximal standardized uptake value (SUVmax) and combined qualitative scores according to liver uptake (Leuven, Leuven/Groningen, and Besançon Scores) were used for assessment of [18F] FDG uptake in regions of interest (ROI) usually affected in PMR. Student's t-test was applied to evaluate the clinical, biological, and [18F] FDG uptake variation difference in ABA and placebo groups between W0 and W12. Subgroup analysis by GC rescue was performed. RESULTS: At W12, there was no significant difference according to SUVmax between the ABA and the placebo groups in all ROI. Subgroup analysis according to GC administration demonstrated a significant (p 0.047) decrease in SUVmax within the left sternoclavicular joint ROI in the ABA group (- 0.8) compared to the placebo group (+ 0.6) without GC rescue. Other results did not reveal any significant difference between the ABA and placebo groups. According to combined qualitative scores, there was no significant difference between ABA and placebo groups for the direct comparison analysis and subgroup analysis according to GC rescue. CONCLUSION: [18F] FDG PET/CT uptake did not decrease significantly after ABA compared to placebo in anatomical areas usually affected in PMR patients. These results are correlated with the clinical-biological therapeutic assessment. CLINICAL TRIAL REGISTRATION: The study was approved by the appropriate ethics committee (CPP Sud-Est II Ref CPP: 2018-33), and all patients gave their written informed consent before study enrollment. The protocol was registered on Clinicaltrials.gov (NCT03632187).

Hotspot on 18F-FET PET/CT to Predict Aggressive Tumor Areas for Radiotherapy Dose Escalation Guiding in High-Grade Glioma.

The standard therapy strategy for high-grade glioma (HGG) is based on the maximal surgery followed by radio-chemotherapy (RT-CT) with insufficient control of the disease. Recurrences are mainly localized in the radiation field, suggesting an interest in radiotherapy dose escalation to better control the disease locally. We aimed to identify a similarity between the areas of high uptake on O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography/computed tomography (PET) before RT-CT, the residual tumor on post-therapy NADIR magnetic resonance imaging (MRI) and the area of recurrence on MRI. This is an ancillary study from the IMAGG prospective trial assessing the interest of FET PET imaging in RT target volume definition of HGG. We included patients with diagnoses of HGG obtained by biopsy or tumor resection. These patients underwent FET PET and brain MRIs, both after diagnosis and before RT-CT. The follow-up consisted of sequential brain MRIs performed every 3 months until recurrence. Tumor delineation on the initial MRI 1 (GTV 1), post-RT-CT NADIR MRI 2 (GTV 2), and progression MRI 3 (GTV 3) were performed semi-automatically and manually adjusted by a neuroradiologist specialist in neuro-oncology. GTV 2 and GTV 3 were then co-registered on FET PET data. Tumor volumes on FET PET (MTV) were delineated using a tumor to background ratio (TBR) ≥ 1.6 and different % SUVmax PET thresholds. Spatial similarity between different volumes was performed using the dice (DICE), Jaccard (JSC), and overlap fraction (OV) indices and compared together in the biopsy or partial surgery group (G1) and the total or subtotal surgery group (G2). Another overlap index (OV') was calculated to determine the threshold with the highest probability of being included in the residual volume after RT-CT on MRI 2 and in MRI 3 (called "hotspot"). A total of 23 patients were included, of whom 22% (n = 5) did not have a NADIR MRI 2 due to a disease progression diagnosed on the first post-RT-CT MRI evaluation. Among the 18 patients who underwent a NADIR MRI 2, the average residual tumor was approximately 71.6% of the GTV 1. A total of 22% of patients (5/23) showed an increase in GTV 2 without diagnosis of true progression by the multidisciplinary team (MDT). Spatial similarity between MTV and GTV 2 and between MTV and GTV 3 were higher using a TBR ≥ 1.6 threshold. These indices were significantly better in the G1 group than the G2 group. In the FET hotspot analysis, the best similarity (good agreement) with GTV 2 was found in the G1 group using a 90% SUVmax delineation method and showed a trend of statistical difference with those (poor agreement) in the G2 group (OV' = 0.67 vs. 0.38, respectively, p = 0.068); whereas the best similarity (good agreement) with GTV 3 was found in the G1 group using a 80% SUVmax delineation method and was significantly higher than those (poor agreement) in the G2 group (OV'= 0.72 vs. 0.35, respectively, p = 0.014). These results showed modest spatial similarity indices between MTV, GTV 2, and GTV 3 of HGG. Nevertheless, the results were significantly improved in patients who underwent only biopsy or partial surgery. TBR ≥ 1.6 and 80-90% SUVmax FET delineation methods showing a good agreement in the hotspot concept for targeting standard dose and radiation boost. These findings need to be tested in a larger randomized prospective study.

Radiotherapy Target Volume Definition in Newly Diagnosed High-Grade Glioma Using 18F-FET PET Imaging and Multiparametric MRI: An Inter Observer Agreement Study.

Background: The aim of this prospective monocentric study was to assess the inter-observer agreement for tumor volume delineations by multiparametric MRI and 18-F-FET-PET/CT in newly diagnosed, untreated high-grade glioma (HGG) patients. Methods: Thirty patients HGG underwent O-(2-[18F]-fluoroethyl)-l-tyrosine(18F-FET) positron emission tomography (PET), and multiparametric MRI with computation of rCBV map and K2 map. Three nuclear physicians and three radiologists with different levels of experience delineated the 18-F-FET-PET/CT and 6 MRI sequences, respectively. Spatial similarity (Dice and Jaccard: DSC and JSC) and overlap (Overlap: OV) coefficients were calculated between the readers for each sequence. Results: DSC, JSC, and OV were high for 18F-FET PET/CT, T1-GD, and T2-FLAIR (>0.67). The Spearman correlation coefficient between readers was ≥0.6 for these sequences. Cross-comparison of similarity and overlap parameters showed significant differences for DSC and JSC between 18F-FET PET/CT and T2-FLAIR and for JSC between 18F-FET PET/CT and T1-GD with higher values for 18F-FET PET/CT. No significant difference was found between T1-GD and T2-FLAIR. rCBV, K2, b1000, and ADC showed correlation coefficients between readers <0.6. Conclusion: The interobserver agreements for tumor volume delineations were high for 18-F-FET-PET/CT, T1-GD, and T2-FLAIR. The DWI (b1000, ADC), rCBV, and K2-based sequences, as performed, did not seem sufficiently reproducible to be used in daily practice.

Central Nervous System Involvement of Hemophagocytic Lymphohistiocytosis: When 18F-FDG PET/CT Solves a Complex Diagnostic Investigation.

ABSTRACT: Hemophagocytic lymphohistiocytosis is rare life-threatening syndrome, hereditary or acquired, mainly affecting children. Hemophagocytic lymphohistiocytosis is an immune deficiency characterized by severe inflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages. The usual biological and clinical data may associate polyadenopathy, hepatosplenomegaly, fever, multivisceral damages, and cytopenias with potential multiorgan dysfunction and death. We report the case of a 4-year-old girl, hospitalized for recurrent cerebellar symptoms (ataxia) associated later with fever and pancytopenia. 18F-FDG PET/CT revealed a node pathological uptake, which was biopsied and confirmed a diagnosis of hemophagocytic lymphohistiocytosis.