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.
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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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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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DOI: https://doi.org/10.1007/s00259-020-04757-3