18F-FDG uptake in PET/CT is a potential predictive biomarker of response to anti-PD-1 antibody therapy in non-small cell lung cancer

Kazuki Takada,Isamu Okamoto,Yasuto Yoneshima,Atsushi Osoegawa,Kentaro Tanaka,Mototsugu Shimokawa,Yoichi Nakanishi,Masaki Mori,Tetsuzo Tagawa,Yoshinao Oda,Akira Haro,Gouji Toyokawa,Sho Wakasu

doi:10.1038/s41598-019-50079-2

Kazuki Takada, Isamu Okamoto + Show 11 more

Open Access

https://doi.org/10.1038/s41598-019-50079-2

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Abstract

To examine the association between 18F-fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography/computed tomography (PET/CT) and the response to anti-programmed cell death-1 (PD-1) monoclonal antibody therapy in non-small cell lung cancer (NSCLC) patients, 89 patients with advanced or recurrent NSCLC were retrospectively analysed. Maximum standardized uptake value (SUVmax) in 18F-FDG PET/CT and the response to anti-PD-1 antibodies were recorded. A cut-off value of SUVmax was determined by receiver operating characteristic curve analysis for patient stratification. Among the 89 patients evaluated, 24 were classified as responders (all partial response), and 65 as non-responders. The average SUVmax of the responders was 15.60 (range, 6.44–51.10), which was significantly higher than that of the non-responders (11.61; range, 2.13–32.75; P = 0.0168, Student’s t-test). The cut-off SUVmax value selected for stratification was 11.16 (sensitivity and specificity, 0.792 and 0.585, respectively). The response rate of patients with SUVmax value ≥ 11.16 (41.3% [19/46]) was significantly higher than that of patients with SUVmax < 11.16 (11.6% [5/43], P = 0.0012, Chi-squared test). The SUVmax in 18F-FDG PET/CT is a potential predictive marker of response to anti-PD-1 antibody therapy in NSCLC patients. Further prospective studies of large populations are necessary to validate these results.

Highlights

The interaction between programmed cell death-1 (PD-1), expressed on activated T lymphocytes, and programmed cell death-ligand 1 (PD-L1), expressed on antigen-presenting cells and tumour cells, has a major role in suppression of the anti-tumour immune response[1]
We evaluated the relationship between 18F-FDG uptake on positron emission tomography/computed tomography (PET/CT) and the response to anti-PD-1 monoclonal antibodies (mAbs) in patients with advanced or recurrent non-small cell lung cancer (NSCLC) patients by dichotomizing the cohort according to the maximum standardized uptake value (SUVmax) on imaging
We evaluated the relationship between 18F-FDG uptake on PET/CT and the response to anti-PD-1 therapy in patients with advanced or recurrent NSCLC

Summary

Introduction

The interaction between programmed cell death-1 (PD-1), expressed on activated T lymphocytes, and programmed cell death-ligand 1 (PD-L1), expressed on antigen-presenting cells and tumour cells, has a major role in suppression of the anti-tumour immune response[1]. Monoclonal antibodies (mAbs) against PD-1 (e.g. nivolumab and pembrolizumab) or PD-L1 (e.g. atezolizumab) have become one of the standard treatments for patients with advanced or recurrent non-small cell lung cancer (NSCLC). Detection of PD-L1 expression in tumour samples is routinely conducted by immunohistochemistry (IHC) before initiation of treatment with anti-PD-1 or anti-PD-L1. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is an essential imaging modality for lung cancer[2,3] and the majority of patients undergo 18F-FDG PET/CT before treatment initiation. PD-L1 expression in NSCLC patients[4,5,6] These studies examined patients with surgically resectable NSCLC, not those with advanced or recurrent cancer; it is unknown whether the relationship between 18F-FDG uptake and the efficacy of anti-PD-1 mAbs is true in more advanced disease

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