scholarly journals 68Ga-DOTATOC PET/CT to detect immune checkpoint inhibitor-related myocarditis

2021 ◽  
Vol 9 (10) ◽  
pp. e003594
Author(s):  
Sarah Boughdad ◽  
Sofiya Latifyan ◽  
Craig Fenwick ◽  
Hasna Bouchaab ◽  
Madeleine Suffiotti ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Early Stage ◽  
Elevated Serum ◽  
Myocardial Inflammation ◽  
Myocardial Uptake ◽  
Immune Correlates ◽  
Pet Ct ◽  
Cmr Imaging

BackgroundImmune checkpoint inhibitor (ICI)-related myocarditis is a rare but potentially fatal adverse event that can occur following ICI exposure. Early diagnosis and treatment are key to improve patient outcomes. Somatostatin receptor-based positron emission tomography–CT (PET/CT) showed promising results for the assessment of myocardial inflammation, yet information regarding its value for the diagnosis of ICI-related myocarditis, especially at the early stage, is limited. Thus, we investigated the value of 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) PET/CT for the early detection and diagnosis of ICI-related myocarditis.MethodsConsecutive patients with clinically suspected ICI-related myocarditis from July 2018 to February 2021 were retrospectively evaluated in this single-center study. All patients underwent imaging for the detection of ICI-related myocarditis using either cardiac magnetic resonance (CMR) imaging or 68Ga-DOTATOC PET/CT. PET/CT images were acquired 90 min after the injection of 2 MBq/kg 68Ga-DOTATOC with pathological myocardial uptake in the left ventricle (LV) suggestive of myocarditis defined using a myocardium-to-background ratio of peak standard uptake value to mean intracavitary LV standard uptake (MBRpeak) value above 1.6. Patients had a full cardiological work-up including ECG, echocardiography, serum cardiac troponin I (cTnI), cardiac troponin T and creatine kinase (CK), CK-MB. Endomyocardial biopsy and inflammatory cytokine markers were also analyzed. The detection rate of ICI-related myocarditis using 68Ga-DOTATOC PET/CT and CMR was assessed.ResultsA total of 11 patients had clinically suspected ICI-related myocarditis; 9 underwent 68Ga -DOTATOC PET/CT. All nine (100%) patients with 68Ga-DOTATOC PET/CT presented with pathological myocardial uptake in the LV that was suggestive of myocarditis (MBRpeak of 3.2±0.8, range 2.2–4.4). Eight patients had CMR imaging and 3/8 (38%) patients had lesions evocative of myocarditis. All PET-positive patients were previously treated with a high dose of steroids and intravenous immunoglobulin prior to PET/CT had elevated serum cTnI except for one patient for whom PET/CT was delayed several days. Interestingly, in 5/6 (83%) patients who presented with concomitant myositis, pathological uptake was seen on whole-body 68Ga-DOTATOC PET/CT images in the skeletal muscles, suggesting an additional advantage of this method to assess the full extent of the disease. In contrast, four patients with CMR imaging had negative findings despite having elevated serum cTnI levels (range 20.5–5896.1 ng/mL), thus defining possible myocarditis. Newly identified immune correlates could provide specific biomarkers for the diagnosis of ICI-related myocarditis. Most tested patients (six of seven patients) had serum increases in the inflammatory cytokine interleukin (IL)-6 and in the chemokines CXCL9, CXCL10, and CXCL13, and the mass cytometry phenotypes of immune cell populations in the blood also showed correlations with myocardial inflammation. Four of five patients with myocarditis exhibited a Th1/Th2 imbalance favoring a pronounced inflammatory Th1, Th1/Th17, and Th17 CD4 memory T-cell response. The high proportion of non-classical monocytes and significantly reduced levels of CD31 in four to five patients was also consistent with an inflammatory disease.ConclusionThe use of 68Ga-DOTATOC PET/CT along with immune correlates is a highly sensitive method to detect ICI-related myocarditis especially in the early stage of myocardial inflammation, as patients with elevated cTnI may present normal CMR imaging results. 68Ga-DOTATOC PET/CT is also useful for detecting concomitant myositis. These results need to be confirmed in a larger population of patients and validated against a histological gold standard if available.

scholarly journals Tumor response evaluation in patients with malignant melanoma undergoing immune checkpoint inhibitor therapy and prognosis prediction using 18F-FDG PET/CT: multicenter study for comparison of EORTC, PERCIST, and imPERCIST

2021 ◽  
Author(s):  
Kazuhiro Kitajima ◽  
Tadashi Watabe ◽  
Masatoyo Nakajo ◽  
Mana Ishibashi ◽  
Hiromitsu Daisaki ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Malignant Melanoma ◽  
Fdg Pet ◽  
Immune Checkpoint Inhibitor ◽  
Metabolic Response ◽  
Checkpoint Inhibitor ◽  
Response Evaluation ◽  
Pet Ct ◽  
Melanoma Patients ◽  
Fdg Pet Ct

Abstract Objective In malignant melanoma patients treated with immune checkpoint inhibitor (ICI) therapy, three different FDG-PET criteria, European Organization for Research and Treatment of Cancer (EORTC), PET Response Criteria in Solid Tumors (PERCIST), immunotherapy-modified PERCIST (imPERCIST), were compared regarding response evaluation and prognosis prediction using standardized uptake value (SUV) harmonization of results obtained with various PET/CT scanners installed at different centers. Materials and methods Malignant melanoma patients (n = 27) underwent FDG-PET/CT examinations before and again 3 to 9 months after therapy initiation (nivolumab, n = 21; pembrolizumab, n = 6) with different PET scanners at five hospitals. EORTC, PERCIST, and imPERCIST criteria were used to evaluate therapeutic response, then concordance of the results was assessed using Cohen’s κ coefficient. Log-rank and Cox methods were employed to determine progression-free (PFS) and overall (OS) survival. Results Complete metabolic response (CMR)/partial metabolic response (PMR)/stable metabolic disease (SMD)/progressive metabolic disease (PMD) with harmonized EORTC, PERCIST, and imPERCIST was seen in 3/5/4/15, 4/5/3/15, and 4/5/5/13 patients, respectively. Nearly perfect concordance between each pair of criteria was noted (κ = 0.939–0.972). Twenty patients showed progression and 14 died from malignant melanoma after a median 19.2 months. Responders (CMR/PMR) showed significantly longer PFS and OS than non-responders (SMD/PMD) (harmonized EORTC: p < 0.0001 and p = 0.011; harmonized PERCIST: p < 0.0001 and p = 0.0012; harmonized imPERCIST: p < 0.0001 and p = 0.0012, respectively). Conclusions All harmonized FDG-PET criteria (EORTC, PERCIST, imPERCIST) showed accuracy for response evaluation of ICI therapy and prediction of malignant melanoma patient prognosis. Additional studies to determine their value in larger study populations will be necessary.

Immune checkpoint inhibitor related adverse effects and FDG PET/CT findings

2021 ◽  
pp. jnmt.121.262151
Author(s):  
Jan-Henning Schierz ◽  
Ismet Sarikaya ◽  
Uwe Wollina ◽  
Leonore Unger ◽  
Ali Sarikaya
Keyword(s):  
Adverse Effects ◽  
Immune Checkpoint ◽  
Fdg Pet ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Ct Findings ◽  
Pet Ct ◽  
Fdg Pet Ct

Abstract B79: PET CT might be better than CT scan when evaluating immune checkpoint inhibitor response

2020 ◽  
Author(s):  
JuWhan Choi ◽  
Hyun Seock Shin ◽  
Jee Youn Oh ◽  
Young Seok Lee ◽  
Kyung Hoon Min ◽  
...  
Keyword(s):  
Ct Scan ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Pet Ct ◽  
Better Than

scholarly journals Prognostic Significance of SUVmax Combined With Lactate Dehydrogenase in Advanced Lung Cancer Patients Treated With Immune Checkpoint Inhibitor Plus Chemotherapy: A Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Linping Ke ◽  
Lu Wang ◽  
Jinming Yu ◽  
Xue Meng
Keyword(s):  
Lung Cancer ◽  
Platelet Count ◽  
Lactate Dehydrogenase ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Pet Ct

PurposeThis research aims to investigate the predictive capacity of PET/CT quantitative parameters combined with haematological parameters in advanced lung cancer patients treated with immune checkpoint inhibitor (ICI) plus chemotherapy.MethodsA total of 120 patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were enrolled before therapy. The following parameters were calculated: the maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); total tumour volume (MTV) and total lesion glycolysis (TLG); and whole-body metabolic values (MTVwb, TLGwb, SUVmeanwb, and SUVmaxwb). Lactate dehydrogenase (LDH) levels, absolute neutrophil count, absolute platelet count, albumin levels and derived neutrophil to lymphocyte ratio (dNLR) were also computed. The associations between the variables and therapy outcome (evaluated by iRECIST) were analyzed.ResultsBased on iRECIST, 32 of 120 patients showed iPD, 43 iSD, 36 iPR and 9 iCR. Multivariate analysis found that SUVmax, MTVwb, LDH and absolute platelet count were associated with treatment response (P =0.015, P =0.005, P &lt;0.001 and P =0.015, respectively). Kaplan-Meier survival analyses showed that SUVmax ≥11.42 and LDH ≥245 U/L were associated with shorter OS (P = 0.001 and P = 0.004, respectively). Multivariate Cox regression revealed that SUVmax and LDH alone were not correlated with survival prognosis (p&gt;0.05), but the combination of SUVmax and LDH was independently associated with OS (P=0.015, P=0.001, respectively). The median survival time (MST) for the low (LDH&lt;245 and SUVmax&lt;11.42), intermediate(LDH&lt;245 or SUVmax&lt;11.42), and high(SUVmax≥11.42 and LDH≥245) groups was 24.10 months (95% CI: 19.43 to 28.77), 17.41 months (95% CI: 15.83 to 18.99), and 13.76 months (95% CI: 12.51 to 15.02), respectively.ConclusionThis study identified that SUVmax plus LDH correlated with the survival outcome in patients with advanced lung cancer receiving PD-1/PD-L1 blockade plus chemotherapy.

Mediastinal FDG-positive lymph nodes simulating melanoma progression: drug-induced sarcoidosis like/lymphadenopathy related to ipilimumab

2021 ◽  
Vol 14 (1) ◽  
pp. e237310
Author(s):  
Carlos González-Cruz ◽  
Domingo Bodet ◽  
Eva Muñoz-Couselo ◽  
Vicente García-Patos
Keyword(s):  
Lymph Nodes ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Tumour Progression ◽  
Emission Tomography ◽  
Drug Induced ◽  
Positron Emission ◽  
Pet Ct ◽  
Granulomatous Diseases

Drug-induced sarcoidosis-like reactions (DISRs) are systemic granulomatous diseases that develop in the context of a new drug onset. Ipilimumab is an immune checkpoint inhibitor (ICI) approved for the treatment of advanced melanoma which has been associated with DISR. Differential diagnosis between tumour progression and DISR by positron emission tomography/computed tomography (PET/CT) in patients treated with an ICI can be a challenge. A 31-year-old woman was diagnosed with a stage IIIB melanoma in her back. Ipilimumab 10 mg/kg was initiated. After 1 month of finishing the treatment a routine, PET/CT showed multiple enlarged mediastinal and hilar lymph nodes FDG-positive. A transbronchial biopsy showed sarcoid-like granulomatous infiltration which favoured the diagnosis of DISR related to ipilimumab. The patient remained asymptomatic and lymphadenopathy regressed progressively after 11 months. Our work highlights the importance of differentiating DISR from tumour progression, before unnecessary changes in therapeutic strategies. PET/CT is a useful diagnostic tool for its follow-up.

scholarly journals Prediction of response to immune checkpoint inhibitor therapy using 18F-FDG PET/CT in patients with melanoma

Medicine ◽  
2019 ◽  
Vol 98 (29) ◽  
pp. e16417 ◽  
Author(s):  
Karim Amrane ◽  
Delphine Le Goupil ◽  
Gilles Quere ◽  
Olivier Delcroix ◽  
Sylvie Gouva ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Fdg Pet ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Prediction Of Response ◽  
Pet Ct ◽  
Checkpoint Inhibitor Therapy ◽  
18F Fdg ◽  
Fdg Pet Ct

scholarly journals Serum Troponin T Concentrations Are Frequently Elevated in Advanced Skin Cancer Patients Prior to Immune Checkpoint Inhibitor Therapy: Experience From a Single Tertiary Referral Center

2021 ◽  
Vol 8 ◽  
Author(s):  
Jonas K. Kurzhals ◽  
Tobias Graf ◽  
Katharina Boch ◽  
Ulrike Grzyska ◽  
Alex Frydrychowicz ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Troponin T ◽  
Elevated Serum ◽  
Cancer Center ◽  
Predictive Values ◽  
Tertiary Referral Center ◽  
Patients At Risk

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of several human malignancies, particularly metastatic skin cancer. However, immune-related myocarditis (irM), an immune-mediated adverse event (irAE), is often fatal. In the absence of a reliable biomarker, measurement of pre-ICI therapy serum troponin concentration has been proposed to identify patients at risk of developing irM, although real-world studies examining this strategy are lacking. Thus, we retrospectively analyzed the case records of all patients who commenced ICI therapy between January 2018 and December 2019 in a single university skin cancer center (n = 121) to (i) determine the incidence of irM, (ii) establish the frequency of pretreatment serum hsTnT elevations, and (iii) to establish whether this identified patients who subsequently developed irM. Only one patient developed irM, resulting in an overall incidence of 0.8%. Pretreatment hsTnT was measured in 47 patients and was elevated in 13 (28%). Elevated serum hsTnT concentrations were associated with chronic renal failure (p = 0.02) and diabetes (p &lt; 0.0002). Pretreatment hsTnT was not elevated in the patient who developed fulminant irM. Pre-immunotherapy serum hsTnT concentrations were often asymptomatically elevated in patients with advanced skin cancer, none of whom subsequently developed irM during ICI therapy. However, large studies are required to assess the positive and negative predictive values of hsTnT for the development of irM. In the meantime, elevated hsTnT concentrations should be investigated before initiation of immunotherapy and closely monitored during early treatment cycles, where the risk of irM is greatest.

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