Adaptive radiotherapy (up to 74 Gy) or standard radiotherapy (66 Gy) for patients with stage III non-small-cell lung cancer, according to [18F]FDG-PET tumour residual uptake at 42 Gy (RTEP7-IFCT-1402): a multicentre, randomised, controlled phase 2 trial.

BACKGROUND: Thoracic radiation intensification is debated in patients with stage III non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of a boost radiotherapy dose up to 74 Gy in a functional sub-volume given according to on-treatment [18F]fluorodeoxyglucose ([18F]FDG)-PET results. METHODS: In this multicentre, randomised, controlled non-comparative phase 2 trial, we recruited patients aged 18 years or older with inoperable stage III NSCLC without EGFR mutation or ALK rearrangement with an Eastern Cooperative Oncology Group performance status of 0-1, and who were affiliated with or a beneficiary of a social benefit system, with evaluable tumour or node lesions, preserved lung function, and who were amenable to curative-intent radiochemotherapy. Patients were randomly allocated using a central interactive web-response system in a non-masked method (1:1; minimisation method used [random factor of 0·8]; stratified by radiotherapy technique [intensity-modulated radiotherapy vs three-dimensional conformal radiotherapy] and by centre at which patients were treated) either to the experimental adaptive radiotherapy group A, in which only patients with positive residual metabolism on [18F]FDG-PET at 42 Gy received a boost radiotherapy (up to 74 Gy in 33 fractions), with all other patients receiving standard radiotherapy dosing (66 Gy in 33 fractions over 6·5 weeks), or to the standard radiotherapy group B (66 Gy in 33 fractions) over 6·5 weeks. All patients received two cycles of induction platinum-based chemotherapy cycles (paclitaxel 175 mg/m2 intravenously once every 3 weeks and carboplatin area under the curve [AUC]=6 once every 3 weeks, or cisplatin 80 mg/m2 intravenously once every 3 weeks and vinorelbine 30 mg/m2 intravenously on day 1 and 60 mg/m2 orally [or 30 mg/m2 intravenously] on day 8 once every 3 weeks). Then they concomitantly received radiochemotherapy with platinum-based chemotherapy (three cycles for 8 weeks, with once per week paclitaxel 40 mg/m2 intravenously and carboplatin AUC=2 or cisplatin 80 mg/m2 intravenously and vinorelbine 20 mg/m2 intravenously on day 1 and 40 mg/m2 orally (or 20 mg/m2 intravenously) on day 8 in 21-day cycles). The primary endpoint was the 15-month local control rate in the eligible patients who received at least one dose of concomitant radiochemotherapy. This RTEP7-IFCT-1402 trial is registered with ClinicalTrials.gov (NCT02473133), and is ongoing. FINDINGS: From Nov 12, 2015, to July 7, 2021, we randomly assigned 158 patients (47 [30%] women and 111 [70%] men) to either the boosted radiotherapy group A (81 [51%]) or to the standard radiotherapy group B (77 [49%)]. In group A, 80 (99%) patients received induction chemotherapy and 68 (84%) received radiochemotherapy, of whom 48 (71%) with residual uptake on [18F]FDG-PET after 42 Gy received a radiotherapy boost. In group B, all 77 patients received induction chemotherapy and 73 (95%) received radiochemotherapy. At the final analysis, the median follow-up for eligible patients who received radiochemotherapy (n=140) was 45·1 months (95% CI 39·3-48·3). The 15-month local control rate was 77·6% (95% CI 67·6-87·6%) in group A and 71·2% (95% CI 60·8-81·6%) in group B. Acute (within 90 days from radiochemotherapy initiation) grade 3-4 adverse events were observed in 20 (29%) of 68 patients in group A and 33 (45%) of 73 patients in group B, including serious adverse events in five (7%) patients in group A and ten (14%) patients in group B. The most common grade 3-4 adverse events were febrile neutropenia (seven [10%] of 68 in group A vs 16 [22%] of 73 in group B), and anaemia (five [7%] vs nine [12%]). In the acute phase, two deaths (3%) occurred in group B (one due to a septic shock related to chemotherapy, and the other due to haemotypsia not related to study treatment), and no deaths occurred in group A. After 90 days, one additional treatment-unrelated death occurred in group A and two deaths events occurred in group B (one radiation pneumonitis and one pneumonia unrelated to treatment). INTERPRETATION: A thoracic radiotherapy boost, based on interim [18F]FDG-PET, led to a meaningful local control rate with no difference in adverse events between the two groups in organs at risk, in contrast with previous attempts at thoracic radiation intensification, warranting a randomised phase 3 evaluation of such [18F]FDG-PET-guided radiotherapy dose adaptation in patients with stage III NSCLC. FUNDING: Programme Hospitalier de Recherche Clinique National 2014.

Prognosis and follow-up of patients with prosthetic valve endocarditis treated conservatively in relation to WBC-SPECT imaging.

BACKGROUND: Our objective was to evaluate in patients with prosthetic valve endocarditis (PVE) treated conservatively, the prognostic value of white blood cell (WBC) signal intensity on SPECT and to describe the evolution of the WBC signal under antibiotics. METHODS: Patients with PVE treated conservatively and positive WBC-SPECT imaging were identified retrospectively. Signal intensity was classified as intense if equal to or higher, or mild if lower, than the liver signal. Clinical, biological, imaging and follow-up information were collected from medical files. RESULTS: Among 47 patients, WBC signal was classified as intense in 10 patients and as mild, in 37. The incidence of the primary composite endpoint (death, late cardiac surgery, or relapse) was significantly higher in patients with intense vs. mild signal (90% vs. 11%). Twenty-five patients underwent a second WBC-SPECT imaging during follow-up. The prevalence of WBC signal decreased progressively from 89% between 3 and 6 weeks to 42% between 6 and 9 weeks and 8% more than 9 weeks after initiation of antibiotics. CONCLUSIONS: In patients with PVE treated conservatively, intense WBC signal was associated with poor outcome. WBC-SPECT imaging appears as an interesting tool for risk stratification and to monitor locally the efficacy of antibiotic treatment.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in polymyalgia rheumatica: an observational study.

OBJECTIVES: Polymyalgia rheumatica (PMR) is an inflammatory disease with a diagnosis that is sometimes difficult to establish. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) might be helpful. We analysed the usefulness of 18F-FDG PET/CT for the diagnosis of PMR. METHODS: This was an observational retrospective study of individuals with PMR who underwent 18F-FDG PET/CT and a control group. We assessed clinical and 18F-FDG PET/CT characteristics. Sixteen sites were studied. The number of sites with significant FDG uptake, the mean maximum standardised uptake value (SUVmax) and the highest SUVmax value were assessed for each patient. RESULTS: Data for 123 patients with PMR (37 with corticosteroids [CSTs] use) were analysed; 85 had new-onset PMR. As compared with the 75 controls, patients with new-onset PMR had higher mean ± SD number of sites with significant FDG uptake (11.3 ± 3.3 vs. 0.9 ± 1.1, p<0.001) and higher SUVmax scores (p<0.001). A cut-off of 5 hypermetabolic sites provided sensitivity of 96.5% and specificity 100%. For the total SUVmax score, a cut-off of 3 had the best sensitivity (92.6%) and specificity (86.1%). As compared with PMR patients using CSTs, those who were CST-naive had significantly higher CRP level (p<0.001), number of sites with significant FDG uptake (p<0.001) and SUVmax scores (p<0.01). In contrast, large-vessel vasculitis was more frequent in patients receiving CSTs than CST-naive patients (27% vs. 8%, p<0.01). CONCLUSIONS: The number of hypermetabolic sites or SUVmax quantification might be useful for PMR diagnosis, and CSTs might affect the results of 18F-FDG PET/CT.

Diagnosis and staging of cardiac masses: additional value of CMR with 18F-FDG-PET compared to CMR with CECT.

PURPOSE: Characterization of malignant cardiac masses is usually performed with cardiac magnetic resonance (CMR) and staging with whole-body contrast-enhanced computed tomography (CECT). In this study, our objective was to evaluate the role of 18Fluor-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) with CMR for both characterization and staging of cardiac masses. METHODS: Patients with cardiac masses who underwent CMR, CECT, and 18F-FDG-PET were retrospectively identified. For the characterization of cardiac masses, we calculated the respective performances of CMR alone, 18F-FDG-PET alone, and the combination of 18F-FDG-PET and CMR. For staging, we compared head-to-head the respective performances of 18F-FDG-PET and CECT. Histology served as gold standard for malignancy, and response to anticoagulation for thrombus. RESULTS: In a total of 28 patients (median age 60.5 years, 60.7% women), CMR accurately distinguished malignant from benign masses with sensitivity (Se) of 86.7%, specificity (Sp) of 100%, positive predictive value (PPV) of 100%, negative predictive value (NPV) of 86.7%, and accuracy of 92.9%. 18F-FDG-PET demonstrated 93.3% Se, 84.6% Sp, 87.5% PPV, 91.7% NPV, and 89.3% accuracy. Combining CMR with 18F-FDG-PET allowed to benefit from the high sensitivity of 18F-FDG-PET (92.9%) and the excellent specificity of CMR (100%) for malignant diseases. For staging, 18F-FDG-PET outperformed CECT on per-patient (66.7% vs 55.6% correct diagnosis, respectively), per-organ (10 vs 7 organs, respectively), and per-lesion basis (> 29 vs > 25 lesions, respectively). CONCLUSION: Combining 18F-FDG-PET with CMR improved the characterization of cardiac masses compared to each modality alone. Additionally, the diagnostic performance of 18F-FDG-PET was better than CECT for staging. This study suggests that the combination of CMR and 18F-FDG-PET is the most effective for the characterization of cardiac masses and the staging of these lesions.

Diagnostic performance of White Blood Cell SPECT imaging against intra-operative findings in patients with a suspicion of prosthetic valve endocarditis.

AIM: The objective of this study was to evaluate the diagnostic performance of white blood cells (WBC)-SPECT imaging in patients with suspicion of prosthetic valve endocarditis (PVE) against intra-operative findings. METHODS: 36 consecutive patients who underwent cardiac surgery 30 days after WBC-SPECT imaging were identified retrospectively. Clinical, imaging, and biological results were collected from reports. WBC-SPECT results were classified as positive or negative and, if positive, the intensity of signal graded as intense or mild. Lesions observed during cardiac surgery were collected from surgeons' reports. RESULTS: The 20 patients with positive WBC-SPECT study had confirmed PVE intra-operatively. Patients with intense signal on WBC-SPECT had high prevalence of abscesses (83%) compared to patients with only mild signal (12%). The three patients with negative WBC-SPECT but confirmed PVE had longer duration of antibiotic treatment before imaging and had no perivalvular abscess. Sensitivity, specificity, positive predictive and negative values, and accuracy of WBC-SPECT were measured at 87%, 100%, 100%, 81%, and 92%, respectively. Addition of WBC-SPECT results to the modified Duke score helped re-classify correctly 25% of patients from possible to definite PVE. CONCLUSION: In patients with suspicion of PVE, WBC-SPECT imaging provides excellent diagnostic performance against intra-operative findings.

Musculoskeletal Tuberculosis: New Insights on Diagnosis Strategy and Treatment.

BACKGROUND/ OBJECTIVE: Skeletal tuberculosis (TB) is rare. We aimed to report on diagnostic strategy and treatment of skeletal TB. METHODS: In this multidisciplinary single-center medical records review study, all adult patients admitted between January 2009 and December 2019 with microbiologically proven skeletal TB were included. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records. RESULTS: Among 184 patients identified with TB, 21 (16 women, 42 years [27, 48 years]) had skeletal involvement. Skeletal TB included spondylitis (n = 11), lytic bone lesions (n = 7), sacroiliitis (n = 5), arthritis (n = 3), osteitis (n = 2), and diffuse muscle abscesses without bone lesion (n = 1). Lytic lesions involved both axial and peripheral skeleton at multiple sites in most cases. 18F-fluorodeoxyglucose positron emission tomography was performed in 13 patients and helped to detect multifocal asymptomatic lesions and to target biopsy. All patients were treated with anti-TB therapy for 7 to 18 months. Fifteen patients (71.4%) received steroids as an adjunct therapy. Eleven patients needed an orthopedic immobilization corset, and 3 patients underwent surgery. All patients clinically improved under treatment, but 2 relapsed over a median follow-up of 24 months (12-30 months). No patient died or suffered long-term disabilities. CONCLUSION: Our study emphasizes the diversity of skeletal involvement in TB. 18F-fluorodeoxyglucose positron emission tomography scanner at diagnosis is key to assess the extension of skeletal involvement and guide extraskeletal biopsy. Neurological complications might be prevented by adding corticosteroids to anti-TB therapy.

Infliximab use for corticosteroid-resistant tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in an immunocompetent patient.

In non-human immunodeficiency virus (HIV)-infected patients, tuberculosis (TB) immune reconstitution inflammatory syndrome (IRIS) is unusual. The management of corticosteroids-refractory IRIS is unclear. We report on infliximab efficacy for treatment of corticosteroid-resistant TB-IRIS occurring in an immunocompetent patient.

FDG atrial uptake is associated with an increased prevalence of stroke in patients with atrial fibrillation.

PURPOSE: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with an increased risk of stroke. Indeed, silent AF is frequently identified in unexplained ischemic stroke. 18F-FDG-PET/CT is a powerful tool for assessing myocardial metabolic shift and inflammation, both potentially at stake in AF. This case-control study investigated whether AF could promote FDG uptake in atria after physiological myocardial glucose uptake suppression, and the potential relationship between FDG atrial uptake and prevalence of stroke. METHODS: We retrospectively enrolled 128 patients (64 consecutive patients with AF and 64 without AF as the control group, matched for age and sex) who underwent 18F-FDG-PET/CT after a high-fat low-carbohydrate diet. We analyzed visual and quantitative FDG uptake parameters of the right and left atria (RA/LA) and the right and left appendages (RAA/LAA), and selected clinical features including history of stroke. RESULTS: Diffuse right atrial uptake was present in a third of patients with AF and only two patients in the control group. FDG uptake intensity of both atria was significantly associated with the underlying heart rhythm. The occurrence of stroke was strongly associated with detectable atrial uptake in multivariate analysis, with an odds ratio superior to that of other known risk factors. CONCLUSIONS: This study shows a significant correlation between FDG atrial uptake and AF. While inconsistent, this pattern seems to be associated with an increased prevalence of cardioembolic stroke.

18F-FDG-PET/CT Imaging to Diagnose Septic Emboli and Mycotic Aneurysms in Patients with Endocarditis and Cardiac Device Infections.

PURPOSE OF REVIEW: This review analyzes recent studies evaluating the diagnostic value of 18F-FDG-PET/CT for the detection of peripheral emboli and secondary infectious foci in patients with infective endocarditis and cardiac device infections. RECENT FINDINGS: Detection of extracardiac septic localizations in patients with infective endocarditis and cardiac device infections is crucial, as it may impact the diagnosis, prognosis, and therapeutic management. Recent literature substantiated the clinical usefulness of 18F-FDG-PET/CT in this setting. 18F-FDG-PET/CT has proven its high diagnostic value for the detection of peripheral emboli in patients with infective endocarditis and cardiac device infections, substantially affecting patients' outcome and treatment. A multimodal approach, combining the high sensitivity of 18F-FDG-PET/CT with morphological imaging seems promising.

Uterine intravascular lymphoma as a cause of fever of unknown origin.

Primary intravascular large B cell lymphoma (IVL) remains a diagnostic challenge because of non-specific clinical, laboratory and imaging findings. The aim of the study was to analyse the major characteristics of IVL with uterine involvement. We retrospectively collected features of IVL with uterine involvement that was proven histologically or demonstrated by significant 18FDG uptake on 18FDG-PET/CT. Findings were compared to a comprehensive literature review. Five patients were identified. All of them were admitted for fever of unknown origin (FUO), with haemophagocytic lymphohistiocytosis in three cases. None had gynaecological symptom, contrasting with the literature data. Structural imaging (including whole-body CT scan and pelvic RMI) failed to yield any diagnosis. 18FDG-PET/CT showed intense uterine uptake in all cases. Endometrial biopsy was performed in three cases and was positive in one. Diagnosis was obtained from coelioscopic iliac adenopathy biopsy in one case and from total hysterectomy in another. Punch biopsy of skin lesions led to diagnosis in the two remaining cases. Bone marrow biopsy was normal in all cases. Clinicians should be aware of potential isolated uterine involvement in IVL, especially in elderly women with FUO. Normal structural imaging does not rule out the diagnosis and 18FDG-TEP/CT should be performed to guide high-yielding biopsy.

Diagnostic value of 99mTc-HMPAO-labeled leukocytes scintigraphy in suspicion of post-sternotomy mediastinitis relapse.

BACKGROUND: The diagnostic value of radiolabeled white blood cells (WBCs) scintigraphy in mediastinitis is well established, but data in the specific context of relapse are lacking. The present study aimed at evaluation of the diagnostic value of WBCs scintigraphy in suspicion of mediastinitis relapse after prior surgical revision. METHODS AND RESULTS: Multiple planar incidences of the chest were acquired 4 and 20 hours after injection of labeled WBC in 43 patients. In case of non-conclusive scintigraphy, a second scan was performed 2-3 weeks after the first one. The diagnosis of infection was based on positive bacteriological results; otherwise patients were followed up for at least 1 year. Out of 39 analyzable patients, 17 (44%) were diagnosed with mediastinitis relapse. After the first scan, 32 of 39 were correctly classified, 2 were false positive, and 5 were not conclusive. After completion of an additional scan in the latter 5 patients, 36 of 39 were correctly classified and 3 were false positive (100% sensitivity, 86% specificity, 85% positive predictive value, and 100% negative predictive value). CONCLUSIONS: In the specific context of suspicion of mediastinitis relapse, the optimal diagnostic value was achieved by repeating the scan when the first one was not conclusive. In this context, a negative WBC scintigraphy was able to rule out infection, with potential major impact on therapeutic management in patients with poor clinical status.

Preclinical validation of 99mTc-annexin A5-128 in experimental autoimmune myocarditis and infective endocarditis: comparison with 99mTc-HYNIC-annexin A5.

Hydrazinonicotinamide-annexin A5 (HYNIC-Anx), a 99m technetium (99mTc)-labeled agent targeting phosphatidylserine, proved to be sensitive for the detection of apoptosis and thrombosis but is no longer available for clinical use. A mutant of human annexin designed for direct 99mTc labeling (referred to as Anx A5-128) showed improved binding affinity to phosphatidylserine and is expected to be used in humans. We compared both radiotracers with regard to pharmacokinetics and diagnostic ability in animal models. Biodistribution studies were performed in normal rats. Radiolabeled Anx A5-128 and HYNIC-Anx were compared in cardiovascular settings involving phosphatidylserine expression: experimental autoimmune myocarditis and infective endocarditis. Initial blood clearance was faster for Anx A5-128 than for HYNIC-Anx, and tissue biodistribution was similar overall for both tracers. The diagnostic sensitivity of Anx A5-128 was excellent and comparable to that of HYNIC-Anx. Anx A5-128 showed biodistribution and diagnostic ability similar to those of the HYNIC-Anx derivative, supporting its translation to clinical use.

Limb arteries involvement assessed by FDG/PET CT at diagnosis of giant cell arteritis and risk of relapse: An observational study.

INTRODUCTION: Steroids and anti-IL6 biotherapy are highly effective in obtaining remission in patients with giant cell arteritis (GCA) but the risk of relapses remains high. We aimed to identify predictors of relapse in GCA. METHODS: All consecutive patients admitted with a new diagnosis of GCA - according to the 2022 American College of Rheumatology/EULAR (ACR/EULAR) classification criteria - between May 2011 and May 2022 were eligible for this study. The primary outcome was the GCA relapse rate over the 36-months follow up. Factors associated with the primary outcome and time to first relapse were analyzed. RESULTS: One hundred and eight patients (74 [69-81] years, 64.8% women) with a new diagnosis of GCA were studied. GCA was biopsy-proven in 65 (60.2%) cases. Ninety-eight (90.7%) FDG/PET CT scans performed at diagnosis were available for review. All patients received steroids given for 21.0 [18.0-28.5] months, associated with methotrexate (n=1, 0.9%) or tocilizumab (n=2, 1.9%). During a median follow-up of 27.5 [11.4-35.0] months, relapse occurred in 40 (37%) patients. Multivariable Cox regression model, including general signs, gender, aortic wall thickness, FDG uptake in arterial wall and IV steroid pulse as covariates, showed that both general signs (HR 2.0 [1.0-4.0, P<0.05) and FDG uptake in limb arteries (HR 2.7 [1.3-5.5], P<0.01) at diagnosis were associated with GCA relapse. CONCLUSION: FDG uptake in limb arteries at diagnosis is a predictor of relapse in newly diagnosed GCA.

FDG PET/CT Imaging of Sarcoidosis.

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. The diagnostic can be made by histological identification of non-caseous granuloma or by a combination of clinical criteria. Active inflammatory granuloma can lead to fibrotic damage. Although 50% of cases resolve spontaneously, systemic treatments are often necessary to decrease symptoms and avoid permanent organ dysfunction, notably in cardiac sarcoidosis. The course of the disease can be punctuated by exacerbations and relapses and the prognostic depends mainly on affected sites and patient management. FDG-PET/CT along with newer FDG-PET/MR have emerged as key imaging modalities in sarcoidosis, namely for certain diagnostic purposes, staging and biopsy guiding. By identifying with a high sensitivity inflammatory active granuloma, FDG hybrid imaging is a main prognostic tool and therapeutic ally in sarcoidosis. This review aims to highlight the actual critical roles of hybrid PET imaging in sarcoidosis and display a brief perspective for the future which appears to include other radiotracers and artificial intelligence applications.

Squamous cell carcinoma of the tongue with cardiac metastasis on 18F-FDG PET/CT: A case report and literature review.

INTRODUCTION: The most common malignancies metastasizing to the heart are cancers of the lung, breast, mesothelioma, melanoma, leukemia, and lymphoma. Cardiac metastasis from a tongue cancer is a rare finding and only a few cases have been reported previously in the literature. In this case report and literature review, we discuss the main clinical features of patients with cardiac metastases secondary to a tongue cancer and imaging modalities performed, especially the 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). PATIENT CONCERNS: This is a case of a 39-year-old woman who in April 2018 was diagnosed with an invasive well differentiated squamous cell carcinoma of the movable tongue. She underwent a left hemiglossectomy followed by a revision of hemiglossectomy and ipsilateral selective neck lymph nodes dissection levels II to III because of pathological margins. An early inoperable clinical recurrence was diagnosed and she received radiochemotherapy with good clinical and metabolic response. She remained asymptomatic thereafter. DIAGNOSIS: In January 2020, a pre-scheduled 18F-FDG PET/CT showed a diffuse cardiac involvement. In February 2020, a biopsy of the lesion revealed a metastatic squamous cell carcinoma. INTERVENTIONS: She was deemed to not be a cardiac surgical candidate and treated by palliative chemotherapy: taxol-carboplatin associated with cetuximab then cetuximab alone because of adverse effects. A re-evaluation imaging performed in April 2020 evidenced a progression of the cardiac involvement, which led to switch chemotherapy by immunotherapy with nivolumab. OUTCOMES: This patient had a very poor prognosis and succumbed to major heart failure 4 months after the diagnosis of cardiac metastasis. CONCLUSION: In this case report, 18F-FDG PET/CT proved to be useful in detecting cardiac metastasis and changed the therapeutic management of the patient. It suggests that patients with tongue malignancies in a context of poor initial prognosis should be followed-up early by 18F-FDG PET/CT with HFLC diet to facilitate detection of recurrence.