Abstract 15809: 68 Gallium Fibroblast Activating Protein Inhibitor Positron Emission Tomography is Able to Diagnose Checkpoint Inhibitor-induced Myocarditis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniel Finke ◽  
Markus B Heckmann ◽  
Esther Herpel ◽  
Hugo A Katus ◽  
Uwe Haberkorn ◽  
...  

Introduction: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-induced myocarditis. Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n=23) to three patients with suspected ICI-induced myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. Myocardial biopsies were examined, especially in regard to the infiltration of immune cells. Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients’ FAPI PET/CTs showed a locally defined cardiac enrichment of the marker which was absent in patients receiving ICIs without any signs of immunological adverse effects and cardiac impairment (n=23) (Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)). Conclusions: Myocardial biopsy, the current gold standard of the diagnosis of ICI-induced myocarditis, is susceptible to sampling errors and results arrive within a few days. We provide first evidence that FAPI PET/CT is able to diagnose ICI-induced myocarditis and can demonstrate locally enhanced manifestation of ICI-induced myocarditis on time.

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniel Finke ◽  
Markus B. Heckmann ◽  
Esther Herpel ◽  
Hugo A. Katus ◽  
Uwe Haberkorn ◽  
...  

Objective: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-associated myocarditis.Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n = 23) to three patients with suspected ICI-associated myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. All three patients' myocardial biopsies were examined for inflammatory cells.Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1,771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients' FAPI PET/CTs showed cardiac enrichment of the marker which was less distinct or absent in patients receiving ICIs without any signs of immunological adverse effects or cardiac impairment (n = 23) [Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)].Conclusions: Apart from the successful implementation of ICIs in oncological treatments, ICI-associated myocarditis is still a challenging adverse effect. FAPI PET/CT may be used in order to identify affected patients at an early stage. Moreover, when integrated into cancer stage diagnostics, it contributes to cardiac risk stratification besides biomarker, ECG and echocardiography.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hye Seong ◽  
Yong Hyu Jeong ◽  
Woon Ji Lee ◽  
Jun Hyoung Kim ◽  
Jung Ho Kim ◽  
...  

AbstractKikuchi-Fujimoto disease (KFD) is usually self-limiting, but prolonged systemic symptoms often result in frequent hospital visits, long admission durations, or missed workdays. We investigated the role of fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing KFD severity. We reviewed the records of 31 adult patients with pathologically confirmed KFD who underwent 18F-FDG PET/CT between November 2007 and April 2018 at a tertiary-care referral hospital. Disease severity was assessed using criteria based on clinical manifestations of advanced KFD. Systemic activated lymph nodes and severity of splenic activation were determined using semi-quantitative and volumetric PET/CT parameters. The median of the mean splenic standardized uptake value (SUVmean) was higher in patients with severe KFD than those with mild KFD (2.38 ± 1.18 vs. 1.79 ± 0.99, p = 0.058). Patients with severe KFD had more systemically activated volume and glycolytic activity than those with mild KFD (total lesion glycolysis: 473.5 ± 504.4 vs. 201.6 ± 363.5, p = 0.024). Multivariate logistic regression showed that myalgia (odds ratio [OR] 0.035; 95% confidence interval [CI] 0.001–0.792; p = 0.035), total lymph node SUVmax (cutoff 9.27; OR 24.734; 95% CI 1.323–462.407; p = 0.032), and spleen SUVmean (cutoff 1.79; OR 37.770; 95% CI 1.769–806.583; p = 0.020) were significantly associated with severe KFD. 18F-FDG PET/CT could be useful in assessing KFD severity.


2021 ◽  
Author(s):  
Ke Zhao ◽  
Ke Rao ◽  
Xin Chen ◽  
Si Chen ◽  
Haifeng Xu

Abstract BackgroundChoriocarcinoma is a rare malignant tumor and rarely occurs outside the gonads. Primary hepatic choriocarcinoma is more infrequent, with hidden clinical manifestations, rapid progress, and extremely poor prognosis. Only more than 10 cases were publicly reported in the world. Therefore, there is still a lack of deep understanding of the diagnosis and treatment of the disease.Case presentationWe report a case of primary hepatic choriocarcinoma in a man diagnosed by pathology. A 65-year-old male patient presented with fever and anorexia, nothing but mild jaundice of the skin and sclera was found on physical examination. Abdominal enhanced magnetic resonance imaging (MRI) showed a huge mass in the right hepatic lobe. Fludeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) scan showed increased uptake in the liver and sigmoid colon and no uptake in the testes. The patient underwent the right hepatectomy, and postoperative pathology showed that the tumor was primary hepatic choriocarcinoma. Then he received one course of adjuvant chemotherapy. Then he developed severe myelosuppression and was transferred to the intensive care unit for further treatment. He eventually died of severe liver failure about 100 days after surgery. Primary hepatic choriocarcinoma is extremely rare, and its diagnosis is challenging.ConclusionsPrimary hepatic choriocarcinoma is a rare and highly malignant tumor with a poor prognosis. We believe that this differential diagnosis should be considered in liver tumor patients. The effective treatment for this disease is still to be explored.


2020 ◽  
Vol 9 (3) ◽  
pp. 890 ◽  
Author(s):  
Ruth G.M. Keijsers ◽  
Jan C. Grutters

Sarcoidosis is a granulomatous disease of which the etiology remains unknown. The diverse clinical manifestations may challenge clinicians, particularly when conventional markers are inconclusive. From various studies, it has become clear that fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT aids in sarcoidosis care. In this article, an update on FDG PET/CT in sarcoidosis is provided. The use of FDG PET/CT in the diagnostic process of sarcoidosis is explained, especially in determining treatable inflammatory lesions in symptomatic patients with indecisive conventional tests. Furthermore, FDG PET/CT for evaluating the potential benefit of additional inflammatory treatment is described and its use in cardiac sarcoidosis is highlighted.


2021 ◽  
Vol 11 (3) ◽  
pp. 217
Author(s):  
Cristina Ferrari ◽  
Nicola Maggialetti ◽  
Tamara Masi ◽  
Anna Giulia Nappi ◽  
Giulia Santo ◽  
...  

Immunotherapy is a promising therapeutic strategy both for solid and hematologic tumors, such as in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). In particular, immune-checkpoint inhibitors, such as nivolumab and pembrolizumab, are increasingly used for the treatment of refractory/relapsed HL. At the same time, evidence of chimeric antigen receptor (CAR)-T-cell immunotherapy efficacy mostly in NHL is growing. In this setting, the challenge is to identify an appropriate imaging method to evaluate immunotherapy response. The role of 18F-Fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), especially in early evaluation, is under investigation in order to guide therapeutic strategies, taking into account the possible atypical responses (hyperprogression and pseudoprogression) and immune-related adverse events that could appear on PET images. Herein, we aimed to present a critical overview about the role of 18F-FDG PET/CT in evaluating treatment response to immunotherapy in lymphoma patients.


2020 ◽  
Vol 9 (11) ◽  
pp. 3483
Author(s):  
David Lang ◽  
Gerald Wahl ◽  
Nikolaus Poier ◽  
Sebastian Graf ◽  
David Kiesl ◽  
...  

Cancer immunotherapy using immune-checkpoint inhibitors (ICI) has revolutionized the therapeutic landscape of various malignancies like non-small-cell lung cancer or melanoma. Pre-therapy response prediction and assessment during ICI treatment is challenging due to the lack of reliable biomarkers and the possibility of atypical radiological response patterns. Positron emission tomography/computed tomography (PET/CT) enables the visualization and quantification of metabolic lesion activity additional to conventional CT imaging. Various biomarkers derived from PET/CT have been reported as predictors for response to ICI and may aid to overcome the challenges clinicians currently face in the management of ICI-treated patients. In this narrative review, experts in nuclear medicine, thoracic oncology, dermatooncology, hemato- and internal oncology, urological and head/neck tumors performed literature reviews in their respective field and a joint discussion on the use of PET/CT in the context of ICI treatment. The aims were to give a clinical overview on present standards and evidence, to identify current challenges and fields of research and to enable an outlook to future developments and their possible implications. Multiple promising studies concerning ICI response assessment or prediction using biomarkers derived from PET/CT alone or as composite biomarkers have been identified for various malignancies and disease stages. Of interest, additional major incentives in the field may evolve from novel tracers specifically targeting immune-checkpoint molecules which could allow not only response assessment and prognosis, but also visualization of histological tumor cell properties like programmed death-ligand (PD-L1) expression in vivo. Despite the broad range of existing literature on PET/CT-derived biomarkers in ICI therapy, implications for daily clinical practice remain elusive. High-quality prospective data are urgently warranted to determine whether patients benefit from the application of PET/CT in terms of prognosis. At the moment, the lack of such evidence as well as the absence of standardized imaging methods and biomarkers still precludes PET/CT imaging to be included in the relevant clinical practice guidelines.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christos Sachpekidis ◽  
Annette Kopp-Schneider ◽  
Jessica C. Hassel ◽  
Antonia Dimitrakopoulou-Strauss

Abstract Background The usage of immune checkpoint inhibitors (ICIs) is the standard practice for the treatment of metastatic melanoma. However, a significant amount of patients show no response to immunotherapy, while issues on its reliable response interpretation exist. Aim of this study was to investigate the phenomenon of early disease progression in 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in melanoma patients treated with ICIs. Methods Thirty-one patients under ICIs serially monitored with 18F-FDG PET/CT were enrolled. All patients exhibited progressive metabolic disease (PMD) after two ICIs’ cycles according to the European Organization for Research and Treatment of Cancer (EORTC) criteria, and were characterized as unconfirmed PMD (uPMD). They were further followed with at least one PET/CT for either confirmation of PMD (cPMD) or demonstration of pseudoprogression remission. Patients were also evaluated with the PET Response Evaluation Criteria for Immunotherapy (PERCIMT). Moreover, in an attempt to investigate immune activation, the spleen to liver ratios (SLRmean, SLRmax) of 18F-FDG uptake were measured. Results Median follow up was 69.7 months [64.6–NA]. According to EORTC, 26/31 patients with uPMD eventually showed cPMD (83.9%) and 5/31 patients showed pseudoprogression (16.1%). Patients with cPMD (n = 26) had a median OS of 10.9 months [8.5–NA], while those with pseudoprogression (n = 5) did not reach a median OS [40.9–NA]. Respectively, after application of PERCIMT, 2/5 patients of the pseudoprogression group were correctly classified as non-PMD, reducing the uPMD cohort to 29 patients; eventually, 26/29 patients demonstrated cPMD (89.7%) and 3/29 pseudoprogression (10.3%). One further patient with pseudoprogression exhibited transient, sarcoid-like, mediastinal/hilar lymphadenopathy, a known immune-related adverse event (irAE). Finally, patients eventually showing cPMD exhibited a significantly higher SLRmean than those showing pseudoprogression after two ICIs’ cycles (p = 0.038). Conclusion PET/CT, performed already after administration of two ICIs’ cycles, can identify the majority of non-responders in melanoma immunotherapy. In order to tackle however, the non-negligible phenomenon of pseudoprogression, another follow-up PET/CT, the usage of novel response criteria and vigilance over emergence of radiological irAEs are recommended. Moreover, the investigation of spleen glucose metabolism may offer further prognostic information in melanoma patients under ICIs.


2020 ◽  
pp. 107815522094714
Author(s):  
Yun Liu ◽  
Lindi Jiang

Introduction Immune checkpoint inhibitors (ICI) has demonstrated significant clinical benefit in advanced cancer. Despite favorable benefits, the use of ICI is accompanied by various side effects, which are inflammatory side effects potentially affecting any organ. Among which myocarditis is the most severe and has a relatively high mortality. However, there is no effective treatments, and many patients respond poorly to glucocorticoids and immunosuppressants. Therefore, it is urgent to explore effective treatments. Cases report Here we describe two patients with metastatic cancer who developed immune-mediated myocarditis after receiving anti-programmed cell death protein (PD)-1 antibody. The main clinical manifestations are dyspnea. All patients had an elevation of cardiac enzyme, a variety of atypical electrocardiographic (ECG) abnormalities and preserved left ventricular ejection fraction (LVEF). All our patients underwent cardiac MRI (CMRI) and suggested typical features of myocarditis, including myocardial oedema and delayed enhancement. Management and outcome: All patients were treated promptly with glucocorticoids, followed by other immunosuppressive treatments include plasma exchange and intravenous immunoglobulin (IVIG). However, no significant improvement was observed and we then administered tofacitinib 5 mg twice daily to treat the refractory myocarditis and the elevated levels of pro-inflammatory cytokines. All patients recovered and were discharged. No major adverse reaction was reported during tofacitinib therapy. Discussion To our knowledge, this is the first report in the world of patients with ICI-associated myocarditis treated with oral tofacitinib. Our results can at least provide a new option for clinical treatment of refractory myocarditis or other immune-related adverse events.


2005 ◽  
Vol 44 (S 01) ◽  
pp. S46-S50 ◽  
Author(s):  
M. Dawood ◽  
N. Lang ◽  
F. Büther ◽  
M. Schäfers ◽  
O. Schober ◽  
...  

Summary:Motion in PET/CT leads to artifacts in the reconstructed PET images due to the different acquisition times of positron emission tomography and computed tomography. The effect of motion on cardiac PET/CT images is evaluated in this study and a novel approach for motion correction based on optical flow methods is outlined. The Lukas-Kanade optical flow algorithm is used to calculate the motion vector field on both simulated phantom data as well as measured human PET data. The motion of the myocardium is corrected by non-linear registration techniques and results are compared to uncorrected images.


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