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

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Abstract

Purpose

To compare the prognostic value of imaging biomarkers derived from a quantitative analysis of baseline 18F-FDG-PET/CT in patients with mucosal melanoma (Muc-M) or cutaneous melanoma (Cut-M) treated with immune checkpoint inhibitors (ICIs).

Methods

In this retrospective monocentric study, we included 56 patients with non-resectable Muc-M (n = 24) or Cut-M (n = 32) who underwent baseline 18F-FDG-PET/CT before treatment with ICIs between 2011 and 2017. Parameters were extracted from (i) tumoral tissues: SUVmax, SUVmean, TMTV (total metabolic tumor volume), and TLG (total lesion glycolysis) and (ii) lymphoid tissues: BLR (bone marrow-to-liver SUVmax ratio) and SLR (spleen-to-liver SUVmax ratio). Association with survival and response was evaluated using Cox prediction models, Student’s t tests, and Spearman’s correlation respectively. p < 0.05 was considered significant.

Results

Majority of ICIs were anti-PD1 (92.9%, n = 52/56). All 18F-FDG-PET/CT were positive. Overall (Muc-M to Cut-M), ORR was 33%:42%, DCR was 56%:69%, median follow-up was 25.0:28.9 months, median PFS was 4.7:10.7 months, and median OS was 23.9:28.3 months. In Muc-M, increased tumor SUVmax was associated with shorter OS while it was not correlated with PFS, ORR, or DCR. In Cut-M, increased TMTV and increased BLR were independently associated with shorter OS, shorter PFS, and lower response (ORR, DCR).

Conclusion

While all Muc-M and Cut-M were FDG avid, prognostic imaging biomarkers differed. For Muc-M patients treated with ICI, the only prognostic imaging biomarker was a high baseline maximal glycolytic activity (SUVmax), whereas for Cut-M patients, baseline metabolic tumor burden or bone marrow metabolism was negatively correlated to ICI response duration.

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Abbreviations

18F-FDG:

18fluor-Fluorodeoxyglucose

BLR:

Bone marrow-to-liver ratio

BOR:

Best overall response

CI:

Confidence interval

CR:

Complete response

CT:

Computed tomography

CTLA-4:

Cytotoxic T lymphocyte-associated protein 4

Cut-M:

Cutaneous melanoma

DCR:

Disease control rate

HR:

Hazard ratio

ICI:

Immune checkpoint inhibitor

IgG:

Immunoglobulin G

iRECIST:

Immune response evaluation criteria in solid tumors

LYSO:

Lu1.8Y.2SiO5:Ce (lutetium, yttrium, orthosilicate, cerium)

Muc-M:

Mucosal melanoma

ORR:

Overall response rate

OS:

Overall survival

PET:

Positron emission tomography

PD:

Progression disease

PD-1:

Programmed cell death-1

PERCIST:

Positron emission tomography evaluation response criteria in solid tumors

PFS:

Progression-free survival

PR:

Partial response

RECIST 1.1:

Response evaluation criteria in solid tumors version 1.1

SLR:

Spleen-to-liver ratio

SD:

Stable disease

SUVmax:

Maximum standard uptake value

SUVmean:

Mean standard uptake value

TLG:

Total lesion glycolysis

TMTV:

Total metabolic tumor volume

VOI:

Volume of interest

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Funding

L. Dercle’s work was partially funded by grants from Fondation Philanthropia and Fondation Nuovo-Soldati.

Author information

Author notes

  1. Samy Ammari and Laurent Dercle are co-senior authors.

Authors and Affiliations

  1. Département of Medical Imaging, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France

    Romain-David Seban, Lara Antonios & Samy Ammari

  2. Inserm U981, Melanoma Group, Gustave Roussy Cancer Campus, Villejuif, France

    Antoine Moya-Plana & Caroline Robert

  3. Department of Radiology, New York Presbyterian Hospital, Columbia University Medical Center, 168th Street, New York, NY, 10039, USA

    Randy Yeh, Lawrence H. Schwartz & Laurent Dercle

  4. Drug Development Department (DITEP), Gustave Roussy, Villejuif, France

    Aurélien Marabelle & Eric Deutsch

  5. UMR1015, Institut Gustave Roussy, Université Paris Saclay, 94800, Villejuif, France

    Aurélien Marabelle & Laurent Dercle

  6. Department of Radiotherapy, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France

    Eric Deutsch

  7. Département d’oncologie CHUV-UNIL, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, CH, Switzerland

    Ruth Gabriela Herrera Gómez

  8. Department of Medicine, Division of Hematology Oncology, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA

    Yvonne Saenger

Authors
  1. Romain-David Seban
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  2. Antoine Moya-Plana
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  10. Caroline Robert
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Corresponding author

Correspondence to Laurent Dercle.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Informed consent

This retrospective data collection was HIPAA compliant with a waiver of informed consent. All patients gave their informed consent for 18F-FDG PET/CTs which were performed as part of standard of care and not for the purpose of this study. All patients gave their informed consent for treatments with anti-PD1 and/or anti-CTLA4 which were performed as part of clinical care and not for the purpose of this study.

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Seban, RD., Moya-Plana, A., Antonios, L. et al. Prognostic 18F-FDG PET biomarkers in metastatic mucosal and cutaneous melanoma treated with immune checkpoint inhibitors targeting PD-1 and CTLA-4. Eur J Nucl Med Mol Imaging 47, 2301–2312 (2020). https://doi.org/10.1007/s00259-020-04757-3

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