Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF)

Thida Win,Pauline T Lukey,Robert I Shortman,Toby M Maher,Peter J Ell,Aiden Flynn,Nicholas J Screaton,Francesco Fraioli,Beverley F Holman,Ashley M Groves,Brian F Hutton,Alaleh Rashidnasab,Kris Thielemans,Raymondo Endozo,Lynn Hurrell,Joanna C Porter,Balaji Ganeshan

doi:10.1007/s00259-017-3917-8

Abstract

PurposeThere is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of 18F-FDG-PET/ CT to predict mortality in IPF.MethodsA total of 113 IPF patients (93 males, 20 females, mean age ± SD: 70 ± 9 years) were prospectively recruited for 18F-FDG-PET/CT. The overall maximum pulmonary uptake of 18F-FDG (SUVmax), the minimum pulmonary uptake or background lung activity (SUVmin), and target-to-background (SUVmax/ SUVmin) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan–Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary 18F-FDG-PET measurements and GAP score for risk stratification in IPF patients.ResultsDuring a mean follow-up of 29 months, there were 54 deaths. The mean TBR ± SD was 5.6 ± 2.7. Mortality was associated with high pulmonary TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor (TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003). Stepwise forward-Wald–Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p = 0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24 months. Combining PET data with GAP data (“PET modified GAP score”) refined the ability to predict mortality.ConclusionsA high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

Highlights

Interstitial lung disease (ILD) has an incidence of ~57/100,000 per year and is associated with significant morbidity [1]
In a population of 113 idiopathic pulmonary fibrosis (IPF) patients, we have shown that baseline objective measures of 18F-FDG uptake on Positron emission tomography (PET) are related to patient survival
The patients’ physicians need information to determine the required intensity of follow-up, to enable them to balance the risks of entering their patients into drug trials versus the possible benefits, and guide them in the timing of referral for lung transplant assessment and the listing of patients on an active transplant waiting list. We show that those IPF patients with a pulmonary FDG uptake with a to-background (SUVmax/ SUVmin) ratio (TBR) > 4.9 have twice the risk of death compared to those with low measurements

Summary

Introduction

Interstitial lung disease (ILD) has an incidence of ~57/100,000 per year and is associated with significant morbidity [1]. The. ILDs consist of a heterogeneous group of diseases with varying amounts of interstitial inflammation and fibrosis [2]. There is heterogeneity in outcome, with survival in idiopathic pulmonary fibrosis (IPF) poor. UK 3 CITR, UCL and Interstitial Lung Disease Centre, UCLH, London, UK. Much of the prognostic data heralds from an era when the criteria for diagnosing IPF were less well and differently defined than at present [2,3,4]

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