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.

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.

Clinical implications of non-breast cancer related findings on FDG-PET/CT scan prior to neoadjuvant chemotherapy in patients with breast cancer.

PURPOSE: Breast cancer (BC) patients undergoing FDG-PET/CT scans for neoadjuvant chemotherapy (NAC) may have additional non-BC related findings. The aim of this study is to describe the clinical implications of these findings. METHODS: We included BC patients who underwent an FDG-PET/CT scan in our institute between 2011-2020 prior to NAC. We focused on patients with an additional non-BC related finding (i.e. BC metastases were excluded) for which diagnostic work-up was performed. Information about the diagnostic work-up and the clinical consequences was retrospectively gathered. A revision of all FDG-PET/CT scans was conducted by an independent physician to assess the suspicion level of the additional findings. RESULTS: Of the 1337 patients who underwent FDG-PET/CT, 202 patients (15%) had an non-BC related additional finding for which diagnostic work-up was conducted, resulting in 318 examinations during the first year. The non-BC related findings were mostly detected in the endocrine region (26%), gastro-intestinal region (16%), or the lungs (15%). Seventeen patients (17/202: 8%, 17/1337: 1.3%) had a second primary malignancy. Only 8 patients (8/202: 4%, 8/1337: 0.6%) had a finding that was considered more prognosis-determining than their BC disease. When revising all FDG-PET/CT scans, 57 (202/57: 28%) of the patients had an additional finding categorized as low suspicious, suggesting no indication for diagnostic work-up. CONCLUSION: FDG-PET/CT scans used for dissemination imaging in BC patients detect a high number of non-BC related additional findings, often clinically irrelevant and causing a large amount of unnecessary work-up. However, in 8% of the patients undergoing diagnostic work-up for an additional finding, a second primary malignancy was detected, warranting diagnostic attention in selected patients.

Therapeutic impact of 18F-FDG PET/CT for initial staging in patients with clinical stage I and IIA, HER2-positive, or triple-negative breast cancer.

PURPOSE: While 18F-FDG PET/CT (FDG-PET/CT) is consensual for clinical stage ≥ IIB breast cancers (BC), its benefit for stage I or IIA HER2+ or triple-negative breast cancer (TNBC) patients lacks sufficient evidence. We reported a single-institution, retrospective study evaluating FDG-PET/CT impact on patient management and staging for stage I or IIA HER2+ or Triple-Negative BC. METHODS: Patients who underwent FDG-PET/CT staging before any treatment between January 2015 and December 2020 at Oscar Lambret Center were included. EXCLUSIONS: patients with symptoms or conventional imaging suggestive of metastatic dissemination, or with prior malignancies. Initial stage was determined from mammography, breast ultrasound, breast MRI, and clinical examination. Staging and therapeutic impact based on FDG-PET/CT findings collected, including intra- (modification of dose/site/strategy in a type of management previously indicated) and inter-modality (modification of planned treatment strategy) changes. RESULTS: The cohort included 287 female patients with clinical stage I or IIA, HER2+ , or TNBC. Therapeutic impact observed for 18% of patients (n = 52), with 2% (n = 7) undergoing inter-modality change with omission of planned surgery. The impact on patient management was higher for stage IIA patients (20%, 47/237) than for stage I patients (10%, 5/50). Among stage IIA disease, changes in management were more important for T2N0 patients (22%, 44/205) than for T1N1 patients (9%, 3/32). While not statistically significant, trends suggest usefulness of FDG-PET/CT for T2N0 patients. CONCLUSION: Considering substantial therapeutic implications, our study suggests the usefulness of FDG-PET/CT for patients with stage IIA, HER2-positive, or Triple-Negative BC with tumor size > 2 cm (T2N0).

Improved Diagnostic Accuracy for Polymyalgia Rheumatica using FDG-PET/CT with Clinical Diagnosis or 2012 ACR/EULAR Classification Criteria.

PURPOSE: In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) computed tomography (CT) to validate their initial clinical diagnosis of polymyalgia rheumatica (PMR). Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR. METHODS: An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven-score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after twelve or six months in the investigation and validation cohorts, respectively. RESULTS: In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven-score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven-score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven-score. CONCLUSION: Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR.

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.

The effect of prednisolone and a short-term prednisolone discontinuation for the diagnostic accuracy of FDG-PET/CT in polymyalgia rheumatica-a prospective study of 101 patients.

PURPOSE: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation. METHODS: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year. RESULTS: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%. CONCLUSION: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.

FDG-PET/CT for investigation of pyrexia of unknown origin: a cost of illness analysis.

BACKGROUND: Our study aims to explore the current utilisation of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the diagnostic pathway of pyrexia of unknown origin (PUO) and associated cost of illness in a large tertiary teaching hospital in Australia. METHOD: 1257 febrile patients between June 2016 and September 2022 were retrospectively reviewed. There were 57 patients who met the inclusion criteria of "classical PUO", of which FDG-PET/CT was performed in 31 inpatients, 15 outpatients and 11 inpatients did not have an FDG-PET/CT scan. The patient demographics, clinical characteristics and inpatient cost were analysed, together with the diagnostic performance of FDG-PET/CT and impact on clinical management. RESULT: The mean age, length of stay and total cost of admission were higher for inpatients who received FDG-PET/CT versus those who did not. The median cost per patient-bed-day did not differ between the two groups. Inpatients who received earlier FDG-PET/CTs (≤ 7 days from admission) had shorter length of stays and lower total cost compared to those who received a later scan. A negative FDG-PET/CT scan, demonstrating no serious or life-threatening abnormalities resulted in subsequent discharge from hospital or outpatient clinic in 7/10 (70%) patients. There were 11/40 (28%) scans where ancillary abnormalities were identified, requiring further evaluation. CONCLUSION: FDG-PET/CT showed high diagnostic accuracy and significant impact on patient management in patients with PUO. FDG-PET/CT performed earlier in admission for PUO was associated with shorter length of stay and lower total cost.

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.

[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).

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.

[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.

Identifying the primary tumour in patients with cancer of unknown primary (CUP) using [18F]FDG PET/CT: a systematic review and individual patient data meta-analysis.

PURPOSE: In this systematic review and individual patient data (IPD) meta-analysis, we analysed the diagnostic performance of [18F]FDG PET/CT in detecting primary tumours in patients with CUP and evaluated whether the location of the predominant metastatic site influences the diagnostic performance. METHODS: A systematic literature search from January 2005 to February 2024 was performed to identify articles describing the diagnostic performance of [18F]FDG PET/CT for primary tumour detection in CUP. Individual patient data retrieved from original articles or obtained from corresponding authors were grouped by the predominant metastatic site. The diagnostic performance of [18F]FDG PET/CT in detecting the underlying primary tumour was compared between predominant metastatic sites. RESULTS: A total of 1865 patients from 32 studies were included. The largest subgroup included patients with predominant bone metastases (n = 622), followed by liver (n = 369), lymph node (n = 358), brain (n = 316), peritoneal (n = 70), lung (n = 67), and soft tissue (n = 23) metastases, leaving a small group of other/undefined metastases (n = 40). [18F]FDG PET/CT resulted in pooled detection rates to identify the primary tumour of 0.74 (for patients with predominant brain metastases), 0.54 (liver-predominant), 0.49 (bone-predominant), 0.46 (lung-predominant), 0.38 (peritoneal-predominant), 0.37 (lymph node-predominant), and 0.35 (soft-tissue-predominant). CONCLUSION: This individual patient data meta-analysis suggests that the ability of [18F]FDG PET/CT to identify the primary tumour in CUP depends on the distribution of metastatic sites. This finding emphasises the need for more tailored diagnostic approaches in different patient populations. In addition, alternative diagnostic tools, such as new PET tracers or whole-body (PET/)MRI, should be investigated.

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.

Quantitative evaluation of lesion response heterogeneity for superior prognostication of clinical outcome.

PURPOSE: Standardized reporting of treatment response in oncology patients has traditionally relied on methods like RECIST, PERCIST and Deauville score. These endpoints assess only a few lesions, potentially overlooking the response heterogeneity of all disease. This study hypothesizes that comprehensive spatial-temporal evaluation of all individual lesions is necessary for superior prognostication of clinical outcome. METHODS: [18F]FDG PET/CT scans from 241 patients (127 diffuse large B-cell lymphoma (DLBCL) and 114 non-small cell lung cancer (NSCLC)) were retrospectively obtained at baseline and either during chemotherapy or post-chemoradiotherapy. An automated TRAQinform IQ software (AIQ Solutions) analyzed the images, performing quantification of change in regions of interest suspicious of cancer (lesion-ROI). Multivariable Cox proportional hazards (CoxPH) models were trained to predict overall survival (OS) with varied sets of quantitative features and lesion-ROI, compared by bootstrapping with C-index and t-tests. The best-fit model was compared to automated versions of previously established methods like RECIST, PERCIST and Deauville score. RESULTS: Multivariable CoxPH models demonstrated superior prognostic power when trained with features quantifying response heterogeneity in all individual lesion-ROI in DLBCL (C-index = 0.84, p < 0.001) and NSCLC (C-index = 0.71, p < 0.001). Prognostic power significantly deteriorated (p < 0.001) when using subsets of lesion-ROI (C-index = 0.78 and 0.67 for DLBCL and NSCLC, respectively) or excluding response heterogeneity (C-index = 0.67 and 0.70). RECIST, PERCIST, and Deauville score could not significantly associate with OS (C-index < 0.65 and p > 0.1), performing significantly worse than the multivariable models (p < 0.001). CONCLUSIONS: Quantitative evaluation of response heterogeneity of all individual lesions is necessary for the superior prognostication of clinical outcome.

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.