Is there a link between very early changes of primary and secondary lymphoid organs in 18F-FDG-PET/MRI and treatment response to checkpoint inhibitor therapy?
Open Access
- 4 August 2020
- journal article
- research article
- Published by BMJ in Journal for ImmunoTherapy of Cancer
- Vol. 8 (2), e000656
- https://doi.org/10.1136/jitc-2020-000656
Abstract
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 number NCT03132090, DRKS00013925.Funding Information
- Wilhelm Sander-Stiftung (2014.157.1)
This publication has 39 references indexed in Scilit:
- Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2013
- Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in MelanomaThe New England Journal of Medicine, 2013
- Nivolumab plus Ipilimumab in Advanced MelanomaThe New England Journal of Medicine, 2013
- Cancer immunotherapy comes of ageNature, 2011
- Whole-Body Diffusion-weighted MR Imaging in Cancer: Current Status and Research DirectionsRadiology, 2011
- Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response CriteriaClinical Cancer Research, 2009
- From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid TumorsJournal of Nuclear Medicine, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2′-deoxycytidine analogNature Medicine, 2008
- Molecular analysis of the RET and NTRK1 gene rearrangements in papillary thyroid carcinoma in the Polish populationMutation research. Reviews in mutation research, 2006