The recent development of “liquid biopsy” technologies that analyze circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) allows physicians to obtain molecular data for guiding individual patient’s treatment approaches . CTCs are cells that have shed into the bloodstream from a primary or metastatic tumor, representing an alternative source of tumor material for non-invasive disease assessment [7,8]. Importantly, liquid biopsies provide a systemic representation of existing tumor clones, giving insight into tumor heterogeneity, emergence of new drivers, and the divergence between primary and metastatic tumors [6,9].
Here we describe a patient with recurrent breast cancer, who at one point declined an additional bone biopsy. Biocept’s Target Selector™ liquid biopsy  (Figure 1) revealed ER expression and HER2 gene amplification in CTCs (Figure 2). Based on these data, the patient was able to receive anti-HER2 therapy earlier, providing a clinical example of the utility of liquid biopsy testing to gather molecular data that was unsuccessful by standard image-guided biopsy. In this case, CTC results of newly found HER2 amplification were paramount towards altering treatment strategies and inclusion of HER2 targeted therapies, which ultimately extended patient survival and quality of life.
Each Biocept’s TargetSelector™ ctDNA assay shows >99% analytical sensitivity and >99% analytical specificity.
TargetSelector™ ctDNA assays show single mutant copy detection based on experimental data compared to theoretical estimates, with sensitivity at 0.02% MAF or better in a background of excess WT DNA.
Biocept’s ctDNA assays detected no false positives from 20 healthy donors, and showed >99% clinical specificity.
Implementation of the QuantStudio 5 qPCR platform into Biocept’sTargetSelector™ ctDNA assays ranslated into high clinical sensitivity and fast turnaround time for patients in Biocept’s CLIA certified and CAP accredited laboratory.
ROS1 is a receptor tyrosine kinase of the insulin receptor family, and ROS1 gene fusions are uncommon oncogenic drivers of NSCLC. Liquid biopsy represents a valuable alternative for molecular analyses when a traditional biopsy of the primary tumor yields insufﬁcient tissue.1 Moreover, liquid biopsies can detect aberrations missed in tissue testing of heterogeneous tumors. Here, we report the pioneering detection of ROS1 rearrangements in circulating tumor cells (CTCs) in cases in which next-generation sequencing (NGS) of plasma failed to identify a genetic alteration. Lung adenocarcinoma in a right pleural effusion was diag-nosed a 44-year-old male Hispanic nonsmoker. Molecu-lar testing of collected ﬂuid failed to reveal a genetic aberration. Palliative chemotherapy was initiated; it consisted of carboplatin/pemetrexed/bevacizumab for six cycles, followed by maintenance chemotherapy with pemetrexed/bevacizumab for 23 cycles. At the time of disease progression, the patient’s tumor was insufﬁcient for further molecular tests. Blood analysis was per-formed using the VeriStrat test (Biodesix, Boulder, CO). The patient began second-line erlotinib therapy, which was continued for 22 months until disease progression with peritoneal carcinomatosis. NGS done on plasma failed to reveal actionable gene aberrations; a biopsy was done, and a ROS1 gene translocation was identiﬁed in tissue and concordant with the results of subsequent ﬂuorescence in situ hybridization analysis of blood CTCs (Fig. 1). The patient began crizotinib therapy with disease stabilization. Brain metastases were detected 21 and 34 months later, and both were treated with stereotactic brain radiation. Because of the emergence of resistance, the patient was switched to ceritinib and has been stable for 6 months. ROS1 rearrangements have been detected in CTCs from four patients known to harbor ROS1 translocations in tumor tissue.2 However, our case is the ﬁrst in which ROS1 rearrangements were detected in CTC analysis of a peripheral blood sample when NGS evaluation of plasma failed to reveal genetic alterations. Thanks to conﬁrmation of the ROS1 rearrangement, the patient has been alive for 40 months while being treated with anaplastic lymphoma kinase inhibitors (criztonib ﬁrst and cetinib later). Moreover, detection of a ROS1 rearrangement in CTCs but not by NGS analysis of plasma suggests that CTC analysis may improve detection of this alteration, as we have seen with other genetic aberrations. We therefore encourage future comparisons of ROS1 detection techniques. Whether tumor tissue is truly the criterion standard for molecular analysis is currently disputed, as blood tests can reveal alterations not discovered in tumor tissue.3 Our study underscores the need to deﬁne an analytical criterion standard for identifying the largest possible amount of druggable alterations. In conclusion, we report that CTC analysis can identify ROS1 rearrangements. This and other liquid biopsies can improve patient clinical outcomes (i.e., expand therapeutic options) compared with tissue testing alone.