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

Abstract

BackgroundCirculating 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 MethodsA 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.ResultsDynamic 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).ConclusionsThe 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.

The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

“…patients who carried driver mutations showed longer OS and PFS. Several studies have reported the use of NGS to detect the oncogenic driver mutations could guide therapy decisions and thus prolong the survival of NSCLC patients [16,17]. We believe that our real-world data may add new evidence for it.…”

Current and Future Molecular Testing in NSCLC, What Can We Expect from New Sequencing Technologies?

“…Resistance mutations to ALK-inhibitors can also be detected on ctDNA: in a cohort of 31 patients, McCoach et al showed that 16 samples (53%) contained 1–3 ALK resistance mutations [ 109 ]. ctDNA could, in the future, have wider clinical application as a prognostic marker and a marker of response to treatment independent of treatment type [ 110 ]. A recent study on 177 NSCLC highlighted that high ctDNA concentration was and independent prognostic factor for progression-free survival and overall survival.…”

Clinical utility of liquid biopsy for the diagnosis and monitoring of EML4-ALK NSCLC patients

“…cfDNA profiling has proved to be useful to guide personalized treatments based on the molecular profile, for early detection of resistance mechanisms [35,36], early detection of disease recurrences, as well as tumor response to therapy monitoring [37] by means of sequential liquid biopsies. Furthermore, several studies comparing the detection of EML4-ALK translocation by formalin-fixed paraffinembedded (FFPE) tissuesand liquidbiopsy havereportedthat indeed cfDNA can be used as a surrogate of FFPE DNA [38].…”

“…The sensitivity and specificity for the detection of EML4-ALK rearrangements in RNA isolated from platelets in patients has been reported to be between 65% and 100% respectively [56]. Even with the optimization of the preanalytical conditions of liquid biopsy samples, the sensitivity of the detection of EML4-ALK rearrangements using cfRNA was lower compared to platelet RNA (21% and 65% respectively) [36].…”