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Assessing immune organs on 18F-FDG PET/CT imaging for therapy monitoring of immune checkpoint inhibitors: inter-observer variability, prognostic value and evolution during the treatment course of melanoma patients

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Abstract

Background

Immune checkpoint inhibitors (ICIs) have significantly improved survival in advanced melanoma. There is a need for robust biomarkers to identify patients who do not respond. We analysed 14 baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metrics and their evolution to assess their correlation with patient outcome, compared with 7 established biological markers and 7 clinical variables.

Methods

We conducted a retrospective monocentric observational study of 29 patients with advanced melanoma who underwent baseline 18F-FDG PET/CT, followed by an early monitoring PET/CT (iPET) scan after 1 month of treatment and follow-up studies at 3rd (M3PET) and 6th month (M6PET). 18F-FDG uptake in immune organs (spleen, bone marrow, ileocecal valve) and derived spleen-to-liver (SLR) and bone-to-liver (BLR) ratios were reviewed by two PET readers for reproducibility analysis purposes including 14 PET variables. The most reproducible indexes were used for evaluation as predictors of overall survival (OS) in comparison with PET response using imPERCIST5, whole-body metabolic active tumour volume (WB-MATV) and biological parameters (lactate dehydrogenases (LDH), reactive protein c (CRP), white blood count (WBC), absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and derived neutrophils to lymphocyte ratio).

Results

Strong reproducibility’s (intraclass coefficients of correlation (ICC) > 0.90) were observed for spleen anterior SUVpeak, spleen MV, spleen TLG, spleen length and BLRmean. ICC for SLRmean and ileocecal SUVmean were 0.86 and 0.65, respectively. In the 1-year OS 1 group, SLRmean tended to increase at each time point to reach a significant difference at M6-PET (p = 0.019). The same trends were observed with spleen SUVpeak anterior and spleen length. In the 1-year OS 0 group, a significative increase of spleen length was found at iPET, as compared with baseline PET (p = 0.014) and M3-PET (p = 0.0239). Univariable Kaplan-Meier survival analysis found that i%var spleen length, M3%var SLRmean, baseline LDH, i%var NLR and response at M6PET were all predictors of 1-year OS.

Conclusions

SLRmean is recommended as a prognosticator in melanoma patients under immunotherapy: its increase greater than 25% at 3 months, compared with baseline, was associated with poor outcome after ICIs.

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Acknowledgements

Ms Helen Lapasset is thanked for English editing

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Author notes

  1. Kevin Prigent, Charline Lasnon and Emilien Ezine contributed equally to this work.

Authors and Affiliations

  1. Nuclear Medicine Department, University Hospital, Avenue Côte de Nacre, 14000, Caen, France

    Kevin Prigent, Nicolas Coudrais & Nicolas Aide

  2. Nuclear Medicine Department, François Baclesse Cancer Centre, Caen, France

    Charline Lasnon

  3. Dermatology Department, University Hospital, Caen, France

    Emilien Ezine, Elisa Joly, Laure Césaire, Andrea Stefan & Michel Depontville

  4. Normandy University, Caen, France

    Mélanie Janson & Nicolas Aide

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  1. Kevin Prigent
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Contributions

KP PET data analysis and manuscript writing

EE Clinical data collection and analysis and manuscript writing

CL statistical analysis and manuscript writing

MJ PET data analysis

NC PET Data analysis

EJ Clinical data collection

LC Clinical data collection

AS Clinical data collection

MD Clinical data collection

NA Study design, statistical analysis, manuscript writing

Corresponding author

Correspondence to Nicolas Aide.

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The authors declare that they have no competing interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Institutional review board approval was not required because in accordance with European regulation, French observational studies without any additional therapy or monitoring procedure do not need the approval of an ethics committee. Nonetheless, in accordance with the European General Data Protection Regulation, we sought approval to collect and publish data for this work from the national committee for data privacy, with the registration no. 2081250 v 0.

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Prigent, K., Lasnon, C., Ezine, E. et al. Assessing immune organs on 18F-FDG PET/CT imaging for therapy monitoring of immune checkpoint inhibitors: inter-observer variability, prognostic value and evolution during the treatment course of melanoma patients. Eur J Nucl Med Mol Imaging 48, 2573–2585 (2021). https://doi.org/10.1007/s00259-020-05103-3

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