Phase II clinical trial with metronomic oral vinorelbine and tri-weekly cisplatin as induction therapy, subsequently concomitant with radiotherapy (RT) in patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC). Analysis of survival and value of ctDNA for patient selection

Provencio, Mariano; Majem, Margarita; Guirado, M.; Massutí, Bartomeu; Peñas, R. de las; Ortega, Ana Laura; Dómine, Manuel; Marsé, Raquel; Sala, María; Paredes, Alfredo; Morán, Teresa; Vázquez‐Estévez, Sergio; Coves, Juan; Larriba, José Luis González; Sánchez, José Miguel; Vicente, David; Farré, Núria; Fornos, L. Fernández; Zapata, I.; Franco, Fernando; Serna‐Blasco, Roberto; Romero, Atocha; Isla, Dolores

doi:10.1016/j.lungcan.2021.01.005

Cited by 20 publications

(9 citation statements)

References 31 publications

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“…Change of ctDNA was shown to be predictive for treatment efficacy in advanced cancers (20)(21)(22)(23). In locally advanced, unresectable, NSCLC ctDNA has been shown to predict survival outcomes (35). Similarly, its use to evaluate response to NAT has also been investigated.…”

Section: Discussionmentioning

confidence: 99%

Circulating tumor DNA predicts neoadjuvant immunotherapy efficacy and recurrence-free survival in surgical non-small cell lung cancer patients

Yue¹,

Liu²,

Chen³

et al. 2022

Transl Lung Cancer Res

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Background: There is currently a lack of effective biomarkers to evaluate efficacy of neoadjuvant therapy (NAT) for resectable non-small cell lung cancer (NSCLC) patients. Circulating tumor DNA (ctDNA) has been investigated as a non-invasive tool for the assessment of tumor burden and minimal residual disease (MRD). The utility of ctDNA profiling in reflecting NAT efficacy, however, has not been confirmed. This study explored the association of ctDNA change with treatment response to NAT and recurrence-free survival (RFS) after surgery.Methods: Eligible patients with stage IB-IIIA NSCLC were retrospectively included if they had received neoadjuvant immunotherapy combined with chemotherapy (IO+Chemo), dual immunotherapy (IO+IO), or chemotherapy alone (Chemo). We conducted ctDNA profiling before and after NAT, after surgery, and during follow-ups using an ultra-deep lung cancer-specific MRD (LC-MRD) sequencing panel.Results: A total of 22 patients who received NAT followed by surgery between August 2018 and July 2019 were included in this study. The major pathological response (MPR) rates were 58.33% (7/12) in the IO+Chemo group, 25.00% (1/4) in the IO+IO group, and 16.67% (1/6) in the Chemo group. The ctDNA dynamics during NAT were highly concordant with pathologic response, demonstrating 100% sensitivity and 83.33% specificity, for an overall accuracy of 91.67%. Pre-surgery detectable ctDNA (after NAT) trended to correlate with inferior RFS [hazard ratio (HR), 7.41; 95% confidence interval (CI): 0.91-60.22, log-rank P=0.03]. At 3-8 days after surgery, ctDNA was detectable in 31.8% of patients and was an independent risk factor for recurrence (HR, 5.37; 95% CI: 1.27-22.67; log-rank P=0.01). The presence of ctDNA at 3 months after surgery showed 83% sensitivity and 90% specificity for predicting relapse (C-index, 0.79; 95% CI: 0.62-0.95). During disease monitoring after surgery, molecular recurrence by means of ctDNA preceded radiographic relapse, with a median time of 6.83 months.Conclusions: This study investigated the potential of ctDNA in evaluating NAT efficacy in NSCLC, implying the high concordance between ctDNA and pathological response. We also set out the prognostic value of perioperative ctDNA in predicting recurrence.

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Section: Discussionmentioning

confidence: 99%

Circulating tumor DNA predicts neoadjuvant immunotherapy efficacy and recurrence-free survival in surgical non-small cell lung cancer patients

Yue¹,

Liu²,

Chen³

et al. 2022

Transl Lung Cancer Res

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“… Kim et al, 2019 ; Z. Li Y. et al, 2021 ; Perdrizet et al, 2021 ; Provencio et al, 2021 ; Yamaguchi et al, 2021 ). Erlotinib, the first approved target drug for NSCLC, is a reversible tyrosine kinase inhibitor that targets the epidermal growth factor receptor and can significantly improve the survival of LUAD patients ( Faehling et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Prognosis and Immunotherapy Response With a Novel Golgi Apparatus Signature-Based Formula in Lung Adenocarcinoma

Jiang

Ouyang

Zhang

et al. 2022

Front. Cell Dev. Biol.

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The Golgi apparatus (GA) is a cellular organelle that participates in the packaging, modification, and transport of proteins and lipids from the endoplasmic reticulum to be further fabricated before being presented to other cellular components. Recent studies have demonstrated that GA facilitates numerous cellular processes in cancer development. Therefore, this study aimed to establish a novel lung adenocarcinoma (LUAD) risk evaluation model based on GA gene signatures. In this study, we used TCGA-LUAD (n = 500) as the training cohort and GSE50081 (n = 127), GSE68465 (442), and GSE72094 (398) as the validation cohorts. Two immunotherapy datasets (GSE135222 and GSE126044) were also obtained from a previous study. Based on machine algorithms and bioinformatics methods, a GA gene-related risk score (GARS) was established. We found that the GARS independently predicted the prognosis of LUAD patients and remained effective across stages IA to IIIA. Then, we identified that the GARS was highly correlated with mutations in P53 and TTN. Further, this study identified that GARS is related to multiple immune microenvironmental characteristics. Furthermore, we investigated GSE135222 and GSE126044 and found that a lower GARS may be indicative of an improved therapeutic effect of PD-1/PD-L1 therapy. We also found that high GARS may lead to a better response to multiple anticancer drugs. Finally, we established a nomogram to better guide clinical application. To our knowledge, this is the first study to demonstrate a novel GA signature-based risk score formula to predict clinical prognosis and guide the treatment of LUAD patients.

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“…In summary, ctDNA levels increase proportionally according to tumor burden, disease stage, and metastasis, highlighting the use of ctDNA as a prognostic biomarker. Indeed, it is well established that patients with high levels of ctDNA have worsened survival outcomes compared with those with lower or even undetectable levels of ctDNA (82)(83)(84)(85).…”

Section: Ctdna As a Surrogate Of Tumor Burden Stage And Metastasismentioning

confidence: 99%

Circulating Tumor DNA as a Cancer Biomarker: An Overview of Biological Features and Factors That may Impact on ctDNA Analysis

et al. 2022

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Cancer cells release nucleic acids, freely or associated with other structures such as vesicles into body fluids, including blood. Among these nucleic acids, circulating tumor DNA (ctDNA) has emerged as a minimally invasive biomarker for tumor molecular profiling. However, certain biological characteristics of ctDNA are still unknown. Here, we provide an overview of the current knowledge about ctDNA biological features, including size and structure as well as the mechanisms of ctDNA shedding and clearance, and the physio-pathological factors that determine ctDNA levels. A better understanding of ctDNA biology is essential for the development of new methods that enable the analysis of ctDNA.

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Phase II clinical trial with metronomic oral vinorelbine and tri-weekly cisplatin as induction therapy, subsequently concomitant with radiotherapy (RT) in patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC). Analysis of survival and value of ctDNA for patient selection

Cited by 20 publications

References 31 publications

Circulating tumor DNA predicts neoadjuvant immunotherapy efficacy and recurrence-free survival in surgical non-small cell lung cancer patients

Circulating tumor DNA predicts neoadjuvant immunotherapy efficacy and recurrence-free survival in surgical non-small cell lung cancer patients

Prognosis and Immunotherapy Response With a Novel Golgi Apparatus Signature-Based Formula in Lung Adenocarcinoma

Circulating Tumor DNA as a Cancer Biomarker: An Overview of Biological Features and Factors That may Impact on ctDNA Analysis

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