• 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2020-03
  • 2020-07
  • 2020-08
  • 2021-03
  • At present we do not


    At present, we do not suggest, that baseline STM should be used as a priori predictive biomarkers to guide therapy decisions. Current treatment guidelines depict clear indications for all available therapeutic options, so there is no clinical need for another baseline biomarker now. Future research may however provide further knowledge on molecular profiling of the tumor Lycopene and the immunological status [4], where perhaps baseline STM may play a role as one factor in panel of predictive biomarkers. At the moment however, rather than for baseline biomarkers, there is a need for additional dynamic parameters to be measured longitudinally throughout therapy that can supplement radiological re-staging examinations in unclear situations. Clearly, we do not suggest the application of STM analyses over the undisputed gold standard, which remains CT imaging. As shown by our data, initial radiological tumor regression is a sufficiently robust predictor or favorable patient outcomes with only little (but present) additional prognostic benefit of a concurrent STM decrease. The true highlight of our reported findings is the significantly improved PFS and OS that comes with STM decrease in the group of patients with initial SD or PD, as these are the very cases, where the treating physician needs additional biomarker information. Whether STM analyses can ultimately help clinicians overcome the challenges facing indeterminate initial radiological response to ICI therapy, needs to be elucidated in future larger-scale prospective study settings. r> Conflicts of interest statement
    Introduction Tyrosine-kinase inhibitors (TKIs) induce relatively durable responses in most patients with EGFR, ALK, or ROS1-altered non-small-cell lung cancer (NSCLC) patients, but resistance invariably develops at a median of about 10–15 months of therapy [[1], [2], [3], [4], [5]]. Next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) could be utilized to select appropriate molecularly-guided therapies in oncogene-driven NSCLC patients progressing on TKI therapy. The main advantage of this technology in the resistance setting includes the assessment of target-dependent as well as target-independent actionable resistance alterations in a single assay, avoiding the need of repeated tumor biopsies in some cases [6]. However, the utility of plasma-based NGS to impact the therapeutic management of TKI-resistant NSCLC patients in routine clinical practice has not been properly addressed in prospective studies thus far. In the present study, we have performed targeted ctDNA NGS in a multi-institutional prospective cohort of EGFR, ALK, or ROS1-altered NSCLC patients with TKI resistance. Our primary objective was to prospectively assess the real-world clinical utility of plasma-based NGS in the TKI resistance setting.
    Methods Institutional Ethics Committee approval was obtained before this study was initiated. A single protocol was contemporaneously distributed across 12 Spanish academic institutions that participated in this prospective study. Between January and September 2017, consecutive patients with EGFR, ALK, or ROS1-altered advanced-stage NSCLC who experienced clinical or radiological progression on prior TKI therapy were eligible for plasma-based NGS, irrespective of the timepoint when TKI progression had occurred or what the most recent treatment was. All patients provided signed informed consents before plasma genotyping and were subsequently registered in the study. We obtained blood samples from patients and ctDNA was isolated from plasma. Digital NGS of ctDNA was performed by Guardant Health, Inc. (Redwood City, CA) in all patients, using a hybrid-capture-based NGS panel detecting all four major types of genetic alterations in 73 genes (Guardant360 assay, supplementary methods). Detailed protocols for ctDNA isolation, sequencing and data analysis have been previously described [7,8] (supplementary methods).