Abstract:Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non‐small‐cell lung cancer and melanoma patients. Cell‐free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA‐Q‐PCR or next‐generation sequencing. All 42… Show more
“…The prior reports showed that there was discordance in EGFR mutation status between primary tumor and CSF (35). It may result from low cellularity or ctDNA in the small amount of CSF or the low concentrations of the first and second generation of EGFR TKIs in CSF inadequate to drive the occurrence of T790M (36).…”
tissue samples or complications. In conclusion, this study showed that patients who progressed from gefitinib treatment, bearing common EGFR mutations, and with longer EGFR-TKI treatment duration had increased incidence of T790M acquisition and, therefore, were suitable for subsequent osimertinib treatment.
“…The prior reports showed that there was discordance in EGFR mutation status between primary tumor and CSF (35). It may result from low cellularity or ctDNA in the small amount of CSF or the low concentrations of the first and second generation of EGFR TKIs in CSF inadequate to drive the occurrence of T790M (36).…”
tissue samples or complications. In conclusion, this study showed that patients who progressed from gefitinib treatment, bearing common EGFR mutations, and with longer EGFR-TKI treatment duration had increased incidence of T790M acquisition and, therefore, were suitable for subsequent osimertinib treatment.
“…In this regard, other body fluids have been evaluated as an alternative source of tumor derived DNA. In fact, cfDNA from fluids in sites adjacent to metastases such as cerebrospinal fluid, pleural effusion, and ascites was found at higher levels, resulting in a more effective method in for detecting relevant mutations [50].…”
Non-small cell lung cancer is one leading cause of death worldwide, and patients would greatly benefit from an early diagnosis. Since targeted and immunotherapies have emerged as novel approaches for more tailored treatments, repeated assessments of the tumor biology have become pivotal to drive clinical decisions. Currently, tumor tissue biopsy is the gold standard to investigate potentially actionable biomarkers, but this procedure is invasive and may prove inadequate to represent the whole malignancy. In this regard, liquid biopsy represents a minimally invasive and more comprehensive option for early detection and investigation of this tumor. Today, cell-free DNA is the only approved circulating marker to select patients for a targeted therapy. Conversely, the other tumor-derived markers (i.e., circulating tumor cells, miRNAs, exosomes, and tumor educated platelets) are still at a pre-clinical phase, although they show promising results for their application in screening programs or as prognostic/predictive biomarkers. The main challenges for their clinical translation are the lack of reliable cutoffs and, especially for miRNAs, the great variability among the studies. Moreover, no established tool has been approved for circulating tumor cells and exosome isolation. Finally, large prospective clinical trials are mandatory to provide evidence of their clinical utility.
“…One of the alternate, more readily accessible liquid biopsy sources that has been exploited for molecular profiling is ctDNA obtained from serous body cavity effusion fluids. 30,46 A large percentage of patients with advanced stage NSCLC initially present with a malignant pleural effusion that may be the only tissue source for diagnosis and biomarker testing. Recent studies evaluating the cellfree component of these samples for tumor mutational profiling have highlighted the role of centrifuged supernatant fluids from these effusion samples in providing clinically relevant genomic information for primary driver mutations as well as those in a resistance setting.…”
Section: Pleural Effusion and Ascitic Fluidmentioning
Biomarker testing in patients with advanced stage non–small cell lung cancer provides essential information that can be used to select the most appropriate therapy. The regular updates of guideline recommendations reflect the growing number of biomarkers that must be assessed, and as such signal the shift from single‐gene assays to more comprehensive genomic profiling using next‐generation sequencing modalities. Cytology and small biopsy specimens have proven to be more than adequate substrates for these types of ancillary molecular testing; however, other alternative testing substrates are beginning to emerge. These include so‐called liquid biopsies as well the supernatant fluid from cytology specimens, both of which have demonstrated promise for use in the clinical realm. This review will briefly cover the current state of non–small cell lung cancer biomarker testing in the United States, with a focus on these novel nonconventional substrates that are increasingly being incorporated into testing paradigms.
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