Metabolic Tumor Volume Assessed by 18F FDG-PET CT Scan as a Predictive Biomarker for Immune Checkpoint Blockers in Advanced NSCLC and Its Biological Correlates

Filippo G. Dall'Olio, Wael Zrafi, Veronique Roelants, Valentina Ambrosini, Aloyse Fourquet, Cristina Mitea, Francesco Passiglia, Matteo Bauckneht, Gerald Bonardel, Nicole Conci, Jose Carlos Benitez, Vincenzo Arena, Céline Namour, Marie Naigeon, Isabelle Monnet, Kristi Beshiri, Delphine Hoton, Safiye Dursun, François Xavier Danlos, Giulia ArgaliaMihaela Aldea, Guido Rovera, Lisa Derosa, Valerio Iebba, Hester A. Gietema, Valerie Gounant, Valérie Lacroix, Jordi Remon, Daniel Gautheret, Nathalie Chaput, Bastien Job, Patricia L. Kannouche, Monica Velasco-Nuño, Laurence Zitvogel, Eugenia Cella, José Reinaldo Chícharo de Freitas, Damien Vasseur, Mohamed Aymen Bettaieb, Marco Tagliamento, Lizza Hendriks, Antoine Italiano, David Planchard, Aurelien Marabelle, Fabrice Barlesi, Silvia Novello, Desiree De Andreis, Frank Aboubakar Nana, Andrea Ardizzoni, Gerard Zalcman, Camilo Garcia, Benjamin Besse

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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    Résumé

    Purpose: This study aimed to explore metabolic tumor volume (MTV) as assessed by 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) and understand its biological meaning in patients with non-small cell lung cancer (NSCLC) exposed to immune checkpoint blockers (ICB). Experimental Design: In this study, patients with advanced NSCLC and a positive PET scan within 42 days of first-line treatment were enrolled in 11 institutions across four countries. Total MTV (tMTV) was analyzed, with a 42% maximum standardized uptake value threshold. Survival was analyzed according to high tMTV (=median). Plasma proteomic profile, whole exome, transcriptome, and other analyses were performed on monocentric cohorts to explore its biological correlates. Results: Of the 518 patients included, 167 received ICBs, 257 had chemotherapy plus ICBs, and 94 had chemotherapy. Median tMTV was 99 cm3. Median overall survival (OS) for patients with high tMTV treated with ICBs was 11.4 vs. 29.6 months (P < 0.0012) for those with low tMTV. In patients who received chemotherapy-ICB, tMTV did not correlate with OS (P = 0.099). In patients with programmed death-ligand 1 (PD-L1) =1% and high tMTV, chemotherapy-ICB combination was associated with longer OS compared with ICBs alone (20 vs. 11.4 months; P = 0.026), while no survival differences were observed in the low tMTV group. High tMTV correlated (and its detrimental effect seems to be driven) with a specific proteomic profile and increase in genomic instability. Conclusions: Our analysis indicates high tMTV is linked to an increase in systemic inflammation, specific cytokines production, and chromosomal instability. tMTV may serve as one of the biomarkers to select the best upfront strategy in patients with PD-L1-positive advanced NSCLC.

    langue originaleAnglais
    Pages (de - à)352-364
    Nombre de pages13
    journalClinical Cancer Research
    Volume31
    Numéro de publication2
    Les DOIs
    étatPublié - 15 janv. 2025

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