Integration of Circulating Tumor DNA and Metabolic Parameters on 18F‐Fludeoxyglucose Positron Emission Tomography for Outcome Prediction in Unresectable Locally Advanced Non‐Small Cell Lung Cancer

Abstract This prospective study explores the prognostic value of circulating tumor DNA (ctDNA) and positron emission tomography/computed tomograpy (PET/CT) in unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC) treated with definitive chemoradiotherapy (CRT). The discovery set includ...

Full description

Saved in:
Bibliographic Details
Main Authors: Leilei Wu, Zhenshan Zhang, Chenxue Jiang, Li Li, Xiaojiang Sun, Menglin Bai, Ming Liu, Kangli Xiong, Jinbiao Shang, Jinming Yu, Shuanghu Yuan, Yang Yang, Yaping Xu
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202413125
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849767236315643904
author Leilei Wu
Zhenshan Zhang
Chenxue Jiang
Li Li
Xiaojiang Sun
Menglin Bai
Ming Liu
Kangli Xiong
Jinbiao Shang
Jinming Yu
Shuanghu Yuan
Yang Yang
Yaping Xu
author_facet Leilei Wu
Zhenshan Zhang
Chenxue Jiang
Li Li
Xiaojiang Sun
Menglin Bai
Ming Liu
Kangli Xiong
Jinbiao Shang
Jinming Yu
Shuanghu Yuan
Yang Yang
Yaping Xu
author_sort Leilei Wu
collection DOAJ
description Abstract This prospective study explores the prognostic value of circulating tumor DNA (ctDNA) and positron emission tomography/computed tomograpy (PET/CT) in unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC) treated with definitive chemoradiotherapy (CRT). The discovery set includes 62 patients, with 62 baseline and 53 post‐CRT plasma samples. PET/CT is performed at baseline, and 33 patients undergo mid‐treatment scans after 40 Gy. Baseline ctDNA is detected in 71.0% of patients. Pre‐treatment ctDNA concentration correlates with total metabolic tumor volume (TMTV) (p < 0.001) and total lesion glycolysis (TLG) (p = 0.001) but not treatment response or survival. However, patients with undetectable ctDNA and low TMTV show significantly longer progression‐free survival (PFS) (34.2 vs 10.1 months, p = 0.027). Post‐CRT, ctDNA is detected in 47.2% of patients, while ctDNA concentration (p = 0.005) and variant allele frequency (VAF) (p = 0.005) significantly decline. Undetectable post‐CRT ctDNA associates with longer PFS (p < 0.001) and overall survival (OS) (p = 0.001). Higher ∆TMTV correlates with improved PFS and OS. Similar findings were obtained in a test of 19 patients. These results highlight post‐CRT ctDNA and ∆TMTV as robust prognostic markers, potentially identifying patients who may forgo ICI consolidation.
format Article
id doaj-art-add2fddcec25466e976918bac96f19bc
institution DOAJ
issn 2198-3844
language English
publishDate 2025-04-01
publisher Wiley
record_format Article
series Advanced Science
spelling doaj-art-add2fddcec25466e976918bac96f19bc2025-08-20T03:04:17ZengWileyAdvanced Science2198-38442025-04-011213n/an/a10.1002/advs.202413125Integration of Circulating Tumor DNA and Metabolic Parameters on 18F‐Fludeoxyglucose Positron Emission Tomography for Outcome Prediction in Unresectable Locally Advanced Non‐Small Cell Lung CancerLeilei Wu0Zhenshan Zhang1Chenxue Jiang2Li Li3Xiaojiang Sun4Menglin Bai5Ming Liu6Kangli Xiong7Jinbiao Shang8Jinming Yu9Shuanghu Yuan10Yang Yang11Yaping Xu12Department of Radiation Oncology Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Thoracic Surgery Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Radiation Oncology Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Radiation Oncology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui 230001 ChinaDepartment of Radiation Oncology Zhejiang Cancer Hospital Hangzhou 310022 ChinaDepartment of Radiation Oncology Qilu Hospital of Shandong University Jinan Shandong 250012 ChinaDepartment of Radiation Oncology Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaGeneseeq Research Institute Nanjing Geneseeq Technology Inc Nanjing 210008 ChinaDepartment of Thyroid Surgery Zhejiang Cancer Hospital Hangzhou 310022 ChinaDepartment of Radiation Oncology Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan Shandong 250117 ChinaDepartment of Radiation Oncology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui 230001 ChinaDepartment of Thoracic Surgery Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Radiation Oncology Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaAbstract This prospective study explores the prognostic value of circulating tumor DNA (ctDNA) and positron emission tomography/computed tomograpy (PET/CT) in unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC) treated with definitive chemoradiotherapy (CRT). The discovery set includes 62 patients, with 62 baseline and 53 post‐CRT plasma samples. PET/CT is performed at baseline, and 33 patients undergo mid‐treatment scans after 40 Gy. Baseline ctDNA is detected in 71.0% of patients. Pre‐treatment ctDNA concentration correlates with total metabolic tumor volume (TMTV) (p < 0.001) and total lesion glycolysis (TLG) (p = 0.001) but not treatment response or survival. However, patients with undetectable ctDNA and low TMTV show significantly longer progression‐free survival (PFS) (34.2 vs 10.1 months, p = 0.027). Post‐CRT, ctDNA is detected in 47.2% of patients, while ctDNA concentration (p = 0.005) and variant allele frequency (VAF) (p = 0.005) significantly decline. Undetectable post‐CRT ctDNA associates with longer PFS (p < 0.001) and overall survival (OS) (p = 0.001). Higher ∆TMTV correlates with improved PFS and OS. Similar findings were obtained in a test of 19 patients. These results highlight post‐CRT ctDNA and ∆TMTV as robust prognostic markers, potentially identifying patients who may forgo ICI consolidation.https://doi.org/10.1002/advs.202413125ctDNAdefinitive chemoradiotherapyimmune checkpoint inhibitorsLA‐NSCLCPET metabolic parameters
spellingShingle Leilei Wu
Zhenshan Zhang
Chenxue Jiang
Li Li
Xiaojiang Sun
Menglin Bai
Ming Liu
Kangli Xiong
Jinbiao Shang
Jinming Yu
Shuanghu Yuan
Yang Yang
Yaping Xu
Integration of Circulating Tumor DNA and Metabolic Parameters on 18F‐Fludeoxyglucose Positron Emission Tomography for Outcome Prediction in Unresectable Locally Advanced Non‐Small Cell Lung Cancer
Advanced Science
ctDNA
definitive chemoradiotherapy
immune checkpoint inhibitors
LA‐NSCLC
PET metabolic parameters
title Integration of Circulating Tumor DNA and Metabolic Parameters on 18F‐Fludeoxyglucose Positron Emission Tomography for Outcome Prediction in Unresectable Locally Advanced Non‐Small Cell Lung Cancer
title_full Integration of Circulating Tumor DNA and Metabolic Parameters on 18F‐Fludeoxyglucose Positron Emission Tomography for Outcome Prediction in Unresectable Locally Advanced Non‐Small Cell Lung Cancer
title_fullStr Integration of Circulating Tumor DNA and Metabolic Parameters on 18F‐Fludeoxyglucose Positron Emission Tomography for Outcome Prediction in Unresectable Locally Advanced Non‐Small Cell Lung Cancer
title_full_unstemmed Integration of Circulating Tumor DNA and Metabolic Parameters on 18F‐Fludeoxyglucose Positron Emission Tomography for Outcome Prediction in Unresectable Locally Advanced Non‐Small Cell Lung Cancer
title_short Integration of Circulating Tumor DNA and Metabolic Parameters on 18F‐Fludeoxyglucose Positron Emission Tomography for Outcome Prediction in Unresectable Locally Advanced Non‐Small Cell Lung Cancer
title_sort integration of circulating tumor dna and metabolic parameters on 18f fludeoxyglucose positron emission tomography for outcome prediction in unresectable locally advanced non small cell lung cancer
topic ctDNA
definitive chemoradiotherapy
immune checkpoint inhibitors
LA‐NSCLC
PET metabolic parameters
url https://doi.org/10.1002/advs.202413125
work_keys_str_mv AT leileiwu integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT zhenshanzhang integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT chenxuejiang integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT lili integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT xiaojiangsun integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT menglinbai integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT mingliu integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT kanglixiong integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT jinbiaoshang integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT jinmingyu integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT shuanghuyuan integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT yangyang integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer
AT yapingxu integrationofcirculatingtumordnaandmetabolicparameterson18ffludeoxyglucosepositronemissiontomographyforoutcomepredictioninunresectablelocallyadvancednonsmallcelllungcancer