Plasma cell-free DNA and circulating tumor cells as prognostic biomarkers in small cell lung cancer patients

Abstract

Background: Lack of biomarkers for treatment selection and monitoring in small-cell lung cancer (SCLC) patients with the limited therapeutic options, result in poor outcomes. Therefore, new prognostic biomarkers are needed to improve their management. The prognostic value of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) have been less explored in SCLC.Methods: We quantified cfDNA in 46 SCLC patients at different times during first-line of chemotherapy or chemo-immunotherapy. Moreover, CTCs were analyzed in 21 patients before therapy onset using CellSearch ® system. The possible association between both biomarkers and patients' outcomes was investigated in order to develop a prognostic model.Results: High cfDNA levels before therapy were associated with shorter progression-free survival (PFS) and overall survival (OS). Furthermore, cfDNA levels at 3 weeks and at progression disease were also associated with patients' outcomes. Multivariate analyses confirmed the independence of cfDNA levels as a prognostic biomarker. Finally, the three-risk category prognostic model developed included Eastern Cooperative Oncology Group Performance Status (ECOG PS), gender and baseline cfDNA levels was associated with a higher risk of progression and death. Conclusions:We confirmed the prognostic utility of cfDNA quantitative analysis in SCLC patients before and during therapy. Our novel risk prognostic model in clinical practice will allow to identify patients who could benefit with actual therapies.

Applied models and molecular characteristics of small cell lung cancer

“…Consistent with other studies, ctDNA monitoring has also been shown to identify disease recurrence prior to disease progression seen on imaging or in cases where imaging is equivocal [ 121 , 122 , 127 ]. Similar results were found in other studies, where cfDNA levels were found to be associated with disease outcome, as patients with high levels had a worse prognosis [ 129 ].…”

ROLE OF cfDNA AND ctDNA TO IMPROVE THE RISK STRATIFICATION AND THE DISEASE FOLLOW-UP IN PATIENTS WITH ENDOMETRIAL CANCER: TOWARDS THE CLINICAL APPLICATION

“…CfDNA levels are influenced by multiple factors such as age, metabolic activity, immune processes and disease, such as cancer (33). In patients with different solid tumour types cfDNA levels are found increased in comparison with healthy people and has been associated with poor prognosis in advanced stages (30,34) and, appart from the contribution of the tumour derived cfDNA in this increment, the neoplasic transformation may have systemic effect on cell turnover or DNA clearance associated with the cfDNA dynamic (30). In the present study we have shown that pre-surgery assessment of cfDNA levels correlates with poor clinical outcome, being a robust and independent prognostic biomarker for EC patients.…”

Clinical Significance of PD-L1 Status in Circulating Tumor Cells for Cancer Management during Immunotherapy

“…Tamminga et al have shown that CTCs occur in one-third of advanced NSCLC patients, and their presence is of high prognostic and predictive value before and after immunotherapy [ 30 ]. In SCLC, that 5-year relative survival rate is extremely low; the use of a much higher cut-off equivalent to 150 CTCs/7.5 mL of whole blood also has clinical utility [ 31 ]. In a phase II multicenter adaptive immunotherapy trial of 457 longitudinal liquid biopsies from 104 patients with Metastatic Renal Cell Carcinoma (mRCC), the change over time of CTC enumeration is of prognostic importance [ 32 ].…”