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Prognostic value of total tumour volume, adding necrosis to metabolic tumour volume, in advanced or metastatic non-small cell lung cancer treated with first-line pembrolizumab

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Abstract

Background

Metabolic tumour volume (MTV) measured on fluorodeoxyglucose F18 (FDG) positron emission tomography coupled with computed tomography (PET/CT) is a prognostic factor of advanced non-small cell lung cancer (NSCLC) treated by first-line immunotherapy. However, these tumours are often necrotic and the necrosis, which is hypometabolic in PET FDG, is not included in the MTV. The aim of this study was to evaluate the prognostic value of total tumour volume (TTV), adding necrotic tumour volume (NTV) to metabolic tumour volume (MTV).

Methods

We retrospectively included 65 patients with NSCLC treated with pembrolizumab as monotherapy. All patients had a pretreatment FDG PET/CT. PET/CT measured parameters were MTV, NTV and TTV. Clinical, biological and tumour parameters were also retrieved. Receiver operator characteristics (ROC) analysis was performed and overall survival at 1 year was studied using Kaplan–Meier and uni/multivariate Cox analysis.

Results

In the ROC analysis, MTV, NTV, TTV, age at diagnosis, polynuclear blood neutrophil, derived neutrophil/leukocyte ratio (dNLR), and haemoglobin had an area under the curve (AUC) significantly higher than 0.5. In Kaplan–Meier analysis, prognosis was worse for patients with high MTV (p = 0.02), high TTV (p = 0.003), high NTV (p = 0.014), low haemoglobin (p < 0.001), older people (p = 0.002), neutrophil polynucleosis (p < 0.001) and dNLR (p = 0.022). All these parameters, except age and neutrophil polynucleosis, were significant prognostic factors in univariate Cox analysis (p < 0.05). In a stepwise multivariate Cox analysis focused on PET parameters, the only significant parameter was TTV (HR = 3.66, p = 0.002) and in a stepwise multivariate Cox analysis exploring all the parameters, a model combining TTV, performance status and brain metastasis was found (p = 0.002).

Conclusions

TTV and NTV measured on pretreatment FDG PET/CT are significant prognosis factor for stage III–IV NSCLC treated by pembrolizumab and TTV could have a higher prognostic value than MTV.

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Data availability

The data that support the findings of this study are available from the corresponding author, P.D., upon reasonable request.

Abbreviations

FDG:

18F-fluorodeoxyglucose

ALK:

Anaplastic lymphoma kinase

dNLR:

Derived neutrophil-to-lymphocyte radio

EGFR:

Epidermal growth factor receptor

ICI:

Immune checkpoint inhibitor

MTV:

Metabolic tumour volume

MTVR:

Metabolic-total volume ratio

NTV:

Necrotic tumour volume

NTVR:

Necrotic-total volume ratio

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PS:

Performance status

PET:

Positron emission tomography

PD-1:

Programmed cell death 1

PD-L:

Programmed death-ligand

PFS:

Progression-free survival

ROS1:

ROS proto-oncogene 1

SUV:

Standardised uptake value

SCLC:

Small cell lung cancers

TTV:

Total tumour volume

TPS:

Tumour proportion score

WHO:

World Health Organization

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Funding

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Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Henri Becquerel Cancer Center, Rue d’Amiens-CS 11516, 76038, Rouen Cedex 1, France

    Florian Eude, Pierre Vera & Pierre Decazes

  2. Department of Pulmonology, Thoracic Oncology and Respiratory Intensive Care, Rouen University Hospital, Rouen, France

    Florian Guisier, Mathieu Salaün & Luc Thiberville

  3. QuantIF-LITIS (EA [Equipe d’Accueil] 4108), Faculty of Medicine, University of Rouen, Rouen, France

    Florian Eude, Florian Guisier, Mathieu Salaün, Luc Thiberville, Pierre Vera & Pierre Decazes

  4. Clinical Research Unit, Henri Becquerel Cancer Center, Rouen, France

    Thibault Pressat-Laffouilhere

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  1. Florian Eude
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Correspondence to Pierre Decazes.

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Ethics approval and consent to participate

This study was performed in accordance with the Helsinki Declaration and local laws, and the protocol was approved by the Institutional Review Board of Henri Becquerel Center (n° 2003B). Patients were informed about the study and their right to oppose the use of the data.

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Supplementary Information

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12149_2021_1694_MOESM1_ESM.png

Supplemental Figure 1. Plot representing clusters of Spearman’s correlations for PET parameters and clinoco-biological parameters. (PNG 214 KB)

12149_2021_1694_MOESM2_ESM.jpg

Supplemental Figure 2. ROC curves for PET parameters. AUC: area under the curve; threshold in dL for MTV, TTV and NTV; NTVR: ratio necrotic tumour volume without unit. (JPG 251 KB)

12149_2021_1694_MOESM3_ESM.jpg

Supplemental Figure 3. ROC curves for biological parameters and age. AUC: area under the curve; threshold in G/L for polynuclear neutrophils at baseline, in g/dL for hemoglobinemia at baseline, in year for age; dNLR: derived neutrophil-to lymphocyte ratio without unit. (JPG 251 KB)

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Eude, F., Guisier, F., Salaün, M. et al. Prognostic value of total tumour volume, adding necrosis to metabolic tumour volume, in advanced or metastatic non-small cell lung cancer treated with first-line pembrolizumab. Ann Nucl Med 36, 224–234 (2022). https://doi.org/10.1007/s12149-021-01694-5

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  • DOI: https://doi.org/10.1007/s12149-021-01694-5

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