Abstract
Purpose
We aimed to evaluate if imaging biomarkers on FDG PET are associated with clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).
Methods
In this retrospective monocentric study, we included 109 patients with advanced NSCLC who underwent baseline FDG PET/CT before ICI initiation between July 2013 and September 2018. Clinical, biological (including dNLR = neutrophils/[leukocytes minus neutrophils]), pathological and PET parameters (tumor SUVmax, total metabolic tumor volume [TMTV]) were evaluated. A multivariate prediction model was developed using Cox models for progression-free survival (PFS) and overall survival (OS). The association between biomarkers on FDG PET/CT and disease clinical benefit (DCB) was tested using logistic regression.
Results
Eighty patients were eligible. Median follow-up was 11.6 months (95%CI 7.7–15.5). Sixty-four and 52 patients experienced progression and death, respectively. DCB was 40%. In multivariate analyses, TMTV > 75 cm3 and dNLR > 3 were associated with shorter OS (HR 2.5, 95%CI 1.3–4.7 and HR 3.3, 95%CI 1.6–6.4) and absence of DCB (OR 0.3, 95%CI 0.1–0.9 and OR 0.4, 95%CI 0.2–0.9). Unlike TMTV, dNLR was a significant prognostic factor for PFS (HR 1.9, 95%CI 1.1–3.3) along with anemia (HR 1.9, 95%CI 1.2–3.8). No association was observed between tumor SUVmax and PFS or OS.
Conclusion
Baseline tumor burden (TMTV) on FDG PET/CT scans and inflammatory status (dNLR) were associated with poor OS and absence of DCB for ICI treatment in advanced NSCLC patients, unlike tumor SUVmax, and may be used together to improve the selection of appropriate candidates.
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1) All authors made substantial contributions to the design of the work; or the acquisition, analysis or interpretation of data.
2) All authors revised it critically for important intellectual content.
3) All authors approved the version to be published.
4) All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Material preparation, data collection and analysis were performed by R-D. Seban, L. Mezquita, A. Berenbaum and B. Besse.
The first draft of the manuscript was written by R-D Seban, L. Mezquita and B. Besse.
All authors commented on previous versions of the manuscript. All authors read and approved the manuscript.
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Conflict of interest
The following competing interests have been declared.
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R-D S, A.B, L.D, A.B, C.C, E.D, S.G, J.A, S.A, S.L: The authors declare that they have no conflict of interest.
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L.Mezquita:
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Consulting, advisory role: Roche Diagnostics
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Lectures and educational activities: Bristol-Myers Squibb, Tecnofarma, Roche, AstraZeneca
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Travel, Accommodations, Expenses: Chugai
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C.Le Pechoux:
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Consulting advisory role: Amgen, Astra Zeneca, Nanobiotix, Roche
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Lectures and educational activities: Astra Zeneca, Lilly
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D. Planchard:
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Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, Roche. Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche
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Clinical trials research as principal or co-investigator (Institutional financial interests): AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo
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Travel, Accommodations, Expenses: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer
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B. Besse:
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Sponsored Research at Gustave Roussy Cancer Center
Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharm
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Ethical approval
All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration.
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Seban, RD., Mezquita, L., Berenbaum, A. et al. Baseline metabolic tumor burden on FDG PET/CT scans predicts outcome in advanced NSCLC patients treated with immune checkpoint inhibitors. Eur J Nucl Med Mol Imaging 47, 1147–1157 (2020). https://doi.org/10.1007/s00259-019-04615-x
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DOI: https://doi.org/10.1007/s00259-019-04615-x