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, Francois 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 - Aboubakar Nan, Frank
AU - Ardizzoni, Andrea
AU - Zalcman, Gerard
AU - Garcia, Camilo
AU - Et al.
PY - 2024/10/22
Y1 - 2024/10/22
N2 - PURPOSE: This study aimed to explore metabolic tumor volume (tMTV) as assessed 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT), and understand its biological meaning in patients with NSCLC exposed to immune checkpoint blockers(ICBs). 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 4 countries. Total MTV (tMTV) was analyzed, with a 42% SUVmax threshold. Survival was analyzed according to high tMTV (= median). Plasma proteomic profile, whole exome, transcriptome and other analysis 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 months vs 29.6 months (P<0.0012) for those with low tMTV. In patients receiving chemotherapy-ICB tMTV did not correlate with OS (P=0.099). In patients with 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 observed in low tMTV group. High tMTV correlated (and its detrimental effect seems to be driven by) a specific proteomic profile and increase in genomic instability. CONCLUSION: Our analysis indicates high tTMV is linked to an increase in systemic inflammation, specific cytokines production and chromosomal instability. tTMV may serve as one of the biomarker to select the best upfront strategy in patients with PD-L1 positive advanced NSCLC.
AB - PURPOSE: This study aimed to explore metabolic tumor volume (tMTV) as assessed 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT), and understand its biological meaning in patients with NSCLC exposed to immune checkpoint blockers(ICBs). 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 4 countries. Total MTV (tMTV) was analyzed, with a 42% SUVmax threshold. Survival was analyzed according to high tMTV (= median). Plasma proteomic profile, whole exome, transcriptome and other analysis 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 months vs 29.6 months (P<0.0012) for those with low tMTV. In patients receiving chemotherapy-ICB tMTV did not correlate with OS (P=0.099). In patients with 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 observed in low tMTV group. High tMTV correlated (and its detrimental effect seems to be driven by) a specific proteomic profile and increase in genomic instability. CONCLUSION: Our analysis indicates high tTMV is linked to an increase in systemic inflammation, specific cytokines production and chromosomal instability. tTMV may serve as one of the biomarker to select the best upfront strategy in patients with PD-L1 positive advanced NSCLC.
U2 - 10.1158/1078-0432.CCR-24-1993
DO - 10.1158/1078-0432.CCR-24-1993
M3 - Article
SN - 1078-0432
JO - Clinical Cancer Research
JF - Clinical Cancer Research
ER -