[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).

Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study.

BACKGROUND: Glucocorticoids are the cornerstone treatment of polymyalgia rheumatica (PMR) but induce adverse events. OBJECTIVES: To evaluate the efficacy and safety of first-line tocilizumab in PMR. METHODS: In a prospective open-label study (ClinicalTrials.gov: NCT01713842), 20 glucocorticoid-free patients fulfilling Chuang's PMR criteria, with symptom onset within the last 12 months and a PMR activity score (PMR-AS) >10, each received three tocilizumab infusions at 4-week intervals, without glucocorticoids, followed by oral prednisone from weeks 12 to 24 (0.15 mg/kg if PMR-AS ≤10 and 0.30 mg/kg otherwise). The primary end point was the proportion of patients with PMR-AS≤10 at week 12. RESULTS: Baseline median PMR-AS was 36.6 (IQR 30.4-43.8). At week 12, all patients had PMR-AS≤10 and received the low prednisone dosage. Median PMR-AS at weeks 12 and 24 was 4.5 (3.2-6.8) and 0.95 (IQR 0.4-2), respectively (p<0.001 vs baseline for both time points). No patient required rescue treatment. Positron emission tomography-CT showed significant improvements. The most common adverse events were transient neutropenia (n=3) and leucopenia (n=5); in one patient, the second tocilizumab infusion was omitted due to leucopenia. CONCLUSIONS: Tocilizumab monotherapy is effective in recent-onset PMR. Randomised controlled trials are warranted. TRIAL REGISTRATION NUMBER: NCT01713842.

Safety of ventilation/perfusion single photon emission computed tomography for pulmonary embolism diagnosis.

PURPOSE: The aim of this management outcome study was to assess the safety of ventilation/perfusion single photon emission computed tomography (V/Q SPECT) for the diagnosis of pulmonary embolism (PE) using for interpretation the criteria proposed in the European Association of Nuclear Medicine (EANM) guidelines for V/Q scintigraphy. METHODS: A total of 393 patients with clinically suspected PE referred to the Nuclear Medicine Department of Brest University Hospital from April 2011 to March 2013, with either a high clinical probability or a low or intermediate clinical probability but positive D-dimer, were retrospectively analysed. V/Q SPECT were interpreted by the attending nuclear medicine physician using a diagnostic cut-off of one segmental or two subsegmental mismatches. The final diagnostic conclusion was established by the physician responsible for patient care, based on clinical symptoms, laboratory test, V/Q SPECT and other imaging procedures performed. Patients in whom PE was deemed absent were not treated with anticoagulants and were followed up for 3 months. RESULTS: Of the 393 patients, the prevalence of PE was 28 %. V/Q SPECT was positive for PE in 110 patients (28 %) and negative in 283 patients (72 %). Of the 110 patients with a positive V/Q SPECT, 78 (71 %) had at least one additional imaging test (computed tomography pulmonary angiography or ultrasound) and the diagnosis of PE was eventually excluded in one patient. Of the 283 patients with a negative V/Q SPECT, 74 (26 %) patients had another test. The diagnosis of PE was finally retained in one patient and excluded in 282 patients. The 3-month thromboembolic risk in the patients not treated with anticoagulants was 1/262: 0.38 % (95 % confidence interval 0.07-2.13). CONCLUSION: A diagnostic management including V/Q SPECT interpreted with a diagnostic cut-off of "one segmental or two subsegmental mismatches" appears safe to exclude PE.

Mismatch Between Brain MRIs and 18 F-DOPA PET/CT : Impact on the Management of a Long Survivor With EGFR-Mutated Lung Adenocarcinoma.

ABSTRACT: After receiving erlotinib for 4 years, a man with advanced lung adenocarcinoma was treated with stereotactic radiotherapy for a left cerebellar brain metastasis. Local relapse of the metastasis was suspected 14 months after and confirmed on 18 F-DOPA PET. Three additional uptakes were described with no unequivocal MRI pathological signal. A second radiotherapy course was delivered. One year later, isolated local recurrence was suspected on a 3 T MRI, with a suspicious 18 F-DOPA uptake. Five additional 18 F-DOPA uptakes were described among which one increased between the 2 PETs. Because of these MRI/PET mismatches, a switch from erlotinib to osimertinib was preferred over surgery.

PET/CT-Based Radiogenomics Supports KEAP1/NFE2L2 Pathway Targeting for Non-Small Cell Lung Cancer Treated with Curative Radiotherapy.

In lung cancer patients, radiotherapy is associated with a increased risk of local relapse (LR) when compared with surgery but with a preferable toxicity profile. The KEAP1/NFE2L2 mutational status (MutKEAP1/NFE2L2) is significantly correlated with LR in patients treated with radiotherapy but is rarely available. Prediction of MutKEAP1/NFE2L2 with noninvasive modalities could help to further personalize each therapeutic strategy. Methods: Based on a public cohort of 770 patients, model RNA (M-RNA) was first developed using continuous gene expression levels to predict MutKEAP1/NFE2L2, resulting in a binary output. The model PET/CT (M-PET/CT) was then built to predict M-RNA binary output using PET/CT-extracted radiomics features. M-PET/CT was validated on an external cohort of 151 patients treated with curative volumetric modulated arc radiotherapy. Each model was built, internally validated, and evaluated on a separate cohort using a multilayer perceptron network approach. Results: The M-RNA resulted in a C statistic of 0.82 in the testing cohort. With a training cohort of 101 patients, the retained M-PET/CT resulted in an area under the curve of 0.90 (P < 0.001). With a probability threshold of 20% applied to the testing cohort, M-PET/CT achieved a C statistic of 0.7. The same radiomics model was validated on the volumetric modulated arc radiotherapy cohort as patients were significantly stratified on the basis of their risk of LR with a hazard ratio of 2.61 (P = 0.02). Conclusion: Our approach enables the prediction of MutKEAP1/NFE2L2 using PET/CT-extracted radiomics features and efficiently classifies patients at risk of LR in an external cohort treated with radiotherapy.

Correlation between rCBV Delineation Similarity and Overall Survival in a Prospective Cohort of High-Grade Gliomas Patients: The Hidden Value of Multimodal MRI?

PURPOSE: The accuracy of target delineation in radiation treatment planning of high-grade gliomas (HGGs) is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Magnetic resonance imaging (MRI) represents the standard imaging modality for delineation of gliomas with inherent limitations in accurately determining the microscopic extent of tumors. The purpose of this study was to assess the survival impact of multi-observer delineation variability of multiparametric MRI (mpMRI) and [18F]-FET PET/CT. MATERIALS AND METHODS: Thirty prospectively included patients with histologically confirmed HGGs underwent a PET/CT and mpMRI including diffusion-weighted imaging (DWI: b0, b1000, ADC), contrast-enhanced T1-weighted imaging (T1-Gado), T2-weighted fluid-attenuated inversion recovery (T2Flair), and perfusion-weighted imaging with computation of relative cerebral blood volume (rCBV) and K2 maps. Nine radiation oncologists delineated the PET/CT and MRI sequences. Spatial similarity (Dice similarity coefficient: DSC) was calculated between the readers for each sequence. Impact of the DSC on progression-free survival (PFS) and overall survival (OS) was assessed using Kaplan-Meier curves and the log-rank test. RESULTS: The highest DSC mean values were reached for morphological sequences, ranging from 0.71 +/- 0.18 to 0.84 +/- 0.09 for T2Flair and T1Gado, respectively, while metabolic volumes defined by PET/CT achieved a mean DSC of 0.75 +/- 0.11. rCBV variability (mean DSC0.32 +/- 0.20) significantly impacted PFS (p = 0.02) and OS (p = 0.002). CONCLUSIONS: Our data suggest that the T1-Gado and T2Flair sequences were the most reproducible sequences, followed by PET/CT. Reproducibility for functional sequences was low, but rCBV inter-reader similarity significantly impacted PFS and OS.

Abatacept in early polymyalgia rheumatica (ALORS): a proof-of-concept, randomised, placebo-controlled, parallel-group trial.

BACKGROUND: Medium-dose glucocorticoids can improve symptoms in nearly all patients with polymyalgia rheumatica. According to its good safety profile, abatacept could be used instead of glucocorticoids in early polymyalgia rheumatica. We aimed to determine whether the efficacy of abatacept is sufficient to justify larger studies in early polymyalgia rheumatica. METHODS: To evaluate whether abatacept allows low disease activity without glucocorticoids in early polymyalgia rheumatica, we conducted a proof-of-concept, randomised, double-blind, placebo-controlled, parallel-group trial. Participants were recruited from five centres in France (in Brest, Le Mans, Morlaix, Dinan and Saint Malo, and Strasbourg) and were included if they had recent-onset (<6 months) polymyalgia rheumatica with a C-reactive protein (CRP) polymyalgia rheumatica activity score (PMR-AS) of more than 17 without any signs or symptoms of giant cell arteritis (clinical and [18F]fluorodeoxyglucose PET-CT evaluation). Participants were randomly assigned (1:1) to receive weekly subcutaneous abatacept (125 mg) or matching placebo, with glucocorticoid rescue therapy allowed in cases of high disease activity, for 12 weeks, and then glucocorticoid treatment based on disease activity, until week 36. Investigators, patients, outcome assessors, and sponsor personnel were masked to group assignments. The primary endpoint was low disease activity (CRP PMR-AS ≤10) at week 12 without glucocorticoids and without rescue treatment. The study was powered to demonstrate a 60% difference in response rates between groups. Open-ended adverse events were collected at each visit by clinicians and were categorised following system organ class classification after study completion. The ALORS trial is registered with ClinicalTrials.gov, NCT03632187. FINDINGS: 34 patients (22 women and 12 men) were randomly assigned between Dec 13, 2018, and Oct 21, 2021. All patients who had been randomly assigned were included in the analysis. The primary endpoint was reached by eight (50%) of 16 patients in the abatacept group and four (22%) of 18 patients in the placebo group (relative risk 2·2 [0·9-5·5]); crude p=0·15; adjusted p=0·070). Eight (50%) patients in the abatacept and 15 (83%) in the placebo group had adverse events. Four patients (one [6%] in the abatacept group and three [17%] in the placebo group) had serious adverse events. There were no deaths or new safety concerns. INTERPRETATION: This study suggests that the effect of abatacept alone is not strong enough to justify larger studies in early polymyalgia rheumatica. This is only a first step in deciding whether a larger study should be conducted in early polymyalgia rheumatica and does not exclude a potential effect of abatacept in glucocorticoid-dependent polymyalgia rheumatica. FUNDING: BMS Pharma France.

Early prediction of survival following induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) using FDG PET/CT imaging in patients with locally advanced head and neck squamous cell carcinoma.

PURPOSE: Locally advanced head and neck squamous cell carcinoma (HNSCC) has a high rate of recurrence. Induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) before chemoradiotherapy could lead to the best disease control of inoperable stage III/IV HNSCC but with an increased risk of acute toxicity. Early assessment of therapeutic efficacy is a key issue in considering the benefit of escalation in a poor prognosis population. METHODS: Patients with stage III/IV HNSCC, in whom DCF induction chemotherapy followed by concurrent chemoradiotherapy had been validated by a multidisciplinary team, were prospectively included in the study. FDG PET/CT scans were performed in all patients before and after two of the three cycles of DCF. EORTC99 criteria were used to evaluate PET responses as follows: group 1 (metabolic responders) showing a complete response (CR) or partial response (PR), and subgroup 0 (metabolic nonresponders) showing stable disease (SD) or progressive disease (PD). The primary endpoint for monitoring patients was event-free survival (EFS). EFS probabilities between the two groups were estimated by the Kaplan-Meier method and statistically compared using the log-rank test. RESULTS: Fifteen consecutive patients (14 men, 1 woman; age 57.5 ± 6.2 years, mean ± SD) were analysed. Therapeutic assessment by PET/CT demonstrated CR in four patients, PR in six, SD in four and PD in one. Among the ten patients with a metabolic response (group 1), none had relapsed at the time of this report, while four of five patients with no metabolic response (group 0) showed recurrence within an average of 9.0 ± 1.6 months. Median EFS was, respectively, 18.9 months (3.8-25.3 months) and 10.2 months (7.5-12.7 months) in group 1 and group 0. The corresponding 1-year EFS rates were 100 % and 20 %, respectively. The difference in EFS between the two groups was statistically significant (p = 0.0014). CONCLUSION: Early therapeutic response demonstrated on FDG PET/CT after two cycles of induction chemotherapy with DCF in patients with inoperable stage III/IV HNSCC seems to be a predictive factor for EFS.

Identification of patients with indolent B cell lymphoma sensitive to rituximab monotherapy.

The potential predictive value of tumor bulk, genetic, and immunological variants in patients with low-grade non-Hodgkin's lymphoma to respond to treatment with rituximab (RTX) monotherapy was evaluated. Thus, the value of assessing the effect of 18-fluoro-desoxy-D-glucose (FDG) uptake on PET scan, polymorphisms in Fc gamma receptor (FcγR) IIIa-158, FcγRIIa-131, and C1qA-276 genes in predicting the response to treatment were evaluated in 50 low-grade non-Hodgkin's lymphoma patients. The influence of RTX pharmacokinetics, plasma levels of the B cell-activating factor (BAFF), and human antichimeric antibodies was also investigated. The therapeutic response was evaluated 10 weeks after treatment using revised Cheson's criteria. Lower maximal standardized uptake values (SUV(max)) at baseline were predictive of complete response. FcγRIIIa-158 polymorphism was also associated with complete response to RTX confirming previous findings, whereas polymorphisms in the FcγRIIa-131 and C1qA-276 genes were not. Lower blood levels of RTX were observed in males, but the effectiveness of RTX in males and females was the same. BAFF was not detectable in plasma before or after treatment, and no patients developed human antichimeric antibodies. Low-grade non-Hodgkin's lymphoma patients with a low SUV(max) at baseline and an FcγRIIIa-158 V/V genotype generally had a complete response to RTX.

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.

Prognostic value of interim FDG PET/CT in Hodgkin's lymphoma patients treated with interim response-adapted strategy: comparison of International Harmonization Project (IHP), Gallamini and London criteria.

PURPOSE: Interim 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) has shown to be an accurate predictor of prognosis in Hodgkin's lymphoma (HL). However, FDG PET response criteria are a matter of ongoing debate. The aim of this study was to confirm the prognostic value of interim PET/CT in HL patients treated with an interim response-adapted strategy and to compare the respective performances of different published criteria. METHODS: Newly diagnosed patients with HL underwent interim PET/CT after four courses of Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The treatment strategy was adapted according to prognostic factors at diagnosis and interim PET/CT and CT results. PET images were prospectively interpreted visually: a negative result was defined as no residual uptake above local background. All other findings were considered as positive. Retrospectively, interim PET/CT was analysed according to International Harmonization Project (IHP), Gallamini and London criteria RESULTS: The analysis included 90 patients; 6 of 31 patients with positive interim PET/CT and 7 of 59 patients with negative interim result presented treatment failure. The negative predictive value (NPV) and positive predictive value (PPV) for predicting 2-year progression-free survival (PFS) was 95 and 16%, respectively. With the other criteria, NPV remained very high (from 95 to 96%). The PPV increased from 19 to 45% according to the threshold used. Interim PET/CT was significantly correlated with PFS with Gallamini (p = 0.01) and London criteria (p < 0.0001). CONCLUSION: Our study confirms the high NPV of interim PET/CT for predicting treatment outcome in HL and a probably better prognostic value using a higher threshold for positivity even after four cycles of chemotherapy as used in Gallamini and London criteria.

18F-FET PET/CT in Early Subventricular Zone Recurrence of Adult Glioblastoma.

ABSTRACT: Glioma stem cells (GSCs) are the source of tumor recurrence in glioblastoma and are capable of whole tumor regeneration once the treatment has concluded. Compelling evidence from the last decade suggests that GSC may arise from neural stem cells residing in the adult subventricular zone (SVZ). We report the findings of an 18F-FET PET/CT showing pathological uptake in SVZ with a tumor-background ratio of greater than 1.6, giving evidence for glioblastoma recurrence. This case highlights the particular attention to be paid to the SVZ given the possible development of GSC.

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.

Assessment of Image Quality and Lesion Detectability With Digital PET/CT System.

Purpose: The aim of this study was to assess image quality and lesion detectability acquired with a digital Positron Emission Tomography/Computed Tomography (PET/CT) Siemens Biograph Vision 600 system. Material and Methods: Consecutive patients who underwent a FDG PET/CT during the first week of use of a digital PET/CT (Siemens Biograph Vision 600) at the nuclear medicine department of the university hospital of Brest were analyzed. PET were realized using list mode acquisition. For all patients, 4 datasets were reconstructed. We determined, according to phantom measurements, an equivalent time acquisition/reconstruction parameters pair of the digital PET/CT corresponding to an analog PET/CT image quality ("analog-like") as reference dataset. We compared the reference dataset with 3 others digital PET/CT reconstruction parameters, allowing a decrease of emission duration: 60, 90, and 120 s per bed position. Three nuclear medicine physicians evaluated independently, for each dataset, overall image quality [Maximal Intensity Projection (MIP), noise, sharpness] using a 4-point scale. Physicians assessed also lesion detection capability by reporting new visible lesions on each digital datasets with their confidence level in comparison with analog-like dataset. Results: Ninety-eight patients were analyzed. Image quality of MIP (IQMIP), sharpness (IQSHARPNESS), and noise (IQNOISE) of all digital datasets (60, 90, and 120 s) were better than those evaluated with analog-like reconstruction. Moreover, digital PET/CT system improved IQMIP, IQNOISE, and IQSHARPNESS whatever the BMI. Lesion detection capability and confidence level were higher for 60, 90, 120 s per bed position, respectively, than for analog-like images. Conclusion: Our study demonstrated an improvement of image quality and lesion detectability with a digital PET/CT system.

Complete Metabolic Response Assessed by FDG PET/CT to Paclitaxel-Ramucirumab in Patients With Metastatic Gastroesophageal Junction Cancer.

Paclitaxel-ramucirumab chemotherapy is indicated in second line of metastatic gastroesophageal junction cancer (mGEJC) after progression under platinum-5-FU chemotherapy. Nevertheless, the reported common response after treatment is only partial within series. To date, only 1 case report of negative posttreatment FDG PET/CT was published without baseline examination from RAINBOW trial. We illustrated the interest of FDG PET/CT to evaluate treatment especially paclitaxel-ramucirumab with 2 examples of complete metabolic responses in 2 patients having different HER2 biomarker profiles of mGEJC. As illustrated, FDG PET/CT emerges as a useful approach for therapeutic assessment of targeted drugs in mGEJC.

V/Q SPECT for the Assessment of Regional Lung Function: Generation of Normal Mean and Standard Deviation 3-D Maps.

Background: V/Q SPECT/CT is attractive for regional lung function assessment, but accurate delineation and quantification of functional lung volumes remains a challenge. Physiological intra and inter patient non-uniformity of V/Q SPECT images make conventional delineation methods of functional lung volumes inaccurate. In that context it would be of interest to build statistical maps of normal V/Q SPECT to assess the physiological variability of radiotracers. The aim of this study was to generate normal mean and standard deviation maps of regional lung function as assessed with V/Q SPECT/CT, with (AC) and without (NoAC) attenuation correction. Methods: During a 13 month period, 73 consecutive patients referred for suspected acute pulmonary embolism, that had normal V/Q SPECT/CT based on the interpretation of 2 independent nuclear medicine physicians, were selected. Four set of images were reconstructed: perfusion and ventilation images, AC, and NoAC, respectively. Statistical maps were created as follows: all cases were registered to a reference scan using the CT data, first with a rigid then with a non-rigid method. SPECTs reconstructions were then co-registered and normalized, and mean and standard deviation voxel-wise maps were calculated. To assess the consistency of generated maps to lung physiology and the potential impact of non-rigid registration, visual analysis and quantitative comparison with non-registered data were performed in the whole series. Quantitative comparison was also conducted in two randomly sampled independent subsets. Results: Perfusion mean maps showed a continuous negative posterior to anterior gradient, majored on the AC mean map. Perfusion standard deviation maps showed higher variability in the periphery of the lungs, but especially in the posterior areas. The ventilation mean map showed a slightly positive posterior to anterior gradient on NoAC mean ventilation map, while the AC mean map showed no gradient. The NoAC ventilation SD map showed a higher variability in the periphery of the lungs as compared with AC SD map. No statistical difference in the posterior to anterior gradient measurements was found between the generated mean statistical maps and the non-registered data, either in the whole series or across the two independent datasets. Conclusion: We proposed a methodology to create statistical normal maps for V/Q SPECTs. Maps were consistent with the known physiological non-uniformity and showed the impact of attenuation correction on the posterior to anterior gradient. These maps could be used for a Z-score analysis, and a better segmentation of healthy uptake areas.

Radiotherapy target volume definition in newly diagnosed high grade glioma using 18F-FET PET imaging and multiparametric perfusion MRI: A prospective study (IMAGG).

PURPOSE: The aim of this study was to prospectively investigate tumor volume delineation by amino acid PET and multiparametric perfusion magnetic resonance imaging (MRI) in patients with newly diagnosed, untreated high grade glioma (HGG). MATERIALS AND METHODS: Thirty patients with histologically confirmed HGG underwent O-(2-[18F]-fluoroethyl)-l-tyrosine (18F-FET) positron emission tomography (PET), conventional Magnetic Resonance Imaging (MRI) as contrast-enhanced (CE) and fluid-attenuated inversion recovery (FLAIR) and multiparametric MRI as relative cerebral blood volume (rCBV) and permeability estimation map (K2). Areas of MRI volumes were semi-automatically segmented. The percentage overlap volumes, Dice and Jaccard spatial similarity coefficients (OV, DSC, JSC) were calculated. RESULTS: The 18F-FET tumor volume was significantly larger than the CE volume (median 43.5 mL (2.5-124.9) vs. 23.8 mL (1.4-80.3), p = 0.005). The OV between 18F-FET uptake and CE volume was low (median OV 0.59 (0.10-1)), as well as spatial similarity (median DSC 0.52 (0.07-0.78); median JSC 0.35 (0.03-0.64)). Twenty-five patients demonstrated both rCBV and CE on MRI: The median rCBV tumor volume was significantly smaller than the median CE volume (p < 0.001). The OV was high (median 0.83 (0.54-1)), but the spatial similarity was low (median DSC 0.45 (0.04-0.83); median JSC 0.29 (0.07-0.71)). Twenty-eight patients demonstrated both K2 and CE on MRI. The median K2 tumor volume was not significantly larger than the median CE volume. The OV was high (median OV 0.90 (0.61-1)), and the spatial similarity was moderate (median DSC 0.75 (0.01-0.83); median JSC 0.60 (0.11-0.89)). CONCLUSION: We demonstrated that multiparametric perfusion MRI volumes (rCBV, K2) were highly correlated with CE T1 gadolinium volumes whereas 18F-FET PET provided complementary information, suggesting that the metabolically active tumor volume in patients with newly diagnosed untreated HGG is critically underestimated by contrast enhanced MRI. 18F-FET PET imaging may help to improve target volume delineation accuracy for radiotherapy planning.

Prognostic value of 18F-FET PET/CT in newly diagnosed WHO 2016 high-grade glioma.

O-(2-[F]fluoroethyl)-L-tyrosine positron-emission tomography/computed tomography (F-FET PET/CT) is well known in brain tumor management. Our study aimed to identify the prognostic value of F-FET PET/CT in high-grade gliomas (HGG) according the current 2016 World Health Organization (WHO) classification.Patients with histologically proven WHO 2016 HGG were prospectively included. A dynamic F-FET PET/CT was performed allowing to obtain 2 static PET frames (static frame 1: 20-40 minutes and static frame 2: 2-22 minutes). We analyzed static parameters (standard uptake value [SUV]max, SUVmean, SUVpeak, TBRmax, TBRmean, tumoral lesion glycolysis, and metabolic tumoral volume) for various isocontours (from 10% to 90%). PET parameters, clinical features, and molecular biomarkers were compared with progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analysis.Twenty-nine patients were included (grade III n = 3, grade IV n = 26). Mean PFS and OS were, respectively, 8.8 and 13.9 months. According to univariate analysis, SUVmean, SUVpeak, TBRmax, and TBRmean were significantly correlated with OS. In static 1 analysis, TBRmax seemed to be the best OS prognostic parameter (P = .004). In static 2 analysis, TBRmean was the best parameter (P = .01). In static 1 analysis, only SUVpeak was significant (P = .05) for PFS. Good performance status (PS < 2; P < .0001) and extent of resection (P = .019) identified the subgroup of patients with the best OS. Only TBRmax (P = .026) and extent of resection (P = .025) remained significant parameters in multivariate analysis.Our data suggested that high TBRmax seemed to be the most significant OS independent prognostic factor in patients with newly diagnosed HGG.

Does 18F-FDG PET/CT improve the detection of posttreatment recurrence of head and neck squamous cell carcinoma in patients negative for disease on clinical follow-up?

UNLABELLED: Posttreatment surveillance for the recurrence of head and neck squamous cell carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination, CT, and MRI. Several studies have shown that 18F-FDG PET may be an effective technique for the detection of persistent, recurrent, and distant metastatic HNSCC after treatment. The aim of this prospective study was to determine the benefits of hybrid 18F-FDG PET/CT in detecting a subclinical locoregional recurrence of HNSCC and distant metastases. The study patients were considered cured of HNSCC on the basis of 12 mo of negative findings on conventional follow-up. We also assessed the diagnostic accuracy of 18F-FDG PET/CT in these patients. METHODS: Ninety-one patients cured of HNSCC without any clinical evidence of recurrence were included. Whole-body 18F-FDG PET/CT examination was performed 11.6+/-4.4 mo after the end of the treatment. The gold standard was histopathology or 6 mo of imaging follow-up. RESULTS: The whole-body 18F-FDG PET/CT examinations had negative results in 52 patients and positive results in 39. Nine of these patients who exhibited abnormal 18F-FDG uptake in the head and neck area did not have recurrent HNSCC (false-positive). Thirty had proven recurrence. The sensitivity and specificity of 18F-FDG PET/CT in this study for the diagnosis of HNSCC recurrence were 100% (30/30) and 85% (52/61), respectively. The positive predictive value was 77% (30/39). The negative predictive value was 100% (52/52). The overall accuracy was 90% (82/91). CONCLUSION: The results of our study confirm the high effectiveness of 18F-FDG PET/CT in the assessment of HNSCC recurrence and suggest that 18F-FDG PET/CT is more accurate than conventional follow-up physical examination alone in the assessment of recurrence after previous curative treatment for HNSCC and could be proposed systematically at 12 mo of the usual follow-up.