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; Francois Xavier Danlos; Giulia Argalia; Mihaela 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 Nan; Andrea Ardizzoni; Gerard Zalcman; Camilo Garcia; Et al.

doi:10.1158/1078-0432.CCR-24-1993

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, Francois 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 Nan, Andrea Ardizzoni, Gerard Zalcman, Camilo Garcia^*, Et al.

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 cm ³. 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.

Original language	English
Pages (from-to)	352-364
Number of pages	13
Journal	Clinical Cancer Research
Volume	31
Issue number	2
Early online date	22 Oct 2024
DOIs	https://doi.org/10.1158/1078-0432.CCR-24-1993
Publication status	Published - 15 Jan 2025

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10.1158/1078-0432.CCR-24-1993

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Dall'Olio, F. G., Zrafi, W., Roelants, V., Ambrosini, V., Fourquet, A., Mitea, C., Passiglia, F., Bauckneht, M., Bonardel, G., Conci, N., Benitez, J. C., Arena, V., Namour, C., Naigeon, M., Monnet, I., Beshiri, K., Hoton, D., Dursun, S., Danlos, F. X., ... Et al. (2025). 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. Clinical Cancer Research, 31(2), 352-364. https://doi.org/10.1158/1078-0432.CCR-24-1993

@article{759442a9a00243afb4248d476674d58f,

title = "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",

abstract = "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 cm 3. 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.",

author = "Dall'Olio, \{Filippo G\} and Wael Zrafi and Veronique Roelants and Valentina Ambrosini and Aloyse Fourquet and Cristina Mitea and Francesco Passiglia and Matteo Bauckneht and Gerald Bonardel and Nicole Conci and Benitez, \{Jose Carlos\} and Vincenzo Arena and C{\'e}line Namour and Marie Naigeon and Isabelle Monnet and Kristi Beshiri and Delphine Hoton and Safiye Dursun and Danlos, \{Francois Xavier\} and Giulia Argalia and Mihaela Aldea and Guido Rovera and Lisa Derosa and Valerio Iebba and Gietema, \{Hester A\} and Valerie Gounant and Val{\'e}rie Lacroix and Jordi Remon and Daniel Gautheret and Nathalie Chaput and Bastien Job and Kannouche, \{Patricia L\} and Monica Velasco-Nu{\~n}o and Laurence Zitvogel and Eugenia Cella and \{Ch{\'i}charo de Freitas\}, \{Jos{\'e} Reinaldo\} and Damien Vasseur and Bettaieb, \{Mohamed Aymen\} and Marco Tagliamento and Lizza Hendriks and Antoine Italiano and David Planchard and Aurelien Marabelle and Fabrice Barlesi and Silvia Novello and \{De Andreis\}, Desiree and \{Aboubakar Nan\}, Frank and Andrea Ardizzoni and Gerard Zalcman and Camilo Garcia and \{Et al.\}",

year = "2025",

month = jan,

day = "15",

doi = "10.1158/1078-0432.CCR-24-1993",

language = "English",

volume = "31",

pages = "352--364",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "2",

}

Dall'Olio, FG, Zrafi, W, Roelants, V, Ambrosini, V, Fourquet, A, Mitea, C, Passiglia, F, Bauckneht, M, Bonardel, G, Conci, N, Benitez, JC, Arena, V, Namour, C, Naigeon, M, Monnet, I, Beshiri, K, Hoton, D, Dursun, S, Danlos, FX, Argalia, G, Aldea, M, Rovera, G, Derosa, L, Iebba, V, Gietema, HA, Gounant, V, Lacroix, V, Remon, J, Gautheret, D, Chaput, N, Job, B, Kannouche, PL, Velasco-Nuño, M, Zitvogel, L, Cella, E, Chícharo de Freitas, JR, Vasseur, D, Bettaieb, MA, Tagliamento, M, Hendriks, L, Italiano, A, Planchard, D, Marabelle, A, Barlesi, F, Novello, S, De Andreis, D, Aboubakar Nan, F, Ardizzoni, A, Zalcman, G, Garcia, C & Et al. 2025, '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', Clinical Cancer Research, vol. 31, no. 2, pp. 352-364. https://doi.org/10.1158/1078-0432.CCR-24-1993

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. / Dall'Olio, Filippo G; Zrafi, Wael; Roelants, Veronique et al.
In: Clinical Cancer Research, Vol. 31, No. 2, 15.01.2025, p. 352-364.

Research output: Contribution to journal › Article › Academic › peer-review

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 - 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 cm 3. 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 cm 3. 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.

U2 - 10.1158/1078-0432.CCR-24-1993

DO - 10.1158/1078-0432.CCR-24-1993

M3 - Article

SN - 1078-0432

VL - 31

SP - 352

EP - 364

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 2

ER -

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

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