Dataset Information

Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients.

ABSTRACT:

Background

Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels.

Materials and methods

A total of 251 serial plasma samples from 41 non-small-cell lung cancer patients who carried an activating EGFR mutation were analysed by digital PCR. For survival analysis, ctDNA levels were computed as a time-dependent covariate.

Results

Dynamic ctDNA measurements had prognostic significance (hazard ratio for overall survival and progression free survival according to p.T790M mutant allele frequency; 2.676 and 2.71 respectively; P < 0.05). In the same way, patients with p.T790M-negative or unchanging or decreasing plasma levels of sensitizing EGFR mutation were 12 and 4.8 times more likely to maintain response or stable disease, respectively, than patients in which the opposite occurred (P < 0.05).On average, the p.T790M mutation was detected in plasma 51 days before the assessment of progression disease by CT-scan. Finally, ctDNA outperformed CTCs for assessing tumor progression (P = 0.021).

Conclusions

The appearance or increase in a unit of the p.T790M allele frequency almost triples the risk of death and progression. This information can be used to design clinical trials aiming to estimate whether T790M positive patients should start second line treatment based on molecular data rather than imaging data.

SUBMITTER: Provencio M

PROVIDER: S-EPMC5787483 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients.

Provencio Mariano M Torrente María M Calvo Virginia V Pérez-Callejo David D Gutiérrez Lourdes L Franco Fernando F Pérez-Barrios Clara C Barquín Miguel M Royuela Ana A García-García Francisco F Bueno Coralia C Garcia-Grande Aranzazu A Camps Carlos C Massuti Bartomeu B Sotomayor Eduardo E Romero Atocha A

Oncotarget 20171116 1

<h4>Background</h4>Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels.<h4>Materials and methods</h4>A total of 251 serial plasma samples from 41 non-small-cell lung cancer patients who carried an activating EGFR mutation were analysed by digital PCR. For survival analysis, ctDNA levels were computed as a time-dependent covariate.<h4>Results</h4>Dynamic ctDNA measurements had prog ...[more]

PMID: 29416630

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Project description:BackgroundThe plasma sample has emerged as a promising surrogate sample for EGFR mutation detection in advanced non-small cell lung cancer (NSCLC). In clinical practice, whether EGFR variants in baseline plasma ctDNA of advanced NSCLC can predict prognosis in addition to guiding targeted therapy remains to be further explored.Material and methodsIn total, 315 NSCLC patients were retrospectively enrolled. EGFR mutation data from tissue detected by ARMS-PCR and paired plasma samples within 1 month of admission detected by SuperARMS or ARMS-PCR were collected. The correlation between baseline plasma ctDNA EGFR mutation status and survival was compared.ResultsEGFR mutation detection rates in tumor samples and plasma samples were 65.1% (205/315) and 43.8% (138/315). Referred to tissue results, the consistent rate of test ctDNA EGFR alteration by SuperARMS was higher than that detected by ARMS (79.5% vs. 69.0%, p = 0.04), either in stage I-IIIA patients (85.7% vs. 50.0%, p = 0.4) or stage IIIB-IV patients (79.1% vs. 69.4%, p = 0.04). Patients' treatment status and pathological subtype were the two factors that affected plasma ctDNA EGFR alteration detection accuracy. The concordance in non-adenocarcinoma patients was obviously higher than that in adenocarcinoma (p = 0.02), and the concordance in treatment naïve patients was significantly higher than that in relapse patients (p = 0.047). In treatment naïve patients, the median PFS (mPFS) in plasma ctDNA EGFR-positive patients was shorter than that in plasma ctDNA EGFR negative patients (7.0 vs. 10.0 months, p = 0.01). In relapsed patients, the mPFS in plasma ctDNA EGFR-positive patients was 9.0 months versus 11.0 months in plasma ctDNA EGFR negative patients (p = 0.1).ConclusionsA plasma sample could be an alternative for a molecular test when tissue samples was unavailable. The SuperARMS-PCR detection method has high sensitivity in real-world clinical practice. Furthermore, in patients with stage IIIB-IV, baseline plasma ctDNA EGFR mutation positivity not only guides targeted therapy but also predicts a worse prognosis.

Project description:ImportancePrevious studies have suggested the importance of the baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) level as prognostic markers. The lung immune prognostic index (LIPI) was shown to be associated with progression-free survival (PFS) and overall survival (OS) among patients with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs) but not cytotoxic chemotherapy (CCT).ObjectiveTo determine whether the LIPI is associated with long-term outcomes in pooled analyses of clinical studies of ICI and targeted therapy (TT) for patients with mNSCLC.Design, setting, and participantsAn exploratory pooled analysis was performed of the LIPI on data from 11 randomized clinical multinational trials evaluating ICIs and TT submitted to the US Food and Drug Administration between January 1, 2013, and December 31, 2017, for 4914 patients with mNSCLC. Lung immune prognostic index scores were calculated based on the dNLR and the LDH level per previous publications to generate good, intermediate, and poor composite scores. Multivariable Cox proportional PFS and OS hazard ratios were generated for the dNLR, the LDH level, age, smoking status, histologic characteristics, and Eastern Cooperative Oncology Group performance score.Main outcomes and measuresOverall survival and PFS and their association with good, intermediate, or poor prognostic LIPI scores.ResultsEleven mNSCLC randomized trials were analyzed, including 3987 patients with available data. In 5 ICI trials comprising 2440 patients, 1368 patients received ICIs and 1072 patients received CCT. In 6 TT trials comprising 1547 patients, 1110 patients received TT and 437 patients received CCT. A good LIPI score was associated with better OS among patients receiving ICIs (hazard ratio, 0.34; 95% CI, 0.28-0.42), TT (hazard ratio, 0.28; 95% CI, 0.21-0.37), and CCT (hazard ratio, 0.49; 95% CI, 0.40-0.60 in ICI trials; hazard ratio, 0.41; 95% CI, 0.27-0.61 in TT trials) than those with poor LIPI scores. Similar findings were observed in terms of PFS (ICIs: hazard ratio, 0.59; 95% CI, 0.48-0.72; TT: hazard ratio, 0.46; 95% CI, 0.37-0.57; and CCT: hazard ratio, 0.56; 95% CI, 0.45-0.68 in ICI trials; hazard ratio, 0.51; 95% CI, 0.38-0.69 in TT trials).Conclusions and relevanceThe baseline LDH level and dNLR are important prognostic biomarkers irrespective of treatment modality for patients with mNSCLC. As further prospective clinical trial information is collected, the role of the LIPI score can be better defined.

Dataset Information

Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients.

Background

Materials and methods

Results

Conclusions

Publications

Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients.

Similar Datasets

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