Cell-Free Circulating Tumor DNA for NonInvasive Molecular Profiling Among Patients Undergoing Definitive Chemoradiation for Locally Advanced Lung Cancer

IF 2.2 Q3 ONCOLOGY

Advances in Radiation Oncology Pub Date : 2025-02-02 DOI:10.1016/j.adro.2025.101727

Emily S. Lebow MD , Jordan Eichholz MS , Lillian Boe PhD , Zhigang Zhang PhD , Leah B. Kratochvil BA , Daphna Y. Gelblum MD , Charles B. Simone II MD , Annemarie F. Shepherd MD , Puneeth Iyengar MD, PhD , Jacob Y. Shin MD , Andreas Rimner MD , Bob T. Li MD, PhD, MPH , James M. Isbell MD , Narek Shaverdian MD , Maria T. Thor PhD , Daniel R. Gomez MD, MBA

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引用次数: 0

Abstract

Purpose

We prospectively explored the utility of liquid biopsy for cell-free circulating tumor DNA (ctDNA) as a prognostic and predictive biomarker in patients with non-small cell lung cancer (NSCLC) treated with definitive chemoradiation therapy.

Methods and Materials

This prospective clinical cohort consisted of patients with unresectable, locally advanced NSCLC who had liquid biopsy testing before initiation of cancer therapy. Liquid biopsy testing was performed using an institutional assay that included 129 genes and paired white blood cell sequencing. Variant allele frequency was defined as the proportion of mutant alleles at a particular genetic locus. A US Food and Drug Administration-recognized database (OncoKB) was used to classify alterations. We evaluated progression-free survival from the start of radiation therapy using the log-rank test.

Results

Among 25 patients with prospective testing of ctDNA levels before therapy initiation, 18 patients had adenocarcinoma (72%), 7 patients had squamous cell carcinoma (28%), and 23 (92%) were former or current smokers. Twelve patients (48%) received adjuvant durvalumab. The median radiation dose was 60 Gy in 30 fractions (range, 55-66 Gy in 20-33 fractions). Seventy-six percent of patients (n = 18) had one or more alterations detected (median, 3 alterations, range, 1-8), including genomic markers of radiation response in 3 patients. The most common driver alteration detected was KRAS mutation in 24% of the cohort (n = 6). The detection of ctDNA levels was significantly associated with pretreatment 18F-fluorodeoxyglucose positron emission tomography standardized uptake value metrics, and the association was strengthened by integrating the number of mutations (compared with variant allele frequency) as the outcome variable. Among patients with baseline detectable ctDNA levels, the median progression-free survival was 21.3 months and was not reached among patients without baseline ctDNA level detection (hazard ratio, 4.54, P = .04).

Conclusions

Prospective liquid biopsy testing among patients treated with definitive chemoradiation therapy identifies driver alterations and markers of radiation response with direct implications for therapy personalization.

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来源期刊

Advances in Radiation Oncology Medicine-Radiology, Nuclear Medicine and Imaging

CiteScore

4.60

自引率

4.30%

发文量

208

审稿时长

98 days

期刊介绍： The purpose of Advances is to provide information for clinicians who use radiation therapy by publishing: Clinical trial reports and reanalyses. Basic science original reports. Manuscripts examining health services research, comparative and cost effectiveness research, and systematic reviews. Case reports documenting unusual problems and solutions. High quality multi and single institutional series, as well as other novel retrospective hypothesis generating series. Timely critical reviews on important topics in radiation oncology, such as side effects. Articles reporting the natural history of disease and patterns of failure, particularly as they relate to treatment volume delineation. Articles on safety and quality in radiation therapy. Essays on clinical experience. Articles on practice transformation in radiation oncology, in particular: Aspects of health policy that may impact the future practice of radiation oncology. How information technology, such as data analytics and systems innovations, will change radiation oncology practice. Articles on imaging as they relate to radiation therapy treatment.