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

Leilei Wu ¹, Zhenshan Zhang ², Chenxue Jiang ¹

¹Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
²Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
³Department 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, China.
⁴Department of Radiation Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, 230031, China.
⁵Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
⁶Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
⁷Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
⁸Geneseeq Research Institute, Nanjing Geneseeq Technology Inc, Nanjing, 210008, China.
⁹Department of Thyroid Surgery, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
¹⁰Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
¹¹School of Materials Science and Engineering, Tongji University, Shanghai, 201804, China.

⁰Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.

Advanced Science (weinheim, Baden-Wurttemberg, Germany) +

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March 16, 2025

View abstract on PubMed

Summary

Post-treatment circulating tumor DNA (ctDNA) and changes in metabolic tumor volume (TMTV) are strong predictors of outcomes in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT). These markers may help select patients for immunotherapy.

Area Of Science

Oncology
Radiology
Molecular Diagnostics

Background

Locally advanced non-small cell lung cancer (LA-NSCLC) presents a treatment challenge.
Definitive chemoradiotherapy (CRT) is a standard treatment for unresectable LA-NSCLC.
Identifying reliable prognostic markers is crucial for treatment optimization.

Purpose Of The Study

To evaluate the prognostic significance of circulating tumor DNA (ctDNA) and positron emission tomography/computed tomography (PET/CT) in LA-NSCLC patients undergoing definitive CRT.
To explore the combined prognostic value of baseline and post-treatment biomarkers.

Main Methods

Prospective study of 62 LA-NSCLC patients treated with definitive CRT.
Collection of baseline and post-CRT plasma samples for ctDNA analysis.
Baseline and mid-treatment PET/CT scans to assess metabolic tumor burden (TMTV, TLG).

Main Results

Baseline ctDNA correlated with TMTV and TLG but not survival.
Patients with undetectable ctDNA and low TMTV had significantly longer progression-free survival (PFS).
Post-CRT undetectable ctDNA and greater reduction in TMTV (∆TMTV) were strongly associated with improved PFS and overall survival (OS).

Conclusions

Post-treatment ctDNA and ∆TMTV are robust prognostic indicators in LA-NSCLC treated with CRT.
These markers can potentially identify patients suitable for de-escalation of therapy or those who may not benefit from consolidation immunotherapy (ICI).

Keywords:

LA‐NSCLC PET metabolic parameters ctDNA definitive chemoradiotherapy immune checkpoint inhibitors