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. 2020 Jul;8(2):e000645.
doi: 10.1136/jitc-2020-000645.

Baseline metabolic tumor volume as a strong predictive and prognostic biomarker in patients with non-small cell lung cancer treated with PD1 inhibitors: a prospective study

David Chardin  1   2 , Marie Paquet  3 , Renaud Schiappa  4 , Jacques Darcourt  3   2 , Caroline Bailleux  2   5 , Michel Poudenx  5 , Aurélie Sciazza  3 , Marius Ilie  6 , Jonathan Benzaquen  7 , Nicolas Martin  5 , Josiane Otto  5 , Olivier Humbert  3   2
Affiliations

Baseline metabolic tumor volume as a strong predictive and prognostic biomarker in patients with non-small cell lung cancer treated with PD1 inhibitors: a prospective study

David Chardin et al. J Immunother Cancer. 2020 Jul.

Abstract

Background: Reliable predictive and prognostic markers are still lacking for patients treated with programmed death receptor 1 (PD1) inhibitors for non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic and predictive values of different baseline metabolic parameters, including metabolic tumor volume (MTV), from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scans in patients with NSCLC treated with PD1 inhibitors.

Methods: Maximum and peak standardized uptake values, MTV and total lesion glycolysis (TLG), as well as clinical and biological parameters, were recorded in 75 prospectively included patients with NSCLC treated with PD1 inhibitors. Associations between these parameters and overall survival (OS) were evaluated as well as their accuracy to predict early treatment discontinuation (ETD).

Results: A high MTV and a high TLG were significantly associated with a lower OS (p<0.001). The median OS in patients with MTV above the median (36.5 cm3) was 10.5 months (95% CI: 6.2 to upper limit: unreached), while the median OS in patients with MTV below the median was not reached. Patients with no prior chemotherapy had a poorer OS than patients who had received prior systemic treatment (p=0.04). MTV and TLG could reliably predict ETD (area under the receiver operating characteristic curve=0.76, 95% CI: 0.65 to 0.87 and 0.72, 95% CI: 0.62 to 0.84, respectively).

Conclusion: MTV is a strong prognostic and predictive factor in patients with NSCLC treated with PD1 inhibitors and can be easily determined from routine 18F-FDG PET/CT scans. MTV, could help to personalize immunotherapy and be used to stratify patients in future clinical studies.

Keywords: biomarkers, tumor; immunotherapy; lung neoplasms; tumor biomarkers.

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Conflict of interest statement

Competing interests: MI reports personal fees from AstraZeneca, Bristol-Myers Squibb, Roche, Boehringer-Ingelheim, and Merck & Co outside the submitted work.

Figures

Figure 1
Figure 1
Examples of 18F-FDG PET/CT tumor segmentations for MTV measurement. Included voxels are represented in blue on MIP images. (A.) Example of a small MTV (10.9 mL). (B) Example of a large MTV (142 mL). 18F-FDG PET/CT, 18F-fluorodeoxyglucose positron emission tomography–computed tomography; MIP, maximum intensity projection; MTV, metabolic tumor volume.
Figure 2
Figure 2
Kaplan-Meier curves for OS in relation to (A) SUVmax, (B) SUVpeak, (C) MTV, and (D) TLG (p values for log-rank test). MTV, metabolic tumor volume; OS, overall survival; SUVmax, maximum standardized uptake value; SUVpeak, peak standardized uptake value; TLG, total lesion glycolysis.
Figure 3
Figure 3
Kaplan-Meier curves for OS in relation to (A) age, (B) gender, (C) presence of brain metastases, (D) PDL1 expression (when known), (E) prior chemotherapy and (F) prior local treatment (p values are given for log-rank test). OS, overall survival; PDL1, programmed death receptor ligand 1.
Figure 4
Figure 4
ROC curves representing the value of (A) MTV, (B) TLG, (C) SUVmax and (D) SUVpeak to predict ETD after immunotherapy. AUC, area under the curve; ETD, early treatment discontinuation; MTV, metabolic tumor volume; ROC, receiver operating characteristic; SUVmax, maximum standardized uptake value; SUVpeak, peak standardized uptake value; TLG, total lesion glycolysis.
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