Is there a link between very early changes of primary and secondary lymphoid organs in
| Autor: | Ahmed E. Othman, Konstantin Nikolaou, B. Gückel, Martin Schwartz, Johannes Schwenck, Nina F. Schwenzer, Andrea Forschner, Christian la Fougère, Matthias Fenchel, Claus Garbe, Benjamin Weide, Christina Pfannenberg, Ferdinand Seith |
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| Rok vydání: | 2020 |
| Předmět: |
CTLA-4 antigen
Male Cancer Research medicine.medical_specialty Lymphocyte Immunology Spleen Standardized uptake value Gastroenterology programmed cell death 1 receptor 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Fluorodeoxyglucose F18 Internal medicine Positron Emission Tomography Computed Tomography Immunotherapy Biomarkers melanoma medicine Immunology and Allergy Humans Prospective Studies Immune Checkpoint Inhibitors Pharmacology business.industry Melanoma Eosinophil medicine.disease medicine.anatomical_structure Lymphatic system Oncology 030220 oncology & carcinogenesis Lean body mass Molecular Medicine Female Bone marrow business |
| Zdroj: | Journal for Immunotherapy of Cancer |
| ISSN: | 2051-1426 |
| Popis: | Response assessment or prediction to checkpoint inhibitor therapy (CIT) is an unsolved problem in current routine diagnostics of patients with melanoma. Here, we evaluated very early changes of primary and secondary lymphoid organs under CIT in multiparametric [18F]-labeled fluorodeoxyglucose-positron emission tomography (18F-FDG-PET)/MRI as possible predictors of treatment response and investigated their correlation with baseline blood immune biomarkers. Between October 2014 and November 2017, 17 patients with unresectable melanoma (8 females; 65±11 years) undergoing CIT were prospectively evaluated using whole-body 18F-FDG-PET/MRI before CIT start (t0), 2 weeks (t1) and 3 months after CIT initiation (t2). At each time point, the volume, the 18F-FDG-uptake and the mean apparent diffusion coefficient (ADC) of the spleen as well as the 18F-FDG uptake of the bone marrow were assessed. Relative lymphocyte count (RLC), relative eosinophil count (REC) and neutrophil-lymphocyte ratio (NLR) were assessed at baseline. Response Evaluation Criteria in Solid Tumours modified for immune-based therapeutics (iRECIST) and decisions from an interdisciplinary tumor board were used for treatment response evaluation at t2. iRECIST was compared with PET response criteria in solid tumors for image-based response evaluation at different time points. Comparative analysis was conducted with Mann-Whitney U test with false discovery rate correction for multiple testing and correlation coefficients were computed. In lymphoid organs, significant differences (p18F-FDG-uptake in the spleen at t1 and the increase of the uptake t1-t0 (responders/non-responders: standardized uptake value lean body mass 1.19/0.93; +49%/−1%). The best correlation coefficients to baseline biomarkers were found for the 18F-FDG-uptake in the spleen at t1: NLR, r=−0.46; RLC, r=0.43; REC, r=0.58 (p18F-FDG-uptake of bone marrow (+31%/−9%) at t1 and the ADCmean at t2 (+46%/+15%) compared with t0, however, not reaching significance. Our findings indicate that an effective systemic immune response in patients undergoing CIT can be detected as a significantly increased spleen activity in 18F-FDG-PET as early as 2 weeks after treatment initiation.Trial registration numberNCT03132090, DRKS00013925. |
| Databáze: | OpenAIRE |
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