Prognostic 18F-FDG PET biomarkers in metastatic mucosal and cutaneous melanoma treated with immune checkpoint inhibitors targeting PD-1 and CTLA-4

2020 ◽  
Vol 47 (10) ◽  
pp. 2301-2312 ◽  
Author(s):  
Romain-David Seban ◽  
Antoine Moya-Plana ◽  
Lara Antonios ◽  
Randy Yeh ◽  
Aurélien Marabelle ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Cutaneous Melanoma ◽  
Fdg Pet ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
18F Fdg

scholarly journals 993P Glycolytic tumor burden on pretreatment 18F-FDG PET/CT correlates with response and survival in metastatic NSCLC undergoing immune checkpoint inhibitors

2021 ◽  
Vol 32 ◽  
pp. S846-S847
Author(s):  
S.B. Silva ◽  
C.W.D.S. Wanderley ◽  
J.F.G. Marin ◽  
M.P. de Macedo ◽  
E.C.T. do Nascimento; ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Fdg Pet ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tumor Burden ◽  
Metastatic Nsclc ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

scholarly journals Positron Emission Tomography-Based Response to Target and Immunotherapies in Oncology

Medicina ◽  
2020 ◽  
Vol 56 (8) ◽  
pp. 373 ◽  
Author(s):  
Maria Isabella Donegani ◽  
Giulia Ferrarazzo ◽  
Stefano Marra ◽  
Alberto Miceli ◽  
Stefano Raffa ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Immune Checkpoint ◽  
Fdg Pet ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Emission Tomography ◽  
Positron Emission ◽  
Target Therapies ◽  
18F Fdg ◽  
Complementary Value

2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a promising tool to support the evaluation of response to either target therapies or immunotherapy with immune checkpoint inhibitors both in clinical trials and, in selected patients, at the single patient’s level. The present review aims to discuss available evidence related to the use of [18F]FDG PET (Positron Emission Tomography) to evaluate the response to target therapies and immune checkpoint inhibitors. Criteria proposed for the standardization of the definition of the PET-based response and complementary value with respect to morphological imaging are commented on. The use of PET-based assessment of the response through metabolic pathways other than glucose metabolism is also relevant in the framework of personalized cancer treatment. A brief discussion of the preliminary evidence for the use of non-FDG PET tracers in the evaluation of the response to new therapies is also provided.

18 F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography imaging for the diagnosis of immune checkpoint inhibitors associated myocarditis

2021 ◽  
Author(s):  
Stéphane Ederhy ◽  
Perrine Devos ◽  
Bruno Pinna ◽  
Elisa Funck-Brentano ◽  
Baptiste Abbar ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Fdg Pet ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Diagnostic Value ◽  
Predictive Values ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Medicine Physician ◽  
Oncology Unit

Abstract Immune-checkpoint inhibitors (ICI) have profoundly improved the prognosis of cancer patients but are associated with life-threatening myocarditis (incidence≤1%).The diagnosis of ICI-myocarditis remains challenging necessitating the need for novel diagnostic strategies.This single center cohort included 61 consecutive patients referred to our cardio-oncology unit for a suspicion of ICI-myocarditis with a positive troponin, between March 2019 and March 2021. In the 31 patients with suspected ICI-myocarditis with available FDG-PET, the median delay between admission and the first available FDG-PET performed was 12 days [interquartile-range:9-30]. Patients received ICI (ICI-monotherapy: 24/31, 77% and ICI-combination therapy: 7/31, 23%), mainly for lung cancer (n=10), melanoma (n=5), and kidney cancer (n=3). FDG-PET was performed using a standardized protocol involving dietary measures prior to PET, including fasting of at least 6h and a fat enriched diet without carbohydrates for 24h. FDG-PET platforms included Biograph-mCT-Flow Siemens (n=9/34, 26%) or Discovery-MI-5-Ring General Electric (n=25/34, 74%) devices and analysed using Singo.via Workstation (Siemens) by a nuclear medicine physician blinded to patients’ medical records. Interpretation of FDG-PET was based on the following classification: 1/No FDG uptake, 2/Diffuse FDG uptake, 3/Focal FDG uptake, 4/Focal on diffuse FDG uptake.An abnormal cardiac fixation on FDG-PET suggestive of myocarditis was observed in only 2/21 (9.5%) patients with otherwise definite ICI-myocarditis (1 diffuse, 1 focal), not different in proportion versus 1/7 (14.3%, 1 focal) patient without ICI-myocarditis (p>0.99). The sensitivity, specificity, positive predictive and negative predictive values (with their 95% confidence-interval) of FDG-PET for ICI-myocarditis was 9.5% (1.2-30.4%), 85.7% (42.1-99.6%), 66% (17.5-95%), 24% (18.5-30.6%), respectively. Only 2/14(14.2%) FDG-PET were positive despite being performed at a time in which ICI-myocarditis was fully active with troponin levels over ten-times the normal values versus 0/6(0%,p>0.99) for FDG-PET performed when troponin levels were abnormal but below ten-times the upper limit. Similarly, there was no difference in FDG-PET positivity rate for exams performed within 14 days (1/7, 14.3%; plus 3 inconclusive exams) versus those performed after 14 days (1/14, 7.2%; no inconclusive exams; p>0.99) of hospital admission.Altogether, our study suggests that FDG-PET has a limited diagnostic value for the diagnosis of ICI-Myocarditis.

scholarly journals Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4289
Author(s):  
Luca G. Campana ◽  
Barbara Peric ◽  
Matteo Mascherini ◽  
Romina Spina ◽  
Christian Kunte ◽  
...  
Keyword(s):  
Cancer Registry ◽  
Immune Checkpoint ◽  
Cutaneous Melanoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Locoregional Therapy ◽  
Tumor Control ◽  
Melanoma Metastases ◽  
Melanoma Patients ◽  
Cutaneous Melanoma Metastases

Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC–IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation.

Volume increase of spleen in melanoma patients undergoing immune checkpoint blockade

Immunotherapy ◽  
2021 ◽  
Author(s):  
Laura Susok ◽  
Dominik Reinert ◽  
Carsten Lukas ◽  
Eggert Stockfleth ◽  
Thilo Gambichler
Keyword(s):  
Immune Checkpoint ◽  
Cutaneous Melanoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Clinical Parameters ◽  
Spleen Volume ◽  
Volume Increase ◽  
Computer Tomographic ◽  
Melanoma Patients

Aim: To find out whether treatment with immune checkpoint inhibitors (ICIs) results in volume increase of the spleen. Patient & methods: We studied 49 stage III and IV melanoma patients with an indication for ICIs. Computer tomographic-assisted volumetry of spleens was performed. Results: After 3 months, median spleen volume was significantly increased when compared with the baseline volume. At 3 months, the increase of spleen volume was significantly associated with the use of ipilimumab and ipilimumab plus nivolumab. There was no significant association between spleen volume increase and clinical parameters. Conclusion: The median spleen volume of patients with cutaneous melanoma increases during the first months of ICI treatment, which was particularly attributable to the use of anti-CTLA-4 and anti-CTLA-4/anti-PD-1 regimens.

scholarly journals Successful Treatment of a Patient with anti-PD1 Antibody-Resistant Advanced Mucosal Melanoma with Nivolumab, Ipilimumab plus Denosumab Combination Therapy

2020 ◽  
Vol 13 (1) ◽  
pp. 271-275 ◽  
Author(s):  
Taku Fujimura ◽  
Yumi Kambayashi ◽  
Kentaro Ohuchi ◽  
Ryo Amagai ◽  
Yota Sato ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Combination Therapy ◽  
Nasal Cavity ◽  
Immune Checkpoint ◽  
Cutaneous Melanoma ◽  
Japanese Population ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Mucosal Melanoma ◽  
Mutation Burden

Since the incidence of mucosal melanoma is higher in the Japanese population compared to Caucasians, and since mucosal melanoma possesses a lower mutation burden compared to cutaneous melanoma, the efficacy of anti-PD1 antibody (Ab) monotherapy for mucosal melanoma is limited. Therefore, other targeting molecules that enhance the anti-tumor effects of immune checkpoint inhibitors are needed. In this report, we present a case with anti-PD1 Ab-resistant recurrent malignant melanoma of the nasal cavity successfully treated with nivolu­mab, ipilimumab plus denosumab combination therapy.

scholarly journals Incidence of New Primary Cutaneous Melanoma in Patients With Metastatic Melanoma Treated With Immune Checkpoint Inhibitors

2020 ◽  
Author(s):  
Japbani K. Nanda ◽  
Stephen W. Dusza ◽  
Cristian Navarrete-Dechent ◽  
Konstantinos Liopyris ◽  
Ashfaq A. Marghoob ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Cutaneous Melanoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Cutaneous Melanoma

scholarly journals Association Between FSIP2 Mutation and an Improved Efficacy of Immune Checkpoint Inhibitors in Patients With Skin Cutaneous Melanoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Haoxuan Ying ◽  
Anqi Lin ◽  
Junyi Liang ◽  
Jian Zhang ◽  
Peng Luo
Keyword(s):  
Immune Checkpoint ◽  
Cutaneous Melanoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Response To Treatment ◽  
Interacting Protein ◽  
Tumor Immunogenicity

BackgroundImmune checkpoint inhibitors (ICIs) have shown remarkable success in treating skin cutaneous melanoma (SKCM); however, the response to treatment varies greatly between patients. Considering that the efficacy of ICI treatment is influenced by many factors, we selected the Fibrosheath interacting protein 2 (FSIP2) gene and systematically analyzed its potential to predict the efficacy of ICI treatment.MethodsPatient data were collected from an ICI treatment cohort (n = 120) and a The Cancer Genome Atlas (TCGA)-SKCM cohort (n = 467). The data were divided into an FSIP2-mutant (MT) group and FSIP2-wild-type (WT) group according to FSIP2 mutation status. In this study, we analyzed the patients’ overall survival rate, tumor mutational burden (TMB), neoantigen load (NAL), copy number variation (CNV), cell infiltration data and immune-related genes. We used gene set enrichment analysis (GSEA) to delineate biological pathways and processes associated with the efficacy of immunotherapy.ResultsThe efficacy of ICI treatment of SKCM patients with FSIP2 mutation was significantly better than that of patients without FSIP2 mutation. The patients in the FSIP2-MT group had higher tumor immunogenicity and lower regulatory T cell (Treg) infiltration. Results of GSEA showed that pathways related to tumor progression (MAPK and FGFR), immunomodulation, and IL-2 synthesis inhibition were significantly downregulated in the FSIP2-MT group.ConclusionOur research suggests that the FSIP2 gene has the potential to predict the efficacy of ICI treatment. The high tumor immunogenicity and low Treg levels observed may be closely related to the fact that patients with FSIP2-MT can benefit from ICI treatment.

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