Kinetics of Plasma cfDNA Predicts Clinical Response in Non-Small Cell Lung Cancer Patients

Zhou, Xiaorong; Li, Chenchen; Zhang, Zhao; Li, Daniel Y.; Du, Jiang; Ding, Peng; Meng, Hua; Xu, Hui; Li, Ronglei; Ho, Effie; Zhang, Aiguo; Okunieff, Paul; Lu, Jianwei; Sha, Michael Y.

doi:10.2139/ssrn.3687360

Cited by 2 publications

(3 citation statements)

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“…Moreover, analyses using combinations of multiple liquid biopsy biomarkers are being conducted to improve the accuracy of detection [14,15]. Some studies have suggested that monitoring cfDNA dynamics might help clinicians select patients with NSCLC who will benefit most from immunotherapy [15][16][17]. In this study, we explored the value of the cfDNA determination to anticipate the evolution of metastatic NSCLC in patients receiving first-line pembrolizumab as a monotherapy or combination therapy.…”

Section: Introductionmentioning

confidence: 99%

Clinical potential of circulating free DNA and circulating tumour cells in patients with metastatic non‐small‐cell lung cancer treated with pembrolizumab

et al. 2021

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Immune checkpoint inhibitors (ICIs), such as pembrolizumab, are revolutionizing therapeutic strategies for different cancer types, including non-small cell lung cancer (NSCLC). However, only a subset of patients benefits from this therapy, and new biomarkers are needed to select better candidates. In this study, we explored the value of liquid biopsy analyses, including circulating free DNA (cfDNA) and circulating tumour cells (CTCs), as a prognostic or predictive tool to guide pembrolizumab therapy. For this purpose, a total of 109 blood samples were collected from 50 patients with advanced NSCLC prior to treatment onset and at 6 and 12 weeks after the initiation of pembrolizumab. Plasma cfDNA was measured using hTERT quantitative PCR assay.The CTC levels at baseline were also analysed using two enrichment technologies (CellSearch ® and Parsortix systems) to evaluate the efficacy of both approaches at detecting the presence of programmed cell death ligand 1 (PD-L1) on CTCs. Notably, patients with high baseline hTERT cfDNA levels had significantly shorter progression-free survival (PFS) and overall survival (OS) than those with low baseline levels. Moreover, patients with unfavourable changes in the hTERT cfDNA levels from baseline to 12 weeks showed a higher risk of disease progression.Additionally, patients in whom CTCs were detected using the CellSearch ® system had significantly shorter PFS and OS than patients who had no CTCs. Finally, multivariate regression analyses confirmed the value of the combination of CTCs and cfDNA levels as an early independent predictor of disease progression, identifying a subgroup of patients who were negative for CTCs and presented low levels of cfDNA who particularly benefited from the treatment.

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Section: Introductionmentioning

confidence: 99%

Clinical potential of circulating free DNA and circulating tumour cells in patients with metastatic non‐small‐cell lung cancer treated with pembrolizumab

et al. 2021

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“…Apart from divergent results regarding the relationship between cfDNA level and tumor size/activity, the usefulness of cfDNA as a marker for disease monitoring/response to treatment has been repeatedly demonstrated. The results proving the applicability of cfDNA were obtained from studies with different histological types and stages of tumors, with various methods of treatment and methods of cfDNA detection -NSCLC [18], various treatment modalities; chemotherapy in advanced gastric cancer [19]; perioperative cfDNA kinetics in resectable colon cancer [20]; combined treatment of glioblastoma [21]. It should be noted, however, that some of the publications dealing with this issue failed to demonstrate a relationship between cfDNA kinetics and treatment response [22].…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that in our study only cases of locally advanced ASCC were analyzed. Morbelli et al presented a detailed study of the correlation between cfDNA concentration and tumor metabolism, assessed using 18 F-FDG PET/CT, in cases of stage IV metastatic lung cancer. Of the eight 18 F-FDG PET/CT volumetric and metabolic parameters studied, only the SUVmax of the largest metastatic lesion correlated with the baseline cfDNA level [11].…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of plasma DNA in anal cancer patients

Małusecka¹,

Giglok²,

Suwiński³

et al. 2022

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Introduction The availability and non-invasiveness of circulating cell-free DNA (cfDNA) opens up new possibilities for real-time serial testing. The relationship between cfDNA concentration, clinical factors and suitability for monitoring was analyzed in patients with newly diagnosed anal squamous cell carcinoma (ASCC). Material and methods Blood samples were collected at several points during and after treatment. Patients were homogeneously treated with chemoradiotherapy. Results The concentration of cfDNA strongly correlated with the tumor volume ( r = 0.9, p = 0.00006) and number of neutrophils ( r = 0.706, p = 0.0069). Monitoring of cfDNA levels during treatment showed an increase after initiation of therapy, a peak at the end of treatment with significantly higher values for advanced than in T1/T2 tumors, and a decrease (T3/T4) during follow-up. However, neither the concentration of cfDNA before treatment nor its changes correlated with the response to chemoradiotherapy. There was no association between baseline cfDNA levels and T, N, age and gender. Conclusions Substantial changes in plasma cfDNA content can be observed after chemoradiotherapy for ASCC. However, the small number of cases studied makes it difficult to assess the usefulness of the cfDNA test.

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Kinetics of Plasma cfDNA Predicts Clinical Response in Non-Small Cell Lung Cancer Patients

Cited by 2 publications

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Clinical potential of circulating free DNA and circulating tumour cells in patients with metastatic non‐small‐cell lung cancer treated with pembrolizumab

Clinical potential of circulating free DNA and circulating tumour cells in patients with metastatic non‐small‐cell lung cancer treated with pembrolizumab

Quantitative analysis of plasma DNA in anal cancer patients

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