TY - JOUR
T1 - 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
AU - Dall'Olio, Filippo G.
AU - Zrafi, Wael
AU - Roelants, Veronique
AU - Ambrosini, Valentina
AU - Fourquet, Aloyse
AU - Mitea, Cristina
AU - Passiglia, Francesco
AU - Bauckneht, Matteo
AU - Bonardel, Gerald
AU - Conci, Nicole
AU - Benitez, Jose Carlos
AU - Arena, Vincenzo
AU - Namour, Céline
AU - Naigeon, Marie
AU - Monnet, Isabelle
AU - Beshiri, Kristi
AU - Hoton, Delphine
AU - Dursun, Safiye
AU - Danlos, François Xavier
AU - Argalia, Giulia
AU - Aldea, Mihaela
AU - Rovera, Guido
AU - Derosa, Lisa
AU - Iebba, Valerio
AU - Gietema, Hester A.
AU - Gounant, Valerie
AU - Lacroix, Valérie
AU - Remon, Jordi
AU - Gautheret, Daniel
AU - Chaput, Nathalie
AU - Job, Bastien
AU - Kannouche, Patricia L.
AU - Velasco-Nuño, Monica
AU - Zitvogel, Laurence
AU - Cella, Eugenia
AU - Chícharo de Freitas, José Reinaldo
AU - Vasseur, Damien
AU - Bettaieb, Mohamed Aymen
AU - Tagliamento, Marco
AU - Hendriks, Lizza
AU - Italiano, Antoine
AU - Planchard, David
AU - Marabelle, Aurelien
AU - Barlesi, Fabrice
AU - Novello, Silvia
AU - De Andreis, Desiree
AU - Nana, Frank Aboubakar
AU - Ardizzoni, Andrea
AU - Zalcman, Gerard
AU - Garcia, Camilo
AU - Besse, Benjamin
N1 - Publisher Copyright:
© 2024 American Association for Cancer Research.
PY - 2025/1/15
Y1 - 2025/1/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85215544268&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-24-1993
DO - 10.1158/1078-0432.CCR-24-1993
M3 - Article
C2 - 39437011
AN - SCOPUS:85215544268
SN - 1078-0432
VL - 31
SP - 352
EP - 364
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -