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

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.Electronic supplementary materialThe online version of this article (10.1007/s00259-017-3917-8) contains supplementary material, which is available to authorized users.

Assessment of 18F-FDG uptake in idiopathic pulmonary fibrosis: influence of lung density changes

“…Altogether PET/CT evaluation in IPF could provide some additional information about disease activity and prognosis. This is supported by a recent publication showing that adding uncorrected PET parameters to the GAP stage (PET-modified GAP staging) increases the predictive power of the GAP classification (Win et al, 2018). In our study, we demonstrate that the SUVmean-corr is also higher in GAP stage 3.…”

Pirfenidone in restrictive allograft syndrome after lung transplantation: A case series

“…17 Interestingly, stabilization of pulmonary function with pirfenidone was later also shown in a case of BOS. 19,20 These findings were recently confirmed by our group in a retrospective study comparing LTx recipients with RAS, BOS, or stable condition, demonstrating a significantly higher pulmonary 18 F-FDG uptake in RAS vs BOS or stable patients. 19,20 These findings were recently confirmed by our group in a retrospective study comparing LTx recipients with RAS, BOS, or stable condition, demonstrating a significantly higher pulmonary 18 F-FDG uptake in RAS vs BOS or stable patients.…”

“…18 Moreover, increased 18 F-fluorodeoxyglucose (FDG) uptake in fibrotic subpleural regions at RAS diagnosis was seen, suggestive of active local inflammation and/or parenchymatous remodeling, similar to what has been described in IPF. 19,20 These findings were recently confirmed by our group in a retrospective study comparing LTx recipients with RAS, BOS, or stable condition, demonstrating a significantly higher pulmonary 18 F-FDG uptake in RAS vs BOS or stable patients. Moreover, a possible prognostic role for 18 F-FDG positron emission tomography (PET)/CT regarding subsequent pulmonary function and graft survival in RAS was recently demonstrated.…”

“…months and are currently alive, while 3 other patients demonstrate long-term stabilization of pulmonary function, after 26.6 (range 18.4-46.6) months of pirfenidone treatment. We hypothesize that the subpleural metabolic activity in RAS may represent local inflammation and active tissue remodeling/angiogenesis/fibrogenesis, which is in line with the increased pulmonary 18 F-FDG uptake seen in the regions with interstitial changes in IPF 19,20. However, the actual clinical benefit of pirfenidone cannot be sufficiently assessedin the context of this study design and requires further investigation in a larger randomized trial.…”

Immunometabolism of pro-repair cells

“…Lactate also shifts tumor macrophages toward an M2-like macrophage phenotype (117), which could promote fibrosis in nonmalignant clinical settings. Interestingly, fluorodeoxyglucose-PET scan activity, which measures cellular glucose uptake, can predict progression-free survival and provide risk stratification for patients with idiopathic pulmonary fibrosis (118,119). One hypothesis is that an increased glycolytic state in fibrosis could lead to local elevations in tissue lactate, M2-like macrophage polarization, and further fibrogenesis.…”