Imaging of the brain-heart axis: prognostic value in a European setting.

BACKGROUND AND AIMS: Increasing data suggest that stress-related neural activity (SNA) is associated with subsequent major adverse cardiovascular events (MACE) and may represent a therapeutic target. Current evidence is exclusively based on populations from the U.S. and Asia where limited information about cardiovascular disease risk was available. This study sought to investigate whether SNA imaging has clinical value in a well-characterized cohort of cardiovascular patients in Europe. METHODS: In this single-centre study, a total of 963 patients (mean age 58.4 ± 16.1 years, 40.7% female) with known cardiovascular status, ranging from 'at-risk' to manifest disease, and without active cancer underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography between 1 January 2005 and 31 August 2019. Stress-related neural activity was assessed with validated methods and relations between SNA and MACE (non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, and cardiovascular death) or all-cause mortality by time-to-event analysis. RESULTS: Over a maximum follow-up of 17 years, 118 individuals (12.3%) experienced MACE, and 270 (28.0%) died. In univariate analyses, SNA significantly correlated with an increased risk of MACE (sub-distribution hazard ratio 1.52, 95% CI 1.05-2.19; P = .026) or death (hazard ratio 2.49, 95% CI 1.96-3.17; P < .001). In multivariable analyses, the association between SNA imaging and MACE was lost when details of the cardiovascular status were added to the models. Conversely, the relationship between SNA imaging and all-cause mortality persisted after multivariable adjustments. CONCLUSIONS: In a European patient cohort where cardiovascular status is known, SNA imaging is a robust and independent predictor of all-cause mortality, but its prognostic value for MACE is less evident. Further studies should define specific patient populations that might profit from SNA imaging.

Evaluation of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Criteria in a Multicenter Cohort of Patients With Suspected Infective Endocarditis.

BACKGROUND: Since publication of Duke criteria for infective endocarditis (IE) diagnosis, several modifications have been proposed. We aimed to evaluate the diagnostic performance of the Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) 2023 criteria compared to prior versions from 2000 (Duke-Li 2000) and 2015 (Duke-ESC [European Society for Cardiology] 2015). METHODS: This study was conducted at 2 university hospitals between 2014 and 2022 among patients with suspected IE. A case was classified as IE (final IE diagnosis) by the Endocarditis Team. Sensitivity for each version of the Duke criteria was calculated among patients with confirmed IE based on pathological, surgical, and microbiological data. Specificity for each version of the Duke criteria was calculated among patients with suspected IE for whom IE diagnosis was ruled out. RESULTS: In total, 2132 episodes with suspected IE were included, of which 1101 (52%) had final IE diagnosis. Definite IE by pathologic criteria was found in 285 (13%), 285 (13%), and 345 (16%) patients using the Duke-Li 2000, Duke-ESC 2015, or the Duke-ISCVID 2023 criteria, respectively. IE was excluded by histopathology in 25 (1%) patients. The Duke-ISCVID 2023 clinical criteria showed a higher sensitivity (84%) compared to previous versions (70%). However, specificity of the new clinical criteria was lower (60%) compared to previous versions (74%). CONCLUSIONS: The Duke-ISCVID 2023 criteria led to an increase in sensitivity compared to previous versions. Further studies are needed to evaluate items that could increase sensitivity by reducing the number of IE patients misclassified as possible, but without having detrimental effect on specificity of Duke criteria.

Evaluation of the Therapeutical Effect of Matricaria Chamomilla Extract vs. Galantamine on Animal Model Memory and Behavior Using 18F-FDG PET/MRI.

The memory-enhancing activity of Matricaria chamomilla hydroalcoholic extract (MCE) is already being investigated by behavioral and biochemical assays in scopolamine-induced amnesia rat models, while the effects of scopolamine (Sco) on cerebral glucose metabolism are examined as well. Nevertheless, the study of the metabolic profile determined by an enriched MCE has not been performed before. The present experiments compared metabolic quantification in characteristic cerebral regions and behavioral characteristics for normal, only diseased, diseased, and MCE- vs. Galantamine (Gal)-treated Wistar rats. A memory deficit was induced by four weeks of daily intraperitoneal Sco injection. Starting on the eighth day, the treatment was intraperitoneally administered 30 min after Sco injection for a period of three weeks. The memory assessment comprised three maze tests. Glucose metabolism was quantified after the 18F-FDG PET examination. The right amygdala, piriform, and entorhinal cortex showed the highest differential radiopharmaceutical uptake of the 50 regions analyzed. Rats treated with MCE show metabolic similarity with normal rats, while the Gal-treated group shows features closer to the diseased group. Behavioral assessments evidenced a less anxious status and a better locomotor activity manifested by the MCE-treated group compared to the Gal-treated group. These findings prove evident metabolic ameliorative qualities of MCE over Gal classic treatment, suggesting that the extract could be a potent neuropharmacological agent against amnesia.

18F-FDG PET/CT for early prediction of pathological complete response in breast cancer neoadjuvant therapy: a retrospective analysis.

BACKGROUND: Neoadjuvant treatment has been developed as a systematic approach for patients with early breast cancer and has resulted in improved breast-conserving rate and survival. However, identifying treatment-sensitive patients at the early phase of therapy remains a problem, hampering disease management and raising the possibility of disease progression during treatment. METHODS: In this retrospective analysis, we collected 2-deoxy-2-[F-18] fluoro-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) images of primary tumor sites and axillary areas and reciprocal clinical pathological data from 121 patients who underwent neoadjuvant treatment and surgery in our center. The univariate and multivariate logistic regression analyses were performed to investigate features associated with pathological complete response (pCR). An 18F-FDG PET/CT-based prediction model was trained, and the performance was evaluated by receiver operating characteristic curves (ROC). RESULTS: The maximum standard uptake values (SUVmax) of 18F-FDG PET/CT were a powerful indicator of tumor status. The SUVmax values of axillary areas were closely related to metastatic lymph node counts (R = 0.62). Moreover, the early SUVmax reduction rates (between baseline and second cycle of neoadjuvant treatment) were statistically different between pCR and non-pCR patients. The early SUVmax reduction rates-based model showed great ability to predict pCR (AUC = 0.89), with all molecular subtypes (HR+HER2-, HR+HER2+, HR-HER2+, and HR-HER2-) considered. CONCLUSION: Our research proved that the SUVmax reduction rate of 18F-FDG PET/CT contributed to the early prediction of pCR, providing rationales for utilizing PET/CT in NAT in the future.

Prognostic value of hypermetabolic bone sarcoidosis observed by 18F-fluorodeoxyglucose positron emission tomography.

OBJECTIVES: Sarcoidosis is a multisystemic granulomatosis diagnosed mainly in young adults.18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) is useful in sarcoidosis cases to search for a biopsiable site or assess disease activity.18F-FDG PET-CT can reveal bone hypermetabolism in sarcoidosis patients, even in the absence of osteoarticular symptoms. The aim of this study was to describe metabolic bone involvement in sarcoidosis patients and to evaluate its prognostic impact. METHODS: This was an observational, comparative, retrospective, monocentric study. Inclusion criteria were a confirmed diagnosis of sarcoidosis according to the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) criteria and at least one 18F-FDG PET-CT scan during follow-up. Metabolic bone involvement of sarcoidosis was defined as focal bone hypermetabolism with no argument for a differential diagnosis of bone 18F-FDG uptake. Patients with and without bone involvement were compared. RESULTS: Among the 175 included patients, 32 (18%) had metabolic bone involvement of sarcoidosis. The metabolic bone involvement was mainly axial and mostly without bone abnormalities on CT. Metabolic bone involvement was associated with intrathoracic and extrathoracic lymph node involvement and with a higher number of organs involved. Patients with metabolic bone involvement more frequently received corticosteroids, methotrexate and tumor necrosis factor (TNF)-α inhibitors and a higher number of treatments. Relapse of sarcoidosis occurred sooner in patients with metabolic bone involvement. CONCLUSION: These results suggest that metabolic bone involvement is associated with more diffuse and more severe sarcoidosis.

Advances in the diagnosis of myocarditis in idiopathic inflammatory myopathies: an overview of diagnostic tests.

Cardiac involvement in idiopathic inflammatory myopathies (IIM) purports to worse clinical outcomes, and therefore early identification is important. Research has focused on blood biomarkers and basic investigations such as ECG and echocardiography, which have the advantage of wide availability and low cost but are limited in their sensitivity and specificity. Imaging the myocardium to directly look for inflammation and scarring has therefore been explored, with a number of new methods for doing this gaining wider research interest and clinical availability. Cardiovascular magnetic resonance (CMR) with contemporary multiparametric mapping techniques and late gadolinium enhancement imaging, is an extremely valuable and increasingly used non-invasive imaging modality for the diagnosis of myocarditis. The recently updated CMR-based Lake Louise Criteria for the diagnosis of myocarditis incorporate the newer T1 and T2 mapping techniques, which have greatly improved the diagnostic accuracy for IIM myocarditis.18F-FDG-PET/CT is a well-utilized imaging modality in the diagnosis of malignancies in IIM, and it also has a role for the diagnosis of myocarditis in multiple systemic inflammatory diseases. Endomyocardial biopsy, however, remains the gold standard technique for the diagnosis of myocarditis and is necessary for the diagnosis of specific cases of myocarditis. This article provides an overview of the important tests and imaging modalities that clinicians should consider when faced with an IIM patient with potential myocarditis.

18F-FDG PET/CT Radiomics-Based Multimodality Fusion Model for Preoperative Individualized Noninvasive Prediction of Peritoneal Metastasis in Advanced Gastric Cancer.

PURPOSE: This study was designed to develop and validate a machine learning-based, multimodality fusion (MMF) model using 18F-fluorodeoxyglucose (FDG) PET/CT radiomics and kernelled support tensor machine (KSTM), integrated with clinical factors and nuclear medicine experts' diagnoses to individually predict peritoneal metastasis (PM) in advanced gastric cancer (AGC). METHODS: A total of 167 patients receiving preoperative PET/CT and subsequent surgery were included between November 2006 and September 2020 and were divided into a training and testing cohort. The PM status was confirmed via laparoscopic exploration and postoperative pathology. The PET/CT signatures were constructed by classic radiomic, handcrafted-feature-based model and KSTM self-learning-based model. The clinical nomogram was constructed by independent risk factors for PM. Lastly, the PET/CT signatures, clinical nomogram, and experts' diagnoses were fused using evidential reasoning to establish the MMF model. RESULTS: The MMF model showed excellent performance in both cohorts (area under the curve [AUC] 94.16% and 90.84% in training and testing), and demonstrated better prediction accuracy than clinical nomogram or experts' diagnoses (net reclassification improvement p < 0.05). The MMF model also had satisfactory generalization ability, even in mucinous adenocarcinoma and signet ring cell carcinoma which have poor uptake of 18F-FDG (AUC 97.98% and 89.71% in training and testing). CONCLUSIONS: The 18F-FDG PET/CT radiomics-based MMF model may have significant clinical implications in predicting PM in AGC, revealing that it is necessary to combine the information from different modalities for comprehensive prediction of PM.

Sex-specific differences in myocardial glucose metabolic rate in non-diabetic, pre-diabetic and type 2 diabetic subjects.

BACKGROUND: Evidence has shown that women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than men with T2DM. Subjects with either T2DM or prediabetes exhibit myocardial insulin resistance, but it is still unsettled whether sex-related differences in myocardial insulin resistance occur in diabetic and prediabetic subjects. METHODS: We aimed to evaluate sex-related differences in myocardial glucose metabolic rate (MRGlu), assessed using dynamic PET with 18F-FDG combined with euglycemic-hyperinsulinemic clamp, in subjects with normal glucose tolerance (NGT; n = 20), prediabetes (n = 11), and T2DM (n = 26). RESULTS: Women with prediabetes or T2DM exhibited greater relative differences in myocardial MRGlu than men with prediabetes or T2DM when compared with their NGT counterparts. As compared with women with NGT, those with prediabetes exhibited an age-adjusted 35% lower myocardial MRGlu value (P = 0.04) and women with T2DM a 74% lower value (P = 0.006), respectively. Conversely, as compared with men with NGT, men with T2DM exhibited a 40% lower myocardial MRGlu value (P = 0.004), while no significant difference was observed between men with NGT and prediabetes. The statistical test for interaction between sex and glucose tolerance on myocardial MRGlu (P < 0.0001) was significant suggesting a sex-specific association. CONCLUSIONS: Our data suggest that deterioration of glucose homeostasis in women is associated with a greater impairment in myocardial glucose metabolism as compared with men. The sex-specific myocardial insulin resistance could be an important factor responsible for the greater effect of T2DM on the excess risk of cardiovascular disease in women than in men.

Mitigating SUV uncertainties using total body PET imaging.

PURPOSE: Standardised uptake values (SUV) are commonly used to quantify 18F-FDG lesion uptake. However, SUVs may suffer from several uncertainties and errors. Long-axial field-of-view (LAFOV) PET/CT systems might enable image-based quality control (QC) by deriving 18F-FDG activity and weight from total body (TB) 18F-FDG PET images. In this study, we aimed to develop these image-based QC to reduce errors and mitigate SUV uncertainties. METHODS: Twenty-five out of 81 patient scans from a LAFOV PET/CT system were used to determine regression fits for deriving of image-derived activity and weight. Thereafter, the regression fits were applied to 56 independent 18F-FDG PET scans from the same scanner to determine if injected activity and weight could be obtained accurately from TB and half-body (HB) scans. Additionally, we studied the impact of image-based values on the precision of liver SUVmean and lesion SUVpeak. Finally, 20 scans were acquired from a short-axial field-of-view (SAFOV) PET/CT system to determine if the regression fits also applied to HB scans from a SAFOV system. RESULTS: Both TB and HB 18F-FDG activity and weight significantly predicted reported injected activity (r = 0.999; r = 0.984) and weight (r = 0.999; r = 0.987), respectively. After applying the regression fits, 18F-FDG activity and weight were accurately derived within 4.8% and 3.2% from TB scans and within 4.9% and 3.1% from HB, respectively. Image-derived values also mitigated liver and lesion SUV variability compared with reported values. Moreover, 18F-FDG activity and weight obtained from a SAFOV scanner were derived within 6.7% and 4.5%, respectively. CONCLUSION: 18F-FDG activity and weight can be derived accurately from TB and HB scans, and image-derived values improved SUV precision and corrected for lesion SUV errors. Therefore, image-derived values should be included as QC to generate a more reliable and reproducible quantitative uptake measurement.

Comparative assessment of radiation therapy-induced vasculitis using [18F]FDG-PET/CT in patients with non-small cell lung cancer treated with proton versus photon radiotherapy.

PURPOSE: To assess radiation therapy (RT)-induced vasculitis in patients with non-small cell lung cancer (NSCLC) by examining changes in the uptake of 18F-fluoro-D-deoxyglucose ([18F]FDG) by positron emission tomography/computed tomography (PET/CT) images of the ascending aorta (AA), descending aorta (DA), and aortic arch (AoA) before and after proton and photon RT. METHOD: Thirty-five consecutive locally advanced NSCLC patients were definitively treated with proton (n = 27) or photon (n = 8) RT and concurrent chemotherapy. The patients were prospectively enrolled to undergo [18F]FDG-PET/CT imaging before and 3 months after RT. An adaptive contrast-oriented thresholding algorithm was applied to generate mean standardized uptake values (SUVmean) for regions of interest (ROIs) 3 mm outside and 3 mm inside the outer perimeter of the AA, DA, and AoA. These ROIs were employed to exclusively select the aortic wall and remove the influence of blood pool activity. SUVmeans before and after RT were compared using two-tailed paired t-tests. RESULTS: RT treatments were associated with increased SUVmeans in the AA, DA, and AoA-1.9%, 0.3%, and 1.3% for proton and 15.8%, 9.5%, and 15.5% for photon, respectively. There was a statistically significant difference in the ∆SUVmean (post-RT SUVmean - pre-RT SUVmean) in patients treated with photon RT when compared to ∆SUVmean in patients treated with proton RT in the AA (p = 0.043) and AoA (p = 0.015). There was an average increase in SUVmean that was related to dose for photon patients (across structures), but that was not seen for proton patients, although the increase was not statistically significant. CONCLUSION: Our results suggest that patients treated with photon RT for NSCLC may exhibit significantly more RT-induced inflammation (measured as ∆SUVmean) in the AA and AoA when compared to patients who received proton RT. Knowledge gained from further analyses in larger cohorts could aid in treatment planning and help prevent the significant morbidity and mortality associated with RT-induced vascular complications. TRIAL REGISTRATION: NCT02135679.

[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).

Clinicopathological and molecular predictors of [18F]FDG-PET disease detection in HER2-positive early breast cancer: RESPONSE, a substudy of the randomized PHERGain trial.

BACKGROUND: The PHERGain study (NCT03161353) is assessing early metabolic responses to neoadjuvant treatment with trastuzumab-pertuzumab and chemotherapy de-escalation using a [18Fluorine]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) and a pathological complete response-adapted strategy in HER2-positive (HER2+) early breast cancer (EBC). Herein, we present RESPONSE, a PHERGain substudy, where clinicopathological and molecular predictors of [18F]FDG-PET disease detection were evaluated. METHODS: A total of 500 patients with HER2 + EBC screened in the PHERGain trial with a tumor size > 1.5 cm by magnetic resonance imaging (MRI) were included in the RESPONSE substudy. PET[-] criteria entailed the absence of  ≥ 1 breast lesion with maximum standardized uptake value (SUVmax) ≥ 1.5 × SUVmean liver + 2 standard deviation. Among 75 PET[-] patients screened, 21 with SUVmax levels < 2.5 were randomly selected and matched with 21 PET[+] patients with SUVmax levels ≥ 2.5 based on patient characteristics associated with [18F]FDG-PET status. The association between baseline SUVmax and [18F]FDG-PET status ([-] or [+]) with clinicopathological characteristics was assessed. In addition, evaluation of stromal tumor-infiltrating lymphocytes (sTILs) and gene expression analysis using PAM50 and Vantage 3D™ Cancer Metabolism Panel were specifically compared in a matched cohort of excluded and enrolled patients based on the [18F]FDG-PET eligibility criteria. RESULTS: Median SUVmax at baseline was 7.2 (range, 1-39.3). Among all analyzed patients, a higher SUVmax was associated with a higher tumor stage, larger tumor size, lymph node involvement, hormone receptor-negative status, higher HER2 protein expression, increased Ki67 proliferation index, and higher histological grade (p < 0.05). [18F]FDG-PET [-] criteria patients had smaller tumor size (p = 0.014) along with the absence of lymph node involvement and lower histological grade than [18F]FDG-PET [+] patients (p < 0.01). Although no difference in the levels of sTILs was found among 42 matched [18F]FDG-PET [-]/[+] criteria patients (p = 0.73), [18F]FDG-PET [-] criteria patients showed a decreased risk of recurrence (ROR) and a lower proportion of PAM50 HER2-enriched subtype than [18F]FDG-PET[+] patients (p < 0.05). Differences in the expression of genes involved in cancer metabolism were observed between [18F]FDG-PET [-] and [18F]FDG-PET[+] criteria patients. CONCLUSIONS: These results highlight the clinical, biological, and metabolic heterogeneity of HER2+ breast cancer, which may facilitate the selection of HER2+ EBC patients likely to benefit from [18F]FDG-PET imaging as a tool to guide therapy. TRIAL REGISTRATION: Clinicaltrials.gov; NCT03161353; registration date: May 15, 2017.

[18F]FDG PET/CT for prognosis and toxicity prediction of diffuse large B-cell lymphoma patients with chimeric antigen receptor T-cell therapy.

PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy has been confirmed to benefit patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL). It is important to provide precise and timely predictions of the efficacy and toxicity of CAR T-cell therapy. In this study, we evaluated the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) combining with clinical indices and laboratory indicators in predicting outcomes and toxicity of anti-CD19 CAR T-cell therapy for DLBCL patients. METHODS: Thirty-eight DLBCL patients who received CAR T-cell therapy and underwent [18F]FDG PET/CT within 3 months before (pre-infusion) and 1 month after CAR T-cell infusion (M1) were retrospectively reviewed and regularly followed up. Maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), clinical indices, and laboratory indicators were recorded at pre-infusion and M1 time points, and changes in these indices were calculated. Progression-free survival (PFS) and overall survival (OS) were as endpoints. Based on the multivariate Cox regression analysis, two predictive models for PFS and OS were developed and evaluated the efficiency. Pre-infusion indices were subjected to predict the grade of cytokine release syndrome (CRS) resulting from toxic reactions. RESULTS: For survival analysis at a median follow-up time of 18.2 months, patients with values of international prognostic index (IPI), SUVmax at M1, and TLG at M1 above their optimal thresholds had a shorter PFS (median PFS: 8.1 months [IPI ≥ 2] vs. 26.2 months [IPI < 2], P = 0.025; 3.1 months [SUVmax ≥ 5.69] vs. 26.8 months [SUVmax < 5.69], P < 0.001; and 3.1 months [TLG ≥ 23.79] vs. 26.8 months [TLG < 23.79], P < 0.001). In addition, patients with values of SUVmax at M1 and ∆SUVmax% above their optimal thresholds had a shorter OS (median OS: 12.6 months [SUVmax ≥ 15.93] vs. 'not reached' [SUVmax < 15.93], P < 0.001; 32.5 months [∆SUVmax% ≥ -46.76] vs. 'not reached' [∆SUVmax% < -46.76], P = 0.012). Two novel predictive models for PFS and OS were visualized using nomogram. The calibration analysis and the decision curves demonstrated good performance of the models. Spearman's rank correlation (rs) analysis revealed that the CRS grade correlated strongly with the pre-infusion SUVmax (rs = 0.806, P < 0.001) and moderately with the pre-infusion TLG (rs = 0.534, P < 0.001). Multinomial logistic regression analysis revealed that the pre-infusion value of SUVmax correlated with the risk of developing a higher grade of CRS (P < 0.001). CONCLUSION: In this group of DLBCL patients who underwent CAR T-cell therapy, SUVmax at M1, TLG at M1, and IPI were independent risk factors for PFS, and SUVmax at M1 and ∆SUVmax% for OS. Based on these indicators, two novel predictive models were established and verified the efficiency for evaluating PFS and OS. Moreover, pre-infusion SUVmax correlated with the severity of any subsequent CRS. We conclude that metabolic parameters measured using [18F]FDG PET/CT can identify DLBCL patients who will benefit most from CAR T-cell therapy, and the value before CAR T-cell infusion may predict its toxicity in advance.

Targeting Fn14 as a therapeutic target for cachexia reprograms the glycolytic pathway in tumour and brain in mice.

PURPOSE: Cachexia is a complex syndrome characterized by unintentional weight loss, progressive muscle wasting and loss of appetite. Anti-Fn14 antibody (mAb 002) targets the TWEAK receptor (Fn14) in murine models of cancer cachexia and can extend the lifespan of mice by restoring the body weight of mice. Here, we investigated glucose metabolic changes in murine models of cachexia via [18F]FDG PET imaging, to explore whether Fn14 plays a role in the metabolic changes that occur during cancer cachexia. METHODS: [18F]FDG PET/MRI imaging was performed in cachexia-inducing tumour models versus models that do not induce cachexia. SUVaverage was calculated for all tumours via volume of interest (VOI) analysis of PET/MRI overlay images using PMOD software. RESULTS: [18F]FDG PET imaging demonstrated increased tumour and brain uptake in cachectic versus non-cachectic tumour-bearing mice. Therapy with mAb 002 was able to reduce [18F]FDG uptake in tumours (P < 0.05, n = 3). Fn14 KO tumours did not induce body weight loss and did not show an increase in [18F]FDG tumour and brain uptake over time. In non-cachectic mice bearing Fn14 KO tumours, [18F]FDG tumour uptake was significantly lower (P < 0.01) than in cachectic mice bearing Fn14 WT counterparts. As a by-product of glucose metabolism, l-lactate production was also increased in cachexia-inducing tumours expressing Fn14. CONCLUSION: Our results demonstrate that Fn14 receptor activation is linked to glucose metabolism of cachexia-inducing tumours.

2-[18F]FDG PET-based quantification of lymph node metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer.

BACKGROUND AND PURPOSE: The pre-surgical estimation of lymph node (LN) metastasis in colorectal cancer (CRC) poses a significant diagnostic predicament. The associations between LN morphology, density, and metabolic heterogeneity and LN metastasis status in CRCs have been seldomly examined through the lens of radiomics. This research aimed to assess 2-[18F]FDG PET-based quantification of intratumoral metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer. MATERIALS AND METHODS: The construction of the model utilized data from 264 CRC patients, all of whom underwent preoperative 2-[18F]FDG PET/CT. Radiomic features were extracted from PET and CT images of LNs. Least absolute shrinkage and selection operator (LASSO) regression was implemented for selecting pertinent imaging features with a tenfold cross-validation. The predictive accuracy for LN metastasis status was juxtaposed against traditional methodologies (comprising CT-reported LN status and PET/CT-reported LN status) by deploying the receiver operating characteristic (ROC) curve analysis. The radiomics signature was evaluated based on discrimination, calibration, and clinical utility parameters. The model was further subjected to validation using an independent cohort of 132 patients from the period of January 2012 to June 2020. RESULTS: The radiomics model was composed of eight significant radiomic features (five from PET and three from CT), encapsulating metabolic and density heterogeneity. The radiomics signature (area under the curve (AUC), 0.908) showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.563, P < 0.001) and PET/CT-reported LN status (AUC, 0.64, P < 0.001) for predicting LN-positive or LN-negative status. The radiomics signature (AUC, 0.885) also showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.587, P < 0.001) and PET/CT-reported LN status (AUC, 0.621, P < 0.001) to identify N1 and N2. This signature maintained its independence from clinical risk factors and exhibited robustness in the validation test set. Decision curve analysis attested to the clinical utility of the radiomics signature. CONCLUSIONS: The radiomics signature based on 2-[18F]FDG PET/CT, which derived image features directly from LNs irrespective of clinical risk factors, displayed enhanced diagnostic performance compared to conventional CT or PET/CT-reported LN status. This allows for the identification of pre-surgical LN metastasis status and facilitates a patient-specific prediction of LN metastasis status in CRC patients.

End of induction [18F]FDG PET is prognostic for progression-free survival and overall survival in follicular lymphoma patients enrolled in the FOLL12 trial.

PURPOSE: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [18F]FDG PET (PET) in follicular lymphoma patients. METHODS: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). RESULTS: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97) and 82% (95%CI: 72%-89%) in EOI PET negative (DS1-3) and positive (DS4-5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1-2 with high FLIPI-2 (3-5) experienced worse OS than patients with DS1-2 and low FLIPI-2 (1-2) (p = 0.003). CONCLUSION: This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients.

Analysis of image data from the EuroNet PHL-C2 trial indicates a potential reduction in injected F-18 FDG activities in children: a proposal to update the EANM Paediatric Dosage Card.

BACKGROUND: The aim of this work is to provide the currently missing evidence that may allow an update of the Paediatric Dosage Card provided by the European Association of Nuclear Medicine (EANM) for conventional PET/CT systems. METHODS: In a total of 2082 consecutive [18F]FDG-PET scans performed within the EuroNet-PHL-C2 trial, the administered [18F]FDG activity was compared to the activity recommended by the EANM Paediatric Dosage Card. None of these scans had been rejected beforehand by the reference nuclear medicine panel of the trial because of poor image quality. For detailed quality assessment, a subset of 91 [18F]FDG-PET scans, all performed in different patients at staging, was selected according to pre-defined criteria, which (a) included only patients who had received substantially lower activities than those recommended by the EANM Paediatric Dosage Card, and (b) included as wide a range of different PET systems and imaging parameters as possible to ensure that the conclusions drawn in this work are as generally valid as possible. The image quality of the subset was evaluated visually by two independent readers using a quality scoring system as well as analytically based on a volume-of-interest analysis in 244 lesions and the healthy liver. Finally, recommendations for an update of the EANM Paediatric Dosage Card were derived based on the available data. RESULTS: The activity recommended by the EANM Paediatric Dosage Card was undercut by a median of 99.4 MBq in 1960 [18F]FDG-PET scans and exceeded by a median of 15.1 MBq in 119 scans. In the subset analysis (n = 91), all image data were visually classified as clinically useful. In addition, only a very weak correlation (r = 0.06) between activity reduction and tumour-to-background ratio was found. Due to the intended heterogeneity of the dataset, the noise could not be analysed statistically sound as the high range of different imaging variables resulted in very small subsets. Finally, a suggestion for an update of the EANM Paediatric Dosage Card was developed, based on the analysis presented, resulting in a mean activity reduction by 39%. CONCLUSION: The results of this work allow for a conservative update of the EANM Paediatric Dosage Card for [18F]FDG-PET/CT scans performed with conventional PET/CT systems.

Multicentric development and evaluation of [18F]FDG PET/CT and CT radiomic models to predict regional and/or distant recurrence in early-stage non-small cell lung cancer treated by stereotactic body radiation therapy.

PURPOSE: To develop machine learning models to predict regional and/or distant recurrence in patients with early-stage non-small cell lung cancer (ES-NSCLC) after stereotactic body radiation therapy (SBRT) using [18F]FDG PET/CT and CT radiomics combined with clinical and dosimetric parameters. METHODS: We retrospectively collected 464 patients (60% for training and 40% for testing) from University Hospital of Liège and 63 patients from University Hospital of Brest (external testing set) with ES-NSCLC treated with SBRT between 2010 and 2020 and who had undergone pretreatment [18F]FDG PET/CT and planning CT. Radiomic features were extracted using the PyRadiomics toolbox®. The ComBat harmonization method was applied to reduce the batch effect between centers. Clinical, radiomic, and combined models were trained and tested using a neural network approach to predict regional and/or distant recurrence. RESULTS: In the training (n = 273) and testing sets (n = 191 and n = 63), the clinical model achieved moderate performances to predict regional and/or distant recurrence with C-statistics from 0.53 to 0.59 (95% CI, 0.41, 0.67). The radiomic (original_firstorder_Entropy, original_gldm_LowGrayLevelEmphasis and original_glcm_DifferenceAverage) model achieved higher predictive ability in the training set and kept the same performance in the testing sets, with C-statistics from 0.70 to 0.78 (95% CI, 0.63, 0.88) while the combined model performs moderately well with C-statistics from 0.50 to 0.62 (95% CI, 0.37, 0.69). CONCLUSION: Radiomic features extracted from pre-SBRT analog and digital [18F]FDG PET/CT outperform clinical parameters in the prediction of regional and/or distant recurrence and to discuss an adjuvant systemic treatment in ES-NSCLC. Prospective validation of our models should now be carried out.

Baseline [18F]FDG PET/CT and MRI first-order breast tumor features do not improve pathological complete response prediction to neoadjuvant chemotherapy.

PURPOSE: To verify the ability of pretreatment [18F]FDG PET/CT and T1-weighed dynamic contrast-enhanced MRI to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients. METHODS: This retrospective study includes patients with BC of no special type submitted to baseline [18F]FDG PET/CT, NAC and surgery. [18F]FDG PET-based features reflecting intensity and heterogeneity of tracer uptake were extracted from the primary BC and suspicious axillary lymph nodes (ALN), for comparative analysis related to NAC response (pCR vs. non-pCR). Multivariate logistic regression was performed for response prediction combining the breast tumor-extracted PET-based features and clinicopathological features. A subanalysis was performed in a patients' subsample by adding breast tumor-extracted first-order MRI-based features to the multivariate logistic regression. RESULTS: A total of 170 tumors from 168 patients were included. pCR was observed in 60/170 tumors (20/107 luminal B-like, 25/45 triple-negative and 15/18 HER2-enriched surrogate molecular subtypes). Higher intensity and higher heterogeneity of [18F]FDG uptake in the primary BC were associated with NAC response in HER2-negative tumors (immunohistochemistry score 0, 1 + or 2 + non-amplified by in situ hybridization). Also, higher intensity of tracer uptake was observed in ALN in the pCR group among HER2-negative tumors. No [18F]FDG PET-based features were associated with pCR in the other subgroup analyses. A subsample of 103 tumors was also submitted to extraction of MRI-based features. When combined with clinicopathological features, neither [18F]FDG PET nor MRI-based features had additional value for pCR prediction. The only significant predictors were estrogen receptor status, HER2 expression and grade. CONCLUSION: Pretreatment [18F]FDG PET-based features from primary BC and ALN are not associated with response to NAC, except in HER2-negative tumors. As compared with pathological features, no breast tumor-extracted PET or MRI-based feature improved response prediction.

Prognostic value of baseline and interim [18F]FDG PET metabolic parameters in pediatric Hodgkin's lymphoma.

BACKGROUND: Hodgkin lymphoma (HL) in pediatric populations has a high survival rate but poses risks for long-term morbidities. Although [18F]fluoro­2­deoxy­2­d­glucose positron emission tomography ([18F]FDG PET) scans offer potential for improved risk stratification, the definitive prognostic value of quantitative [18F]FDG PET parameters remains unclear for pediatric HL. METHODS: A single-center, retrospective study included pediatric patients diagnosed with HL between 2016 and 2023 treated according to EuroNet-PHL-C1 and DAL/GPOH-HD protocols. Patients underwent baseline and interim PET/CT scans after two chemotherapy cycles. Event-free survival (EFS) was the primary endpoint, Deauville score was the secondary endpoint. Quantitative [18F]FDG PET parameters included SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) that were evaluated using two segmentation methods (SUV 2.5, 41% SUVmax). Survival outcomes were assessed using Cox regression analysis. RESULTS: A total of 115 patients (50 males, median age 14.2 years) were studied, with a median follow-up period of 35 months. During this period, 16 cases (13.9%) of relapse or progression were noted. Baseline and interim MTV 2.5, MTV 41%, TLG 2.5, and TLG 41%, along with interim SUVmax, were significantly associated with worse EFS and correlated with post-treatment Deauville scores. In multivariable analysis, interim MTV 2.5 > 0 ml (adj. hazard ratio, HR: 3.89, p = 0.009) and interim TLG 41% ≥ 30 g (adj. HR: 7.98, p = 0.006) were independent risk factors for EFS. CONCLUSION: Baseline and interim [18F]FDG PET parameters can serve as significant prognostic indicators for EFS and treatment response in pediatric HL. These quantitative measures could enhance individualized, risk-adapted treatment strategies for children and adolescents with HL.